Nullity of CCSS agreements on drug purchasing requirementsNulidad de acuerdos de la CCSS sobre requisitos para compra de medicamentos

JUDGMENT 120-2013 CONTENTIOUS-ADMINISTRATIVE AND CIVIL TREASURY TRIBUNAL, SECOND JUDICIAL CIRCUIT OF SAN JOSÉ, ANNEX A, SECTION FOUR, at fifteen hours thirty minutes of December twentieth, two thousand thirteen.

Ordinary proceeding processed under case file number 11-5719-1027-CA, brought by the CENTRAL AMERICAN FEDERATION OF PHARMACEUTICAL LABORATORIES (hereinafter FEDEFARMA), legal identification number CED87542, represented by its General Agent without sum limit, Álvaro Soto Monge, of legal age, married, resident of Moravia, identity card number CED87543, against the COSTA RICAN SOCIAL SECURITY FUND, the former represented in the proceedings by attorneys Carlos Ubico Durán, single, identity card number CED87544, resident of San José, and Alejandra Castro Bonilla, married, resident of Moravia, identity card number CED87545, all of legal age and lawyers, and the latter by its Judicial General Agent, attorney Eder José Ramírez Segura, of legal age, lawyer. Case file number xxxxxx.

WHEREAS

1- Based on the filed complaint (folios 1 to 49), the judgment orders: "(...) 2- That the following be declared absolutely null and void, for being contrary to the legal system, and therefore that the total annulment proceed of: // i) the agreement adopted in session No. 2010-44 of the Central Pharmacotherapy Committee (agreement number CCF 3376-11-10) published in the Official Gazette No. 10 of January 14, 2011 by the Logistics Management of the Costa Rican Social Security Fund, by virtue of which the 2009 Regulation with Requirements for Bidders of Biotechnological and Biological Drugs is modified and in its place the 2009 Regulation with Requirements for the Registration of Bidders for Biotechnological and Biological Drugs be applied; and // ii) the agreement adopted by the Central Pharmacotherapy Committee of the Costa Rican Social Security Fund in session 2011-08 held on February 23, 2011, in which it modified Point 6 of the requirements for drugs called antineoplastic and other drugs for specific use in oncological and hematological pathologies, published in Gazette No. 58 of March 23, 2011, and in its place the previous provision published in Gazette No. 47 of March 9, 2010 be applied. // 3- Given that the challenged agreements are null and void, we request that the validity of the following agreements be restored: // a- 2009 Regulation with Requirements for Bidders of Biotechnological and Biological Drugs and in its place the 2009 Regulation with Requirements for the Registration of Bidders for Biotechnological and Biological Drugs be applied, which corresponds to the version prior to the reform published in the Official Gazette No. 10 of January 14, 2011, relating to the agreement of the Logistics Management of the Costa Rican Social Security Fund (CCSS) adopted in session No. 2010-44 of the Central Pharmacotherapy Committee (agreement number CCF 3376-11-10). // b- Agreement called "Requirements for antineoplastic drugs and others for specific use in oncological and hematological pathologies" published in Gazette No. 47 of March 9, 2010, which corresponds to the version prior to the amending reform introduced in session 2011-08 held on February 23, 2011, by the Central Pharmacotherapy Committee of the CCSS, published in Gazette No. 58 of March 23, 2011. // 4- That the defendant be ordered to pay the procedural and personal costs of this proceeding." 2- At the opening of the oral and public trial, new facts were formulated and adjustments to the claims were made, adding (folio 451): "That the Costa Rican Social Security Fund apply the content of Decree 37006-S published in Official Gazette Number 59 of March 22, 2012, called Regulations for the Registration and Control of Biological Drugs, which is consistent with the prior regulations of the Costa Rican Social Security Fund, whose validity we requested be restored in point 3 of the claims of the complaint." 3- The defendant's representation answered the complaint in the negative, raising the defenses of Lack of Standing and Lack of Right.

4- The oral and public trial was held in the first and second hearings of August 20 and 21, the first hearings of August 22, 23, and September 17, and the second hearings of October 29 and November 26, all in 2013, which both parties attended.

5- Judge Ricardo Madrigal Jiménez, a member of the Tribunal, was on medical leave from September 9 to 13, 2013 (folios 459, 460, 462, and 463).

6- On October 3, 2013, in accordance with article 110 of the Contentious-Administrative Procedural Code, the reopening of the debate was ordered, and the plaintiff was warned to present its proof of authority (folio 465); the reopening hearing took place on October 29, 2013, which both parties attended.

7- Judge Loaiza Sánchez, a member of the Tribunal, was on medical leave from November 4 to 8, 2013 (folio 564).

8- On November 21, 2013, in accordance with article 110 of the Contentious-Administrative Procedural Code, the reopening of the debate was ordered to submit for discussion evidence for a better decision offered during the deliberation stage by the defendant, which was admitted by the Tribunal (folio 573). The reopening hearing took place on November 26, 2013 (folio 576).

9- Judge Loaiza Sánchez was on medical leave from November 29 to December 6, 2013 (see folios 577 and 578).

10- During the oral and public trial, evidence for a better decision was ordered, which was brought to the parties' attention and discussed during the trial reopening.

11- The legal requirements have been observed in the proceedings; there are no defects capable of producing nullity, and this resolution is issued within the period established in article 111 of the Contentious-Administrative Procedural Code for complex proceedings, after deliberation and unanimously:

Judge Loaiza Sánchez writes;

CONSIDERING:

I- NEW FACTS: These were formulated as such in the oral and public trial hearing by the plaintiff, in the following terms: "TWENTY-SECOND FACT: That in Gazette 59 of March 22, 2012, Executive Decree No. 37006-S, Regulations for the Registration and Control of Biological and Biotechnological Drugs, was approved, regulating the requirements for the registration of drugs of biological origin, that is, biological and biotechnological drugs. TWENTY-THIRD FACT: That the agreement adopted in session No. 2010-44 of the Central Pharmacotherapy Committee (agreement Number CCF- 3376-11-10), published in the Official Gazette No. 10 of January 14, 2011 by the Logistics Management of the Costa Rican Social Security Fund, by virtue of which the 2009 Regulation with Requirements for the Registration of Bidders for Biotechnological and Biological Drugs is modified, presents significant contradictions with respect to Executive Decree No. 37006-S, which we detail below: //1. In Article 5.6 of Executive Decree No. 37006-S, the Ministry of Health requires that the biosimilarity exercise related to quality must be submitted, in comparison with the reference biotechnological drug, to determine that there are no additional implications for safety and efficacy, for which the regulation details a series of studies related to the drug's structure, among others. Similarly, article 5.12 details the information on safety and efficacy that must be provided, including preclinical studies (in vivo and in vitro) as well as comparative clinical studies with the original reference drug. The requirements detailed in these articles of the regulation are not required by the CCSS, which only requests the qualitative-quantitative formula of the drug (see norms that contradict decree 37006-S: Group 1, point 3; Group 2, point 2 of the challenged norm). // 2. The Regulation issued by the Ministry of Health establishes in article 5.12 that experience with biosimilar products shall be measured in accordance with what the World Health Organization establishes, for which it requests preclinical and clinical studies as well as the detail required by the guidelines of strict authorities (FDA, EMA, and ICH) and the detail of the biosimilarity studies applied. Such tests are not required by the CCSS's regulation, which instead requests as the sole experience of the biotechnological product that the product has "extensive clinical experience" within the CCSS. Therefore, the CCSS's regulation (see norms that contradict decree 37006-S: Group 1, point 8; Group 2, point 7 of the challenged norm) contradicts the regulation issued by the Ministry of Health. // 3. In note 2 of article 5 of Executive Decree No. 37006-S, the Ministry of Health requires for all biosimilarity studies that the WHO guidelines (provided in the record at folios 41 to 91 of the precautionary measure file) or the norms issued by strict authorities (FDA, EMA, and ICH) must be used. However, the CCSS's regulation allows the CCSS to even dispense with those studies, even though the Ministry of Health establishes no exception for not requesting them (Norms that contradict decree 37006-S: Group 1, point 8; Group 2, point 7 of the challenged norm). // 4. Article 5.3 of Decree No. 37006-S establishes as requirements for the sanitary registration of biological drugs, information on the product's regulatory status internationally, as well as inspections of international laboratories. This information ensures that the biotechnological products introduced to the market have experience in other markets and therefore proves their effective experience, safety, and efficacy at the time of registration, as well as that the drug has had positive or negative effects in a specific population. However, the CCSS's regulation exclusively requests experience of the product within the CCSS itself, not at the international regulatory level (see norms that contradict decree 37006-S; Group 1, point 8; Group 2, point 7 of the challenged norm). // 5. Article 10 of Decree 37006-S requires reports of Risk Management and Pharmacovigilance Plans, which the CCSS does not require in its regulation and which are essential to monitor the immunogenicity of a biotechnological drug. // 6. The Ministry of Health does not endorse the interchangeability of biotechnological drugs, while the CCSS allows such interchangeability without restrictions (see norms that contradict decree 37006-S: Group 1, point 8; Group 2, point 7 of the challenged norm). The consequence of this contradiction lies in the fact that if the CCSS is endorsing products by virtue of their "extensive clinical experience" demonstrated in the CCSS, it is not possible to prove said successful clinical experience through pharmacovigilance, because if interchangeability is endorsed, it becomes impossible to track the behavior of one therapeutic solution versus the other, and therefore impossible to verify what the product's experience is; especially when dealing with narrow therapeutic margin drugs that treat extremely serious conditions. TWENTY-FOURTH FACT: Executive Decree No. 37006-S is the only one that complies with the stipulations of the World Health Organization, because unlike the CCSS's regulation, it requires that for the marketing authorization of a biotechnological drug, a series of essential requirements that the WHO demands be fulfilled, through the "Procedure for prequalification of pharmaceutical products issued by the World Health Organization" (folio 54-41 precautionary measure) and the "Guidelines on the evaluation of similar biotherapeutic products issued by the World Health Organization" (Folio 91-55 precautionary measure). It is extremely important to maintain these requirements demanded for the sanitary registration of biotechnological drugs, as well as those detailed in the Ministry of Health regulation, especially considering that the CCSS may, and in fact does, purchase drugs that do not have sanitary registration in Costa Rica; they could acquire products that only comply with the scarce CCSS requirements and not with those of the Ministry of Health." In accordance with article 68 of the Contentious-Administrative Procedural Code, and the preceding facts having been rebutted within the established procedural stage, this Tribunal proceeds to admit them as new facts, which are incorporated into the initial complaint, and will proceed in the following recitals to their analysis. Note that these correspond to factual situations that occurred after the complaint was filed and are intimately related to the proceeding at hand; in this way, the applicable regulatory conditions are satisfied.

II- PROVEN FACTS. THE FOLLOWING ARE CONSIDERED AS DEMONSTRATED:

1- By means of executive decree 28466 of February 8, 2000, the Regulations for the Registration, Control, Importation, and Advertising of Drugs (General Data) were issued, with the objective of establishing the requirements and procedures necessary for the registration, control, importation, and advertising of drugs, applicable to all persons who manufacture, import, and market drugs in the national territory (publicly accessible document); 2- By means of agreement CCF-1445-06-09, session 2009-21 of June 10, 2009, the Central Pharmacotherapy Committee of the Costa Rican Social Security Fund established the requirements to be met for the registration of bidders for biotechnological drugs, for both Group 1, drugs of biological origin whose manufacturing process does not use raw material from blood products (human plasma), and Group 2, drugs of biological origin whose manufacturing process uses raw material from blood products (human plasma) (see folios 222 to 226 of the administrative file, volume I, and 117 of volume 2); 3- In the first (1) Group of Drugs of Biological Origin, the bidder had to submit the following requirements: "1. Certificate of sanitary registration of the drug issued by the Ministry of Health of Costa Rica. 2. For innovator drugs, the complete qualitative-quantitative formula must be attached with the excipients used and the permitted ranges of related substances, as well as the drug characterization studies. 3. For biosimilar drugs, the complete qualitative-quantitative formula must be attached with the excipients used and the permitted ranges of related substances, as well as the drug characterization studies; in addition, they must present the drug characterization studies compared with the reference drug marketed in Costa Rica. 4. Drugs whose manufacturing process does not use blood product raw material but whose formulation, and by means of their qualitative formula, is verified to include human plasma excipients such as albumin, must comply with all the current guidelines established in the Blood Products Decree No. 19981-S of October 3, 1990. 5. They must comply with the quality specifications established in the official technical data sheet corresponding to each drug. 6. The Bidder Registry of the Drug Standards and Quality Laboratory and the Central Pharmacotherapy Committee clearly establish that only biological products, whether registered with the Ministry of Health of Costa Rica or not, but which are used in the following countries, are endorsed: United States (FDA), and/or countries of the European Community (EMEA), and/or Canada, and/or Japan, and/or Switzerland. 7. In the case of innovator drugs, the manufacturing laboratories must present Free Sale Certificates for the drug in the country of origin, such as the United States, European Economic Community, Canada, Japan, Switzerland, issued by the regulatory health authority of that country. 8. In the case of biosimilar drugs, the manufacturing laboratories must present Free Sale Certificates for the drug in the country of origin, such as the United States, European Economic Community, Canada, Japan, Switzerland, issued by the regulatory health authority of that country, as well as a certificate issued by the same health entity, guaranteeing that the drug meets the quality criteria requested for biological drugs and that it has clinical safety and efficacy studies that gave rise to its sanitary registration in the country of origin, that it has clinical studies of immunogenicity (applicable only for drugs marked with *****), safety and efficacy, in the same official indications as the reference product marketed in the country, as well as the characterization and comparability studies demonstrating that the product is biosimilar to the reference product marketed in Costa Rica. In addition, the complete qualitative-quantitative formula must be attached with the excipients used and the permitted ranges of related substances, and the certification from the Health Authority (EMEA and/or FDA) accrediting it as a biosimilar drug. 9. All documents that are requested to be issued abroad (other countries) must be consularized and presented in the Spanish language. 10. The Institution, based on the extensive clinical experience acquired over the years with the use of biological drugs, reserves its judgment on certain specifications and requirements to be evaluated for the inclusion of new drugs sharing the same code, in the bidder registry and unregistered drugs; and only endorses the interchangeability of biological products that have documented safety and efficacy proven through their clinical use in the Institution over the years." (See folios 224 and 225 of the administrative file); 4- In the second (2) Group of Drugs of Biological Origin, the bidder had to submit the following requirements: "1. Certificate of the Sanitary Registration of the Drug issued by the Ministry of Health of Costa Rica. 2. Attach the complete qualitative-quantitative formula with the excipients used and the permitted ranges of related substances. 3. Must comply with the Quality Specifications specified in each corresponding technical data sheet for each drug. 4. Must comply with all regulations required by the Ministry of Health of CR and everything requested by the Drug Standards and Quality Laboratory of the CCSS regarding blood products. 5. The Bidder Registry of the Drug Standards and Quality Laboratory and the Central Pharmacotherapy Committee clearly establish that only biological products, whether registered with the Ministry of Health of Costa Rica or not, but which are used in the following countries, are endorsed: United States (FDA), and/or countries of the European Community (EMEA), and/or Canada, and/or Japan, and/or Switzerland. 6. All documents that are requested to be issued abroad (other countries) must be consularized and presented in the Spanish language. 7. The Institution, based on the extensive clinical experience acquired over the years with the use of biological drugs, reserves its judgment on certain specifications and requirements to be evaluated for the inclusion of new drugs sharing the same code in the bidder registry; and only endorses what has documented safety and efficacy proven through their clinical use in the Institution over the years. 8. The manufacturing laboratory must guarantee that the human plasma used as raw material in the manufacture of each of the biological drugs must come from healthy human beings and be entirely free of viruses or other pathogens, and must comply with the current guidelines established in the Blood Products Decree No. 19981-S of October 3, 1990." (see folio 226 of the administrative file); 5- Said agreement was published in the official journal La Gaceta, number 127, of July 2, 2009 (see folio 222 of the administrative file); 6- The Central Pharmacotherapy Committee, through session 2010-44, agreement 3376-11-10 of November 17, 2010, proceeded to modify the regulation with requirements to be met for the registration of bidders for biotechnological and biological drugs, issuing a new regulation, which was published in Gazette number 10 of January 14, 2011 (see folios 230 to 239 and 264 of volume II of the administrative file); 7- The cited regulation was approved in the following terms: "In this first Group of Drugs (Group 1) of biological origin, the bidder must submit the following requirements: 1. Certificate of sanitary registration of the drug issued by the Ministry of Health of Costa Rica. 2. For innovator drugs, the complete qualitative-quantitative formula must be attached with the excipients used and the permitted ranges of related substances, as well as the drug characterization studies (physicochemical and pharmacological). 3. For biosimilar drugs, the complete qualitative-quantitative formula must be attached with the excipients used and the permitted ranges of related substances, as well as the drug characterization studies (physicochemical and pharmacological). 4. Drugs whose manufacturing process does not use blood product raw material but whose formulation, and by means of their qualitative formula, is verified to include human plasma excipients such as albumin, must comply with all the current guidelines established in the Blood Products Decree No. 19981-8 of October 3, 1990. 5. Must comply with the quality specifications established in the official technical data sheet corresponding to each drug. 6. All those suppliers of biological or biotechnological drugs who need to prequalify before the Supplier Registry or bid their products to the Institution must present a certificate that said drugs are registered and/or marketed in any of the following countries: United States (FDA), Canada (Health Canada), Japan (MHLW), Switzerland (Swissmedic), and member countries of the European Economic Community that are registered with the European Medicines Agency (EMA) or that have Mutual Recognition in any of the reference member states of the European Economic Community. These countries are considered as reference because they have high standards in drug regulation. 7. All documents that are requested and that are issued abroad must be consularized and certified by a notary public, as required by Costa Rican legislation and the consular legalization chain of our country, and ratified by the Ministry of Foreign Affairs. All documents must be presented in the Spanish language, and if in another language, the official translation of the original document into Spanish must be attached. 8. "The Institution, based on the extensive clinical experience acquired over the years with the use of biological drugs, reserves its judgment on certain specifications and requirements to be evaluated, not only for the inclusion of new drugs sharing the same code in the bidder registry and unregistered drugs, but also for their acquisition, technically endorsing the interchangeability of biological products that have documented safety and efficacy, proven through their clinical use in the Institution over the years. In the case of biological drugs (same manufacturing laboratory) that have been historically acquired and used at the Institutional Level, with proven experience of use and support of their efficacy and safety, it is permissible to exempt them from the requirements established in point 6, without prejudice to compliance with the rest of the established requirements. Bidders of biological drugs (same manufacturing laboratory) with which there is historical experience of Institutional use and that would be exempted from the requirements indicated in point 6 must attach the free sale certification of the drug in the country of origin of the manufacturing laboratory, complying with the provisions of point 7." Regarding the second Group of Drugs (Group 2) of biological origin, the bidder must submit the following requirements: "1. Certificate of Sanitary Registration of the Drug issued by the Ministry of Health of Costa Rica. 2. Attach the complete qualitative-quantitative formula with the excipients used and the permitted ranges of related substances. 3. Must comply with the Quality Specifications indicated in each corresponding technical data sheet for each drug. 4. Must comply with all the regulations requested by the Ministry of Health of CR and everything requested by the Drug Standards and Quality Laboratory of the CCSS regarding blood products. 5. All those suppliers of biological or biotechnological drugs who need to prequalify before the Supplier Registry or bid their products to the Institution must present a certificate that said drugs are registered and/or marketed in any of the following countries: United States (FDA), Canada (Health Canada), Japan (MHLW), Switzerland (Swissmedic), and member countries of the European Economic Community that are registered with the European Medicines Agency (EMA) or that have Mutual Recognition in any of the reference member states of the European Economic Community. These countries are considered as reference because they have high standards in drug regulation. 6. All documents that are requested and that are issued abroad must be consularized and certified by a notary public, as required by Costa Rican legislation and the consular legalization chain of our country, and ratified by the Ministry of Foreign Affairs. All documents must be presented in the Spanish language, and if in another language, the official translation of the original document into Spanish must be attached. 7. "The Institution, based on the extensive clinical experience acquired over the years with the use of biological drugs, reserves its judgment on certain specifications and requirements to be evaluated, not only for the inclusion of new drugs sharing the same code in the bidder registry and unregistered drugs, but also for their acquisition, technically endorsing the interchangeability of biological products that have documented safety and efficacy, proven through their clinical use in the Institution over the years. In the case of biological drugs (same manufacturing laboratory) that have been historically acquired and used at the Institutional Level, with proven experience of use and support of their efficacy and safety, it is permissible to exempt them from the requirements established in point 5, without prejudice to compliance with the rest of the established requirements. Bidders of biological drugs (same manufacturing laboratory) with which there is historical experience of Institutional use and that would be exempted from the requirements indicated in point 5 must attach the free sale certification of the drug in the country of origin of the manufacturing laboratory, complying with the provisions of point 6." 8. The manufacturing laboratory must guarantee that the human plasma used as raw material in the manufacture of each of the biological drugs must come from healthy human beings and be entirely free of viruses or other pathogens, and must comply with the current guidelines established in the Blood Products Decree No. 19981-8 of October 3, 1990.

These requirements are mandatory for any new biotechnological or biological medication of group 1 or group 2 that is included in the LOM" (see folios 236 to 239 of volume II of the administrative file); 8 - By agreement CCF-0275-02-09, session 2009-21, the Central Pharmacotherapy Committee of the Caja Costarricense del Seguro Social established the Specific conditions for the acquisition of medications called antineoplastics and other medications for specific use in oncological and hemato-oncological pathologies, published in gazette number 47 of March 9, 2010 (see folios 266 and 267 verso of the administrative file); 9- The cited general act was issued in the following terms: "Point 1: For antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies, a certification issued by the General Medical Directorate of the General or Oncological Hospital or Cancer Institute of the country of origin of the manufacturing laboratory must be submitted, signed by the highest authority in medical oncology and the General Medical Director of the Medical Center, indicating the annual quantity consumed by patients of the medication manufactured by said laboratory, the number of beds in that hospital designated for adults and the occupancy rate (for parenteral medications), and the number of oncology and onco-hematology consultations (for oral medications). All information must correspond to the same year in which it is registered with the Caja or preferably to the year prior to the registration date. When the CCSS performs the analysis, if the drug has a consumption level in the General or Oncological Hospital or Cancer Institute of the country of origin equal to or greater than 100% of that consumed at the Hospital Nacional San Juan de Dios, it will be determined through a comparative study of defined daily dose (DDD) per 100 hospital beds/day for parenteral medications, and with a comparative study of defined daily dose (DDD) per 1000 consultations/day for oral medications; they will be given supplier endorsement and will be incorporated into the Caja's Registry. In the case of suppliers that are National Laboratories, based on a comparative study of defined daily dose (DDD) per 100 hospital beds/day (parenteral medications) or 1000 consultations/day (oral medications) using the Hospital San Juan de Dios as a reference, if the result is equal to or greater than the DDD study from the year prior to the medication's Registration with the Caja, they will be given supplier endorsement and will be incorporated into the Caja's Registry. For national laboratories, the information related to consumption at the Hospital San Juan de Dios (National reference hospital) will be obtained through the internal information mechanisms available at the institution. Point 2: The specific medication (oral or parenteral) for which entry into the Caja's supplier registry is requested for its registration, or the medication to be acquired at the Central or Local level, must present certification issued by the Medical Directorate of the General or Oncological Hospital or Cancer Institute of the country of origin of the manufacturing laboratory, signed by the highest authority in medical oncology and the General Medical Director of the Medical Center, presenting the annual consumption in patients corresponding to the same year, efficacy and safety results obtained with the use of the medicinal product in the treatment of patients with hemato-oncological pathology, and the type of oncological pathologies treated. The documents must completely and concisely contain the type and percentage of side effects presented by patients who have received treatment with said product for analysis. Point 3: Certification from the Ministry of Public Health or the highest equivalent Public Health authority in the country of origin of the manufacturing Laboratory, presented by its representative, recognizing the General or Oncological Hospital or Cancer Institute seeking to be registered. Point 4: All requested certification must be submitted individually, and the information must refer to the closest previous year to the date of its inclusion in the Medication Suppliers Registry before the CCSS for medications included in the Official List of Medications, or correspond to the closest previous year to the tender for medications not included in the Official List of Medications that are acquired at the Central or local level. These certifications must be updated each time renewal of the registration is requested before the CCSS for medications included in the LOM; if not registered, each time a purchase is made at the Central or local level in the case of non-LOM medications. Point 5: All requested documents must bear the signatures of health authorities, duly authenticated as required by Costa Rican legislation, in addition to completing the consular legalization chain of our country and ratified by the Ministry of Foreign Affairs of Costa Rica. Point 6: Antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies for parenteral or oral use that are registered and consumed in any of the following countries shall be exempt from the requirements set forth in points 1, 2, 3, and 4: United States (FDA), Canada (Health Canada), Japan (MHLW), Switzerland (Swissmedic), Germany, England, Sweden, France, Italy, Spain, Belgium, Denmark, Austria, Netherlands, Finland, Norway. It is important to note that laboratories must present the certificate of free sale of their product in the United States (FDA), Canada, Japan (MHLW), Switzerland (Swissmedic), Germany, England, Sweden, France, Italy, Spain, Belgium, Denmark, Austria, Netherlands, Finland, Norway; or with registration and commercialization in these same countries. Likewise, those medications whose origin does not correspond to any of the above-listed countries, but that have the Mutual Recognition certificate issued by the EMEA for their commercialization in any of the reference member states of the European Union, shall be exempt. This certificate must be issued by the highest competent regulatory authority in public health of the respective country. Point 7: A supplier already registered in the CCSS supplier registry may revalidate their registration by submitting the information indicated in the corresponding points above. Said registration shall be valid until the expiration of the sanitary registration (registro sanitario) issued by the Ministry of Health of Costa Rica. Point 8: Those suppliers who are registered but prefer to submit their data at the time of the purchasing process and not revalidate their registration with the CCSS until its expiration must submit the requirements for antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies for each purchasing process. Point 9: In the case of the acquisition of antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies included in the Official List of Medications (LOM), the Medications and Clinical Therapeutics Area attached to the Directorate of Pharmacoepidemiology shall be responsible for performing the data analysis and the corresponding Defined Daily Dose (DDD) study. Point 10: In the case of NON-LOM antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies acquired by each center, the data analysis and the corresponding Defined Daily Dose (DDD) study shall be performed each time a purchasing process is initiated and shall be carried out and analyzed by each Pharmacy Service. Point 11: Once the Executive Decree of the Ministry of Public Health regulating Medication Registration is published, which contemplates the specific requirements for molecular target therapy products, these requirements are based on ICH recommendations and form part of these conditions. Point 12: In the case of offers for antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies for parenteral or oral use not included in the Official List of Medications that are acquired at the Central or local level and are under equal conditions, as a tie-breaking mechanism, priority shall be given to the medication that is registered and consumed in any of the following countries: United States (FDA), Canada, Japan, Switzerland, Germany, England, Sweden, France, Italy, Spain, Belgium, Denmark, Austria, Netherlands, Finland, Norway. The supplier must present certification issued by the highest regulatory authority of the country stating that it is registered and consumed in one of the aforementioned countries. In response to the Cancer Council's request regarding bioequivalence requirements and requirements for antineoplastic medications of biotechnological origin, the mechanism established by the Ministry of Health and CCSS shall continue." (see folios 266 and 267 verso of the administrative file); 10- Through session 2011-08 held on February 23, 2011, by the Central Pharmacotherapy Committee, point 6 was modified in the following terms: "Point 6: Antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies for parenteral or oral use that have a marketing authorization in any of the following countries shall be exempt from the requirements set forth in points 1, 2, 3, and 4: United States (FDA), Canada (Health Canada), Japan (MHLW), Switzerland (Swissmedic), Germany, England, Sweden, France, Italy, Spain, Belgium, Denmark, Austria, Netherlands, Finland, Norway, Colombia (INVIMA), Argentina (ANMAT), Brazil (ANVISA). It is important to note that laboratories must present: the pharmaceutical product certificate (or Certificate of Free Sale plus the Certificate of Good Manufacturing Practices), as backing for their registration and marketing authorization in the United States (FDA), Canada, Japan (MHLW), Switzerland (Swissmedic), Germany, England, Sweden, France, Italy, Spain, Belgium, Denmark, Austria, Netherlands, Finland, Norway, Colombia (INVIMA), Argentina (ANMAT), Brazil (ANVISA). Likewise, those medications whose origin does not correspond to any of the above-listed countries, but that have the Mutual Recognition certificate for their commercialization in any of the reference member states (European Union), shall be exempt. This certificate must be issued by the highest competent regulatory authority in public health of the respective country. To exempt them from the requirements listed in points 1, 2, 3, and 4, it is necessary that the pharmaceutical product certificates (or Certificate of Free Sale) include the name and address of the manufacturing plant, which must coincide with the address of the manufacturing plant of the medication registered with the Ministry of Health of Costa Rica (provided the medication is registered in the country). The manufacturing plant (name and address) from which the registered medication originates, with marketing authorization in one of the countries listed above, must correspond to the same manufacturing plant from which the medication to be delivered to the CCSS will be imported." This was published in gazette number 58 of February 23, 2011 (see folio 310, 311, and 322 of the administrative file); III- UNPROVEN FACTS Of relevance for the resolution of this proceeding, the following is considered unproven: Sole: That the defendant entity followed the procedure regulated in Article 361 of the Ley General de la Administración Pública at the time of issuing the general provisions challenged herein, and which was accepted by the defendant itself (there is no evidence of this in the record).

IV- ON THE PARTIES' ARGUMENTS The plaintiff alleges the nullity of the agreement adopted through Session No. 2010-44 of the Central Pharmacotherapy Committee (agreement number CCF 3376-11-10, which is of a regulatory nature), by modifying the regulations already established in 2009, as well as the nullity of the agreement issued in session 2011-08 of February 23, 2011, which modifies point 6 of the requirements for medications called antineoplastics and other medications for non-specific use of specific use in oncological and hematological pathologies, and requests that instead, the validity of the modified rules be restored. For this purpose, it claims standing under the collective interest conferred by numeral 10, subsection 2 of the Código Procesal Contencioso Administrativo, arguing that the reform carried out by the Central Pharmacotherapy Committee of the Caja Costarricense del Seguro Social, specifically regarding the elimination of mandatory requirements that any biotechnological or biological medication must meet to be a supplier to the Caja Costarricense del Seguro Social, affects the community and violates principles of the World Health Organization. It claims that the challenged regulation mentions biological and biotechnological medications as being of the same typology, when what is intended to be regulated is exclusively biotechnological medications. Additionally, the evaluation criteria for these medications are insufficient to certify their quality. According to the challenged regulation, suppliers are exempted from presenting medication characterization studies, which does not guarantee the quality of the medication by making its use more flexible without verifying compliance with the evaluation guidelines issued by recognized "strict" authorities such as the WHO and the EMA, among other international bodies, which does not guarantee the safety, effectiveness, and efficacy of the medication that is essential for patients. It adds that for innovator medications, the manufacturing laboratories are exempted from presenting the certificate of free sale from the country of origin. It points out that the Caja Costarricense del Seguro Social endorses medication interchangeability (intercambiabilidad), which threatens patient health because, for medications of biotechnological composition, the interchangeability of chemical synthesis products cannot be compared, which could generate serious implications for the patient's health. Since pharmacovigilance (farmacovigilancia) has not been developed satisfactorily and safely in the institution, it is not possible to monitor the effects of interchangeability for the benefit of patient health. It further points out that the regulatory norms regarding pharmacovigilance do not contain risk analysis processes designed to address the nature of the biotechnological product. On the topic of immunogenicity (inmunogenicidad), it argues that with the pharmacovigilance process being absent, it is not possible to determine the immunogenicity of medications, placing patients at risk. It argues the nullity of the administrative acts (actos administrativos) due to defects in their formation, as they were not consulted as established by the Ley General de la Administración Pública for acts of general scope (actos de alcance general) such as those challenged here. At the trial hearing, it presented new facts based on a regulation subsequently issued by the Ministry of Health, pointing out that the challenged acts contradict those established by the cited act of general scope. The representation of the Caja Costarricense del Seguro Social rejects the claim. Firstly, it questions the standing with which the plaintiff appears in the proceedings, alleging an interest of the entire community, highlighting that in its own claim it admits that its primary interest is the impact on all the companies represented by Fedefarma, insofar as the requirements to become suppliers are made more flexible. Regarding the 2010 regulations for the supplier registration for biotechnological and biological medications, the Central Committee of Pharmacodependence, in the absence of specific regulations from the Ministry of Health, is the one that must impose the requirements for suppliers in the medication acquisition process. Concerning medications called antineoplastics and other medications for specific use in oncological and hematological pathologies, the modification referring to the incorporation of countries such as Argentina, Brazil, and Colombia was motivated by the fact that they were classified as Level IV regional reference regulatory authorities by PAHO/WHO in the performance of their functions, and that based on certificates from these regulatory authorities, they would be exempted from the requirements established in points 1, 2, 3, and 4. All of this was the product of a study and technical reasoning by the Central Pharmacotherapy Committee, and therefore it does not entail any risk to public health, as it does not compromise the efficacy and safety of the treatments used for cancer patients; on the contrary, it is based on higher standards established by PAHO/WHO. Regarding the indistinct use of the terms biological and biotechnological, the regulation establishes the requirements for supplier registration for both. Likewise, biotechnological medications must also have immunogenicity and pharmacovigilance studies. The regulation under discussion also establishes that biosimilar medications must attach the complete qualitative-quantitative formula with the excipients used and the permitted ranges of related substances, as well as medication characterization studies. Regarding the topic of immunogenicity, it argues that the country does not have the capacity to carry out this type of study; however, it has an active pharmacovigilance program of spontaneous notifications. It argues that internationally there is no real consensus on the interchangeability of biotechnological products; however, the Social Security institution has extensive clinical experience in the use of biotechnological medications, where therapeutic benefit in managing various pathologies has been documented. Regarding the procedural defect pointed out by the plaintiff concerning the absence of the hearing provided for in numeral 361 of the Ley General de la Administración Pública, it states that the formal defect does not apply because it is specific to acts of a general nature issued by the Executive Branch, not by autonomous Institutions like the defendant here, in addition to the fact that the general provisions issued are technical regulations adopted by technical advisory bodies like the Pharmacotherapy Committee of the Caja Costarricense del Seguro Social in its capacity as a technical advisor. It raises the defense of Lack of Active Standing (Falta de Legitimación Activa), accusing the plaintiff of ultimately having a commercial interest and not seeking to enforce community rights, and Lack of Right (Falta de Derecho). It requests that the claim be dismissed.

V- ON THE REPRESENTATION OF THE PLAINTIFF IN THE PROCEEDING.

By resolution issued at one fifteen in the afternoon on October three, two thousand thirteen, this Collegiate Body, pursuant to numerals 66 subsection b and 92 subsection 1 of the Código Procesal Contencioso, cautioned the plaintiff to provide the proceedings with the legal status (personería) of the Federación Centroamericana de Laboratorios Farmacéuticos (FEDEFARMA), to indicate if it is registered in the [papis], its validity, and if not, to present duly legalized documents proving its constitution, existence, validity, and representation. This was because upon review by this Panel of Judges, only the document on folio 40, the registry inscription of a power of attorney for Mr. Rodolfo Antonio Lambour Chocano as legal representative of the plaintiff, was found contributed to the proceedings. The plaintiff contributed to the proceedings the documents found on folios 482 to 528 and 566 to 572, which effectively record the constitution and registration of the plaintiff in the Republic of Guatemala, as well as the appointment of Mr. Rodolfo Antonio Lambour Chocano as the legal representative of the plaintiff, a person who indeed registered his representation and power of attorney in our country for the cited Federation, who in turn granted special judicial power to attorneys Carlos Ubico Durán and Alejandra Castro Bonilla, who have been pursuing the proceedings. This being the case, let the procedural defect be considered corrected and the plaintiff considered duly represented in the proceedings.

VI- REGULATIONS GOVERNING MEDICATIONS AND COMPETENCIES OF THE CAJA COSTARRICENSE DEL SEGURO SOCIAL IN THE MATTER OF MEDICATION PURCHASING: Hospital medical care service is a proper public service insofar as it is executed by a Hospital Center or a Health Care Center (clinic, evais, etc.) under the dependency of the Caja Costarricense del Seguro Social. This Entity, by constitutional provision, is responsible for overseeing (planning, developing, executing, etc.), among other things, everything related to Social Security, including within it, the health care service. Thus, ordinal 75 of our Constitución Política states in the pertinent part: "Social insurance is established for the benefit of manual and intellectual workers, regulated by a system of mandatory contributions from the State, employers, and workers, in order to protect them against the risks of illness, disability, old age, death, and other contingencies as determined by law. The administration and governance of social insurance shall be the responsibility of an autonomous institution, called Caja Costarricense del Seguro Social...". In this way, social security, which naturally encompasses the field of health care, is elevated to the constitutional level, thereby constituting an unavoidable mandate that requires the State, through the aforementioned Institution—CAJA COSTARRICENSE DE SEGURO SOCIAL—to secure, in the most efficient manner possible, the care and treatment of that important sector of social security, i.e., the health field. It is not superfluous to highlight from the outset the preponderance that the Caja Costarricense del Seguro Social acquires in this aspect, as the Entity expressly mandated by constitutional provision to carry out, as previously commented, the administration and governance of social insurance; this point has been addressed by our Sala Constitucional, for instance in Voto 6256-94, which established regarding what interests us: "...b) the norm exclusively grants the Caja Costarricense del Seguro Social the administration and governance of social insurance, a degree of autonomy that is, of course, distinct from and superior to that generally defined in Article 188 idem..." Furthermore, it is worth noting that this right to health can today be defined from a legal perspective as: "the set of mandatory precepts that recognize individuals' rights concerning their health and regulate their conduct regarding all matters in which the health of the individual and the group comes into play." Health itself can be defined as established in the preamble of the Constitution of the World Health Organization (WHO): "Health is a state of complete physical, mental, and social well-being and not merely the absence of disease or infirmity." Despite its transcendental importance, this right is not expressly enshrined in our Constitución Política, as we shall see next. We consider it essential to link the cited Article 73 of the Constitution, due to its fundamental content, with a norm that allows it to be complemented, from the perspective that interests us in this study, namely numeral 21 of the cited Constitution. That norm provides: "Article 21.- Human life is inviolable." When it speaks of "Human life" here, it does not allude exclusively to the right to life in the strict sense, but also alludes to its dimension of "health," meaning the norm does not literally refer only to protecting human life in a restricted sense, but broadly, to the state of "health," as a basic prerequisite of life itself, which is inherent to life as such; therefore, given its consubstantial relationship, that "right to health" is understood to be included in this norm; in that sense it has been stated: "V- Human life is only possible in solidarity with the nature that sustains and supports us, not only for physical nourishment, but also for psychological well-being; it constitutes the right that all citizens have to live in an environment free from contamination, which is the basis of a just and productive society. This is how Article 21 of the Constitución Política states: 'Human life is inviolable'; and it continues; 'It is from this constitutional principle that the right to health, to physical, mental, and social well-being undeniably derives, a human right that is indissolubly linked to the right to health and the State's obligation to protect human life.'" (Votos Número 3705-93, 3341-96. Sala Constitucional, Corte Suprema de Justicia). Furthermore, and given that transcendence of the right we are analyzing, the Sala Constitucional itself has expressly recognized the State's responsibility in ensuring the due protection of that right: "The determining role that the State, and in the case at hand, the State of Costa Rica, represented by the Ministry of Health, must play in this field concerning the establishment of programs for the protection of that fundamental value of all citizens is undeniable nowadays." (Voto number 2522-97, of the Sala Constitucional of the Corte Suprema de Justicia). Likewise, and as a corollary, we indicate that the Sala Constitucional has established that this right to life, protected constitutionally, as we have seen, must be supported and protected through the protection provided to the population by the Caja Costarricense del Seguro Social, through health plans, patient care, and the supply of medications, among other functions, given that the state responsibility has been delegated to it to determine the suitable and safe practices of the service. The foregoing makes it clear that the right to health is a right of constitutional origin, projected as a power-duty on the part of the corresponding authorities, in this case the Caja Costarricense del Seguro Social, and therefore, in this context, the provision of this service has an eminent public nature. Naturally, matters concerning the right to health have not escaped regulation by international instruments, which, as such, bind the actions of the adhering States based on that right. Thus, we find the following regulations: Declaración Universal de Derechos Humanos, in its Article 25, establishes, in what interests us: "Everyone has the right to a standard of living adequate for the health and well-being of himself and of his family, including food, clothing, housing, and medical care and necessary social services, and the right to security in the event of unemployment...". For its part, the Convención Americana de Derechos Humanos, specifically in its Articles 1 and 5, in the pertinent part, state: "Article 1. Every person has the right to have his life respected...", which, as we have said, gives rise to the right to health.... "Article 5.1. Every person has the right to have his physical, mental, and moral integrity respected." The Convención sobre los Derechos de los Niños, Article 24: "States Parties recognize the right of the child to the enjoyment of the highest attainable standard of health and to facilities for the treatment of illness and rehabilitation of health." The Convención sobre Eliminación de toda Forma de discriminación de la mujer: "Article 12. States Parties shall take all appropriate measures to eliminate discrimination against women in the field of health care in order to ensure, on a basis of equality of men and women, access to health care services, including those related to family planning." We also permit ourselves to merely mention other instruments such as the Pacto Internacional de Derechos Económicos, Sociales y Culturales, in its numerals 9, 10, 11, and 12; the Pacto Internacional de Derechos Civiles y Políticos, 6 and 7; the Declaración Americana de los Derechos y Deberes del Hombre, in its numeral 1; the Convención Sobre la Eliminación de todas las Formas de Discriminación Racial, Article 5, subsection e).

Regarding our legal framework, it is certainly exhaustive in focusing on the recognition of such a right, denoting its public nature, just to cite some examples: Civil Code, Article 46: "Every person may refuse to be subjected to a medical or surgical examination or treatment, except in cases of mandatory vaccination, or other measures relating to public health..."; Childhood and Adolescence Code, Article 19: "Minors shall have the right to seek refuge, assistance, and guidance when the threat to their rights entails serious danger to their physical or spiritual health; likewise, to obtain, in accordance with the law, adequate and timely assistance and protection from the competent institutions.", 20, "Minors shall have the right to obtain information, regardless of its source and mode of expression, especially that which promotes their spiritual and emotional well-being, as well as their physical and mental health", 42, 43, 45, 46, 50, 54, 78, 97, and 121, which are not transcribed for obvious reasons; Domestic Violence Law, Article 2; Law on Narcotics, Psychotropic Substances, Drugs of Unauthorized Use, Articles 1, 3, 6, 47; Phytosanitary Protection Law, Placa19473; Urban and Suburban Leases Law, Articles 5, 22, 93, 94, 97, 98, 135; of course the Constitutive Law of the Costa Rican Social Security Fund; The General Health Law, and the Organic Law of the Ministry of Health, without citing others that also highlight the right at hand, and which denotes its public nature. In this regard, there are also a large number of Regulations that protect this right, we cite as an example the National Emergencies Regulation Articles 2 and 11; the Autonomous Regulation of Organization of the Ombudsman's Office Article 21; the Regulation of the General Customs Law, Articles 12, 34, 246, 287, and 386; Regulation of the Law for the Promotion of Competition and Effective Consumer Defense, Articles 6, 8, 24, 41, 43; Regulation of the Smoking Regulation Law, Articles 1 and 5; Law on Equal Opportunities for Persons with Disabilities, Articles 92 and 94, among others. Returning to the competencies of the Costa Rican Social Security Fund, the Political Constitution in Article 73 indicates that the Fund is an autonomous institution in charge of the administration and governance of social security, this with the purpose of protecting workers against the risks of illness, disability, maternity, old age, and death. For the fulfillment of its purposes, the Constitutive Law of the Costa Rican Social Security Fund, number 17 of October 22, 1943, provides in its ordinal 71, that said entity is authorized to import, clear customs, manufacture, buy, sell, and export, directly, medications included in the National Formulary, reagents and biologicals, as well as raw materials and conditioning and packaging materials required in their preparation. It is equally authorized to supply these same articles to public and private institutions that provide health services. In that sense, numeral 72 of the aforementioned law states that such purchases and negotiations may be carried out, as long as the following requirements are met: a) Establish and keep updated a registry of product suppliers, based on their generic name; for these purposes, the Comptroller General of the Republic and the Internal Audit of the Costa Rican Social Security Fund shall have a copy of this registry. The Office in charge of purchases shall freely request quotations from national and foreign companies registered in the supplier registry, and their responses shall be considered formal offers if they meet the requirements of the case. To have the right to be considered, such responses must be given by the suppliers within three business days following receipt of the quotation request. b) The Comptroller General of the Republic must resolve purchase authorizations within a period no longer than five business days. c) In special cases of urgency, purchases may be made with only the approval of the Internal Audit of the Fund, but, in any case, the Comptroller's Office must be informed of the actions taken within the following twenty-four hours. ch) The officials in charge of making the purchases must carry them out under the best conditions of quality and price, and they will be responsible for their acts and for the damages and losses that they may eventually cause, in accordance with the law. For its part, numeral 73 of the ibid regulation indicates that the Costa Rican Social Security Fund may export medications, reagents, and biologicals, provided that national needs are satisfied. It may also exchange medications with state or private organizations from other countries in order to satisfy social needs. The norms and authorizations contained in this article shall be applicable equally to the Ministry of Health. In turn, numeral 102 of the General Health Law, number 5395 of October 30, 1973, states that the importation of medications and their distribution will only be permitted to legal or physical persons registered with the Ministry, with prior authorization and registration from the Colegio de Farmacéuticos, in accordance with the corresponding legal and regulatory provisions. In any case, the Central Government and public institutions with health functions may directly import, prepare, handle, store, sell, or supply medications, raw materials, or medical-surgical materials when the fulfillment of their programs or emergency situations so require, with the sole approval of the Ministry, in accordance with the respective Regulation (ordinal 103 of Law 5395). It being understood that a medication is any substance or natural, synthetic, or semi-synthetic products and any mixture of those substances or products used for the diagnosis, prevention, treatment, and relief of diseases or abnormal physical states, or their symptoms, and for the restoration or modification of organic functions in persons or animals. Included under the same denomination and for the same purposes are dietetic foods and those foods and cosmetics that have been added with medicinal substances. The substances referred to in the first paragraph are not considered medications when used for chemical and clinical-chemical analyses, or when used as raw material in industrial processes. Every medication must comply with the particular regulatory requirements that by its nature are exclusively applicable to it, in addition to the general ones established for all medications in Law 5395 (Article 104). Medications can be presented for use, commerce, distribution, and supply under a generic name or a registered name. Medications with a generic name are those pure medications, presented in pharmaceutical formula or singularly, designated with a common technical name recognized by official pharmacopoeias or by technical works of recognized authority. The generic-name medication may be simple or may be a formula constituted by two or more generic-name medications. Medications with a registered name are those that are delivered for commerce and use under a particular invented name and under a registered trademark (numeral 105 of Law 5395). It is considered that a medication can legally be intended for commerce, public use, and consumption when it satisfies regulatory requirements, or those of the pharmacopoeia declared official by the Executive Branch regarding its identity and qualities, safety, and efficacy for the purposes for which it is used, consumed, or prescribed, and provided that the responsible natural or legal persons involved in its importation, commerce, handling, distribution, and prescription have complied with the legal and regulatory requirements pertinent to each of these actions (numeral 106 of Law 5395). The importation, preparation, commerce, distribution, or supply under any title, handling, use, consumption, and possession for commerce of deteriorated, adulterated, or falsified medications is prohibited (ordinal 107 of Law 5395). It being prohibited to import, trade, use, or supply medications that are in an experimental process, except under the conditions and circumstances and for the time the Ministry authorizes it (numeral 108 of Law 5395). Furthermore, any natural or legal person may only import, manufacture, handle, trade, or use medications registered with the Ministry and whose registration has satisfied the regulatory requirements, especially those relating to: the nature and quantity of the information required about the medication or product submitted for registration; the delivery of necessary samples to perform the required analyses; those pertaining to the name with which the product will be identified; the content of the labeling; the type of containers or packaging to be used; and the payment of the fees indicated by the relevant tariff (Article 112 of Law 5395). The registration of any medication shall be done before the Ministry, where the inscription will be carried out when appropriate according to the corresponding regulatory provisions. Said inscription shall be in charge of a Technical Body whose composition and functions will be determined by the Organic Law of the Ministry and the respective Regulation (Article 113 of Law 5395). The registration of any medication shall last five years, unless infractions in its preparation, commerce, or use incurred by its holder, or experiences demonstrating that the product is unsafe or ineffective under the terms in which it was authorized and registered, warrant its cancellation or the corresponding modification (numeral 114 of Law 5395). Any modification to the name of a medication, its formula, its dosage form, the container and the content of the accompanying labeling, or the advertising, shall require prior permission from the Ministry (numeral 115 ibid). Medications with a registered name, for the purposes of their importation, commerce, and distribution in the country, require for their inscription proof of sanitary registration in the country of origin and a certificate of analysis corresponding to the product, issued by a national or foreign laboratory that, in the judgment of the Ministry, guarantees its identity and quality, according to the official pharmacopoeia or technical texts of recognized authority; this latter certificate may also be issued by the quality control laboratory for chemical and pharmaceutical products of the manufacturing house itself. Generic-name medications require for their inscription and for the same purposes indicated in the preceding paragraph, a certificate of analysis that guarantees their identity and quality, according to the official pharmacopoeia or technical texts of recognized authority, this certificate being issued in the same manner and conditions indicated in the preceding paragraph. The Ministry may exempt from the tests cited above when it concerns a known product and its own nature makes those requirements unnecessary; or, in the case of medications not described in the official pharmacopoeia or technical texts of recognized authority, whether registered trademark pharmaceutical products or generic-name medications, it may require the tests necessary for verification of the identity, quality, and therapeutic and biopharmaceutical efficacy of the product (Article 116 ibid). For its part, ordinal 117 ibid states that the Ministry of Health, the Costa Rican Social Security Fund, and any other state entity with public health or social security functions may acquire unregistered medications at any time or circumstance, and that in cases of urgency or public necessity, that Ministry may authorize the importation of unregistered medications, in addition to the fact that for exclusive research purposes, the importation, production, and use of unregistered medications may be authorized, in accordance with the corresponding regulatory provisions. At this point, it is advisable to be clear on one aspect: the governing body in health matters is the Ministry of Public Health, and the Costa Rican Social Security Fund is the administrative entity for public insurance. These are indeed competencies that interrelate with each other, but some correspond to the Ministry and others to the public entity. Regarding Sanitary Registration, it is clear that the balance tilts in favor of the Ministry and not the Fund, with the natural obligation of coordination in the scope of shared competencies.

VII- ON THE REQUIREMENTS THAT MUST BE MET TO FORM THE SUPPLIER REGISTRY OF THE COSTA RICAN SOCIAL SECURITY FUND TO OFFER BIOTECHNOLOGICAL MEDICATIONS, BIOLOGICALS, ANTINEOPLASTIC DRUGS, AND OTHER MEDICATIONS FOR SPECIFIC USE IN ONCOLOGICAL AND HEMATOLOGICAL PATHOLOGIES: By means of an agreement dated April 28, 2009, issued by the Costa Rican Social Security Fund, published in Gazette 89 of May 11, 2009, and approved by the Comité Central de Farmacoterapia in agreement CCF-0908-04-09 (Session 2009-13), the requirements are established for the supplier registry (registro de oferentes) applicable to biological medications, and specific conditions for the acquisition of medications called antineoplastic drugs (antineoplásicos) and other medications for specific use in oncological and hemato-oncological pathologies. Providing that registered suppliers and suppliers to be registered in the CCSS Supplier Registry for medications of biological origin from Group 1 and/or Group 2, must meet a series of requirements stipulated below for each group. It is indicated in turn that these requirements are also mandatory for those suppliers who participate in the Fund with medications that do not have a Medication Sanitary Registration and that the importation of the medication must proceed under Article 117 of the General Health Law of Costa Rica or with medications with an in-transit code. In the first group are located medications of biological origin that, in their manufacturing process, do not use raw material derived from human blood products (e.g., human plasma), establishing as requirements the following: 1. Certificate of Medication Sanitary Registration issued by the Ministry of Health of Costa Rica. 2. Attach the complete qualitative-quantitative formula with the excipients used and the permitted ranges of related substances (if applicable in this specific case). 3. Those biological medications from Group 1 that contain in their formulation, and corroborated in their qualitative-quantitative formula, excipients of human plasma origin (blood products) must also comply with the requirements for Group 2. 4. Medications that do not have a sanitary registration issued by the Ministry of Health of CR must also present duly certified clinical studies corresponding to those that gave rise to their registration in their country of origin, for the same official indications of use and safety in reference to the innovator. 5. In the event of offers that are in equal conditions, the administration clearly establishes a tie-breaking mechanism, which is to give priority to the biological product that is registered and consumed in the mentioned countries: United States (FDA) and/or countries of the European Economic Community (EMEA), and/or Canada and/or Japan and/or Switzerland. It is important to point out that the manufacturing laboratories of the medication must present the certificate of free sale of their product in the United States and/or Canada and/or European Economic Community and/or Japan and/or Switzerland in the eventuality that offers in equal conditions are presented and it is necessary to apply the tie-breaking mechanism. This document must be issued by the corresponding regulatory authority of the respective country. 6. Any biological medication, whether a new drug or not, that has the approval of at least the FDA and/or EMEA and/or Canada and/or Japan and/or Switzerland will be exempt from the requirements referred to in point 3, if they present the official documentation from the FDA and/or EMEA and/or the regulatory authorities of Japan and/or Switzerland that accredits the product for its commercialization in these countries. 7. Biological medications that do not have a sanitary registration issued by the Ministry of Health of CR must also comply with point 5. 8. All requested documents must be authenticated via the consular route of our country and ratified by the Ministry of Foreign Affairs. In group 2 are located medications of biological origin that use, in their manufacturing process, raw material derived from human blood products (e.g., human plasma), requiring that they provide 1. Certificate of Medication Sanitary Registration issued by the Ministry of Health of Costa Rica. 2. Attach the complete qualitative-quantitative formula with the excipients used and the permitted ranges of related substances (if applicable in this specific case). 3. Must comply with the Quality Specifications specified in each corresponding technical data sheet. 4. Must comply with all the regulations requested by the Ministry of Health of CR and everything requested by the Laboratorio de Normas y Calidad de Medicamentos of the CCSS regarding blood products. 5. Those biological medications from Group 1 that contain in their formulation, and corroborated in their qualitative-quantitative formula, excipients of human plasma origin (blood products) must also comply with the requirements for Group 2. 6. Medications that do not have a sanitary registration issued by the Ministry of Health of CR must also present duly certified clinical studies corresponding to those that gave rise to their registration in their country of origin, for the same official indications of use and safety in reference to the innovator. 7. In the event of offers that are in equal conditions, the administration clearly establishes a tie-breaking mechanism, which is to give priority to the biological product that is registered and consumed in the mentioned countries: United States (FDA) and/or countries of the European Economic Community (EMEA), and/or Canada and/or Japan and/or Switzerland. It is important to point out that the manufacturing laboratories of the medication must present the certificate of free sale of their product in the United States and/or Canada and/or European Economic Community and/or Japan and/or Switzerland in the eventuality that offers in equal conditions are presented and it is necessary to apply the tie-breaking mechanism. This document must be issued by the corresponding regulatory authority of the respective country. 8. All requested documents must be authenticated via the consular route of our country and ratified by the Ministry of Foreign Affairs. 9. The manufacturing laboratory must guarantee that the human plasma used as raw material in the manufacture of each of the biological medications must come from healthy human beings, and it must be entirely free of viruses or other pathogens. For its part, the Comité Central de Farmacoterapia in agreement CCF-0944-04-09 (Session 2009-13) and ratified by means of an agreement issued in Session 2009-14 of April 22, 2009, agreed to update the regulations for the Specific conditions for the acquisition of medications called antineoplastic drugs and other medications for specific use in oncological and Hemato-Oncological pathologies, for the purposes of Medication Registration with the Costa Rican Social Security Fund, whether they are registered or not before the Ministry of Health of Costa Rica; in point one, a certification issued by the General Medical Directorate of the General or Oncological Hospital or Cancer Institute of the country of origin of the manufacturing laboratory must be presented, signed by the highest authority in medical oncology and the General Medical Director of the Medical Center, indicating the annual quantity consumed by patients of the medication manufactured by said laboratory, the number of beds in that hospital designated for adults and the occupancy index (for parenteral use medications), and the number of oncology and onco-hematology consultations (for oral use medications). All information must correspond to the same year in which it is registered with the Fund or preferably to the year prior to the registration date. When the analysis is carried out by the CCSS, if the drug has a consumption in the General or Oncological Hospital or Cancer Institute of the country of origin equal to or greater than 100% of that consumed in Hospital Nacional San Juan de Dios, it will be determined through a comparative study of defined daily dose (DDD) per 100 hospital beds/day for parenteral use medications, and through a comparative study of defined daily dose (DDD) per 1000 consultations/day for oral use medications, they will be given supplier approval and will be incorporated into the Registry with the Fund. In the case of suppliers that are National Laboratories, based on a comparative study of defined daily dose (DDD) per 100 hospital beds/day (parenteral use medications) or 1000 consultations/day (oral use medications) taking Hospital San Juan de Dios as a reference, if the result is equal to or higher than the DDD study from the year prior to the Medication Registration with the Fund, they will be given supplier approval and will be incorporated into the Registry with the Fund. In the case of national laboratories, the information related to consumption in Hospital San Juan de Dios (national reference hospital) will be obtained through the internal information mechanisms available in the institution. In point 2, a certification issued by the Medical Directorate of the General or Oncological Hospital or Cancer Institute of the country of origin of the manufacturing laboratory must be presented, signed by the highest authority in medical oncology and the General Medical Director of the Medical Center, presenting the annual consumption in patients corresponding to the same year, efficacy and safety results obtained with the use of the medicinal product in the treatment of patients with hemato-oncological pathology, and the type of oncological pathologies treated. The documents must contain completely and concretely, the type and percentage of side effects presented by the patients who have received treatment with said product for its analysis. In point 3: Certification from the Ministry of Public Health or the equivalent highest Public Health authority in the country of origin of the manufacturing Laboratory, presented by its representative, which recognizes the General or Oncological Hospital or Cancer Institute requesting to be registered. In point 4: it is mandatory that the certification must be presented individually and the information must refer to the most recent previous year closest to the date of its inclusion in the CCSS Medication Supplier Registry when dealing with medications included in the Official List of Medications (Lista Oficial de Medicamentos, LOM), or correspond to the most recent previous year closest to the competition when dealing with medications not included in the LOM and acquired at the Central or local level. These certifications must be updated each time the renewal of the registration with the CCSS is requested for medications included in the LOM; if they are not registered, each time a purchase is made at the Central or local level in the case of non-LOM medications. In point 5: it is stated that the requested documents must have the signatures of health authorities duly authenticated, as required by Costa Rican legislation, in addition to completing the chain of consular legalization of our country and ratified by the Ministry of Foreign Affairs of Costa Rica. In point six, amended by agreement made in session 2011-08 held on February 23, 2011, it is provided that those antineoplastic drugs and other medications for specific use in oncological and hemato-oncological pathologies, whether for parenteral or oral use, that have marketing authorization in any of the following countries are exempt from the requirements stated in points 1, 2, 3, and 4: United States (FDA), Canada (Health Canada), Japan (MHLW), Switzerland (Swissmedic), Germany, England, Sweden, France, Italy, Spain, Belgium, Denmark, Austria, Holland, Finland, Norway, Colombia (INVIMA), Argentina (ANMAT), Brazil (ANVISA), stating that the laboratories must present: the pharmaceutical product certificate (or Certificate of Free Sale plus the Certificate of Good Manufacturing Practices), as support for their registration and marketing authorization in the United States (FDA), Canada, Japan (MHLW), Switzerland (Swissmedic), Germany, England, Sweden, France, Italy, Spain, Belgium, Denmark, Austria, Holland, Finland, Norway, Colombia (INVIMA), Argentina (ANMAT), Brazil (ANVISA). Likewise, it exempts those medications whose origin does not correspond to any of the previously listed countries, but which have the Mutual Recognition certificate for their commercialization in one of the reference member states (European Union), a certificate that must be issued by the highest competent regulatory authority in public health of the respective country. Providing that to be exempt from the requirements listed in points 1, 2, 3, and 4, it is necessary that the pharmaceutical product certificates (or Free Sale Certificate) include the name and address of the manufacturing plant, which must match the address of the manufacturing plant of the medication registered with the Ministry of Health of Costa Rica (provided the medication is registered in the country). The manufacturing plant (name and address) from which the registered medication originates and which has marketing authorization in one of the countries listed above, must correspond to the same manufacturing plant from which the medication to be delivered to the CCSS will be imported. Point seven establishes that a supplier already registered in the CCSS supplier registry may revalidate its registration by presenting the information indicated in the corresponding points above. Said registration shall be valid until the expiration of the sanitary registration issued by the Ministry of Health of Costa Rica. Point 8 indicates that those suppliers who are registered but prefer to present their data at the time of the purchase process and not revalidate the registration with the CCSS until its expiration, must present the requirements for antineoplastic drugs and other medications for specific use in oncological and hemato-oncological pathologies for each purchase process. Point nine states that in the case of the acquisition of antineoplastic drugs and other medications for specific use in oncological and hemato-oncological pathologies included in the Official List of Medications (LOM), the Área de Medicamentos y Terapéutica Clínica attached to the Dirección de Farmacoepidemiología will be responsible for carrying out the data analysis and the corresponding Defined Daily Dose (DDD) study. In point 10, it stipulates that in the case of antineoplastic drugs and other medications for specific use in oncological and hemato-oncological pathologies, NON-LOM, acquired by each center, the data analysis and the corresponding Defined Daily Dose (DDD) study will be carried out each time a purchase procedure is promoted, and will be performed and analyzed by each Pharmacy Service. Point 11 states that once the Executive Decree of the Ministry of Public Health that regulates the Medication Registry is published, the specific requirements for molecular targeted therapy products contemplated therein are based on the ICH recommendations and form part of these conditions. Point 12 indicates that in the case of offers of antineoplastic drugs and other medications for specific use in oncological and hemato-oncological pathologies, whether for parenteral or oral use, not included in the Official List of Medications, that are acquired at the Central or local level and that are in equal conditions, as a tie-breaking mechanism, priority will be given to the medication that is registered and consumed in any of the following countries: United States (FDA), Canada, Japan, Switzerland, Germany, England, Sweden, France, Italy, Spain, Belgium, Denmark, Austria, Holland, Finland, Norway. The supplier must present certification issued by the highest regulatory authority of the country confirming that it is registered and consumed in one of the previously cited countries, and that in response to the Cancer Council's request regarding bioequivalence requirements and requirements for medications called antineoplastic drugs of biotechnological origin, the mechanism established by the Ministry of Health and CCSS continues. In turn, by means of agreement number 1445 of June 10, 2009, the Costa Rican Social Security Fund established the requirements to be met for the supplier registry of biotechnological medications, which was published in Gazette 127 of July 2, 2009.

Said regulation provides for the obligations that must be fulfilled by registered offerors and offerors seeking registration in the CCSS Offeror Registry for biological origin medicines of Group 1 and/or Group 2, who must comply with the mandatory requirements for those offerors participating with the Caja with medicines that do not have a Sanitary Registration of the Medicine and for which the importation of the medicine must proceed under article 117 of the Costa Rica General Health Law or with medicines having a code in transit. Said groups being, number one corresponding to medicines of biological origin, which in their manufacturing process do not use raw material derived from human blood products (human blood products (hemoderivados)) (for example, human plasma), with the offeror required to submit the following requirements: 1. Certificate of sanitary registration of the medicine issued by the Ministry of Health of Costa Rica. 2. For innovative medicines, the complete qualitative-quantitative formula must be attached with the excipients used and the permitted ranges of related substances, as well as the characterization studies of the medicine. 3. For biosimilar medicines, the complete qualitative-quantitative formula must be attached with the excipients used and the permitted ranges of related substances, as well as the characterization studies of the medicine; in addition, they must submit characterization studies of the medicine compared with the reference medicine commercialized in Costa Rica. 4. Medicines that in their manufacturing process do not use human blood product (hemoderivados) raw material, but whose formulation and qualitative formula confirm the presence of human plasma excipients such as albumin, must comply with all current guidelines established in the Blood Products Decree (Decreto de Hemoderivados) No. 19981-S of October 3, 1990. 5. They must comply with the quality specifications established in the official technical data sheet corresponding to each medicine. 6. The Offeror Registry of the Laboratory of Standards and Quality of Medicines and the Central Pharmacotherapy Committee firmly establish that they only endorse biological products that, whether registered or not with the Ministry of Health of Costa Rica, are consumed in the following countries: United States (FDA), and/or countries of the European Community (EMEA), and/or Canada, and/or Japan, and/or Switzerland. 7. In the case of innovative medicines, the manufacturing laboratories must submit Free Sale Certificates for the medicine in the country of origin, such as the United States, European Economic Community, Canada, Japan, Switzerland, issued by the regulatory health authority of that country. 8. In the case of biosimilar medicines, the manufacturing laboratories must submit Free Sale Certificates for the medicine in the country of origin, such as the United States, European Economic Community, Canada, Japan, Switzerland, issued by the regulatory health authority of that country, as well as a certificate issued by the same health entity, guaranteeing that the medicine meets the quality criteria required for biological medicines and has the clinical safety and efficacy studies that gave rise to its sanitary registration in the country of origin, that it has clinical immunogenicity, safety, and efficacy studies, for the same official indications as the reference product commercialized in the country, as well as the characterization and comparability studies demonstrating that the product is biosimilar to the reference product commercialized in Costa Rica. The complete qualitative-quantitative formula must also be attached with the excipients used and the permitted ranges of related substances, and the certification from the health authority (EMEA and/or FDA) accrediting it as a biosimilar medicine. 9. All documents requested that are issued abroad (other countries) must be consularized and submitted in the Spanish language. 10. The Institution, based on the extensive clinical experience acquired over the years with the use of biological medicines, reserves judgment on certain specifications and requirements to be evaluated for the inclusion of new medicines sharing the same code in the offeror registry and unregistered medicines; and endorses only the interchangeability of biological products that have documented safety and efficacy proven through their clinical use in the Institution over the years. And regarding group 2 of biological origin medicines, it is stated that these are those that use, in their manufacturing process, raw material derived from human blood products (human blood products (hemoderivados)) (for example, human plasma), for which the offeror must meet the following requirements: 1. Certificate of Sanitary Registration of the Medicine issued by the Ministry of Health of Costa Rica. 2. Attach the complete qualitative-quantitative formula with the excipients used and the permitted ranges of related substances. 3. Must comply with the Quality Specifications detailed in each corresponding technical data sheet for each medicine. 4. Must comply with all the regulations requested by the Ministry of Health of CR and everything requested by the Laboratory of Standards and Quality of Medicines of the CCSS regarding human blood products (hemoderivados). 5. The Offeror Registry of the Laboratory of Standards and Quality of Medicines and the Central Pharmacotherapy Committee firmly establish that they only endorse biological products that, whether registered or not with the Ministry of Health of Costa Rica, are consumed in the following countries: United States (FDA), and/or countries of the European Community (EMEA), and/or Canada, and/or Japan, and/or Switzerland. 6. All documents requested that are issued abroad (other countries) must be consularized and submitted in the Spanish language. 7. The Institution, based on the extensive clinical experience acquired over the years with the use of biological medicines, reserves judgment on certain specifications and requirements to be evaluated for the inclusion of new medicines sharing the same code in the offeror registry; and endorses only that safety and efficacy have been documented and proven through their clinical use in the Institution over the years. 8. The manufacturing laboratory must guarantee that the human plasma used as raw material in the manufacture of each of the biological medicines must come from healthy human beings and be entirely free of viruses or other pathogens, and must comply with the current guidelines established in the Blood Products Decree (Decreto de Hemoderivados) No. 19981-S of October 3, 1990. Subsequently, by agreement of March 9, 2010, published in Gazette number 47 of March 9, 2010, approved by agreement CCF-0275-02-10 (session 2010-05) of the Central Pharmacotherapy Committee, the specific conditions for the acquisition of medicines called antineoplastics and other medicines for specific use in oncological and hemato-oncological pathologies are reformed, establishing the following points: Point 1: For antineoplastic medicines and other medicines for specific use in oncological and hemato-oncological pathologies, certification must be submitted issued by the General Medical Directorate of the General or Oncological Hospital or Cancer Institute of the country of origin of the manufacturing laboratory, signed by the highest authority in medical oncology and the General Medical Director of the Medical Center, stating the annual quantity consumed by patients of the medicine manufactured by said laboratory, the number of beds in that hospital intended for adults and the occupancy rate (for parenteral use medicines), and the number of consultations in oncology and onco-hematology (for oral use medicines). All information must correspond to the same year in which it is registered with the Caja or preferably to the year prior to the registration date. When the analysis is carried out by the CCSS, if the drug has consumption in the General or Oncological Hospital or Cancer Institute of the country of origin equal to or greater than 100% of that consumed at the Hospital Nacional San Juan de Dios, it will be determined with a comparative study of defined daily dose (DDD) per 100 hospital beds/day for parenteral use medicines, and with a comparative study of defined daily dose (DDD) per 1000 consultations/day for oral use medicines; they will be given the offeror endorsement and will be incorporated into the Registry with the Caja. In the case of offerors that are National Laboratories, based on a comparative study of defined daily dose (DDD) per 100 hospital beds/day (parenteral use medicines) or 1000 consultations/day (oral use medicines) taking Hospital San Juan de Dios as a reference, if the result is equal to or higher than the DDD study from the year prior to the medicine's registration with the Caja, they will be given the offeror endorsement and will be incorporated into the Registry with the Caja. For national laboratories, the information related to consumption at Hospital San Juan de Dios (National reference hospital) will be obtained through the internal information mechanisms available in the institution. Point 2: The specific medicine (oral or parenteral) for which admission to the Caja's offeror registry is requested for its registration, or the medicine to be acquired at the Central or Local level, will present certification issued by the Medical Directorate of the General or Oncological Hospital or Cancer Institute of the country of origin of the manufacturing laboratory, signed by the highest authority in medical oncology and the General Medical Director of the Medical Center, presenting the annual consumption in patients corresponding to a same year, efficacy and safety results obtained with the use of the medicinal product in the treatment of patients with hemato-oncological pathology, and the type of oncological pathologies treated. The documents must contain, in a complete and concrete manner, the type and percentage of side effects presented by patients who have received treatment with said product for its analysis. Point 3: Certification from the Ministry of Public Health or the equivalent highest authority in Public Health in the country of origin of the manufacturing laboratory, presented by its representative, recognizing the General or Oncological Hospital or Cancer Institute requesting to be registered. Point 4: Every certification requested must be submitted individually, and the information must refer to the most recent previous year closest to the date of its inclusion in the Offeror Registry of medicines before the CCSS when dealing with medicines included in the Official List of Medicines (LOM), or correspond to the most recent previous year closest to the tender when dealing with medicines not included in the Official List of Medicines (LOM) and acquired at the Central or local level. These certifications must be updated each time the renewal of the registration before the CCSS is requested for medicines included in the LOM, or, if not registered, each time a purchase is made at the Central or local level in the case of non-LOM medicines. Point 5: All requested documents must have the signatures of health authorities duly authenticated, as required by Costa Rican legislation, in addition to completing the chain of consular legalization of our country and ratified by the Ministry of Foreign Affairs of Costa Rica. Point 6: The requirements stated in points 1, 2, 3, and 4 shall be waived for those antineoplastic medicines and other medicines for specific use in oncological and hemato-oncological pathologies for parenteral or oral use, that are registered and consumed in any of the following countries: United States (FDA), Canada (Health Canada), Japan (MHLW), Switzerland (Swissmedic), Germany, England, Sweden, France, Italy, Spain, Belgium, Denmark, Austria, Holland, Finland, Norway. It is important to note that laboratories must present the free sale certificate for their product in the United States (FDA), Canada, Japan (MHLW), Switzerland (Swissmedic), Germany, England, Sweden, France, Italy, Spain, Belgium, Denmark, Austria, Holland, Finland, Norway; or with registration and commercialization in these same countries. Likewise, those medicines whose origin does not correspond to any of the countries listed above will be exempted, but which have the Mutual Recognition certificate issued by the EMEA for their commercialization in one of the reference member states of the European Union. This certificate must be issued by the highest competent regulatory authority in public health of the respective country. Point 7: The offeror who is already registered in the CCSS offeror registry can revalidate their registration by submitting the information indicated in the corresponding points above. Said registration will be valid until the expiration of the sanitary registration issued by the Ministry of Health of Costa Rica. Point 8: Those offerors who are registered but prefer to submit their data at the time of the purchase process and not revalidate the registration before the CCSS until its expiration, must submit the requirements for antineoplastic medicines and other medicines for specific use in oncological and hemato-oncological pathologies for each purchase process. Point 9: In the case of the acquisition of antineoplastic medicines and other medicines for specific use in oncological and hemato-oncological pathologies included in the Official List of Medicines (LOM), the Medicines and Clinical Therapeutics Area attached to the Directorate of Pharmacoepidemiology will be responsible for carrying out the data analysis and the corresponding Defined Daily Dose (DDD) study. Point 10: In the case of non-LOM antineoplastic medicines and other medicines for specific use in oncological and hemato-oncological pathologies acquired by each center, the data analysis and the corresponding Defined Daily Dose (DDD) study will be carried out each time a purchase procedure is promoted, and will be performed and analyzed by each Pharmacy Service. Point 11: Once the Executive Decree of the Ministry of Public Health regulating the Registration of Medicines is published, the specific requirements for molecular target therapy products will be contemplated therein; these requirements are based on ICH recommendations and form part of these conditions. Point 12: Regarding offers for antineoplastic medicines and other medicines for specific use in oncological and hemato-oncological pathologies for parenteral or oral use not included in the Official List of Medicines (LOM) that are acquired at the Central or local level and are under equal conditions, as a tie-breaking mechanism, priority will be given to the medicine that is registered and consumed in one of the following countries: United States (FDA), Canada, Japan, Switzerland, Germany, England, Sweden, France, Italy, Spain, Belgium, Denmark, Austria, Holland, Finland, Norway. The offeror must present certification issued by the highest regulatory authority of the country stating that it is registered and consumed in one of the aforementioned countries. Regarding the Cancer Council's request on bioequivalence requirements and requirements for medicines called biotechnological antineoplastics, the mechanism established by the Ministry of Health and CCSS is continued.

Subsequently, the Central Pharmacotherapy Committee, in session 2011-08 held on February 23, 2011, analyzed Point 6 of the requirements for medicines called antineoplastics and other medicines for specific use in oncological and hematological pathologies published in La Gaceta No. 47 of March 9, 2010, agreeing to modify it, leaving it as follows: "The requirements stated in points 1, 2, 3, and 4 shall be waived for those antineoplastic medicines and other medicines for specific use in oncological and hemato-oncological pathologies for parenteral or oral use, that have a marketing authorization in any of the following countries: United States (FDA), Canada (Health Canada), Japan (MHLW), Switzerland (Swissmedic), Germany, England, Sweden, France, Italy, Spain, Belgium, Denmark, Austria, Holland, Finland, Norway, Colombia (INVIMA), Argentina (ANMAT), Brazil (ANVISA). It is important to note that laboratories must present: the certificate of pharmaceutical product (or Free Sale Certificate plus the Certificate of Good Manufacturing Practices), as proof of their registration and marketing authorization in the United States (FDA), Canada, Japan (MHLW), Switzerland (Swissmedic), Germany, England, Sweden, France, Italy, Spain, Belgium, Denmark, Austria, Holland, Finland, Norway, Colombia (INVIMA), Argentina (ANMAT), Brazil (ANVISA). Likewise, those medicines whose origin does not correspond to any of the countries listed above will be exempted, but which have the Mutual Recognition certificate for their commercialization in one of the reference member states (European Union). This certificate must be issued by the highest competent regulatory authority in public health of the respective country. To exempt them from the requirements listed in points 1, 2, 3, and 4, it is necessary that the certificates of pharmaceutical product (or Free Sale Certificate) include the name and address of the manufacturing plant, which must match the address of the manufacturing plant of the medicine registered with the Ministry of Health of Costa Rica (provided the medicine is registered in the country). The manufacturing plant (name and address) from which the registered medicine with marketing authorization in one of the countries listed above originates must correspond to the same manufacturing plant from which the medicine to be delivered to the CCSS will be imported." Meanwhile, the Technical Regulation called Registration and Control of Biological Medicines, number 37006 of November 15, 2011, established that its regulations govern the requirements and procedures necessary for the registration and control of biological medicines for human use and apply to all products of this type, whether produced nationally or imported (first article). In said regulation, in its fifth article, it was established regarding the sanitary registration of biological medicines, "that when the submission of any of the studies or documents mentioned in this Regulation is not scientifically appropriate, the applicant must submit the justification for evaluation by the Ministry of Health, establishing that for the sanitary registration of biological medicines, a dossier must be submitted following the format and content established in article 27 of Decree No. 28466-S of February 8, 2000 "Regulation for the Registration, Control, Importation, and Advertising of Medicines," published in La Gaceta No. 42 of February 29, 2000, and its amendments or the current sanitary registration regulations. Information on the international regulatory status of the product must be submitted: A list of Health Authorities that have registered the product as of the date of the procedure before the Ministry of Health and those that have conducted inspections in the last two years at the laboratories manufacturing the finished products. In addition, information on safety and efficacy for biological medicines. The scientific documentation submitted, referring to the conclusive reports of clinical studies, must have been prepared within a period not exceeding ten years. If the studies mentioned above were conducted more than 10 years ago, the applicant must submit the justification for evaluation by the Ministry of Health. All conclusive reports of clinical studies must refer to the same product and pharmaceutical form presented for its sanitary registration. For biological products containing active ingredients not included in the formulation of a product registered previously in Costa Rica: it is required i) In the case of products containing chemical entities not included in the formulation of a previously registered product: • Conclusive reports of the results of pre-clinical studies (including information on in vivo and in vitro pharmacodynamic parameters). • Conclusive reports of the results of phase I, II, and III clinical studies (including pharmacokinetic, pharmacodynamic studies, clinical studies, and immunogenicity studies). ii) In the case of pharmaceutical products containing chemical entities included in previously registered products whose active ingredient corresponds to new derivatives, such as pegylated ones or others, they must submit: • Conclusive reports of the results of phase I, II, and III clinical studies. For biological medicines containing active ingredients included in the formulation of a product previously registered in Costa Rica but presenting: i) New fixed combinations of active ingredients: • Conclusive reports of the results of phase I, II, and III clinical studies. Such reports must compare the existing and new proportion or dose, including bioavailability studies. ii) New pharmaceutical form with an already registered route of administration: • Conclusive reports of the results of bioavailability studies. iii) New pharmaceutical form with a new route of administration: • Conclusive reports of the results of pre-clinical studies and phase I, II, and III clinical studies. iv) New pharmaceutical form with a new release mechanism: • Conclusive reports of the results of phase I, II, and III clinical studies. v) New potencies or concentrations of previously registered active ingredients: • Conclusive reports of the results of bioavailability studies and phase II and III clinical studies. vi) New routes of administration with an already registered pharmaceutical form: • Conclusive reports of the results of bioavailability studies and phase II and III clinical studies. 5.5. In addition to the requirements mentioned in the previous numeral, for the registration of biological medicines, the documents established in the following sections must be attached to the dossier in the order in which they are mentioned. For recombinant DNA or biotechnological medicines, the following must be submitted: 5.6.a. Quality information related to the physicochemical, biological, and immunological properties of the active ingredient: i) Description, chemical structure, amino acid sequence, post-translational modifications, physicochemical, biological, and immunological properties. ii) Description of the manufacturing process, of the in-process controls, of the cell substrate control, of the control of critical stages and intermediates, and of the process validation. iii) Description of the methodology for characterization, including the description of the chemical structure and impurities related to the product and the process and contaminants. iv) Description of the controls of the active ingredient, including specifications, analytical methods, and validation of the analytical methods. v) Description of the standards or reference materials. vi) Description of the container-closure system. vii) Description and results of the stability study. 5.6.b. Quality information related to the physicochemical, biological, and immunological properties of the finished product: i) Description of the product and its composition. ii) Description of the manufacturing process, of the in-process controls, of the control of critical stages and intermediates, and of the process validation. iii) Description of quality control, including specifications, analytical methods, validation of the analytical methods, analysis of the results of the batches used for the specifications, characterization of impurities and contaminants, and justification of the specifications that guarantee batch-to-batch uniformity. When more than one manufacturer is involved, indicate which step each one participates in. iv) Description of the standards or reference materials. v) Description of the safety assessment against infections by adventitious agents. Details on viral inactivation and elimination. vi) Risk management and post-marketing pharmacovigilance plan. NOTE 1: These requirements apply to the innovative medicine. In the case of biosimilars, they must also submit the biosimilarity exercise related to quality compared to the reference biological medicine, to determine that the differences do not have implications for its safety and efficacy. The documentation provided must specify the name of the medicine it is intended to be biosimilar to and the name of the laboratory that manufactures it. NOTE 2: The biosimilarity exercise must be carried out for both the finished product and the active ingredient, as detailed in numeral 5.12. For this purpose, the international WHO guidelines will be followed; in their absence, those issued by the FDA, EMA, or ICH may be used. Notwithstanding the above, the guidelines of other countries may be adopted as official once the Ministry of Health verifies that they are internationally accepted and they are made official by Administrative Resolution, which must be published in the Official Journal La Gaceta together with the instructions, forms, and any other corresponding documents and placed on the Ministry of Health's website. 5.7. For human blood products (hemoderivados) and vaccines, the manufacturing method must be submitted and must contain the following information: 5.7.a. Master formula, including the batch size. 5.7.b. Description of the starting materials of biological origin such as: strains, cell lines, microorganisms, plasma donations or blood components, cells or cellular substrates, and culture media. Including: quality control specifications, validated analytical methods, and methods for the exclusion of adventitious agents. 5.7.c. Description of the manufacturing process: i) Manufacturing flow diagram indicating the process controls, and when more than one manufacturer participates, indicate in which step each one intervenes. ii) Complete description of the entire process, manufacturing methods, and their controls. Information on the fermentation, harvest, and purification steps, if the product manufacturing applies them, including acceptance and rejection criteria. iii) Process control specifications and analytical methods issued by the manufacturer, which must be validated. iv) Reprocessing criteria for each stage. v) Quality specifications including the characterization and purity of the product obtained at each stage and the analytical techniques used for its verification. vi) Description of the double viral inactivation processes, agent used, and method to verify the effectiveness of the process, as applicable. vii) Document in which the manufacturer states that its manufacturing process achieves, for all manufactured batches, a maximum reduction in prion infectivity, in accordance with the current state of knowledge. 5.7.d. Analytical certificates must contain the quality specifications of the Active Ingredient(s), Excipient(s), In-Process Product, Finished Product, and Reference Material(s). The analytical results of the medicine components must be expressed in units of weight or biological activity as appropriate. These certificates must include: i) Name of the substance or product. ii) Manufacturing stage in the case of in-process products. iii) Date and place of manufacture. iv) Batch number. v) Batch size. vi) Physical, chemical, biological, and microbiological quality parameters with their limits and results. vii) Expiration date when appropriate. viii) Date and place of analysis, name of the person responsible for the analysis, and conformity decision according to the specifications. ix) Reference of the official method used or indication that the manufacturer's validated method was used. 5.7.e. Risk management and post-marketing pharmacovigilance plan. 5.8. For human blood products (hemoderivados), in addition to the information in numerals 5.3., 5.4., and 5.7., the following requirements must be submitted: 5.8.a. Certificate of current sanitary registration of the product issued by the FDA, EMA, or any other competent health authority that performs the Certification of the Plasma Master File (PMF) after the corresponding scientific and technical evaluation. 5.8.b. Information on the selection and control of donors. 5.8.c. Description of the procedures used to guarantee the traceability of the finished product to the donors and vice versa. This description must be accompanied by a detailed Diagram. 5.8.d. Results of the tests performed to detect antibodies to HIV 1 and HIV 2, antibodies to hepatitis C, and the ELISA or RIA test for hepatitis B that detects 0.5 IU per ml of HBs antigen or less. 5.8.e.

Information on the centers where plasma is obtained, location of the plasma collection centers, information on the inspections carried out at said Centers, and on the Quarantine Policy. Detail the type of plasma obtained (donation or plasmapheresis), the type of donation (altruistic or remunerated), data on the seroconversion percentage of regular donors, and data on markers in first-time donations. Also include information on the storage and transport conditions for the plasma established by the manufacturer. 5.9. For vaccines, in addition to the information from sections 5.3., 5.4, and 5.7., the following must be submitted: 5.9.a. Clinical studies of reactogenicity and immunogenicity and of efficacy. The lack of efficacy studies must be justified. 5.9.b. Information on Cell Bank Systems: i) Preparation, description, and controls performed on the Master Cell Bank (MCB) and Working Cell Bank (WCB). ii) Description of the controls used to verify the absence of adventitious agents. iii) Description and characterization of stabilizers, adjuvants, and preservatives. iv) Nucleic acid sequence of the strain and its comparative study with other strains, including vaccine strains. 5.10. For combination vaccines, in addition to the information from sections 5.3., 5.4., and 5.7., the following requirements must be submitted: 5.10.a. Clinical studies of reactogenicity and immunogenicity. 5.10.b. Information on Cell Bank Systems: i) Preparation, description, and controls performed on the Master Cell Bank (MCB) and Working Cell Bank (WCB). ii) Description of the controls used to verify the absence of adventitious agents. iii) Description and characterization of stabilizers, adjuvants, and preservatives. 5.10.c. Information on the characterization and controls of each individual antigen, which must meet the same requirements established for their use in single vaccines. 5.10.d. Information on the tests performed after combination with a view to studying the possible interaction between antigens. 5.10.e. Information about the effects of adjuvants and preservative agents on the stability and activity of the finished product. 5.10.f. Reactogenicity and immunogenicity studies demonstrating safety compared to that of the separate vaccines, but administered simultaneously. 5.11. For antivenoms and antitoxins of animal origin, the manufacturing method must be submitted, containing the following information: 5.11.a. Master formula, including batch size. 5.11.b. Description of the starting materials of biological origin such as: venoms and plasma or blood components. Including: quality control specifications, validated analytical methods, and methods for the exclusion of adventitious agents. 5.11.c. Information on the control of the venom batches used for the immunization of the donor animal. i) Certification signed by the biological regent of the species of snakes used in venom extractions for immunization mixtures, including the scientific and common names of the snakes used. This certification must include a minimum of 10 specimens used per species for each venom batch and the extraction date. ii) Flow chart describing the handling and storage of venom mixtures for immunization, including storage conditions. iii) Results of biological and biochemical tests certifying the consistency of the venoms (HPLC chromatographic profile and LD50 toxicological activity specifically). 5.11.d. Information on the plasma batches obtained from immunized animals: i) Information on endotoxin tests, neutralizing potency of the plasma mixture for a batch, and protein content. ii) Information on the venoms used in immunization, bleeding dates, immunization dates, and identification of the horses for a specific batch. iii) Identification profile of the horses participating in a specific plasma batch, with their respective breed, sex, age, and weight. 5.11.e. Description of the manufacturing process: i) Manufacturing flow diagram indicating the in-process controls and, when more than one manufacturer is involved, indicating at which step each one intervenes. ii) Complete description of the entire process, manufacturing methods, and their controls. Information on the purification steps, including acceptance and rejection criteria. iii) In-process control specifications and the analytical methods issued by the manufacturer, which must be validated. iv) Reprocessing criteria for each stage. v) Quality specifications including the characterization and purity of the product obtained at each stage and the analytical techniques used for verification. vi) Description of the dual viral inactivation process(es), agent used, and method for verifying the effectiveness of the process, as applicable. vii) Document in which the manufacturer states that its manufacturing process achieves, for all manufactured batches, a maximum reduction of prion infectivity, in accordance with the current state of knowledge. This applies to those antivenoms or antitoxins derived from animals in which prion infectivity has been demonstrated. 5.11.f. Analytical certificates must contain the quality specifications of the Active Ingredient(s), Auxiliary Substance(s), In-Process Product, Finished Product, and Reference Material(s). The analytical results of the drug components must be expressed in units of weight, or biological activity as appropriate. These certificates must include: i) Name of the substance or product. ii) Manufacturing stage in the case of in-process products. iii) Date and place of manufacture. iv) Batch number. v) Batch size. vi) Physical, chemical, biological, and microbiological quality parameters with their limits and results. vii) Expiration date when applicable. viii) Date and place of analysis, name of the person responsible for the analysis, and conformity decision according to specifications. ix) Reference to the official method used or indication that the manufacturer's validated method was used. 5.11.g. Risk management plan and post-marketing pharmacovigilance. 5.12. Regarding information on safety and efficacy and for biosimilar drugs not previously registered in Costa Rica and for already registered biosimilars, the biosimilarity exercise must be submitted, including: 5.12.a. Pre-clinical studies (in vitro and in vivo) that must be comparative in nature and designed to detect significant differences between the biosimilar and the innovative reference biologic. 5.12.b. Comparative clinical studies with the reference biologic for each of the indications requested. The following must be submitted: i) Pharmacokinetic studies. ii) Pharmacodynamic studies. iii) Clinical efficacy studies. iv) Safety studies. v) Immunogenicity studies. The type and quantity of studies will depend on the knowledge of the reference biologic and the therapeutic indications being requested; for this, international guidelines will be followed, and in their absence, those issued by the FDA, EMA, and ICH may be used on a case-by-case basis. 5.12.c. Approval letter for the clinical studies indicated in this regulation, issued by the Ethic-Scientific Committee(s), duly legalized or apostilled. Said committees must be recognized by the health authority of the country where these studies were conducted. 5.12.d. Risk management plan and post-marketing pharmacovigilance. Any specific safety monitoring imposed on the reference product must be considered in the risk management plan for the biosimilar product. 5.12.e. Detail on the criteria used to select the reference biologic with which the biosimilarity exercise was conducted. For this, the sequence of criteria from section 6 of this Regulation must be used. 6. SELECTION OF THE REFERENCE BIOLOGIC: The criteria for selecting the reference biologic in order of priority are as follows: 6.1. The first choice must always be the innovative product manufactured in the first country of origin, which has a complete dossier on its quality, efficacy, and safety, provided that this is the same product registered and marketed in Costa Rica. 6.2. The second choice must always be the innovative product manufactured, registered, and marketed in Costa Rica. 6.3. The third choice must be the innovative product manufactured in an alternate origin, registered, and marketed in Costa Rica. 6.4. The fourth choice, and in the event that the previous conditions are not met, the innovative product manufactured in the first country of origin or alternate origin, or the reference product suggested in the WHO lists, may be chosen as the reference product, even if it has not been marketed in Costa Rica. To define the reference product through the application of this section, a written consultation must be made with the Health Regulation Directorate of the Ministry of Health. 6.5. The fifth choice, and in the event that the previous conditions are not met, corresponds to the market-leading product that has demonstrated its quality, efficacy, and safety. To define the reference product through the application of this section, a written consultation must be made with the Health Regulation Directorate of the Ministry of Health. 7. POST-REGISTRATION CHANGES FOR BIOLOGICAL DRUGS: For any change associated with the biological drug that is contemplated in the Post-Registration Changes Guide published on the Ministry of Health website, the specific requirements established in said Guide must be submitted according to the type of change to be made. 8. RENEWAL OF SANITARY REGISTRATION 8.1. For the renewal of the sanitary registration (registro sanitario) of the biological drugs described in this regulation, a dossier must be submitted with the requirements established in Article 34 of Decree No. 28466-S, Regulation for the Registration, Control, Importation, and Advertising of Medications, published in La Gaceta No. 42 of February 29, 2000, and its amendments or the current sanitary registration regulations, also attaching, in the event that they have not been submitted in previous registration procedures, the requirements established in this regulation. 8.2. For biosimilar drugs that have not submitted it in previous procedures, they must submit the Biosimilarity Exercise considering the provisions of this regulation. 9. LOT RELEASE OF BIOLOGICAL PRODUCTS. The Customer Service Directorate (Dirección de Atención al Cliente) will authorize the release of each lot of biological products (with the exception of biotechnological products which, due to their nature, are not subject to lot-by-lot release) once it verifies the correspondence between the documentation of the registration dossier and the following requirements: 9.1. Lot Release Certificate issued by the regulatory authority of the producing country. For national laboratories, the Ministry of Health will review its files to verify compliance with this requirement. 9.2. Summarized manufacturing protocol and certificate of the manufacturer's release test results, and in the case of blood derivatives of human origin or drugs containing them, the certificate must include that the product is free of HIV, cytomegalovirus, parvovirus B19, and hepatitis B and C viruses. 9.3. Letter of commitment from the manufacturer, the product holder, or its legal representative, guaranteeing compliance at all times with the storage conditions established on the labeling of the imported lot, from the manufacturing laboratory to the drugstore in Costa Rica. NOTE: The lot release procedure for biological drugs by the Customer Service Directorate of the Ministry of Health will be carried out at the importing drugstore or at the national manufacturing laboratory within a period of 5 business days counted from the notification to the Ministry of Health. 10. CONTROL OF BIOLOGICAL DRUGS. 10.1. What is stated in the registration declarations and compliance with the required requirements will be carried out by the Health Regulation Directorate, through inspection and sampling in the market, at the pharmaceutical laboratory, or at customs, in accordance with the provisions of the General Health Law (Ley General de Salud) and the Law for the Promotion of Competition and Effective Consumer Defense (Ley de Promoción de la Competencia y Defensa Efectiva del Consumidor). The first quality control carried out on biological drugs will be performed on the first commercialized lot, without diminishing the post-marketing verification and inspection controls that the Health Regulation Directorate may eventually order. 10.2. For control purposes, the manufacturer of the biological drug or its holder must submit to the Ministry of Health the updates of the reports generated by reason of the Risk Management and Pharmacovigilance Plans, which will form part of the product dossier before the Ministry of Health. 10.3. In the event of demonstrating non-compliance or falsity of what was declared in the registration before the Ministry of Health, the health authority will detain, seize, or withdraw the respective product from circulation, or its registration will be canceled as appropriate, after prior notification to the legal representative, who must assume the costs of the applied sanitary measure. The foregoing is without prejudice to other sanctions established by the Law for the Promotion of Competition and Effective Consumer Defense. The Ministry of Health will proceed with the application of these special measures based on the provisions of Article 386 of the General Health Law, without prejudice to the civil or criminal liability incurred by the natural or legal persons responsible for such non-compliance and without prejudice to any other sanction that may proceed in accordance with current legislation." For its part, the Regulation for the Registration, Control, Importation, and Advertising of Medications, number 28466 of February 8, 2000, established the pertinent regulations for the registration, control, importation, and advertising of medications, governing all persons who manufacture, import, and market medications in the national territory (section 2 ibid). Furthermore, in this regulation, Bioavailability is defined as the rate and extent to which the active ingredient or active fraction is absorbed from a pharmaceutical form and becomes available at the site of action; Bioequivalence: as the relationship between two pharmaceutical products that are pharmaceutically equivalent and whose bioavailability in terms of rate and degree, after being administered at the same molar dose, under the same conditions, are so similar that their effects would be essentially the same; Good Manufacturing Practices: as the set of norms and procedures aimed at guaranteeing the uniform production of batches of pharmaceutical products that meet the quality requirements demanded by the needs of users; Certificate of Analysis: as the certificate indicating the specifications and results of the physical, chemical, biological, microbiological, and biopharmaceutical analyses of a pharmaceutical product, issued by a national or foreign laboratory that, in the judgment of the Ministry, guarantees its identity and quality; Certificate of Good Manufacturing Practices: as the document issued by the sanitary authority of the country of origin, certifying that the laboratory to which it refers satisfactorily complies with the Good Manufacturing Practices requirements in force in that country for the pharmaceutical form to which the product belongs. Said requirements must at least meet the WHO standards equivalent to those of the regulations in force in Costa Rica. In the case of beta-lactams, cytotoxics, hormones, and biologicals, the certificate must specifically declare that the manufacturing laboratory is authorized for the manufacture of those pharmaceutical products; Certificate of Free Sale: as the document issued by the regulatory authority or entity responsible for the registration of pharmaceutical products in the country of origin or provenance, duly legalized, certifying that the pharmaceutical product referred to in the certificate has its registration in force and is authorized for sale or distribution in that country. In the case of manufacturing by third parties, it may be from the country where the holder or responsible party for the marketing of the product is located; Certificate of Pharmaceutical Product: the certification proposed by the World Health Organization (WHO) and issued by the Regulatory Authority of the country or region of origin or provenance as part of the quality certification system for pharmaceutical products subject to international trade. In the case of manufacturing by third parties, the certificate of pharmaceutical product must be issued by the Regulatory Authority of the country of the product holder. For subsidiaries, the certificate of pharmaceutical product may be issued by the Regulatory Authority of the manufacturer's or holder's country; and Manufacturing Contract: the Legal document entered into between the medication holder and the manufacturer, which establishes the conditions, commitments, and other circumstances for the manufacture of one or more products; and which must indicate at a minimum: 1) The existing contractual link between the involved parties. 2) That the contractor complies with Good Manufacturing Practices. 3) That the contractor has all the necessary information from the contracting party to carry out the contracted actions, as well as the processes it must implement for the medication subject to the contract. 4) That the contracting party will conduct periodic audits of the contractor. Also defined is the Pharmaceutical Equivalent: Pharmaceutical product that contains identical amounts of the same active ingredients as the product to which it is equivalent, for example, the same salt or ester of the active ingredient, in identical pharmaceutical forms, meeting the established specifications, but not necessarily containing the same excipients. Consequently, two pharmaceutical equivalents may show different bioavailabilities and pharmacological activities; and Therapeutic Equivalence: referring to two pharmaceutical products that are therapeutically equivalent if they are pharmaceutically equivalent and after administration at the same molar dose, their effects with respect to efficacy and safety will be the same, determined by appropriate in vivo bioequivalence, pharmacodynamic, and clinical studies and/or in vitro dissolution studies. The term Biological pharmaceutical product is also conceptualized: as a pharmaceutical product obtained from living organisms or their tissues; and Sanitary Registration (registro sanitario) as an administrative act by which it is established that the pharmaceutical product to be registered meets the sanitary requirements of current regulations regarding quality, efficacy, and safety and that, therefore, it may be marketed in the country. For its part, section four provides that the functions of the technical body, established in Article 113 of the General Health Law, hereinafter centralized in the Customer Service Directorate, will be the approval or denial of the registration of any product referred to in this Regulation, and the Health Regulation Directorate will be responsible for establishing or approving the pharmacological technical standards by which the evaluation of medications is governed and the list of multi-source pharmaceutical products of sanitary risk. For these purposes, section 24 of Decree 28466 provides that the Ministry of Health must publish on its website a list of sanitary registration applications in process within a maximum period of 15 business days from the receipt of the application, and must publish a list of pharmaceutical products that have been granted a sanitary registration within a maximum period of 15 business days counted from the issuance of the sanitary registration. Regarding applications for sanitary registration of multi-source pharmaceutical products, the following must be provided: a) An application for which no information on safety and efficacy is submitted must be considered by the Ministry as an application for the registration of a multi-source pharmaceutical product. The Ministry may only grant sanitary registration to a multi-source pharmaceutical product that is a pharmaceutical equivalent: i) Of a pharmaceutical product for which data on safety and efficacy have been previously submitted to the Ministry by its applicant and for which a sanitary registration has been previously granted in Costa Rica. ii) Of a pharmaceutical product that meets all of the following conditions: a) That it is not protected by patents, b) That it does not contain protected test data, c) That it contains a chemical entity present in the formulation of a product that has previously obtained a sanitary registration in Costa Rica, d) That the applicant demonstrates, by means of a document issued by a regulatory authority, that the active ingredient has been authorized for marketing in any country for more than 5 years; and e) That international information exists guaranteeing the safety and efficacy of the pharmaceutical product before the Ministry of Health. The foregoing is to guarantee access to medications of sanitary interest. b) Applicants requesting a sanitary registration for a multi-source pharmaceutical product must indicate in the application the name of the pharmaceutical product previously registered in the country with which the applicant's product is a pharmaceutical or therapeutic equivalent, as well as the expiration date of any protected test data and any patent covered by the pharmaceutical product previously registered in the country, in accordance with the information contained in the databases of the Ministry of Health. c) The Ministry shall not, without the consent of the legitimate holder of the test data submitted to the Ministry in support of an application for sanitary registration of a new pharmaceutical product, grant sanitary registration to the applicant of a multi-source pharmaceutical product, on the basis of: i) Such test data; or ii) The sanitary registration granted to that new pharmaceutical product, before the expiration of the protection period for said test data. d) The applicant for a sanitary registration of a multi-source pharmaceutical product or its legal representative may request that the Ministry review the test data submitted in support of a sanitary registration application for a new pharmaceutical product as evidence and support for its sanitary registration application, in the cases established in Chapter XI of this Regulation. In turn, regarding applications for a sanitary registration of a new pharmaceutical product, a sworn statement issued before a notary public must be submitted indicating any product or process patent granted and in force in Costa Rica that covers the pharmaceutical product, indicating the patent number and its expiration date. Applicants or their legal representative may update this list to include patents granted after the application for sanitary registration. However, these updates will not suspend the process or the granting of the sanitary registration for applications already submitted, nor will they affect sanitary registrations already granted. The Ministry must publish on its website, for each pharmaceutical product to which a sanitary registration has been granted, the list of product or process patents in force in the country that cover said pharmaceutical products, according to the information provided by the applicant or its legal representative. The Ministry must include this information on its website within a maximum period of 15 business days counted from the receipt of said information. The Ministry will publish in said list the number and expiration date of each patent that is submitted by an applicant or its legal representative. In the case of applications for a sanitary registration for the first time of multi-source pharmaceutical products, when the applicant cannot meet any of the requirements established in subparagraphs i) or ii), the applicant or its legal representative must submit a sworn statement issued before a notary public indicating that no patent granted and in force in Costa Rica claims the pharmaceutical product subject to the sanitary registration, or, when such patents exist, the expiration or termination date of the patent(s) claiming it, and indicating that the multi-source pharmaceutical product will not be marketed until after the expiration date of said patents. The applicant or its legal representative must indicate in its sworn statement issued before a notary public that it has reviewed the Ministry's website for the purpose of verifying this information. In such case, the Ministry will not issue the sanitary registration to the applicant until after the expiration of the protection period of all patents claiming the multi-source pharmaceutical product for which sanitary registration is requested, according to the information provided by the applicant or its legal representative, or the protection period of the test data, whichever is later, except as provided in Chapter XI of this Regulation. For its part, section 27 stipulates the requirements to obtain a sanitary registration for the first time, for which a sanitary registration application file will be opened. Regarding the control of medications, Article 50 ibid states that the post-registration verification will be carried out by the Health Regulation Directorate, through inspectors designated for this purpose, by means of inspection and sampling in the market, at the pharmaceutical laboratory, or at customs, in accordance with the provisions of the General Health Law, Law No. 5395 of October 30, 1973; and the Law for the Promotion of Competition and Effective Consumer Defense, Law No. 7472 of December 20, 1994; and other applicable regulations, and the first quality control carried out on pharmaceutical products will be performed during the first year of commercialization, without diminishing the controls that the Health Regulation Directorate may eventually order.

VIII- ON THE ALLEGED PROCEDURAL VICE OF THE REGULATORY ADMINISTRATIVE ACTS, DUE TO THE ABSENCE OF THE HEARING PROVIDED FOR IN SECTION 361 OF THE GENERAL LAW OF PUBLIC ADMINISTRATION.

As indicated in previous recitals, the Constitutive Law of the Costa Rican Social Security Fund (Caja Costarricense del Seguro Social) in its section 72 imposes that it must establish and maintain an updated registry of offerors for the products. Under the protection of this regulation, the Costa Rican Social Security Fund issued, through agreement CCF-1445-06-209, session 2009-21 of June 10, 2009, the Regulation with Requirements for the Registration of Offerors for Biotechnological Medications, published in Gaceta 127 of July 2, 2009, which, through agreement 3376-11-10, session 2010-44 of November 17, 2010, the Institution's Central Pharmacotherapy Committee proceeded to render null and void all previous agreements issued on that regulation, establishing the following Regulation with Requirements for the Registration of Offerors for Biotechnological and Biological Medications, which was indicated as addressed to registered offerors and offerors to be registered in the CCSS Registry of Offerors for biological medications of Group 1 and Group 2 as stated, also imposing mandatory compliance for those offerors participating with the Fund with medications that do not have a Sanitary Registration for the Medication. Likewise, the Central Pharmacotherapy Committee of the Costa Rican Social Security Fund, through agreement CCF-0275-02-09, session 2009-21 published in March 2009, issued the Specific conditions for the acquisition of medications called antineoplastics and other medications for specific use in oncological and hemato-oncological pathologies, which, through session 2011-08 of February 23, 2011, of the Central Pharmacotherapy Committee, proceeded to modify point 6. The plaintiff presented, in the first instance, substantive arguments and concluded both its statement of claim and its conclusions with arguments tending to highlight the existence of a formal defect in the regulation in its capacity as an administrative act of a general nature. In light of the foregoing, this Panel of Judges clarifies that it is therefore pertinent, in the first instance, to begin the study of the procedural arguments; subsequently, if necessary, in order to fully hear the rest of the plaintiff's claims, substantive considerations will be entered into.

Thus, the plaintiff alleges the non-existence of the hearing required by numeral 361 of the General Public Administration Law for the adoption of provisions of a general nature, which in its opinion constitutes an element of validity and its omission implies absolute nullity. The defendant's representation maintains that such requirement is not applicable to the scientific-technical provisions and/or guidelines issued by the Comité Central de Farmacoterapia, since what is provided by numeral 361 of the General Public Administration Law is for the drafting of provisions of a general nature in the strict sense by the Executive Branch that, in exercise of its executive regulatory authority, deems necessary to adopt; that is, such requirement, in its represented party's view, is not applicable to technical regulations adopted by advisory technical bodies as in this case. In order to address the arguments of both parties, it is important to clarify some concepts. Citizen participation and the glass house doctrine in the exercise of public function establish as a maxim that, except in very exceptional situations, the participation of inhabitants must be allowed both through the exhibition of decisions and the possibility of challenging them. If public action presents its due justification, the Administration has nothing to fear from being able to express the proper justifications based on its different acts. Now, by Regulation we must understand any legal provision of a general nature issued by the Public Administration and with value subordinated to the law; it is one of the manifestations of the exercise of the administrative function, through the creation of a normative body of lower rank and subject to the law, but with the authority to create legal effects. The regulation develops a law upon which its validity depends. The regulation is a norm, hence its dual condition. The regulatory authority is based on the need to generate norms whose approval, repeal, or modification procedure is sufficiently expeditious to ensure agile resolution mechanisms for the ordinary activity of the Administration, whereas the law, in its approval process, is slower due to parliamentary dynamics and furthermore cannot foresee all the situations that may be faced in each particular case when exercising public competencies. Such authority results in the issuance of an administrative act of a general nature called a regulation, subject to certain formal and substantial limits. Regarding its classification, the Constitutional Chamber has ruled in the following terms: "IV.- ON AUTONOMOUS SERVICE AND ORGANIZATION REGULATIONS. It is claimed that through regulations that do not meet the characteristics of an executive regulation, nor of an autonomous service or organization regulation, matters proper to formal law are regulated, by establishing limitations on fundamental rights, in what corresponds to the creation of sanctioning administrative bodies and the establishment of sanctions; in addition to not having been issued by the respective hierarchical body, but by the supplier of the Banco Nacional de Costa Rica. In order to analyze the consulted regulations, it is necessary to recall what this Constitutional Court has previously indicated regarding the different categories or types of regulations that are constitutionally possible: \"The categories into which regulations are distinguished are: a.) executive regulations (reglamentos de ejecución): which tend to carry out the concrete execution of laws, especially when they are of a rather generic scope; b.) independent or autonomous regulations (reglamentos independientes o autónomos) from any legislative provision, and related to matters within the competence of the Executive Branch not regulated by law, or partially regulated. Among these may figure the so-called organization regulations (reglamentos de organización), which refer to the institution and structure of the various public offices. Derived from the above, the proper subject matter of regulations can be defined: administrative matters, which comprise the organizational aspects of the Public Administration – meaning the Executive Branch in the performance of its own functions. Therefore, there is an impediment to regulating matters referring to the rights and obligations of citizens as such, the limitation of their freedom or their rights – including the regime of taxes, penalties, and fundamental rights – via regulations. These concepts have already been indicated by this Chamber on repeated occasions, through resolution number 1876-90, at sixteen hours on December nineteenth, and number 1635-93, at seventeen hours on November fourteenth, among others.\" (Judgment number 5227-94, at fifteen hours six minutes on September thirteenth, nineteen ninety-four.) By virtue of the foregoing, the content of independent regulations or autonomous regulations (reglamentos autónomos) can be clearly differentiated from executive regulations, since they are characterized by regulating the own competence of their author – the Administration – and lower authorities, insofar as they aim to organize and regulate the activity of their author and inferior, to achieve better compliance with the assigned public purpose. They are of two types: autonomous organization regulations (reglamentos autónomos de organización) and autonomous service regulations (reglamentos autónomos de servicio). The former find their basis in the power of self-organization of the administration itself, and the latter have their support in the competence of the administrative head to regulate the provision of the service under their charge, without the need for an existing prior law on the matter. These are regulations that create special subjection regimes and that limit the rights of the administered citizens who have entered into a relationship with the Administration." Vote number 2000-2856 at 15:48 hours on March 29, 2002. In reality, the autonomous regulatory act is reserved for aspects of organization and functioning, where not even the law can establish certain limitations. That led to generating the doctrine of the interna corporis act, as the power of self-organization of the public powers. The national Constitution clearly develops the subject of the executive regulation and the power of the organization regulation. The submission of the latter to the former is clear, since the national legal system does not establish matters reserved to regulatory norms. Regarding the procedure for the formation of regulations, the General Public Administration Law, in its numeral 361, imposes that in the drafting of provisions of a general nature: "1. A hearing shall be granted to decentralized entities regarding draft general provisions that may affect them. 2. Representative entities of general or corporate interests affected by the provision shall be granted the opportunity to express their views within a period of ten days, except when opposed by reasons of public interest or urgency duly recorded in the preliminary draft. 3. When, in the judgment of the Executive Branch or the Ministry, the nature of the provision so advises, the preliminary draft shall be submitted to public information, during the period indicated in each case." From a study of the second subsection of said norm, several legal requirements that must be met are observed, such as: it must involve the process of creating a general norm; it must affect general or corporate interests by denying, aggrieving, suppressing, or limiting subjective rights and/or legitimate and direct interests; and it must involve representative entities thereof. It is not superfluous to indicate that the General Agreement on Tariffs and Trade (GATT) and the Uruguay Round, both legal norms ratified by Costa Rica and having supremacy over legal norms, consider that any regulatory norm that implicitly carries, directly or indirectly, a restriction on trade conditions (non-tariff barriers) must be consulted prior to its entry into force. This allows for a concordance between the legal norm and that established in international regulations. Regarding the first requirement of being a general norm, we must indicate that an administrative act produces individual or concrete effects (administrative resolutions and agreements) and collective or general effects, such as decrees and regulations, by being directed at indeterminate subjects. As for the affectation of general or corporate interests, these refer to private or public entities that represent the community or the population through their activity, or being a corporation, which constitutes "a collective organization duly constituted, personified, and organized that represents and defends the interests of a determinable group or sector of people (e.g., chambers, associations, professional associations) (...)" Jinesta Lobo, Ernesto. Tratado de Derecho administrativo. Volume Three, San José, Costa Rica, Editorial Jurídica Continental, 2007, page 244. Regarding the procedure, the First Chamber of the Supreme Court of Justice, in vote number 10 at 14:20 hours on January 22, 2002, held that "III° The General Public Administration Law devised a special procedure for the drafting of provisions of a general nature, which are administrative acts of normative scope. In the special nature adopted by the legislator lies the answer to the questions raised in the sub judice, as to the value that the hearing process holds within that special process. A simple reading of the articles regulating that special procedure reveals that it was devised precisely with the object of enshrining the hearing process, in some cases, for entities of the state conglomerate itself (Article 361, paragraph 1), in others, for entities – it does not distinguish between public and private – representative of general or corporate interests, affected by the provision (Article 361, paragraph 2). Hence, the value and transcendence of the hearing in the procedure for drafting general provisions is indisputable, this being a substantial, unavoidable formality, except for the concurrence of the exceptional circumstances that the same norm provides. This obligation, in the indicated special procedure, constitutes the legislative development of norms that, as a general principle, inform the administrative procedure. Articles 217, 218, and 220, in relation to 239 and following, of the General Public Administration Law provide for the necessary intervention of the administered party in the procedure. There being no individualized subjects in the adoption of regulatory acts who can be considered directly interested parties, the legislator provided that in such cases the transfer, the hearing, must be made to entities representative of corporate or general interests." By virtue of this, the cited hearing process is recognized as a necessary, unavoidable requirement of validity and efficacy, with legal and supra-legal roots, of the special procedure for the creation of administrative norms of a general nature. In accordance with the foregoing, the hearing that must be granted is an essential requirement of the procedure, which has its basis in constitutional principles not only of due process but also the right of citizen participation, as our Constitutional Court has repeatedly held in its rulings: II.- ON CITIZEN PARTICIPATION. The participation of citizens in public decision-making is provided for in Article 9 of the Political Constitution, therefore acquiring the rank and force of a fundamental constitutional right. It is not a matter of deconstitutionalizing the principle of legality of the Public Administration, although it certainly is a more democratic form of government, which broadens the forums for debate on different issues that affect the community, and which, by virtue thereof, are open to citizen intervention and opinion. We are, therefore, before an option already widely accepted in the evolution of the concept of democracy, and this amparo offers a magnificent opportunity to give it clear and effective validity, so that it does not remain mere discourse. The commented precept, therefore, enshrines the cited principle through access to available information and its dissemination, so that decision-making is not confined to a limited group of interests. In this way, and in accordance with our democratic system, ARESEP is obliged to convene such a hearing, particularly to guarantee the right of defense and access to information that concerns each and every one of the inhabitants of our country, so that decisions are not taken by surprise for the "affected" interested parties. Precisely, in the ARESEP Law and its regulations, the legislator provided a special administrative procedure, which is the public hearing whose main characteristic is to provide transparency in the decisions of the Regulatory Entity and the possibility of giving participation to consumers and users within the process. Likewise, by providing the opportunity for residents, social organizations, the state and private sector, citizen defense institutions, and other governmental institutions to participate in it, greater benefit is achieved, which facilitates a better exchange of information among participants, making the hearing a transcendental instrument in decision-making and an instrument of transparency in a democratic system like ours. By virtue of the foregoing, tariff setting or modification must be submitted to a public hearing in which those citizens who present an opposition based on technical criteria may participate, granting the interested party the right to exercise the use of the floor during the respective act in order to defend their interest in the matter. In this way, the public hearing that the Autoridad Reguladora de los Servicios Públicos must hold in those cases where it is processing a tariff-setting study for public services, aims to allow the exercise of the community's right to participate in a matter that directly affects it, prior to the adoption of the administrative decision, and thus constitutes a manifestation of the democratic principle. This hearing intends that interested persons state whatever they deem appropriate regarding the tariff-setting application under study before the Regulatory Authority, which is why the rigor required for procedures seeking the suppression of a subjective right does not apply (Judgment 2002-08848 at sixteen hours fifty-seven minutes on September ten, two thousand two); however, it is not a simple formal requirement, such that it can be set in a way that renders nugatory the exercise of the right it seeks to protect, by being granted under conditions that prevent or hinder the fulfillment of the objectives it is intended to achieve, in protection of the right to information and citizen participation..." III.- In conclusion, it is clear that in order to guarantee the right of citizen participation provided for in Article 9 of the Political Constitution, the public hearing that the Autoridad Reguladora de los Servicios Públicos must hold in those cases where it is processing a tariff-setting study for public services, must allow the exercise of the community's right to participate in a matter of its interest and must be given within a reasonable period that allows the community to express itself. Thus, it is appropriate to uphold the claim raised for violation of the right of citizen participation and to annul the convocation made by the Autoridad Reguladora de los Servicios Públicos to hear the tariff increase proposed by COOPEMORAVIA, to increase the fare for route 40MB, described as San José-Moravia-Ramales and common corridors of routes 40, 41, 42, and 43 processed in file ET-29-2010." Judgment: 10708 of June 18, 2010.

IX- ON THE SPECIFIC CASE.

It remains then to establish the type of provision of a general nature that the administrative acts challenged here constitute, and whether the hearing pursuant to numeral 361 of the General Public Administration Law should have been granted prior to their adoption. From the foregoing, it is concluded that the Caja Costarricense del Seguro Social indeed issued said regulations under the protection of article 72 of its Constitutive Law, and that the regulations issued are indeed of a technical nature. Due to the body that issued them, they do not constitute executive regulations (reglamentos ejecutivos), but rather independent and highly sui generis regulations. Regarding the act issued through agreement 3376-11-10, session 2010-44 of November 17, 2010, the Comité Central de Farmacoterapia of the Institution proceeded to render without effect all previous agreements issued under those regulations, establishing the following Normative with Requirements for the Registration of Bidders for Biotechnological and Biological Medications (Normativa con Requisitos para el Registro de Oferentes para Medicamentos biotecnológicos y biológicos), issuing a new regulation. From the review of the content of this regulation, we find that the requirements are, in reality, not for the bidder as such, but regarding the product: group 1 medications of biological origin that do not use raw material from hemoderivatives in their manufacturing process, and group 2 of biological origin that use raw material from hemoderivatives in their manufacturing process – understood, according to point 4.53 of executive decree 37006, as that obtained by industrial procedures, whose raw material is human blood or plasma, which, according to the experts who testified in the oral and public trial (Julián Cuesta Ramírez, Renato Murillo Masis, and Albín Chávez Matamoros), are of high complexity in their production and used for very specific and serious diseases. From the review of said regulation, it is extracted that for both group 1 and group 2 medications, technical requirements are imposed, for innovative, biosimilar, biological, and biotechnological medications, among others; certificates in their manufacturing process, production, etc. It is even provided that for the procurement of medications, the Caja Costarricense del Seguro Social may take its clinical experience with the medication as a qualification parameter and exempt from other technical requirements. In relation to the second challenged regulation, issued through session 2011-08 of February 23, 2011, by the Comité Central de Farmacoterapia, in which it proceeded to modify point 6 of the Specific Conditions for the acquisition of medications called antineoplastics and other medications for specific use in oncological and hema-oncological pathologies, issued in agreement CCF-0275-02-09, session 2009-21 published in March 2009, equally technical requirements are imposed for their offer. From the statements of all the experts received in the oral and public trial, it is concluded that medications must indeed possess three basic elements: quality, safety, and efficacy, which are indispensable for the medication to produce the effects in patients for which they were produced. The plaintiff, both regarding the regulations on biological, biotechnological, and antineoplastic medications, argues on the merits that the reforms introduced in the questioned regulations by the Comité Central de Farmacoterapia of the Caja Costarricense del Seguro Social undermine the health and life of Costa Ricans, as there is no guarantee that said medications possess the essential elements of quality, safety, and efficacy, and presents in detail a series of technical questions. From the meticulous review of said regulations, technical requirements are indeed established, or they are exempted with respect to the previous regulations for the purchase of medications, which are ultimately used to fulfill the public purpose entrusted to the institution: public health. It must not be lost sight of that said provisions, without going into the merits of the case, are indeed aimed at regulating the requirements that medications must meet for their purchase. A large number of people in our country depend on these to protect not only their health but also to preserve and rescue their lives; regulations that evidently contain provisions that must guarantee public health, which inevitably makes the discussion of their norms a matter of public interest, because the effects of said provisions, although initially a parameter for the purchase of medications, the implicit objective thereof is precisely to safeguard the health of all patients who attend public health centers in our country seeking to improve and preserve their health and their life. Therefore, the effects of these regulations are not limited to an organizational matter of the Institution, but evidently to a matter of Public Health. General provisions must not only be classified according to the body issuing them, but also according to their effects and to whom they are directed. In the specific case of the challenged regulations, the ultimate objective is the guarantee of the medications supplied to patients. Therefore, in the opinion of this Collegiate Body, the questioned norms are independent technical regulations (reglamentos técnicos independientes), although not executive regulations, due to the effects of their application and compliance; thus, their interest cannot be limited only to organizations or groups, natural or legal persons dedicated to the production, distribution, and commercialization of medications, but also to every person as a guarantee of the fundamental right to health and life as protected by our Political Constitution. Hence, it is not possible to accept the position held by the defendant's representation that, being a technical regulation, it does not require the procedure established in the General Public Administration Law. On the contrary, due to the technical matter it regulates, for its formation it should have granted the hearing provided by numeral 361 of the cited law. It cannot be overlooked that said hearing aims at the participation of citizens in public affairs, provided that the subject regulated in said norms, as in those challenged here, is of public interest, as in the present case the right to life and health. Continuing with the analysis of the special procedure for drafting provisions of a general nature, other norms and general principles regulating the administrative procedure can be cited, an interpretation that is possible in accordance with Article 229, paragraph 1, of the General Public Administration Law, which reads as follows: "This Book shall govern the procedures of all Administrations, except where a provision opposes it." For its part, article 223 establishes that the omission of substantial formalities of the procedure shall cause nullity of the proceedings. 2. A formality shall be understood as substantial if its correct execution would have prevented or changed the final decision in important aspects, or if its omission caused defenselessness." Clarity must be had, as indicated above, regarding the purpose of the hearing provided in numeral 361 of the General Public Administration Law, because for the effects entailed by the challenged regulations, the hearing is essential, not only for organizations like the plaintiff, but also for professional associations, medical and pharmacy professionals who can provide essential information on the quality, safety, and efficacy of medications, as well as on the technical requirements required for their procurement, and even more so, administrative bodies, such as the Ministry of Health. In this regard, the General Health Law, in its numeral 102, states that the importation of medications and their distribution will only be permitted to legal or natural persons registered with the Ministry, with prior authorization and registration with the Colegio de Farmacéuticos, which reinforces this Court's position on the mandatory nature of said hearing. Numeral 106 of the General Health Law imposes that, legally, a medication may be destined for commerce, public use, and consumption when it satisfies regulatory requirements or those of the pharmacopoeia officially declared by the Executive Branch regarding its identity, quality, safety, and efficacy for the purposes for which it is used, consumed, or prescribed, and an additional element, the full knowledge and acceptance of the Caja Costarricense del Seguro Social, which its representative states in the answer to the complaint (folio 239, final paragraph of the main file), where it states "that for the purposes of registration of biotechnological medications, despite the fact that there is no regulation from the Ministry of Health of Costa Rica, the Comité Central de Farmacoterapia, until such regulation issued by the governing body exists, has been visionary and, in order to maintain the principles of Safety and Efficacy in the medications recognized in the Bidders' Registry of my represented party," which absolutely confirms the criterion of this Collegiate Body on the obligation to grant the hearing prior to the issuance of the challenged regulations, because knowing that the governing body in the matter had not issued the specific regulations regarding the sanitary registration of said medications, the legal hearing was necessary, timely, and advisable, so that the public body governing the matter could pronounce itself. Note that the reforms made in 2010 to the Normative with Requirements for the Registration of Bidders for Biotechnological and Biological Medications and, at the beginning of 2011, to the Specific Conditions for the acquisition of medications called antineoplastics and other medications for specific use in oncological and hema-oncological pathologies, are very close to the year 2011 when Executive Decree 37006-S was issued, which Regulates the Registration and Control of Biological Medications, which means that on those dates the technical regulations that the defendant misses from the governing body in the matter were being developed. Therefore, there is no doubt that granting the hearing is a substantial formality, because a modification of the final act could arise from such action. Precisely, the hearing aims to provide the opportunity for the entity or affected party to influence the will of the Administration before it acts in accordance with its regulatory powers. Failure to comply with the hearing process, which is not discretionary but mandatory, is necessarily linked to the validity of the general provision issued (as the culmination of the procedure), and, consequently, its omission may cause invalidity, therefore determining the nullity of all actions taken by the Administration in relation to the issuance of the questioned regulatory provisions. Consequently, the omission of the hearing by the defendant in the adoption of the challenged regulations constitutes a substantial defect in the procedure for issuing them, it not being viable in the present case to make any distinction regarding the validity of parts of the challenged acts, as the defect, being of a procedural nature, affects the entirety of the acts. Consequently, the absolute nullity of the following acts of a general nature is declared: 1- Agreement CCF-3376-11-10, session 2010-44 issued on November 17, 2010, by the Comité Central de Farmacoterapia of the Caja Costarricense del Seguro Social, published in the Official Gazette La Gaceta number 10 of January 14, 2011, and 2- Agreement adopted during session 20011-08, held on February 23, 2011, by the Comité Central de Farmacoterapia, through which it amends point 6 of the Specific Conditions for the acquisition of medications called antineoplastics and other medications for specific use in oncological and hema-oncological pathologies, for lacking a formal prerequisite for validity. It should be noted that although the plaintiff makes a prolific argument regarding the nullity of these norms on different grounds, since one ground has been upheld, it becomes devoid of any interest to rule expressly on the remaining grounds; however, it is advisable to warn the public entity that it must be clear about which competencies are its own, with respect to those reserved for the Ministry of Health as the governing body in the matter. Such that both entities must coordinate the fulfillment of their public purposes, but without one invading the other's domain. In this aspect, we draw attention to how matters regarding sanitary registration, the exception thereof, fall under the Ministry's purview, a topic that must not be lost sight of.

X.

REGARDING THE REMAINING CLAIMS The plaintiff requests that "Since the challenged agreements are null, we require the restoration of the validity of the previous agreements; 2009 Normative on Offeror Requirements for Biotechnological and Biological Medications and in its place the 2009 Normative on Requirements for the Registration of Offerors for Biotechnological and Biological Medications be applied, which corresponds to the previous version of the reform published in the Official Gazette La Gaceta No. 10 of January 14, 2011, relating to the agreement of the Logistics Management of the Caja Costarricense del Seguro Social (CCSS) adopted in session No. 2010-44 of the Central Pharmacotherapy Committee (agreement number CCF 3376-11-10) and the Agreement Denominated 'Requirements for antineoplastic medications and others for specific use in oncological and hematological pathologies' published in Gaceta No. 47 of March 9, 2010, which corresponds to the previous version of the introductory reform session 2011-08 held on February 23, 2011, by the Central Pharmacotherapy Committee of the CCSS, published in Gaceta No. 58 of March 23, 2011, and that the Caja Costarricense del Seguro Social apply the content of Decree 37006-S published in the Official Gazette La Gaceta Number 59 of March 22, 2012, denominated Regulation for the Registration and Control of Biological Medications, which is in accordance with the previous regulations of the Caja Costarricense del Seguro Social, whose validity we request be restored in point 3 of the claims of the complaint." In this regard, it is important to highlight that, although the first two claims, regarding restoring the validity of the previous regulations, the 2009 Normative on Requirements for the Registration of Offerors for Biotechnological and Biological Medications and the Agreement Denominated "Requirements for antineoplastic medications and others for specific use in oncological and hematological pathologies" published in Gaceta No. 47 of March 9, 2010, which corresponds to the previous version of the introductory reform, were outlined by the plaintiff from the beginning of her complaint, and subsequently, upon the issuance of executive decree (decreto ejecutivo) 37006-S (alleged as a new fact), she requests the application of the latter, it is evident that for the Caja Costarricense del Seguro Social the circumstances vary, specifically regarding the matter it regulated due to the absence of technical regulation by the governing body, the Ministry of Health. By reason of the foregoing, it is the Caja Costarricense del Seguro Social that must determine which regulation is applicable, always in fulfillment of its purposes and the exercise of its competence, taking into consideration the existence and validity of executive decree (decreto ejecutivo) 37006-S. That sought by the plaintiff cannot be declared; it is rejected, due to the variation in circumstances that she herself introduced as a new fact. To subject the Caja Costarricense del Seguro Social to the application of a regulation issued by the Central Pharmacology Committee under other circumstances and not those currently prevailing, as indicated supra, would invade the regulatory authority of the autonomous Institution. Therefore, it will be the institution that defines which regulation best suits the fulfillment of its purposes, within its competence and in respect of the competencies of the governing body in health matters, the Ministry of Health. In application of article 131 of the Contentious Administrative Procedural Code (Código Procesal Contencioso Administrativo), it is clarified that the retroactive effects of this declaration of absolute nullity shall not affect third parties who, as of the date this judgment becomes final, have subjectively acquired rights in good faith or consolidated legal situations derived from the aforementioned norm. Additionally, in application of precept 130, subsection 3) of the CPCA, the full publication of this judgment in the official gazette La Gaceta must be ordered at the expense of the Caja Costarricense del Seguro Social.

XI- REGARDING THE ALLEGED DEFENSES.

The defendant alleges a Lack of Standing (Falta de Legitimación) of the plaintiff, stating that Fedefarma does not seek to assert the rights of the community regarding the use of medications, but rather that its underlying strategy is directed at a commercial interest, which is why it lacks standing to sue the Caja Costarricense del Seguro Social. For her part, the plaintiff affirms that her interest is that of the patients, which justifies the defense of collective rights, and the action seeks to enforce quality and safety provisions introduced into the legal system by the Ministry of Health and which are recommended by the World Health Organization. That it is not, as the defendant claims, a commercial matter, but rather ensuring that the population has safe and effective medications, which is why they defend the rights of the community. Therefore, her represented party has standing to file the action. Regarding Standing, it is the necessary correspondence between the defendant and the holder of the right or legitimate interest claimed. It is an essential prerequisite of the procedural legal relationship, indispensable for a favorable judgment. Numeral 10, subsection b of the Contentious Administrative Procedural Code establishes that the following have standing to bring an action: "b) Entities, corporations, and institutions of Public Law and any others that hold the representation and defense of interests or rights of a general, guild, or corporate nature, insofar as such interests or rights are affected, and groups governed by any statute insofar as they defend collective interests." The second subsection of the cited ordinal imposes that those who hold, with respect to regulatory provisions, any legitimate interest, individual or collective, or any subjective right, may directly challenge them, without the need for an individual application act. It is necessary to mention that the norm establishes two different prerequisites: subsection 1.B for specific acts or actions, and subsection 2 for the challenge of regulatory provisions, as in the specific case, and this prerequisite grants standing to appear in defense of collective rights. Therefore, it is essential to determine if the plaintiff, even though she so states, is truly appearing in representation of collective interests. The national jurist Manrique Jiménez Meza defined collective interests as "typical group or minor collective interests, attributable to the organized community, whether through legal entities or through groups not incorporated into such entities, for the protection of the interests embedded in each category of belonging (...) collective interests are category interests and as such, constitute a partial treatment within the context of the broad impersonal, anonymous, and indeterminate collective, but they are no less of vital importance in the social context. Consequently, collective interests are attributable to the subjects representing such interests, whether through associations, organizations, various entities, or even through groups organized by virtue of shared interests against common threats or damages." (Jiménez Meza Manrique, The New Contentious Administrative Process, San José. Judicial Branch. Department of Graphic Arts, 2006, page 89.) Professor Jinesta Lobo defines them as "those belonging to a group or a category, which are subdivided, in turn, into corporate and diffuse. Consequently, collective interests are a species of the genus, whose holder is an organized or unorganized group, personified or not, different from the national community, within another of greater scale that can be considered total or general. Such a category or group can be identified by a common characteristic or feature of social relevance (hobby, occupation, business sector, consumers or users of certain public goods or services, etc.)" JINESTA LOBO, Ernesto. Treatise on Administrative Law Volume III. 1st Edition. Editorial Jurídica Continental. San José, 2007, p. 243. The plaintiff, from her complaint (folio 2), informs that "FEDEFARMA is a civil organization constituted in accordance with the laws of the Republic of Guatemala, which represents the research and development pharmaceutical companies operating in the Central American Isthmus and the Caribbean area (...) it groups together fourteen multinational research pharmaceutical companies." From the review of the evidence provided by the plaintiff in response to the prevention made by this Court regarding her legal capacity (personería), the articles of incorporation of said Federation were examined, and specifically at folio 483, the said articles of incorporation state "ARTICLE 3. The Federation is an entity devoid of all profit and religious purposes. Completely apolitical, created to promote the development and improvement of pharmaceutical activity, defend and coordinate the interests of its associates, and represent them in their relations with other public or private entities and with private individuals." In analyzing the complaint, it is extracted that the plaintiff, within her arguments, has mentioned that her interest lies in defending the quality of the medications supplied to patients, repeatedly alleging that she demands the protection of the right to health of the patients who are ultimately the users of the medications that the Caja Costarricense del Seguro Social acquires to meet health needs. Notwithstanding the foregoing, it is also evident from the complaint itself that the plaintiff always reported that she represents a group of multinational research pharmaceutical companies, and from the articles of its constitution, its objective is indeed to promote the development and improvement of pharmaceutical activity. Therefore, in application of the second subsection of numeral 10 of the Contentious Administrative Procedural Code, the plaintiff does have standing to appear in defense of the collective interests that Fedefarma represents, coupled with the fact that from her very arguments emerges the questioning of the quality of the medications that may be distributed and consumed in our country. So that the core that unites the pharmaceutical companies to form the Federation serves as the basis in the process that concerns us; such that the normative prerequisite is satisfied. Although this argumentation is not developed in the best manner in the complaint document, as already indicated, this is inferred without major questioning. Note that although the cited second subsection limits, for the purpose of challenging regulatory provisions, legitimate, individual, and collective interests, but not diffuse ones, the plaintiff does meet the legal prerequisite to bring an action on behalf of those she represents, a Federation composed of pharmaceutical houses, with the purpose of promoting and protecting the activities of pharmaceutical laboratories. Added to the above, as expressed by this Chamber, the effects of the contested regulations are ultimately directed at a matter of Public Health, and because the protection of the life and health of persons is a fundamental right, standing in this matter cannot be restrictive. Consequently, the defense of lack of active standing (falta de legitimación activa) alleged by the defendant's representation must be rejected. For greater abundance, it should be noted that doctrine has pointed out a series of topics where standing is open to any inhabitant (almost as an actio popularis) due to the level of social relevance, among which are located tax matters and environmental matters; further, some doctrine accepts health topics within this list. The logic that would prevail according to this reasoning is that in those matters where the impact on health is the core of the discussion, any natural or legal person would have standing. A stance that, although not embraced by the Court at this time, does not cease to have its due basis and legal logic. Regarding the Lack of Right (Falta de Derecho), the same is rejected insofar as the ruling indeed ordered the nullity of the contested regulatory provisions, the plaintiff being correct in her arguments, understood as accepted in the remaining claims. So that the right invoked by the defendant lacks its corresponding basis, but rather the scale of justice tilts in another direction, implying the rejection of the preliminary defense.

XII.- REGARDING COSTS. As regards costs, pursuant to numeral 193 of the Contentious Administrative Procedural Code, the costs of the process are borne by the defendant. The foregoing insofar as the plaintiff has had to resort to this avenue in order to assert her right, which determines that if the public entity were not charged, an unjust enrichment would occur for the plaintiff.

THEREFORE (POR TANTO):

The new facts formulated by the plaintiff are admitted. The defenses of Lack of Active Standing (Falta de Legitimación activa) and Lack of Right (Falta de Derecho) raised by the defendant are dismissed, the latter with respect to what was granted, understood as admitted in the remainder. The complaint is partially upheld, understood as denied in what is not expressly granted; consequently, the absolute nullity of the following administrative acts is declared: 1- Agreement CCF- 3376-11-10, session 2010-44 issued on November 17, 2010, issued by the Central Pharmacotherapy Committee of the Caja Costarricense del Seguro Social, published in the Official Gazette La Gaceta number 10 of January 14, 2011, in which the 2009 Normative on Offeror Requirements for Biotechnological and Biological Medications is modified. 2- Agreement adopted through session 20011-08, held on February 23, 2011, by the Central Pharmacotherapy Committee, by which it reforms point 6 of the Specific conditions for the acquisition of medications denominated antineoplastics and other medications for specific use in oncological and hema-oncological pathologies, published in Gaceta 58. The Caja Costarricense del Seguro Social takes note of what is set forth in the recitals (considerativa) of this ruling. Both costs of the process are borne by the losing party. Let it be notified.

In Article 5.6 of Executive Decree No. 37006-S, the Ministry of Health requires that the biosimilarity exercise related to quality be submitted in comparison with the reference biotechnological medicine, in order to determine that it has no additional safety and efficacy implications, for which the regulation details a series of studies related to the structure of the medicine, among others. Similarly, Article 5.12 details the information on safety and efficacy that must be provided, which includes pre-clinical studies (in vivo and in vitro) as well as comparative clinical studies with the original reference medicine. The requirements detailed in these articles of the regulation are not required by the CCSS, which only requests the quali-quantitative formula of the medicine (see norms that contradict Decree 37006-S: Group 1, point 3; Group 2, point 2 of the challenged norm). // 2. The Regulation issued by the Ministry of Health establishes in Article 5.12 that experience with biosimilar products will be measured according to what is established by the World Health Organization, for which it requests pre-clinical and clinical studies as well as the detail required by the guidelines of strict authorities (FDA, EMA, and ICH) and the detail of the applied biosimilarity studies. Such tests are not required by the CCSS regulations, which instead, requests as the sole experience of the biotechnological product that the product possesses "ample clinical experience" in the CCSS. Therefore, the CCSS regulations (see norms that contradict Decree 37006-S: Group 1, point 8; Group 2, point 7 of the challenged norm) contradict the regulations issued by the Ministry of Health. // 3. In note 2 of Article 5 of Executive Decree No. 37006-S, the Ministry of Health requires for all biosimilarity studies that the WHO guidelines (provided in the case file at folios 41 to 91 of the precautionary measure file) or the norms issued by strict authorities (FDA, EMA, and ICH) must be used. However, the CCSS regulations allow the CCSS to dispense with even those studies, even though the Ministry of Health does not establish any exception for not requesting them (Norms that contradict Decree 37006-S: Group 1, point 8; Group 2, point 7 of the challenged norm). // 4. Article 5.3 of Decree No. 37006-S establishes as requirements for the sanitary registration of biological medicines information on the regulatory status of the product at the international level as well as inspections of international laboratories. This information ensures that the biotechnological products introduced to the market have experience in other markets and therefore their effective experience, safety, and efficacy are proven at the time of registration, as well as that the medicine has had positive or negative effects in a specific population. However, the CCSS regulations exclusively request experience of the product within the CCSS itself, not at the international regulatory level (see norms that contradict Decree 37006-S; Group 1, point 8; Group 2, point 7 of the challenged norm). // 5. Article 10 of Decree 37006-S requires reports of Risk Management Plans and Pharmacovigilance that the CCSS does not require in its regulations and which are essential for monitoring the immunogenicity of a biotechnological medicine. // 6. The Ministry of Health does not endorse the interchangeability of biotechnological medicines, whereas the CCSS does allow such interchangeability without restrictions (see norms that contradict Decree 37006-S: Group 1, point 8; Group 2, point 7 of the challenged norm). The consequence of this contradiction lies in the fact that if the CCSS is endorsing products by virtue of their "ample clinical experience" demonstrated in the CCSS, it is not possible to prove said successful clinical experience through pharmacovigilance, because if interchangeability is endorsed, it becomes impossible to follow the behavior of one therapeutic solution with respect to the other and therefore impossible to verify what the experience of the product is; especially when we are dealing with a medicine with a narrow therapeutic margin that treats very serious conditions.

**FACT TWENTY-FOUR:** Executive Decree No. 37006-S is the only one that complies with the stipulations of the World Health Organization, because unlike the CCSS regulations, it requires that for the marketing authorization of a biotechnological product, a series of essential requirements demanded by the WHO must be met, through the "Procedure for the prequalification of pharmaceutical products issued by the World Health Organization" (folio 54-41 precautionary measure) and the "Guidelines on the evaluation of similar biotherapeutic products issued by the World Health Organization" (Folio 91-55 precautionary measure). It is of utmost importance to maintain these required requirements for the sanitary registration of biotechnological medicines as well as those detailed in the Ministry of Health regulation, especially considering that the CCSS can and in fact does purchase medicines that do not possess sanitary registration in Costa Rica; they could acquire products that only meet the scarce requirements of the CCSS and not those of the Ministry of Health." Pursuant to numeral 68 of the Code of Administrative Litigation Procedure, the preceding facts having been raised within the procedural stage provided, this Court proceeds to admit them as new facts, which are incorporated into the initial complaint, and will proceed in the following considerandos to their analysis. Let it be noted that they correspond to factual situations occurring after the filing of the complaint, and are intimately related to the process at hand; thus the normative presuppositions that concern us are satisfied.

**II- PROVEN FACTS. THE FOLLOWING ARE TAKEN AS DEMONSTRATED:**

These certifications must be updated each time the renewal of the registration is requested before the CCSS for medications included in the LOM, and if not registered, each time a purchase is made at the Central or local level in the case of non-LOM medications. Point 5: All requested documents must bear the duly authenticated signatures of health authorities, as required by Costa Rican legislation, in addition to completing the chain of consular legalization of our country and being ratified by the Ministry of Foreign Affairs of Costa Rica. Point 6: The requirements set forth in points 1, 2, 3, and 4 shall be waived for those antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies for parenteral or oral use, which are registered and consumed in any of the following countries: United States (FDA), Canada (Health Canada), Japan (MHLW), Switzerland (Swissmedic), Germany, England, Sweden, France, Italy, Spain, Belgium, Denmark, Austria, Holland, Finland, Norway. It is important to note that laboratories must present the certificate of free sale of their product in the United States (FDA), Canada, Japan (MHLW), Switzerland (Swissmedic), Germany, England, Sweden, France, Italy, Spain, Belgium, Denmark, Austria, Holland, Finland, Norway; or with registration and marketing in these same countries. Likewise, those medications whose origin does not correspond to any of the countries listed above, but which have the Mutual Recognition certificate issued by the EMEA for their marketing in one of the reference member states of the European Union, shall be exempted. This certificate must be issued by the highest competent regulatory authority in public health of the respective country. Point 7: A bidder already registered in the CCSS bidder registry may revalidate their registration by submitting the information indicated in the corresponding points above. Said registration shall be valid until the expiration of the sanitary registration issued by the Ministry of Health of Costa Rica. Point 8: Those bidders who are registered but prefer to submit their data at the time of the purchase process and not revalidate the registration before the CCSS until its expiration, must submit the requirements for antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies for each purchase process. Point 9: In the case of the acquisition of antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies included in the Official List of Medications (LOM), the Área de Medicamentos y Terapéutica Clínica assigned to the Dirección de Farmacoepidemiología shall be responsible for carrying out the data analysis and the corresponding study of the Defined Daily Dose (DDD). Point 10: In the case of non-LOM antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies acquired by each center, the data analysis and the corresponding Defined Daily Dose (DDD) study shall be carried out each time a purchase procedure is promoted, and shall be performed and analyzed by each Pharmacy Service. Point 11: Once the Executive Decree of the Ministry of Public Health regulating the Registration of Medications is published, which contemplates the specific requirements for molecular target therapy products, these requirements are based on ICH recommendations and form part of these conditions. Point 12: In the case of offers for antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies for parenteral or oral use not included in the Official List of Medications that are acquired, at the Central or local level, and are under equal conditions, as a tie-breaking mechanism, priority shall be given to the medication that is registered and consumed in any of the following countries: United States (FDA), Canada, Japan, Switzerland, Germany, England, Sweden, France, Italy, Spain, Belgium, Denmark, Austria, Holland, Finland, Norway. The bidder must present a certification issued by the highest regulatory authority of the country stating that it is registered and consumed in one of the aforementioned countries. Upon the request of the Cancer Council regarding bioequivalence requirements and requirements for so-called antineoplastic medications of biotechnological origin, the mechanism established by the Ministry of Health and CCSS is continued." (see folios 266 and 267 reverse of the administrative record); **10-** By means of session 2011-08 held on February 23, 2011, by the Comité Central de Farmacoterapia, point 6 was amended in the following terms: "Point 6: The requirements set forth in points 1, 2, 3, and 4 shall be waived for those antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies for parenteral or oral use, which have marketing authorization in any of the following countries: United States (FDA), Canada (Health Canada), Japan (MHLW), Switzerland (Swissmedic), Germany, England, Sweden, France, Italy, Spain, Belgium, Denmark, Austria, Holland, Finland, Norway, Colombia (INVIMA), Argentina (ANMAT), Brazil (ANVISA). It is important to note that laboratories must present: the pharmaceutical product certificate (or Certificate of Free Sale plus the Certificate of Good Manufacturing Practices), as backing for their registration and marketing authorization in the United States (FDA), Canada, Japan (MHLW), Switzerland (Swissmedic), Germany, England, Sweden, France, Italy, Spain, Belgium, Denmark, Austria, Holland, Finland, Norway, Colombia (INVIMA), Argentina (ANMAT), Brazil (ANVISA). Likewise, those medications whose origin does not correspond to any of the countries listed above, but which have the Mutual Recognition certificate for their marketing in one of the reference member states (European Union), shall be exempted. This certificate must be issued by the highest competent regulatory authority in public health of the respective country. To exempt them from the requirements listed in points 1, 2, 3, and 4, it is necessary that the pharmaceutical product certificates (or Certificate of Free Sale) include the name and address of the manufacturing plant, which must coincide with the address of the manufacturing plant of the medication registered with the Ministry of Health of Costa Rica (provided the medication is registered in the country). The manufacturing plant (name and address) from which the registered medication with marketing authorization in one of the countries listed above originates, must correspond to the same manufacturing plant from which the medication to be delivered to the CCSS will be imported." which was published in gazette number 58 of February 23, 2011 (see folio 310, 311, and 322 of the administrative record); **III- UNPROVEN FACTS** Of relevance for the resolution of this proceeding, the following is considered not demonstrated: **Sole**: That the defendant entity followed the procedure regulated in Article 361 of the Ley General de la Administración Pública at the time of issuing the general provisions challenged herein, and which was accepted by the defendant itself *(there is no proof of this in the case file).* **IV- REGARDING THE ARGUMENTS OF THE PARTIES** The plaintiff alleges the nullity of the agreement adopted through Session No. 2010-44 of the Comité Central de Farmacoterapia (agreement number CCF 3376-11-10 which has a regulatory nature), by modifying the regulations already in place in 2009, as well as the nullity of the agreement issued in session 2011-08 of February 23, 2011, which modifies point 6 of the requirements for medications called antineoplastics and other medications for non-specific use for specific use in oncological and hematological pathologies, and in its place, the validity of the norms that were modified be restored. For which, according to its criteria, it presents itself under the standing conferred by numeral 10, subsection 2, of the Código Procesal Contencioso Administrativo, a collective interest, alleging that the reform carried out by the Comité Central de Farmacoterapia of the Caja Costarricense del Seguro Social, specifically regarding the elimination of the mandatory compliance requirements that any biotechnological or biological medication must meet to be a bidder with the Caja Costarricense del Seguro Social, affects the community and violates principles of the World Health Organization. It claims that the challenged regulation mentions biological and biotechnological medications as being of the same typology, when what is intended to be regulated are biotechnological medications exclusively. In addition, the evaluation criteria for said medications are not sufficient to certify their quality. According to the challenged regulation, bidders are exempted from presenting the drug characterization studies, which does not guarantee its quality by making its use more flexible without verifying compliance with the evaluation guidelines issued by recognized "strict" authorities such as the WHO and the EMA, among other international bodies, which does not guarantee the safety, effectiveness, and efficacy of the medication that is essential for patients. It adds that regarding innovator medications, the manufacturing laboratories are exempted from presenting the certificate of free sale from the country of origin. It points out that the Caja Costarricense del Seguro Social endorses the interchangeability of the medication, which threatens the health of patients since in medications of biotechnological composition, the interchangeability of chemically synthesized products cannot be compared, which could generate serious implications for the patient's health. As pharmacovigilance has not been satisfactorily and safely developed in the institution, it is not possible to monitor the effects of interchangeability for the benefit of patients' health. It further points out that the regulatory framework regarding pharmacovigilance does not contain risk analysis processes designed to address the nature of the biotechnological product. On the issue of immunogenicity, it alleges that given the absence of the pharmacovigilance process, it is not possible to determine the immunogenicity of the medications, placing patients at risk. It argues the nullity of the administrative acts, as they have defects in their formation by not having been consulted as established by the Ley General de la Administración Pública for acts of general scope like those challenged here. At the trial hearing, it introduced new facts, based on a regulation subsequently issued by the Ministry of Health, pointing out that the challenged acts contradict those set forth in the cited act of general scope. The representation of the Caja Costarricense del Seguro Social rejects the lawsuit. First, it questions the standing with which the plaintiff appears in the proceeding, alleging an interest of the entire community, highlighting that in its same lawsuit it accepts that its primary interest is the impact on all the companies represented by Fedefarma, insofar as the requirements to become bidders are made more flexible. Regarding the 2010 regulations for the registration of bidders for biotechnological and biological medications, the Comité Central de Farmacodependencia, in the absence of specific regulations from the Ministry of Health, is the one that must impose the requirements for bidders in the medication acquisition process. Regarding medications called antineoplastics, and other medications for specific use in oncological and hematological pathologies, the modification referring to the incorporation of countries such as Argentina, Brazil, and Colombia was motivated by the fact that these were classified as Level IV regional reference regulatory authorities by PAHO/WHO, in the performance of their functions, and that based on the certificates from said regulatory authorities, they would be exempted from the requirements established in points 1, 2, 3, and 4. All of the above was the product of a study and technical rationale by the Comité Central de Farmacoterapia, and therefore does not entail any risk to public health, as it does not compromise the efficacy and safety of the treatments used for cancer patients; on the contrary, it is based on higher standards established by PAHO/WHO. Regarding the indiscriminate use of the terms biological and biotechnological, the regulation establishes the requirements for bidder registration, both for one and for the other. Likewise, biotechnological medications must also have immunogenicity and pharmacovigilance studies. It is also established in the regulation under discussion that biosimilar medications must attach the complete qualitative-quantitative formula with the excipients used and the permitted ranges of related substances, as well as drug characterization studies. Regarding the issue of immunogenicity, it alleges that the country does not have the capacity to carry out this type of study; however, it does have an active pharmacovigilance program for spontaneous notifications. It argues that internationally there is no real consensus on the interchangeability of biotechnological products; however, the Social Security institution has extensive clinical experience in the use of biotechnological medications, where the therapeutic benefit in the management of various pathologies has been documented. Regarding the procedural defect pointed out by the plaintiff, concerning the absence of the hearing provided for in numeral 361 of the Ley General de la Administración Pública, it states that the formal defect does not apply, as it pertains to acts of a general nature issued by the Executive Branch, not by autonomous institutions like the defendant here, in addition to the fact that the general provisions issued are technical regulations adopted by technical advisory bodies such as the Comité de Farmacoterapia of the Caja Costarricense del Seguro Social in its capacity as technical advisor. It raises the defense of Lack of Active Standing, accusing the plaintiff of fundamentally having a commercial interest, and not seeking to assert the rights of the community, and Lack of Right. It requests that the lawsuit be dismissed.

**V- ON THE REPRESENTATION OF THE PLAINTIFF PARTY IN THE PROCEEDING.** By resolution at one fifteen in the afternoon on October three, two thousand thirteen, this Collegiate Body, in accordance with numerals 66 subsection b and 92 subsection 1 of the Código Procesal Contencioso, instructed the plaintiff to provide the proceeding with the legal capacity of the Federación Centroamericana de Laboratorios Farmacéuticos (FEDEFARMA), to indicate if it is registered in the relevant registry, its validity, and if not, to present duly legalized documents proving its constitution, existence, validity, and representation. The foregoing was due to the fact that upon the review carried out by this Panel of Judges, only the document on folio 40 was found to have been provided to the proceeding, the registry inscription of a power of attorney of Mr. Rodolfo Antonio Lambour Chocano as legal representative of the plaintiff. The plaintiff provided the proceeding with the documents contained in folios 482 to 528 and 566 to 572, in which the constitution and registration of the plaintiff in the Republic of Guatemala is indeed recorded, as well as the appointment of Mr. Rodolfo Antonio Lambour Chocano as legal representative of the plaintiff, a person who effectively registered his representation and power of attorney of the cited Federation in our country, who in turn granted special judicial power of attorney to attorneys Carlos Ubico Durán and Alejandra Castro Bonilla, who have been proceeding with the action. Therefore, let the procedural defect be considered corrected and the plaintiff be considered duly represented in the proceeding.

**VI- REGULATIONS GOVERNING MEDICATIONS AND COMPETENCIES OF THE CAJA COSTARRICENSE DEL SEGURO SOCIAL IN MATTERS OF MEDICATION PURCHASE:** The hospital medical care service is a public service proper insofar as it is executed by a Hospital Center, or a Health Care Center (clinic, EBAIS, etc.); of those under the dependency of the Caja Costarricense de Seguro Social. This Entity, by constitutional provision, is responsible for ensuring (planning, developing, executing, etc.), among other things, everything related to Social Security, and included within it, the health care service. Thus, Article 75 of the Constitución Política states in the corresponding part: "Social insurance is established for the benefit of manual and intellectual workers, regulated by the system of compulsory contributions from the State, employers, and workers, in order to protect them against the risks of illness, disability, old age, death, and other contingencies that the law determines. The administration and government of social insurance shall be in charge of an autonomous institution, called Caja Costarricense de Seguro Social...". In such a way, social security, which naturally includes the area of health care, is elevated to constitutional rank, thereby constituting an unavoidable mandate that requires the State, through the aforementioned Institution -CAJA COSTARRICENSE DE SEGURO SOCIAL-, to ensure in the most efficient way possible the care and treatment of this important sector of social security, namely the health area. It is worth highlighting from this point onward the preponderance that the Caja Costarricense de Seguro Social acquires in this aspect, as the Entity expressly entrusted by constitutional provision to carry out, as previously mentioned, the administration and government of social insurance; this point has been the subject of treatment by our Constitutional Chamber, thus in vote number 6256-94, in what interests us, it established: "...b) the norm exclusively grants the Caja Costarricense de Seguro Social the administration and government of social insurance, a degree of autonomy that is, of course, distinct and superior to that which is defined in general form in Article 188 idem..." On the other hand, it is worth saying that this right to health can today be defined from a legal perspective as: "the set of mandatory precepts that recognize individuals' rights concerning their health and that regulate their conduct regarding all those matters in which the health of the person and the group comes into play." Health as such can be defined as established in the preamble to the Constitution of the World Health Organization (WHO): "Health is a state of complete physical, mental, and social well-being, and not merely the absence of disease or infirmity." Despite its transcendental importance, this right is not expressly enshrined in our Constitución Política, as we will see next. We consider it essential to link the cited constitutional Article 73, due to its fundamental content, with a norm that allows it to be complemented, from the perspective that interests us in this study, namely numeral 21 of the cited Constitution. Said norm states: "Article 21.- Human life is inviolable." When "Human life" is mentioned here, it does not allude exclusively to the right to life in the strict sense, but also alludes to its "health" dimension, meaning the norm does not literally refer to protecting only human life in a restricted sense, but broadly, to the state of "health," as a basic prerequisite of life itself, which is inherent to life as such, and therefore, given their consubstantial relationship, that "right to health" is understood as encompassed in this norm; in this sense it has been said: "V- Human life is only possible in solidarity with the nature that sustains us and supports us, not only for physical sustenance, but also as psychological well-being; it constitutes the right that all citizens have to live in an environment free of contamination, which is the basis of a just and productive society. This is how Article 21 of the Constitución Política states: 'Human life is inviolable'; and it continues; 'It is from this constitutional principle that the right to health, to physical, mental, and social well-being, undeniably derives, a human right that is indissolubly linked to the right to health and to the State's obligation to protect human life.'" (Votes Number 3705-93, 3341-96. Constitutional Chamber, Supreme Court of Justice). Furthermore, and given that transcendence of the right we analyze, the Constitutional Chamber itself has expressly recognized the State's responsibility in ensuring the due protection of that right: “Modernly, the determining role that the State must play is undeniable, and in the case at hand, the State of Costa Rica, represented by the Ministry of Health in this field, regarding the establishment of programs for the protection of that fundamental value of all citizens.” (Vote number 2522-97, from the Constitutional Chamber of the Supreme Court of Justice). Equally, and as a corollary, we indicate that the Constitutional Chamber has established that this right to life, constitutionally protected, as we have seen, must be supported and protected through the protection that the Caja Costarricense de Seguro Social provides to the population, through health plans, patient care, and medication supply, among other functions, given that state responsibility has been delegated to it to determine the suitable and safe practices of the service. With the above, it is made clear that the right to health is a right of constitutional roots, projected as a power-duty in charge of the corresponding authorities, in this case the Caja Costarricense de Seguro Social, and therefore, under that context, the provision of that service has an imminent public character.

Naturally, the matter of the right to health has not escaped regulation by international instruments, which as such bind the actions of the adhering States based on that right; thus we find the following regulations: the Universal Declaration of Human Rights, in its Article 25, with respect to our interest, establishes: "Everyone has the right to a standard of living adequate for the health and well-being of himself and of his family, including food, clothing, housing and medical care and necessary social services, and the right to security in the event of unemployment...". For its part, the American Convention on Human Rights, specifically in its Articles 1 and 5, state as pertinent: "Article 1. Every person has the right to have his life respected...", from which, as we have already stated, the right to health derives.... "Article 5.1. Every person has the right to have his physical, mental, and moral integrity respected." The Convention on the Rights of the Child, Article 24: "States Parties recognize the right of the child to the enjoyment of the highest attainable standard of health and to facilities for the treatment of illness and rehabilitation of health". The Convention on the Elimination of All Forms of Discrimination against Women: "Article 12. States Parties shall take all appropriate measures to eliminate discrimination against women in the field of health care in order to ensure, on a basis of equality of men and women, access to health care services, including those related to family planning." We also permit ourselves merely to mention other instruments such as the International Covenant on Economic, Social and Cultural Rights, in its numerals 9, 10, 11, and 12; the International Covenant on Civil and Political Rights, 6 and 7; the American Declaration of the Rights and Duties of Man, in its numeral 1; the International Convention on the Elimination of All Forms of Racial Discrimination, Article 5, subsection e). In relation to our domestic legal framework, it is certainly exhaustive in focusing on the recognition of such a right, denoting its public character, just to cite a few examples: Civil Code, Article 46: "Every person may refuse to be subjected to a medical or surgical examination or treatment, with the exception of cases of mandatory vaccination, or other measures relating to public health..."; Childhood and Adolescence Code, Article 19: "Minors shall have the right to seek refuge, assistance, and guidance when the threat to their rights entails serious danger to their physical or spiritual health; likewise, to obtain, in accordance with the law, adequate and timely assistance and protection from the competent institutions.", 20, "Minors shall have the right to obtain information, regardless of its source and mode of expression, especially that which promotes their spiritual and emotional well-being, as well as their physical and mental health", 42, 43, 45, 46, 50, 54, 78, 97, and 121, which are not transcribed for obvious reasons; Domestic Violence Law, Article 2; Law on Narcotics, Psychotropic Substances, Drugs of Unauthorized Use, Articles 1, 3, 6, 47; Phytosanitary Protection Law, Placa19473; Urban and Suburban Leases Law, Articles 5, 22, 93, 94, 97, 98, 135; of course the Constitutive Law of the Costa Rican Social Security Fund (Caja Costarricense de Seguro Social); the General Health Law, and the Organic Law of the Ministry of Health, without citing many others that also highlight the right at hand, and which denotes its public character. In this sense, there is also a large quantity of Regulations that protect this right; we cite by way of example the National Emergencies Regulation, Articles 2 and 11; the Autonomous Regulation of Organization of the Ombudsman's Office, Article 21; the Regulation of the General Customs Law, Articles 12, 34, 246, 287, and 386; Regulation of the Law for the Promotion of Competition and Effective Consumer Defense, Articles 6, 8, 24, 41, 43; Regulation of the Law Regulating Smoking, Articles 1 and 5; Equal Opportunities Law for Persons with Disabilities, Articles 92 and 94, among others. Returning to the competencies of the Costa Rican Social Security Fund (Caja Costarricense del Seguro Social), the Political Constitution in Article 73 states that the Fund is an autonomous institution in charge of the administration and governance of social security, all with the objective of protecting workers against the risks of illness, disability, maternity, old age, and death. For the fulfillment of its purposes, the Constitutive Law of the Costa Rican Social Security Fund (Caja Costarricense del Seguro Social), number 17 of October 22, 1943, provides in its ordinal 71 that said entity is authorized to import, release from customs, manufacture, buy, sell, and export, directly, medications included in the National Formulary, reagents and biologicals, as well as raw materials and conditioning and packaging materials required in their elaboration. It is equally authorized to supply these same articles to public and private institutions that provide health services. In that sense, numeral 72 of the aforementioned law states that such purchases and negotiations may be carried out, insofar as the following requirements are met: a) Establish and keep updated a registry of suppliers (oferentes) of the products, based on their generic name; for such purposes, the Comptroller General of the Republic (Contraloría General de la República) and the Auditing Department of the Costa Rican Social Security Fund (Caja Costarricense de Seguro Social) shall have a copy of this registry. The office in charge of purchases shall freely request quotations from national and foreign companies registered in the registry of suppliers (oferentes), and their responses shall be considered formal offers if they meet the requirements of the case. To have the right to be considered, such responses must be given by the suppliers (oferentes) within the three business days following receipt of the quotation request. b) The Comptroller General of the Republic (Contraloría General de la República) must resolve purchase authorizations within a period of no more than five business days. c) In special cases of urgency, purchases may be made with the sole approval of the Auditing Department of the Fund, but, in any case, the Comptroller (Contraloría) must be informed of the actions taken within the following twenty-four hours. ch) The officials in charge of making purchases must make them under the best conditions of quality and price, and shall be responsible for their acts and for the damages and losses they may eventually cause, in accordance with the law. For its part, numeral 73 of the same regulation indicates that the Costa Rican Social Security Fund (Caja Costarricense de Seguro Social) may export medications, reagents, and biologicals, provided that national needs are satisfied. It may also exchange medications with state or private organizations of other countries for the purpose of satisfying social needs. The rules and authorizations contained in this article shall be equally applicable to the Ministry of Health. In turn, numeral 102 of the General Health Law, number 5395 of October 30, 1973, states that the importation of medications and their distribution shall only be permitted to legal or physical persons registered with the Ministry, after prior authorization and registration with the College of Pharmacists, in accordance with the corresponding legal and regulatory provisions. In any case, the Central Government and public institutions with health functions may, directly import, elaborate, manipulate, store, sell, or supply medications, raw materials, or medical-surgical materials, when the fulfillment of their programs or emergency situations require it, with the sole approval of the Ministry, in accordance with the respective Regulation (ordinal 103 of Law 5395). It being understood that medication means any substance or natural, synthetic, or semi-synthetic products and any mixture of those substances or products used for the diagnosis, prevention, treatment, and alleviation of diseases or abnormal physical states, or the symptoms thereof, and for the restoration or modification of organic functions in persons or animals. Included in the same denomination and for the same purposes are dietary foods and foods and cosmetics that have been added with medicinal substances. The substances referred to in the first paragraph are not considered medications when used for chemical and clinical-chemical analyses, or when used as raw material in industrial processes. Every medication must conform to the particular regulatory requirements that by its nature are exclusively applicable, in addition to the general ones established for all medication in Law 5395 (Article 104). Medications may be presented for use, trade, distribution, and supply with a generic name or with a registered name. Generic-name medications are those pure medications, presented in a pharmaceutical formula or singly, designated with a general technical name recognized by official pharmacopoeias or by technical works of recognized authority. A generic-name medication may be simple or may be a formula constituted by two or more generic-name medications. Registered-name medications are those that are delivered to commerce and use under a particular invented name and under a registered trademark (numeral 105 of Law 5395). It is considered that a medication may, legally, be destined for commerce, public use, and consumption, when it satisfies the regulatory requirements, or those of the pharmacopoeia declared official by the Executive Branch regarding its identity and qualities, safety, and efficacy for the purposes for which it is used, consumed, or prescribed, and insofar as the responsible natural or legal persons who handle its importation, commerce, manipulation, distribution, and prescription have complied with the pertinent legal and regulatory requirements for each of these actions (numeral 106 of Law 5395). The importation, elaboration, commerce, distribution, or supply under any title, manipulation, use, consumption, and possession for trade of deteriorated, adulterated, or falsified medications is prohibited (ordinal 107 of Law 5395). The importation, trade, use, or supply of medications that are in the process of experimentation is prohibited, except under the conditions and circumstances and for the time that the Ministry authorizes (numeral 108 of Law 5395). Furthermore, any physical or legal person may only import, manufacture, manipulate, trade, or use medications registered with the Ministry and whose registration has satisfied the regulatory requirements, especially those relating to: the nature and quantity of the information required about the medication or product submitted for registration; the delivery of samples necessary to carry out the analyses required; those pertinent to the name with which the product will be identified; the content of the labeling; the type of containers or wrappers to be used; and the payment of the fees indicated by the pertinent tariff (Article 112 of Law 5395). The registration of every medication shall be made before the Ministry, where the inscription shall be carried out when appropriate according to the corresponding regulatory provisions. Said inscription shall be in charge of a Technical Body whose composition and functions shall be determined by the Organic Law of the Ministry and the respective Regulation (Article 113 of Law 5395). The registration of every medication shall last five years, unless the infractions in the elaboration, commerce, or use incurred by its holder, or experiences demonstrating that the product is unsafe or ineffective in the terms in which it was authorized and registered, make its cancellation or the corresponding modification appropriate (numeral 114 of Law 5395). Any modification in the name of a medication, in its formula, in the form of its dosage, in the container and content of the labeling that accompanies it, or in the advertising, shall require prior permission from the Ministry (numeral 115 ibid). Registered-name medications, for the purposes of their importation, commerce, and distribution in the country, require for their inscription proof of sanitary registration in the country of origin and a certificate of analysis corresponding to the product, issued by a national or foreign laboratory, which, in the judgment of the Ministry, guarantees its identity and quality, according to the official pharmacopoeia or technical texts of recognized authority; this latter certificate may also be issued by the quality control laboratory for chemical and pharmaceutical products of the manufacturing company itself. Generic-name medications require for their inscription, and for the same purposes indicated in the preceding paragraph, a certificate of analysis that guarantees their identity and quality, according to the official pharmacopoeia or technical texts of recognized authority, this certificate being issued in the same form and conditions indicated in the preceding paragraph. The Ministry may exempt from the aforementioned tests, when it concerns a known product and by its very nature makes those requirements unnecessary; or, in the case of medications not described in the official pharmacopoeia or technical texts of recognized authority, be they registered trademark pharmaceutical products or generic-name medications, it may require the tests that are necessary for the verification of identity, quality, and therapeutic and biopharmaceutical efficacy of the product (Article 116 ibid). For its part, ordinal 117 ibid states that the Ministry of Health, the Costa Rican Social Security Fund (Caja Costarricense de Seguro Social), and any other state entity with public health or social security functions, may acquire unregistered medications at any time or circumstance, and that in cases of urgency or public necessity, that Ministry may authorize the importation of unregistered medications; in addition, for exclusive research purposes, the importation, production, and use of unregistered medications may be authorized, in accordance with the corresponding regulatory provisions. Up to this point, it is convenient to have clarity on one aspect: the governing body in health matters is the Ministry of Public Health, and the Costa Rican Social Security Fund (Caja Costarricense del Seguro Social) is the entity that administers public insurance. These are, in effect, competencies that interrelate, but some correspond to the Ministry and others to the public entity. Regarding the Sanitary Registration, it is clear that the balance tilts in favor of the Ministry and not the Fund, with the natural obligation of coordination in the area of common competencies.

**VII- ON THE REQUIREMENTS THAT MUST BE MET TO FORM THE REGISTRY OF SUPPLIERS (REGISTRO DE OFERENTES) OF THE COSTA RICAN SOCIAL SECURITY FUND (CAJA COSTARRICENSE DEL SEGURO SOCIAL) TO OFFER BIOTECHNOLOGICAL MEDICATIONS, BIOLOGICALS, ANTINEOPLASTIC MEDICATIONS, AND OTHER MEDICATIONS FOR SPECIFIC USE IN ONCOLOGICAL AND HEMATOLOGICAL PATHOLOGIES:** By agreement of April 28, 2009, issued by the Costa Rican Social Security Fund (Caja Costarricense del Seguro Social), published in Gazette 89 of May 11, 2009, and approved by the Central Pharmacotherapy Committee (Comité Central de Farmacoterapia) in agreement CCF-0908-04-09 (Session 2009-13), the requirements are established for the registry of suppliers (oferentes) applicable to biological medications, and specific conditions for the acquisition of medications called antineoplastic and other medications for specific use in oncological and hemato-oncological pathologies. Providing that registered suppliers (oferentes) and suppliers (oferentes) to be registered in the CCSS Registry of Suppliers (Registro de Oferentes) for medications of biological origin in Group 1 and/or Group 2 must comply with a series of requirements stipulated below for each group. It is indicated, in turn, that these requirements are mandatory also for those suppliers (oferentes) who participate with the Fund with medications that do not have a Sanitary Registration of the Medication (Registro Sanitario del Medicamento) and for which the importation of the medication must proceed under Article 117 of the General Health Law of Costa Rica or with medications with a code in transit. In the first group are located medications of biological origin, which in their manufacturing process do not use raw materials from human blood products (for example, human plasma), establishing the following requirements: 1. Certificate of the Sanitary Registration of the Medication (Registro Sanitario del Medicamento) issued by the Ministry of Health of Costa Rica. 2. Attach the complete qualitative-quantitative formula with the excipients used and the permitted ranges of related substances (if applicable in this specific case). 3. Those biological medications from Group 1 that contain in their formulation, and as corroborated in their qualitative-quantitative formula, excipients of human plasma origin (blood products) must also comply with the requirements for Group 2. 4. Medications that do not have a sanitary registration (registro sanitario) issued by the Ministry of Health of CR must also present the duly certified clinical studies corresponding to those that gave rise to their registration in their country of origin, in the same official indications of use and safety in reference to the innovator. 5. In the event of offers under equal conditions, the administration clearly establishes a tie-breaking mechanism, which is to give priority to the biological product that is registered and consumed in the mentioned countries: United States (FDA) and/or countries of the European Economic Community (EMEA), and/or Canada and/or Japan and/or Switzerland. It is important to note that the laboratories manufacturing the medication must present the certificate of free sale of their product in the United States and/or Canada and/or the European Economic Community and/or Japan and/or Switzerland in the eventuality that offers under equal conditions are presented and it is necessary to apply the tie-breaking mechanism. This document must be issued by the corresponding regulatory authority of the respective country. 6. Any biological medication, whether a new drug or not, that has the approval of at least the FDA and/or EMEA and/or Canada and/or Japan and/or Switzerland shall be exempted from the requirements referred to in point 3, if they present the official documentation from the FDA and/or EMEA and/or the regulatory authorities of Japan and/or Switzerland that accredits the product for commercialization in these countries. 7. Biological medications that do not have a sanitary registration (registro sanitario) issued by the Ministry of Health of CR must also comply with point 5. 8. All requested documents must be authenticated through the consular channel of our country and ratified by the Ministry of Foreign Affairs. In group 2 are located medications of biological origin that use, in their manufacturing process, raw materials from human blood products (for example, human plasma), requiring that they provide: 1. Certificate of the Sanitary Registration of the Medication (Registro Sanitario del Medicamento) issued by the Ministry of Health of Costa Rica. 2. Attach the complete qualitative-quantitative formula with the excipients used and the permitted ranges of related substances (if applicable in this specific case). 3. Must comply with the Quality Specifications specified in each corresponding technical data sheet. 4. Must comply with all the regulations requested by the Ministry of Health of CR and everything requested by the Laboratory of Standards and Quality of Medications of the CCSS regarding blood products. 5. Those biological medications from Group 1 that contain in their formulation, and as corroborated in their qualitative-quantitative formula, excipients of human plasma origin (blood products) must also comply with the requirements for Group 2. 6. Medications that do not have a sanitary registration (registro sanitario) issued by the Ministry of Health of CR must also present the duly certified clinical studies corresponding to those that gave rise to their registration in their country of origin, in the same official indications of use and safety in reference to the innovator. 7. In the event of offers under equal conditions, the administration clearly establishes a tie-breaking mechanism, which is to give priority to the biological product that is registered and consumed in the mentioned countries: United States (FDA) and/or countries of the European Economic Community (EMEA), and/or Canada and/or Japan and/or Switzerland. It is important to note that the laboratories manufacturing the medication must present the certificate of free sale of their product in the United States and/or Canada and/or the European Economic Community and/or Japan and/or Switzerland in the eventuality that offers under equal conditions are presented and it is necessary to apply the tie-breaking mechanism. This document must be issued by the corresponding regulatory authority of the respective country. 8. All requested documents must be authenticated through the consular channel of our country and ratified by the Ministry of Foreign Affairs. 9. The manufacturing laboratory must guarantee that the human plasma used as raw material in the manufacture of each of the biological medications must come from healthy human beings, and be entirely free of viruses or other pathogens. **For its part, the Central Pharmacotherapy Committee (Comité Central de Farmacoterapia), in agreement CCF-0944-04-09 (Session 2009-13) and ratified by agreement issued in Session 2009-14 of April 22, 2009, agreed to update the regulations for the Specific Conditions for the Acquisition of medications called antineoplastic and other medications for specific use in oncological and hemato-oncological pathologies**, for the purposes of the Medications Registry (Registro de Medicamentos) in the Costa Rican Social Security Fund (Caja Costarricense de Seguro Social), whether or not they are registered with the Ministry of Health of Costa Rica. In point one, the certification issued by the General Medical Directorate of the General or Oncological Hospital or Cancer Institute of the country of origin of the manufacturing laboratory must be presented, signed by the highest authority in medical oncology and the General Medical Director of the Medical Center, indicating the annual quantity consumed by patients of the medication manufactured by said laboratory, the number of beds in that hospital destined for adults and the occupancy rate (for parenteral-use medications), and the number of consultations in oncology and onco-hematology (for oral-use medications). All information must correspond to the same year in which it is registered with the Fund, or preferably the year prior to the registration date. Upon analysis by the CCSS, if the drug has a consumption in the General or Oncological Hospital or Cancer Institute of the country of origin equal to or greater than 100% of that consumed in the Hospital Nacional San Juan de Dios, it will be determined through a comparative study of the defined daily dose (DDD) per 100 hospital beds/day for parenteral-use medications, and through a comparative study of the defined daily dose (DDD) per 1000 consultations/day for oral-use medications; the supplier (oferente) endorsement will be given and it will be incorporated into the Registry (Registro) in the Fund.

In the case of bidders that are National Laboratories, based on a comparative study of defined daily dose (DDD) per 100 hospital beds/day (parenteral-use medications) or 1000 consultations/day (oral-use medications) taking the Hospital San Juan de Dios as a reference, if the result is equal to or greater than the DDD study from the year prior to the Registration of the medication with the Caja, they will be given the bidder endorsement and will be incorporated into the Registration with the Caja. For the case of national laboratories, the information related to consumption at the Hospital San Juan de Dios (national reference hospital) will be obtained through internal information mechanisms available in the institution. In point 2, a certification issued by the Medical Directorate of the General or Oncological Hospital or Cancer Institute of the country of origin of the manufacturing laboratory must be presented, signed by the highest authority in medical oncology and the General Medical Director of the Medical Center, which presents the annual consumption in patients corresponding to the same year, efficacy and safety results obtained with the use of the medicinal product in the treatment of patients with hemato-oncological pathology (patología hemato-oncológica) and the type of oncological pathologies treated. The documents must contain, in a complete and concrete manner, the type and percentage of side effects presented by patients who have received treatment with said product for its analysis. In point 3: Certification from the Ministry of Public Health (Ministerio de Salud Pública) or the highest equivalent Public Health authority in the country of origin of the manufacturing laboratory, presented by its representative, recognizing the General or Oncological Hospital or Cancer Institute requesting to be registered. In point 4: it is obligatory that the certification be presented individually and the information must refer to the most recent previous year closest to the date of its inclusion in the CCSS Registry of Medication Bidders for medications included in the Official List of Medicines (Lista Oficial de Medicamentos, LOM), or correspond to the most recent previous year closest to the tender for medications not included in the Official List of Medicines and acquired at the Central or local level. These certifications must be updated each time the renewal of registration with the CCSS is requested for medications included in the LOM, and if not registered, each time a purchase is made at the Central or local level in the case of non-LOM medications. In point 5: it is stated that the requested documents must have the signatures of health authorities duly authenticated, as required by Costa Rican legislation, in addition to completing the consular legalization chain of our country and ratified by the Ministry of Foreign Affairs of Costa Rica. In point six, amended by agreement made in session 2011-08 held on February 23, 2011, it is provided that antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies (patologías oncológicas y hemato-oncológicas) for parenteral or oral use, which have a marketing authorization in any of the following countries, are exempted from the requirements set forth in points 1, 2, 3, and 4: United States (FDA), Canada (Health Canadá), Japan (MHLW), Switzerland (Swissmedic), Germany, England, Sweden, France, Italy, Spain, Belgium, Denmark, Austria, Holland, Finland, Norway, Colombia (INVIMA), Argentina (ANMAT), Brazil (ANVISA), stating that the laboratories must present: the certificate of pharmaceutical product (or Free Sale Certificate plus the Good Manufacturing Practices Certificate), as support for their registration and marketing authorization in the United States (FDA), Canada, Japan (MHLW), Switzerland (Swissmedic), Germany, England, Sweden, France, Italy, Spain, Belgium, Denmark, Austria, Holland, Finland, Norway, Colombia (INVIMA), Argentina (ANMAT), Brazil (ANVISA). Likewise, it exempts those medications whose origin does not correspond to any of the countries listed above, but which have the Mutual Recognition certificate for their marketing in any of the reference member states (European Union), a certificate that must be issued by the highest competent regulatory authority in public health of the respective country. It is provided that to exempt from the requirements listed in points 1, 2, 3, and 4, it is necessary that the certificates of pharmaceutical product (or Free Sale Certificate) include the name and address of the manufacturing plant, which must match the address of the manufacturing plant of the medication registered with the Ministry of Health of Costa Rica (as long as the medication is registered in the country). The manufacturing plant (name and address) from which the registered medication with a marketing authorization in one of the countries listed above originates must correspond to the same manufacturing plant from which the medication to be delivered to the CCSS will be imported. Point seven establishes that a bidder already registered in the CCSS registry of bidders can revalidate their registration by presenting the information indicated in the corresponding points above. Said registration will be valid until the expiration of the health registration (registro sanitario) issued by the Ministry of Health of Costa Rica. Point 8 indicates that those bidders who are registered but who prefer to present their data at the time of the procurement process and not revalidate the registration with the CCSS until its expiration must present the requirements for antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies (patologías oncológicas y hemato-oncológicas) for each procurement process. Point nine states that in the case of the acquisition of antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies (patologías oncológicas y hemato-oncológicas) included in the Official List of Medicines (LOM), the Medications and Clinical Therapeutics Area attached to the Pharmacoepidemiology Directorate will be responsible for carrying out the data analysis and the corresponding Defined Daily Dose (DDD) study. In point 10, it stipulates that in the case of non-LOM antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies (patologías oncológicas y hemato-oncológicas) acquired by each center, the data analysis and the corresponding Defined Daily Dose (DDD) study will be carried out each time a procurement process is promoted, and will be performed and analyzed by each Pharmacy Service. Point 11 states that once the Executive Decree of the Ministry of Public Health regulating the Registration of Medicines is published, it will include the specific requirements for molecular target therapy products; these requirements are based on ICH recommendations and form part of these conditions. Point 12 indicates that in the event of bids for parenteral or oral-use antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies (patologías oncológicas y hemato-oncológicas) not included in the Official List of Medicines that are acquired, at the Central or local level, and are in equal conditions, as a tie-breaking mechanism, priority will be given to the medication that is registered and consumed in any of the following countries: United States (FDA), Canada, Japan, Switzerland, Germany, England, Sweden, France, Italy, Spain, Belgium, Denmark, Austria, Holland, Finland, Norway. The bidder must present certification issued by the highest regulatory authority of the country stating that it is registered and consumed in one of the aforementioned countries and that, regarding the Cancer Council's request on bioequivalence requirements and requirements for medications called antineoplastics of biotechnological origin, the mechanism established by the Ministry of Health and CCSS continues.

Furthermore, through agreement number 1445 of June 10, 2009, the Costa Rican Social Security Fund (Caja Costarricense del Seguro Social) established the requirements to be met for the registration of bidders for biotechnological medications, which was published in La Gaceta 127 of July 2, 2009. Said regulation provides that, regarding the obligations that registered bidders and bidders to be registered in the CCSS Registry of Bidders must fulfill for biological origin medications of Group 1 and/or Group 2, they must comply with mandatory requirements for those bidders participating with the Caja with medications that do not have a Health Registration for the Medication (Registro Sanitario del Medicamento) and that must proceed to import the medication under article 117 of the General Health Law of Costa Rica or with medications with a transit code. Said groups being, number one corresponding to medications of biological origin, which in their manufacturing process do not use raw material derived from human blood products (hemoderivados) (for example, human plasma), with the bidder required to present the following requirements: 1. Certificate of health registration (registro sanitario) for the medication issued by the Ministry of Health of Costa Rica. 2. For innovator medications, the complete qualitative-quantitative formula must be attached with the excipients used and the permitted ranges of related substances, as well as the medication characterization studies. 3. For biosimilar medications, the complete qualitative-quantitative formula must be attached with the excipients used and the permitted ranges of related substances, as well as the medication characterization studies; in addition, they must present the characterization studies of the medication compared with the reference medication marketed in Costa Rica. 4. Medications that in their manufacturing process do not use raw material derived from blood products (hemoderivados) but whose formulation and qualitative formula corroborates that they contain excipients from human plasma, such as albumin, must comply with all current guidelines established in the Hemoderivados Decree No. 19981-S of October 3, 1990. 5. They must comply with the quality specifications established in the corresponding official technical data sheet for each medication. 6. The Bidder Registry of the Laboratory of Drug Standards and Quality (Laboratorio de Normas y Calidad de Medicamentos) and the Central Pharmacotherapy Committee (Comité Central de Farmacoterapia) firmly establish that only biological products are endorsed that, whether or not they are registered with the Ministry of Health of Costa Rica, are consumed in the following countries: United States (FDA), and/or countries of the European Community (EMEA), and/or Canada, and/or Japan, and/or Switzerland. 7. In the case of innovator medications, the manufacturing laboratories must present Free Sale Certificates for the medication in the country of origin, such as the United States, European Economic Community, Canada, Japan, Switzerland, issued by the regulatory health authority of that country. 8. In the case of biosimilar medications, the manufacturing laboratories must present Free Sale Certificates for the medication in the country of origin, such as the United States, European Economic Community, Canada, Japan, Switzerland, issued by the regulatory health authority of that country, as well as a certificate issued by the same health entity guaranteeing that the medication meets the quality criteria required for biological medications and that it has the clinical safety and efficacy studies that gave rise to its health registration (registro sanitario) in the country of origin, that it has clinical studies of immunogenicity, safety, and efficacy, in the same official indications as the reference product marketed in the country, as well as the characterization and comparability studies demonstrating that the product is biosimilar to the reference product marketed in Costa Rica. In addition, the complete qualitative-quantitative formula must be attached with the excipients used and the permitted ranges of related substances, and the certification from the health authority (EMEA and/or FDA) that accredits it as a biosimilar medication. 9. All documents requested that are issued abroad (other countries) must be consularized and presented in Spanish. 10. The Institution, based on the extensive clinical experience gained over the years with the use of biological medications, reserves the right to criterion on certain specifications and requirements to be evaluated for the inclusion of new medications sharing the same code, in the registry of bidders and unregistered medications; and only endorses the interchangeability of biological products that have documented proven safety and efficacy through their clinical use in the Institution over the years. And regarding Group 2 of medications of biological origin, it is stated that they are those that use raw material derived from human blood products (hemoderivados) (for example, human plasma) in their manufacturing process, and the bidder must comply with the following requirements: 1. Certificate of Health Registration for the Medication issued by the Ministry of Health of Costa Rica. 2. Attach the complete qualitative-quantitative formula with the excipients used and the permitted ranges of related substances. 3. Must comply with the Quality Specifications specified in each corresponding technical data sheet for each medication. 4. Must comply with all the regulations requested by the Ministry of Health of CR and everything requested by the Laboratory of Drug Standards and Quality (Laboratorio de Normas y Calidad de Medicamentos) of the CCSS regarding blood products (hemoderivados). 5. The Bidder Registry of the Laboratory of Drug Standards and Quality and the Central Pharmacotherapy Committee firmly establish that only biological products are endorsed that, whether or not they are registered with the Ministry of Health of Costa Rica, are consumed in the following countries: United States (FDA), and/or countries of the European Community (EMEA), and/or Canada, and/or Japan, and/or Switzerland. 6. All documents requested that are issued abroad (other countries) must be consularized and presented in Spanish. 7. The Institution, based on the extensive clinical experience gained over the years with the use of biological medications, reserves the right to criterion on certain specifications and requirements to be evaluated for the inclusion of new medications sharing the same code, in the registry of bidders; and only endorses that it has documented proven safety and efficacy through their clinical use in the Institution over the years. 8. The manufacturing laboratory must guarantee that the human plasma used as raw material in the manufacture of each biological medication must come from healthy human beings and be completely free of viruses or other pathogens, and must comply with the current guidelines established in the Hemoderivados Decree No. 19981-S of October 3, 1990.

Subsequently, by agreement of March 9, 2010, published in La Gaceta number 47 of March 9, 2010, approved by agreement CCF-0275-02-10 (session 2010-05) of the Central Pharmacotherapy Committee, the specific conditions for the acquisition of medications called antineoplastics and other medications for specific use in oncological and hemato-oncological pathologies (patologías oncológicas y hemato-oncológicas) are amended, establishing the following points: Point 1: For antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies (patologías oncológicas y hemato-oncológicas), a certification issued by the General Medical Directorate of the General or Oncological Hospital or Cancer Institute of the country of origin of the manufacturing laboratory must be presented, signed by the highest authority in medical oncology and the General Medical Director of the Medical Center, indicating the annual quantity consumed by patients of the medication manufactured by said laboratory, the number of beds in that hospital designated for adults and the occupancy rate (for parenteral-use medications), and the number of consultations in oncology and onco-hematology (for oral-use medications). All information must correspond to the same year in which it is registered with the Caja or preferably to the year prior to the registration date. When the analysis is carried out by the CCSS, if the drug has consumption in the General or Oncological Hospital or Cancer Institute of the country of origin equal to or greater than 100% of that consumed at the Hospital Nacional San Juan de Dios, it will be determined with a comparative study of defined daily dose (DDD) per 100 hospital beds/day for parenteral-use medications, and with a comparative study of defined daily dose (DDD) per 1000 consultations/day for oral-use medications, they will be given the bidder endorsement and will be incorporated into the Registration with the Caja. In the case of bidders that are National Laboratories, based on a comparative study of defined daily dose (DDD) per 100 hospital beds/day (parenteral-use medications) or 1000 consultations/day (oral-use medications) taking the Hospital San Juan de Dios as a reference, if the result is equal to or greater than the DDD study from the year prior to the Registration of the medication with the Caja, they will be given the bidder endorsement and will be incorporated into the Registration with the Caja. For the case of national laboratories, the information related to consumption at the Hospital San Juan de Dios (national reference hospital) will be obtained through internal information mechanisms available in the institution. Point 2: The specific medication (oral or parenteral) for which its entry into the Caja's registry of bidders is requested for its registration, or the medication to be acquired at the Central or Local level, will present a certification issued by the Medical Directorate of the General or Oncological Hospital or Cancer Institute of the country of origin of the manufacturing laboratory, signed by the highest authority in medical oncology and the General Medical Director of the Medical Center, presenting the annual consumption in patients corresponding to the same year, efficacy and safety results obtained with the use of the medicinal product in the treatment of patients with hemato-oncological pathology (patología hemato-oncológica) and the type of oncological pathologies treated. The documents must contain, in a complete and concrete manner, the type and percentage of side effects presented by patients who have received treatment with said product for its analysis. Point 3: Certification from the Ministry of Public Health (Ministerio de Salud Pública) or the highest equivalent Public Health authority in the country of origin of the manufacturing laboratory, presented by its representative, recognizing the General or Oncological Hospital or Cancer Institute requesting to be registered. Point 4: All certification requested must be presented individually and the information must refer to the most recent previous year closest to the date of its inclusion in the CCSS Registry of Medication Bidders for medications included in the Official List of Medicines, or correspond to the most recent previous year closest to the tender for medications not included in the Official List of Medicines and acquired at the Central or local level. These certifications must be updated each time the renewal of registration with the CCSS is requested for medications included in the LOM, and if not registered, each time a purchase is made at the Central or local level in the case of non-LOM medications. Point 5: All requested documents must have the signatures of health authorities duly authenticated, as required by Costa Rican legislation, in addition to completing the consular legalization chain of our country and ratified by the Ministry of Foreign Affairs of Costa Rica. Point 6: Antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies (patologías oncológicas y hemato-oncológicas) for parenteral or oral use, which are registered and consumed in any of the following countries, will be exempted from the requirements set forth in points 1, 2, 3, and 4: United States (FDA), Canada (Health Canadá), Japan (MHLW), Switzerland (Swissmedic), Germany, England, Sweden, France, Italy, Spain, Belgium, Denmark, Austria, Holland, Finland, Norway. It is important to note that the laboratories must present the free sale certificate for their product in the United States (FDA), Canada, Japan (MHLW), Switzerland (Swissmedic), Germany, England, Sweden, France, Italy, Spain, Belgium, Denmark, Austria, Holland, Finland, Norway; or with registration and marketing in these same countries. Similarly, those medications whose origin does not correspond to any of the countries listed above, but which have the Mutual Recognition certificate issued by the EMEA for their marketing in any of the reference member states of the European Union, will be exempted. That certificate must be issued by the highest competent regulatory authority in public health of the respective country.

Point 7: A bidder already registered in the CCSS registry of bidders can revalidate their registration by presenting the information indicated in the corresponding points above. Said registration will be valid until the expiration of the health registration (registro sanitario) issued by the Ministry of Health of Costa Rica. Point 8: Those bidders who are registered but who prefer to present their data at the time of the procurement process and not revalidate the registration with the CCSS until its expiration must present the requirements for antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies (patologías oncológicas y hemato-oncológicas) for each procurement process. Point 9: In the case of the acquisition of antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies (patologías oncológicas y hemato-oncológicas) included in the Official List of Medicines (LOM), the Medications and Clinical Therapeutics Area attached to the Pharmacoepidemiology Directorate will be responsible for carrying out the data analysis and the corresponding Defined Daily Dose (DDD) study. Point 10: In the case of non-LOM antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies (patologías oncológicas y hemato-oncológicas) acquired by each center, the data analysis and the corresponding Defined Daily Dose (DDD) study will be carried out each time a procurement process is promoted, and will be performed and analyzed by each Pharmacy Service.

Point 11: Once the Executive Decree of the Ministry of Public Health regulating the Registration of Medicines is published, it will include the specific requirements for molecular target therapy products; these requirements are based on ICH recommendations and form part of these conditions.

Point 12: In the event of bids for parenteral or oral-use antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies (patologías oncológicas y hemato-oncológicas) not included in the Official List of Medicines that are acquired, at the Central or local level, and are in equal conditions, as a tie-breaking mechanism, priority will be given to the medication that is registered and consumed in any of the following countries: United States (FDA), Canada, Japan, Switzerland, Germany, England, Sweden, France, Italy, Spain, Belgium, Denmark, Austria, Holland, Finland, Norway. The bidder must present certification issued by the highest regulatory authority of the country stating that it is registered and consumed in one of the aforementioned countries. Regarding the Cancer Council's request on bioequivalence requirements and requirements for medications called antineoplastics of biotechnological origin, the mechanism established by the Ministry of Health and CCSS continues.

Subsequently, the Central Pharmacotherapy Committee, in session 2011-08 held on February 23, 2011, analyzed Point 6 of the requirements for medications called antineoplastics and other medications for specific use in oncological and hematological pathologies published in La Gaceta No. 47 of March 9, 2010, agreeing to modify it, leaving it as follows: "Antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies (patologías oncológicas y hemato-oncológicas) for parenteral or oral use, which have a marketing authorization in any of the following countries, will be exempted from the requirements set forth in points 1, 2, 3, and 4: United States (FDA), Canada (Health Canadá), Japan (MHLW), Switzerland (Swissmedic), Germany, England, Sweden, France, Italy, Spain, Belgium, Denmark, Austria, Holland, Finland, Norway, Colombia (INVIMA), Argentina (ANMAT), Brazil (ANVISA). It is important to note that the laboratories must present: the certificate of pharmaceutical product (or Free Sale Certificate plus the Good Manufacturing Practices Certificate), as support for their registration and marketing authorization in the United States (FDA), Canada, Japan (MHLW), Switzerland (Swissmedic), Germany, England, Sweden, France, Italy, Spain, Belgium, Denmark, Austria, Holland, Finland, Norway, Colombia (INVIMA), Argentina (ANMAT), Brazil (ANVISA). Similarly, those medications whose origin does not correspond to any of the countries listed above, but which have the Mutual Recognition certificate for their marketing in any of the reference member states (European Union), will be exempted. That certificate must be issued by the highest competent regulatory authority in public health of the respective country. To exempt them from the requirements listed in points 1, 2, 3, and 4, it is necessary that the certificates of pharmaceutical product (or Free Sale Certificate) include the name and address of the manufacturing plant, which must match the address of the manufacturing plant of the medication registered with the Ministry of Health of Costa Rica (as long as the medication is registered in the country). The manufacturing plant (name and address) from which the registered medication with a marketing authorization in one of the countries listed above originates must correspond to the same manufacturing plant from which the medication to be delivered to the CCSS will be imported".

For its part, the Technical Regulation for the Registration and Control of Biological Medications, number 37006 of November 15, 2011, established that its regulations govern the requirements and procedures necessary for the registration and control of biological medications for human use and applies to all products of this type, whether produced nationally or imported (first article).

In that regulation, in its fifth clause, it was established regarding the health registration (registro sanitario) of biological medicines, "that when the submission of any of the studies or documents mentioned in this Regulation is not scientifically appropriate, the applicant must present the justification for its evaluation by the Ministry of Health, establishing that for the health registration of biological medicines, a dossier must be submitted following the format and content established in Article 27 of Decree No. 28466-S of February 8, 2000, 'Reglamento de Inscripción, Control, Importación y Publicidad de Medicamentos,' published in La Gaceta No. 42 of February 29, 2000, and its amendments or the current health registration regulations. Information on the regulatory status of the product at the international level must be submitted: A list of Health Authorities that have the product registered as of the date of the procedure before the Ministry of Health and those that have conducted inspections in the last two years at the laboratories manufacturing the finished products. In addition, information related to safety and efficacy for biological medicines. The scientific documentation presented, referring to the conclusive reports of clinical studies, must have been prepared within a period not exceeding ten years. In the event that the aforementioned studies were conducted more than 10 years ago, the applicant must present the justification for its evaluation by the Ministry of Health. All conclusive reports of clinical studies must refer to the same product and pharmaceutical form being submitted for health registration. For biological products containing active ingredients not included in the formulation of a product previously registered in Costa Rica: it is required i) In the case of products containing chemical entities not included in the formulation of a previously registered product: • Conclusive reports of the results of preclinical studies (including information on in vivo and in vitro pharmacodynamic parameters). • Conclusive reports of the results of Phase I, II, and III clinical studies (including pharmacokinetic, pharmacodynamic studies, clinical studies, and immunogenicity studies). ii) In the case of pharmaceutical products containing chemical entities included in previously registered products where the active ingredient is a new derivative, such as pegylated ones or others, they must submit: • Conclusive reports of the results of Phase I, II, and III clinical studies. For biological medicines containing active ingredients included in the formulation of a product previously registered in Costa Rica but that present: i) New fixed combinations of active ingredients: • Conclusive reports of the results of Phase I, II, and III clinical studies. Such reports must compare the existing and the new ratio or dose, including bioavailability (biodisponibilidad) studies. ii) New pharmaceutical form with an already registered route of administration: • Conclusive reports of the results of bioavailability studies. iii) New pharmaceutical form with a new route of administration: • Conclusive reports of the results of preclinical studies and Phase I, II, and III clinical studies. iv) New pharmaceutical form with a new release form: • Conclusive reports of the results of Phase I, II, and III clinical studies. v) New potencies or concentrations of previously registered active ingredients: • Conclusive reports of the results of bioavailability studies and Phase II and III clinical studies. vi) New routes of administration with an already registered pharmaceutical form: • Conclusive reports of the results of bioavailability and Phase II and III clinical studies. 5.5. In addition to the requirements mentioned in the preceding section, for the registration of biological medicines, the documents established in the following sections must be attached to the dossier in the order in which they are mentioned. For recombinant DNA or biotechnological medicines, the following must be submitted: 5.6.a. Quality information related to the physicochemical, biological, and immunological properties of the active ingredient: i) Description, chemical structure, amino acid sequence, post-translational modifications, physicochemical, biological, and immunological properties. ii) Description of the manufacturing process, in-process controls, control of the cell substrate, control of critical steps and intermediates, and process validation. iii) Description of the characterization methodology, including the description of the chemical structure and product- and process-related impurities and contaminants. iv) Description of the controls for the active ingredient, including specifications, analytical methods, and validation of the analytical methods. v) Description of reference standards or materials. vi) Description of the container-closure system. vii) Description and results of the stability study. 5.6.b. Quality information related to the physicochemical, biological, and immunological properties of the finished product: i) Description of the product and its composition. ii) Description of the manufacturing process, in-process controls, control of critical steps and intermediates, and process validation. iii) Description of quality control, including specifications, analytical methods, validation of the analytical methods, analysis of the results of the batches used for the specifications, characterization of impurities and contaminants, and justification of the specifications that guarantee batch-to-batch uniformity. When more than one manufacturer is involved, indicate at which step each one intervenes. iv) Description of reference standards or materials. v) Description of the safety evaluation against infection by adventitious agents. Details on viral inactivation and elimination. vi) Risk management plan and post-marketing pharmacovigilance. NOTE 1: These requirements apply to the innovator medicine, and in the case of biosimilars, they must also present the biosimilarity exercise related to quality compared to the reference biological medicine, to determine that the differences do not have implications for its safety and efficacy. In the documentation provided, the name of the medicine to which it is intended to be biosimilar and the name of the laboratory that manufactures it must be specified. NOTE 2: The biosimilarity exercise must be carried out for both the finished product and the active ingredient, as detailed in section 5.12., and for this, international WHO guidelines will be followed; in their absence, those issued by the FDA, EMA, or ICH may be used. Notwithstanding the foregoing, guidelines from other countries may be adopted as official once the Ministry of Health verifies they are internationally accepted and they are made official by Administrative Resolution, which must be published in the Official Gazette La Gaceta along with the instructions, forms, and any other corresponding document, and placed on the Ministry of Health's Web page. 5.7. For blood products (productos hemoderivados) and vaccines, the manufacturing method must be submitted, containing the following information: 5.7.a. Master formula, including batch size. 5.7.b. Description of starting materials of biological origin such as: strains, cell lines, microorganisms, plasma or blood component donations, cells or cell substrates, and culture media. Including: quality control specifications, validated analytical methods, and methods for the exclusion of adventitious agents. 5.7.c. Description of the manufacturing process: i) Manufacturing flow chart indicating process controls, and when more than one manufacturer is involved, indicate at which step each one intervenes. ii) Complete description of the entire process, manufacturing methods, and their controls. Information on the fermentation, harvest, and purification steps, if the product manufacturing applies them, including acceptance and rejection criteria. iii) In-process control specifications and analytical methods issued by the manufacturer, which must be validated. iv) Reprocessing criteria for each stage. v) Quality specifications that include the characterization and purity of the product obtained at each stage and the analytical techniques used for its verification. vi) Description of the double viral inactivation processes, agent used, and method to verify the effectiveness of the process, as applicable. vii) Document in which the manufacturer states that its manufacturing process achieves, for all manufactured batches, a maximum reduction of prion infectivity, in accordance with the current state of knowledge. 5.7.d. Analytical certificates must contain the quality specifications for Active Ingredient(s), Excipient(s), In-process Product, Finished Product, and Reference Material(s). The analytical results for the medicine's components must be expressed in units of weight or biological activity, as appropriate. These certificates must include: i) Name of the substance or product. ii) Processing stage in the case of in-process products. iii) Date and place of manufacture. iv) Batch number. v) Batch size. vi) Physical, chemical, biological, and microbiological quality parameters with their limits and results. vii) Expiration date, when applicable. viii) Date and place of analysis, name of the person responsible for the analysis, and conformity decision according to specifications. ix) Reference of the official method used, or indication that the manufacturer's validated method was used. 5.7.e. Risk management plan and post-marketing pharmacovigilance. 5.8. For blood products, in addition to the information in sections 5.3., 5.4., and 5.7., the following requirements must be submitted: 5.8.a. Certificate of current health registration (registro sanitario) for the product issued by the FDA, the EMA, or any other competent health authority that carries out the Certification of the Plasma Master File (PMF) after conducting the corresponding scientific and technical evaluation. 5.8.b. Information on the selection and control of donors. 5.8.c. Description of the procedures used to guarantee the traceability of the finished product to the donors and vice versa. This description must be accompanied by a detailed diagram. 5.8.d. Results of tests performed to detect HIV 1 and HIV 2 antibodies, hepatitis C antibodies, and the ELISA or RIA test for hepatitis B that detects 0.5 IU per ml of HBs antigen or less. 5.8.e. Information on the centers where plasma is obtained, location of the plasma collection centers, information on inspections carried out at said Centers, and the Quarantine Policy. Detail the type of plasma obtained (donation or plasmapheresis), the type of donation (altruistic or paid), data on the seroconversion percentage of regular donors, and marker data in first donations. Also include information on the storage and transport conditions of the plasma established by the manufacturer. 5.9. For vaccines, in addition to the information in sections 5.3., 5.4., and 5.7., the following must be submitted: 5.9.a. Clinical studies of reactogenicity and immunogenicity, and efficacy. The lack of efficacy studies must be justified. 5.9.b. Information on Cell Bank Systems: i) Preparation, description, and controls performed on the Master Cell Bank (MCB) and Working Cell Bank (WCB). ii) Description of the controls used to verify the absence of adventitious agents. iii) Description and characterization of stabilizers, adjuvants, and preservatives. iv) Nucleic acid sequence of the strain and its comparative study with other strains, including vaccine strains. 5.10. For combined vaccines, in addition to the information in sections 5.3., 5.4., and 5.7., the following requirements must be submitted: 5.10.a. Clinical studies of reactogenicity and immunogenicity. 5.10.b. Information on Cell Bank Systems: i) Preparation, description, and controls performed on the Master Cell Bank (MCB) and Working Cell Bank (WCB). ii) Description of the controls used to verify the absence of adventitious agents. iii) Description and characterization of stabilizers, adjuvants, and preservatives. 5.10.c. Information on the characterization and controls of each individual antigen, which must meet the same requirements established for their use in single vaccines. 5.10.d. Information on the tests performed after combination to study the possible interaction between the antigens. 5.10.e. Information about the effects of adjuvants and preservative agents on the stability and activity of the finished product. 5.10.f. Reactogenicity and immunogenicity studies that demonstrate safety compared to that of the vaccines administered separately but simultaneously. 5.11. For antivenoms (antivenenos) and antitoxins of animal origin, the manufacturing method must be submitted, containing the following information: 5.11.a. Master formula, including batch size. 5.11.b. Description of starting materials of biological origin such as: venoms and plasma or blood components. Including: quality control specifications, validated analytical methods, and methods for the exclusion of adventitious agents. 5.11.c. Information on the control of venom batches used for the immunization of the donor animal. i) Certification signed by the biological supervisor for the snake species used in venom extractions for the immunization mixtures, including the scientific and common names of the snakes used: This certification must include a minimum of 10 specimens used per species for each venom batch and the extraction date. ii) Flow chart describing the handling and storage of venom mixtures for immunization, including storage conditions. iii) Results of biological and biochemical tests that certify the consistency of the venoms (HPLC chromatographic profile and LD50 toxicological activity, specifically). 5.11.d. Information on plasma batches obtained from immunized animals: i) Information on endotoxin tests, neutralizing potency of the plasma mixture for a batch, and protein content. ii) Information on the venoms used in immunization, bleeding dates, immunization dates, and identification of the horses for a specific batch. iii) Identification profile of the horses participating in a specific batch of plasma, with their respective breed, sex, age, and weight. 5.11.e. Description of the manufacturing process: i) Manufacturing flow chart indicating process controls, and when more than one manufacturer is involved, indicate at which step each one intervenes. ii) Complete description of the entire process, manufacturing methods, and their controls. Information on the purification steps, including acceptance and rejection criteria. iii) In-process control specifications and analytical methods issued by the manufacturer, which must be validated. iv) Reprocessing criteria for each stage. v) Quality specifications that include the characterization and purity of the product obtained at each stage and the analytical techniques used for its verification. vi) Description of the double viral inactivation processes, agent used, and method to verify the effectiveness of the process, as applicable. vii) Document in which the manufacturer states that its manufacturing process achieves, for all manufactured batches, a maximum reduction of prion infectivity, in accordance with the current state of knowledge. This applies to those antivenoms or antitoxins derived from animals in which prion infectivity has been demonstrated. 5.11.f. Analytical certificates must contain the quality specifications for Active Ingredient(s), Excipient(s), In-process Product, Finished Product, and Reference Material(s). The analytical results for the medicine's components must be expressed in units of weight or biological activity, as appropriate. These certificates must include: i) Name of the substance or product. ii) Processing stage in the case of in-process products. iii) Date and place of manufacture. iv) Batch number. v) Batch size. vi) Physical, chemical, biological, and microbiological quality parameters with their limits and results. vii) Expiration date, when applicable. viii) Date and place of analysis, name of the person responsible for the analysis, and conformity decision according to specifications. ix) Reference of the official method used, or indication that the manufacturer's validated method was used. 5.11.g. Risk management plan and post-marketing pharmacovigilance. 5.12. Regarding the Information related to safety and efficacy, and for biosimilar medicines not previously registered in Costa Rica and for biosimilars already registered, the biosimilarity exercise must be submitted, including: 5.12.a. Preclinical studies (in vitro and in vivo) that must be comparative in nature and designed to detect significant differences between the biosimilar and the reference innovator biological. 5.12.b. Comparative clinical studies with the reference biological medicine for each of the indications requested. The following must be submitted: i) Pharmacokinetic studies. ii) Pharmacodynamic studies. iii) Clinical efficacy studies. iv) Safety studies. v) Immunogenicity studies. The type and quantity of studies will depend on the knowledge available about the reference biological medicine and the therapeutic indications being requested; for this, international guidelines will be followed, and in their absence, those issued by the FDA, EMA, and ICH may be used on a case-by-case basis. 5.12.c. Letter of approval for the clinical studies indicated in this regulation, issued by the Ethical-Scientific Committee(s) duly legalized or apostilled. Said committees must be recognized by the health authority of the country where these studies were conducted. 5.12.d. Risk management plan and post-marketing pharmacovigilance. Any specific safety monitoring imposed on the reference product must be considered in the risk management plan for the biosimilar product. 5.12.e. Detail on the criterion used to select the reference biological product with which the biosimilarity exercise was conducted. For this, the sequence of criteria in section 6 of this Regulation must be used. 6. SELECTION OF THE REFERENCE BIOLOGICAL MEDICINE: The criteria for selecting the reference biological medicine in order of priority are as follows: 6.1. The first choice must always be the innovator product manufactured in the first country of origin, which has a complete dossier on its quality, efficacy, and safety, provided that this is the same one registered and marketed in Costa Rica. 6.2. The second choice must always be the innovator product manufactured, registered, and marketed in Costa Rica. 6.3. The third choice must be the innovator product manufactured in an alternate origin, registered, and marketed in Costa Rica. 6.4. The fourth choice, and in the event that the above conditions are not met, the reference product may be selected as the innovator product manufactured in the first country of origin or alternate origin, or the reference product suggested in WHO lists, even if it has not been marketed in Costa Rica. To define the reference product through the application of this section, the Health Regulation Directorate of the Ministry of Health must be consulted in writing. 6.5. The fifth choice, and in the event that the above conditions are not met, corresponds to the leading market product that has demonstrated its quality, efficacy, and safety. To define the reference product through the application of this section, the Health Regulation Directorate of the Ministry of Health must be consulted in writing. 7. POST-REGISTRATION CHANGES TO BIOLOGICAL MEDICINES: For any change associated with the biological medicine that is contemplated in the Post-Registration Changes Guide published on the Ministry of Health's website, the specific requirements established in said Guide must be submitted according to the type of change to be made. 8. RENEWAL OF THE HEALTH REGISTRATION 8.1. For the renewal of the health registration of the biological medicines described in this regulation, a dossier must be submitted with the requirements established in Article 34 of Decree No. 28466-S Reglamento de Inscripción, Control, Importación y Publicidad de Medicamentos, published in La Gaceta No. 42 of February 29, 2000, and its amendments or the current health registration regulations, also attaching, in the event that they have not been submitted in previous registration procedures, the requirements established in this regulation. 8.2. For biosimilar medicines that have not submitted it in previous procedures, they must present the Biosimilarity exercise that includes what is established in this regulation. 9. LOT RELEASE OF BIOLOGICAL PRODUCTS. The Customer Service Directorate will authorize the release of each lot of biological products (with the exception of biotechnological products that, by their nature, are not subject to lot-by-lot release) once it verifies the correspondence between the registration dossier documentation and the following requirements: 9.1. Lot Release Certificate issued by the regulatory authority of the producing country. For national laboratories, the Ministry of Health will review its files to verify compliance with this requirement. 9.2. Summarized manufacturing protocol and certificate of the manufacturer's release test results, and in the case of blood derivatives of human origin or medicines containing them, the certificate must include that the product is free of HIV, cytomegalovirus, parvovirus B19, and hepatitis B and C viruses. 9.3. Letter of commitment from the manufacturer, the product holder, or its legal representative, guaranteeing compliance at all times with the storage conditions established on the labeling of the imported lot, from the manufacturing laboratory to the drugstore (droguería) in Costa Rica. NOTE: The lot release procedure for biological medicines by the Customer Service Directorate of the Ministry of Health will be carried out at the importing drugstore or the national manufacturing laboratory within a period of 5 business days counted from the notification to the Ministry of Health. 10. CONTROL OF BIOLOGICAL MEDICINES. 10.1. What is stated in the registration declarations and compliance with the required requirements will be verified by the Health Regulation Directorate, through inspection and sampling in the market, at the pharmaceutical laboratory, or at customs in accordance with the provisions of the Ley General de Salud and the Ley de Promoción de la Competencia y Defensa Efectiva del Consumidor. The first quality control carried out on biological medicines will be performed on the first marketing lot, without diminishing the post-marketing verification and inspection controls that the Health Regulation Directorate eventually orders. 10.2. For control purposes, the manufacturer of the biological medicine or its holder must submit to the Ministry of Health the updates to the reports generated by the Risk Management and Pharmacovigilance Plans, which will form part of the product's dossier before the Ministry of Health. 10.3. In the event of demonstrating non-compliance with or falsehood of what was declared in the registration before the Ministry of Health, the health authority will stop, seize, or withdraw the respective product from circulation, or its registration will be cancelled, as appropriate, after prior notification to the legal representative, who must assume the costs of the sanitary measure applied. The foregoing is without prejudice to other sanctions established by the Ley de Promoción de la Competencia y Defensa Efectiva del Consumidor. The Ministry of Health will proceed to apply these special measures based on the provisions of Article 386 of the Ley General de Salud, without prejudice to the civil or criminal liability incurred by the natural or legal persons responsible for such non-compliance and without prejudice to any other sanction that may proceed in accordance with current legislation." For its part, the Reglamento de Inscripción, Control, Importación y Publicidad de Medicamentos, number 28466 of February 8, 2000, established the pertinent regulations for the registration, control, importation, and advertising of medicines, governing all persons who manufacture, import, and market medicines in the national territory (clause 2 ibid). Furthermore, in that standard, Bioavailability (Biodisponibilidad) is defined as the rate and extent to which the active ingredient or active moiety of a pharmaceutical form is absorbed and becomes available at the site of action; Bioequivalence (Bioequivalencia): as the relationship between two pharmaceutical products that are pharmaceutically equivalent and whose bioavailability, in terms of rate and extent, after being administered at the same molar dose under the same conditions, are similar to such a degree that their effects would be essentially the same; Good Manufacturing Practices (Buenas prácticas de manufactura): as the set of norms and procedures intended to guarantee the uniform production of batches of pharmaceutical products that meet the quality requirements demanded by user needs; certificate of analysis (certificado de análisis): as the certificate indicating the specifications and results of the physical, chemical, biological, microbiological, and biopharmaceutical analyses of a pharmaceutical product, issued by a national or foreign laboratory that, in the judgment of the Ministry, guarantees its identity and quality; Certificate of Good Manufacturing Practices (certificado de Buenas Prácticas de Manufactura): as the document issued by the health authority of the country of origin, certifying that the laboratory to which it refers satisfactorily complies with the requirements of the Good Manufacturing Practices in force in that country for the pharmaceutical form to which the product belongs. Said requirements must comply at least with WHO standards equivalent to those of the regulations in force in Costa Rica. In the case of beta-lactams, cytotoxics, hormones, and biologicals, the certificate must specifically state that the manufacturing laboratory is authorized for the manufacture of those pharmaceutical products; Certificate of Free Sale (Certificado de Libre Venta): as the document issued by the regulatory authority or the body responsible for the registration of pharmaceutical products in the country of origin or provenance, duly legalized, certifying that the pharmaceutical product to which the certificate refers has its registration in force and is authorized for sale or distribution in that country.

In the case of manufacture by third parties, it may be from the country where the holder or the party responsible for the marketing of the product is located. Pharmaceutical Product Certificate: the certification proposed by the World Health Organization (WHO) and issued by the Regulatory Authority of the country or region of origin or provenance as part of the certification system for the quality of pharmaceutical products subject to international trade.

In the case of manufacture by third parties, the pharmaceutical product certificate must be issued by the Regulatory Authority of the country of the product holder. For subsidiaries, the pharmaceutical product certificate may be issued by the Regulatory Authority of the country of the manufacturer or the holder, and as a Manufacturing Contract: the legal document entered into between the drug holder and the manufacturer, which establishes the conditions, commitments, and other circumstances for the manufacture of one or more products; and which must indicate at a minimum: 1) The existing contractual relationship between the involved parties. 2) That the contractor complies with Good Manufacturing Practices. 3) That the contractor has from the contracting party all the necessary information to carry out the contracted actions, as well as the processes that must be implemented for the drug subject to the contract. 4) That the contracting party will conduct periodic audits of the contractor. Furthermore, Pharmaceutical Equivalent is defined as: a pharmaceutical product that contains identical amounts of the same active ingredients as the product to which it is equivalent, for example, the same salt or ester of the active ingredient, in identical dosage forms, that meet the established specifications, but do not necessarily contain the same excipients. Consequently, two pharmaceutical equivalents may show different bioavailabilities and pharmacological activities; and Therapeutic Equivalence: refers to two pharmaceutical products that are therapeutically equivalent if they are pharmaceutically equivalent and after their administration in the same molar dose, their effects with respect to efficacy and safety will be the same, as determined by appropriate in vivo bioequivalence, pharmacodynamic, and clinical studies and/or in vitro dissolution studies. The term Biological Pharmaceutical Product is also conceptualized: as a pharmaceutical product obtained from living organisms or their tissues; and Sanitary Registration as an administrative act whereby it is established that the pharmaceutical product to be registered meets the sanitary requirements of the current regulations relating to quality, efficacy, and safety, and that, therefore, it may be marketed in the country.

For its part, the fourth article provides that the functions of the technical body, established in Article 113 of the General Health Law, hereinafter centralized in the Customer Service Directorate, shall be the approval or denial of the registration of any product referred to in this Regulation, and the Health Regulation Directorate shall be responsible for establishing or approving the technical pharmacological standards governing the evaluation of medicines and the list of multi-source pharmaceutical products of sanitary risk. For such purposes, it is provided in numeral 24 of decree 28466 that the Ministry of Health must publish on its website a list of sanitary registration applications in process within a maximum period of 15 business days from the receipt of the application, and must publish a list of pharmaceutical products to which a sanitary registration has been granted within a maximum period of 15 business days from the issuance of the sanitary registration. Regarding applications for sanitary registration of multi-source pharmaceutical products, the following must be provided: a) An application for which no safety and efficacy information is submitted must be considered by the Ministry as an application for the registration of a multi-source pharmaceutical product. The Ministry may only grant the sanitary registration to a multi-source pharmaceutical product that is a pharmaceutical equivalent: i) Of a pharmaceutical product for which safety and efficacy data have been previously submitted to the Ministry by its applicant and for which a sanitary registration has been previously granted in Costa Rica. ii) Of a pharmaceutical product that meets all the following conditions: a) That it is not protected by patents, b) That it does not contain protected undisclosed test data, c) That it contains a chemical entity present in the formulation of a product that has previously obtained a sanitary registration in Costa Rica, d) That the applicant demonstrates, through a document issued by a regulatory authority, that the active ingredient has been authorized for marketing in any country for more than 5 years; and e) That international information exists guaranteeing the safety and efficacy of the pharmaceutical product before the Ministry of Health. The foregoing is to guarantee access to medicines of sanitary interest. b) Applicants requesting a sanitary registration for a multi-source pharmaceutical product must indicate in the application the name of the pharmaceutical product previously registered in the country with which the applicant's product is a pharmaceutical or therapeutic equivalent, as well as the expiration date of any protected undisclosed test data and any patent covering the pharmaceutical product previously registered in the country, in accordance with the information contained in the databases of the Ministry of Health. c) The Ministry shall not, without the consent of the legitimate holder of the undisclosed test data submitted to the Ministry in support of an application for sanitary registration of a new pharmaceutical product, grant the sanitary registration to the applicant of a multi-source pharmaceutical product, on the basis of: i) Such undisclosed test data; or ii) The sanitary registration granted to that new pharmaceutical product, before the expiration of the protection period for said undisclosed test data. d) The applicant for a sanitary registration of a multi-source pharmaceutical product, or its legal representative, may request that the Ministry review the undisclosed test data submitted in support of a sanitary registration application for a new pharmaceutical product as evidence and support for its sanitary registration application, in the cases established in Chapter XI of this Regulation. **In turn, regarding applications for a sanitary registration of a new pharmaceutical product**, a sworn statement issued before a notary public must be submitted indicating any product or process patent granted and in force in Costa Rica covering the pharmaceutical product, indicating the patent number and its expiration date. Applicants or their legal representative may update this list to include patents granted after the application for the sanitary registration. However, these updates will neither suspend the processing nor the granting of the sanitary registration of applications already submitted, nor will they affect sanitary registrations already granted. The Ministry must publish on its website, for each pharmaceutical product for which a sanitary registration has been granted, the list of product or process patents in force in the country covering said pharmaceutical products, according to the information provided by the applicant or its legal representative. The Ministry must include this information on its website within a maximum period of 15 business days from the receipt of said information. The Ministry will publish on that list the number and expiration date of each patent submitted by an applicant or its legal representative. In the case of applications for sanitary registration for the first time of multi-source pharmaceutical products, when the applicant cannot meet any of the requirements established in subparagraphs i) or ii), the applicant or its legal representative must submit a sworn statement issued before a notary public indicating that no patent exists, granted and in force in Costa Rica, claiming the pharmaceutical product subject to the sanitary registration, or, if such patents exist, the expiration or termination date of the patent(s) claiming it, and indicating that the multi-source pharmaceutical product will not be marketed until after the expiration date of said patents. The applicant or its legal representative must indicate in their sworn statement issued before a notary public that they have reviewed the Ministry's website for the purpose of verifying this information. In such a case, the Ministry will not issue the sanitary registration to the applicant until after the expiration of the protection period of all patents claiming the multi-source pharmaceutical product for which the sanitary registration is requested, according to the information provided by the applicant or its legal representative, or of the protection period for the undisclosed test data, whichever is later, except as established in Chapter XI of this Regulation.

For its part, article 27 stipulates the requirements for obtaining a sanitary registration for the first time, for which a sanitary registration application file will be opened. Regarding the control of medicines, Article 50 ibid states that post-registration verification will be carried out by the Health Regulation Directorate, through inspectors designated for that purpose, through inspection and sampling in the market, in the pharmaceutical laboratory, or at customs, in accordance with the provisions of the General Health Law, Law No. 5395 of October 30, 1973; and the Law for the Promotion of Competition and Effective Consumer Defense, Law No. 7472 of December 20, 1994; and other applicable regulations, and the first quality control carried out on pharmaceutical products will be performed during the first year of marketing, without diminishing the controls that the Health Regulation Directorate may eventually order.

**VIII- ON THE ALLEGED PROCEDURAL DEFECT OF THE REGULATORY ADMINISTRATIVE ACTS, DUE TO THE ABSENCE OF THE HEARING PROVIDED FOR IN NUMERAL 361 OF THE GENERAL LAW OF PUBLIC ADMINISTRATION.** As indicated in previous recitals, the Constitutive Law of the Costa Rican Social Security Fund, in its article 72, imposes that it must establish and keep updated a product supplier registry. Under the protection of that norm, the Costa Rican Social Security Fund issued, through agreement CCF-1445-06-209, session 2009-21 of June 10, 2009, the Regulation with Requirements for the Supplier Registry for Biotechnological Medicines, published in Gazette 127 of July 2, 2009, which, through agreement 3376-11-10, session 2010-44 of November 17, 2010, the Institution's Central Pharmacotherapy Committee proceeded to render void all previous agreements dictated under that regulation, establishing the following Regulation with Requirements for the Supplier Registry for Biotechnological and Biological Medicines, which was indicated to be directed at registered suppliers and suppliers to be registered in the CCSS Supplier Registry for biological medicines of Group 1 and Group 2 as stated, imposing mandatory compliance also for those suppliers participating with the Fund with medicines that do not have a Sanitary Registration for the Medicine. Similarly, the Central Pharmacotherapy Committee of the Costa Rican Social Security Fund, through agreement CCF-0275-02-09, session 2009-21 published in the month of March 2009, issued the Specific Conditions for the Acquisition of Medicines Called Antineoplastics and Other Medicines for Specific Use in Oncological and Hemato-Oncological Pathologies, which through session 2011-08 of February 23, 2011, of the Central Pharmacotherapy Committee, proceeded to modify point 6.

The plaintiff first presented arguments on the merits and concluded both its action brief and its conclusions with arguments aimed at highlighting the existence of a formal defect in the regulation in its condition as a general administrative act. Due to the foregoing, this Panel of Judges clarifies that it is therefore pertinent, first, to begin the study of the formal arguments; subsequently, if necessary, in order to fully address the rest of the plaintiff's claims, considerations on the merits will be entered into.

Thus, it is noted that the plaintiff alleges the non-existence of the hearing required by numeral 361 of the General Law of Public Administration for the adoption of general provisions, which, in its opinion, constitutes an element of validity and its omission implies its absolute nullity. The representation of the defendant maintains that such a requirement is not applicable to the provisions and/or scientific-technical guidelines issued by the Central Pharmacotherapy Committee, since what is provided for in numeral 361 of the General Law of Public Administration is for the preparation of general provisions in the strict sense by the Executive Branch which, in the exercise of its executive regulatory power, deems necessary to adopt; that is, that such a requirement, in the opinion of its represented party, is not applicable to technical regulations adopted by technical advisory bodies, as in this case.

In order to address the arguments of both parties, it is important to clarify some concepts. Citizen participation and the glass house doctrine in the exercise of public function establishes the maxim that, except in very exceptional situations, the participation of the inhabitants must be permitted, both through the display of decisions and the possibility of challenging them. If public action presents its due justification, the Administration has no reason to fear expressing the due justifications for its different acts. Now, by Regulation, we must understand any general legal provision issued by the public Administration with a value subordinate to the law; it turns out to be one of the manifestations of the exercise of the administrative function, through the creation of a normative body of a lower degree and subject to the law, but with the authority to create legal effects. The regulation develops a law on which its validity depends. The regulation is a norm, hence its dual condition. The regulatory power is based on the need to generate norms whose approval, repeal, or modification procedures are sufficiently expeditious to ensure agile resolution mechanisms for the ordinary activity of the Administration itself, while the law, in its approval process, is slower, due to its own parliamentary dynamics, and also cannot foresee all the assumptions that may be faced in each particular case when exercising public competences. This power has as a consequence the issuance of a general administrative act called a regulation, subject to certain formal and substantial limits. Regarding its classification, the Constitutional Chamber has pronounced itself in the following terms: *“* *IV.- ON AUTONOMOUS SERVICE AND ORGANIZATION REGULATIONS.* *It is alleged that through regulations, which do not meet the characteristics of an executive regulation, nor of an autonomous service or organization regulation, matters are regulated that are proper to formal law, by establishing limitations on fundamental rights, regarding the creation of sanctioning administrative bodies and the establishment of sanctions; in addition to not having been issued by the respective hierarchical body, but by the supplier of the National Bank of Costa Rica. In order to analyze the consulted regulations, it is necessary to recall what this Constitutional Court has previously indicated regarding the distinct categories or types of regulations that are constitutionally possible:* *"The categories into which regulations are distinguished are: a.) execution regulations: which tend to carry out the concrete execution of laws, especially when they are of a rather generic scope; b.) regulations independent or autonomous from any legislative provision, and relating to matters within the competence of the Executive Branch not regulated by law, or partially regulated. Among these may figure the so-called organization regulations, which refer to the institution and structure of the various public offices. Derived from the foregoing, the proper matter of regulations can be defined:* *administrative matter*, *which comprises the organizational aspects of the Public Administration – meaning the Executive Branch in the performance of the functions that are proper to it. Therefore, there is an impediment to regulating, via regulation, the matter referring to the rights and obligations of citizens as such, the limitation of their freedom or their rights – including the regime of tributes, penalties, and fundamental rights-. These concepts have already been indicated by this Chamber on repeated occasions, through resolution number 1876-90, at sixteen hours on December nineteenth, and number 1635-93, at seventeen hours on November fourteenth, among others.* * (Judgment number 5227-94, at fifteen hours and six minutes on September thirteenth, nineteen ninety-four.) By virtue of the foregoing, the content of independent regulations or autonomous regulations can clearly be differentiated from executive ones, as they are characterized by regulating the proper competence of their author – Administration – and of the lower authorities, while they have the purpose of organizing and regulating the activity of their author and subordinates, to achieve better compliance with the assigned public purpose. They are of two types: autonomous organization regulations and autonomous service regulations. The former find their basis in the self-organization power of the administration itself, and the latter have their support in the competence of the administrative hierarch to regulate the provision of the service under its charge, without the need for a prior law in the matter. These are regulations that create special subjection regimes and that limit the administrative rights of citizens who have entered into a relationship with the Administration.”* **vote number 2000-2856 of 15:48 hours on March 29, 2002.** In reality, the autonomous regulatory act is reserved for aspects of organization and operation, where even the law cannot establish certain limitations. That led to the generation of the doctrine of the interna corporis act, as the power of the public powers to self-organize. The national Constitution clearly develops the issue of the executive regulation and the power of the organization regulation. The submission of the latter to the former being clear, since the national legal system does not establish matters reserved for regulatory norms.

Regarding the procedure for the formation of regulations, the General Law of Public Administration, in its numeral 361, imposes that in the preparation of general provisions: *"1. A hearing shall be granted to decentralized entities on the projects of general provisions that may affect them. 2. Representative entities of general or corporate interests affected by the provision shall be given the opportunity to express their opinion, within a period of ten days, except when reasons of public interest or urgency, duly recorded in the draft, oppose it. 3. When, in the judgment of the Executive Branch or the Ministry, the nature of the provision advises it, the draft shall be submitted for public information, during the period indicated in each case."* *From a study of the second paragraph of said norm, several legal assumptions that must be met are observed, such as being the process of creating a general norm, affecting general or corporate interests by denying, aggrieving, suppressing, or limiting subjective rights and/or legitimate and direct interests, and being representative entities thereof. It is worth mentioning that the General Agreement on Tariffs and Trade (GATT) and the Uruguay Round, both legal norms ratified by Costa Rica and which have supremacy over legal ones, consider that any regulatory norm that implicitly involves, directly or indirectly, a restriction on trade conditions (non-tariff barriers) must be consulted prior to its entry into force. This allows for harmony between the legal norm and that established in international regulations. Regarding the first requirement of being a general norm, we must indicate that the administrative act produces individual or concrete effects (administrative resolutions and agreements) and collective or general effects, such as decrees and regulations, by being addressed to indeterminate subjects. As for the affectation of general or corporate interests, these refer to private or public entities that represent through their management the community, the population, or to a corporation, which constitutes *"a duly constituted, personified, and organized collective organization that represents and defends the interests of a determinable group or sector of people (e.g. chambers, associations, professional colleges) (...)"* *Jinesta Lobo, Ernesto. Tratado de Derecho administrativo. Tomo tercero, San José, Costa Rica, editorial jurídica Continental, 2007, página 244. Regarding the procedure, the First Chamber of the Supreme Court of Justice, in vote number 10 at 14:20 hours on January 22 of the year 2002, provided that* *"* *III°* *The General Law of Public Administration devised a special procedure for the preparation of general provisions, which are administrative acts of normative scope. The specialty that the legislator adopted holds the answer to the questions that the sub judice raises, regarding the value that the hearing process has within that special procedure. A simple reading of the articles regulating that special procedure reveals that it was devised precisely with the purpose of enshrining the hearing process, in some cases, to entities of the state conglomerate itself (Article 361, paragraph 1), in others, to entities – it makes no distinction between public and private – representative of general or corporate interests, affected by the provision (Article 361, paragraph 2). Hence, the value and importance of the hearing in the procedure for the preparation of general provisions are indisputable, this being a substantial, unavoidable formality, unless due to the concurrence of the exception scenarios that the same norm provides.* This obligation, in the indicated special procedure, constitutes the legislative development of norms that, as a general principle, inform the administrative procedure. Articles 217, 218, and 220, in relation to Article 239 and following, of the Ley General de la Administración Pública provide for the necessary intervention of the administered party in the procedure. Since there are no individualized subjects in the adoption of regulatory acts who can be considered direct interested parties, the legislator provided that in such cases the transfer, the hearing (audiencia), must be made to representative entities of corporate or general interests. By virtue of this, the cited hearing (audiencia) procedure is recognized as a necessary requirement for unavoidable validity and efficacy, of legal and supra-legal roots, of the special procedure for creating general administrative norms. In accordance with the foregoing, the hearing (audiencia) that must be granted is an essential requirement of the procedure, which has its foundation in constitutional principles not only of due process but also the right of citizen participation, as repeatedly provided by our Constitutional Court in its judgments: II.- ON CITIZEN PARTICIPATION. Citizen participation (participación ciudadana) in public decision-making is provided for in Article 9 of the Political Constitution, and thus acquires the rank and force of a fundamental constitutional right. It is not a matter of deconstitutionalizing the principle of legality of the Public Administration, although it is, of course, a more democratic form of government, which broadens the forums for debate on different issues that affect the community, and by virtue of this, are open to citizen intervention and opinion. We are, then, faced with an option already widely accepted in the evolution of the concept of democracy, and this amparo offers a magnificent opportunity to give it clear and effective validity, so that it does not remain mere discourse. The provision commented on, then, embodies the cited principle through access to available information and its dissemination, so that decision-making is not limited to a narrow group of interests. In this way, and in accordance with our democratic system, ARESEP is obligated to convene such a hearing, particularly to guarantee the right of defense and access to information that concerns each and every one of the inhabitants of our country, so that decisions are not taken by surprise for the "affected" interested parties. Precisely, in the Law of ARESEP and its regulations, the legislator provided a special administrative procedure, which is the public hearing (audiencia pública) whose main characteristic is to give transparency to the Regulating Entity's decisions and the possibility of giving participation (participación) to consumers and users within the process. Likewise, by giving the opportunity for neighbors, social organizations, the state and private sector, citizen defense institutions, and other government institutions to participate, greater benefit is obtained, which facilitates a better exchange of information among the participants, making the hearing a transcendental instrument in decision-making and an instrument of transparency in a democratic system like ours. By virtue of the foregoing, the fixing or modification of tariffs (fijación o modificación tarifaria) must be submitted to a public hearing (audiencia pública) in which those citizens who present a reasoned opposition based on technical criteria may participate, giving the interested party the right to exercise the use of the floor at the celebration of the respective act in order to defend their interest in the matter. In this way, the public hearing (audiencia pública) that the Autoridad Reguladora de los Servicios Públicos must conduct in those cases where it processes a tariff-setting study (estudio de fijación tarifaria) for public services, has the purpose of allowing the exercise of the right to community participation (participación) in a matter that directly affects it, prior to the administrative decision being taken, and in that way, constitutes a manifestation of the democratic principle. This hearing is intended for interested persons to express what they deem appropriate, regarding the tariff-setting request under study before the Autoridad Reguladora, thus the rigor demanded for procedures seeking the suppression of a subjective right does not apply to it (sentencia 2002-08848 of sixteen hours fifty-seven minutes of September tenth, two thousand two); however, it is not a simple formal requirement, such that it can be set in a way that makes nugatory the exercise of the right it seeks to protect, by being granted under conditions that prevent or hinder the fulfillment of the objectives it is called upon to achieve, in protection of the right to information and citizen participation (participación ciudadana)…” III.- In conclusion, it is clear that in order to guarantee the right of citizen participation (participación ciudadana) provided for in Article 9 of the Political Constitution, the public hearing (audiencia pública) that the Autoridad Reguladora de los Servicios Públicos must conduct in those cases where it processes a tariff-setting study (estudio de fijación tarifaria) for public services, must allow the exercise of the right to community participation (participación) in a matter of its interest and must be held within a reasonable period that allows the community to express itself. Thus, the appropriate course is to uphold the claim raised for violation of the right to citizen participation (participación ciudadana) and annul the call made by the Autoridad Reguladora de los Servicios Públicos to hear the tariff increase proposed by COOPEMORAVIA, to increase the tariff of route 40MB, described as San José-Moravia-Ramales and common corridors of routes 40, 41, 42, and 43 processed in file ET-29-2010.” Sentencia: 10708 of June 18, 2010.

IX- ON THE SPECIFIC CASE. It remains then to establish the type of general provision constituted by the administrative acts challenged here and whether the hearing (audiencia) under Article 361 of the Ley General de la Administración Pública should have been granted prior to their adoption. From the foregoing, it is concluded that the Caja Costarricense del Seguro Social did issue said regulation under the protection of Article 72 of its Constitutive Law, and that the regulations issued are indeed of a technical nature. Due to the body that issued them, they do not constitute executive regulations, but rather independent and highly sui generis regulations. Regarding the act issued by Agreement 3376-11-10, session 2010-44 of November 17, 2010, the Comité Central de Farmacoterapia of the Institution proceeded to render null and void all previous agreements issued under that regulation, establishing the following Regulations with Requirements for the Registration of Suppliers for Biotechnological and Biological Medicines, issuing a new regulation. From a review of the content of said regulation, we find that the requirements, in reality, are not for the supplier as such, but rather regarding the product: group 1 medicines of biological origin that in their manufacturing process do not use raw material derived from blood products, and group 2 of biological origin that use raw material from blood products in their manufacturing process – understood, according to point 4.53 of Decreto Ejecutivo 37006, as those obtained by industrial procedures, whose raw material is human blood or plasma. According to the experts who testified in the oral and public trial (Julián Cuesta Ramírez, Renato Murillo Masis, and Albín Chávez Matamoros), these are highly complex in their production and used for very specific and serious diseases. From the review of said regulation, it is extracted that for both group 1 and group 2 medicines, it imposes technical requirements for innovative, biosimilar, biological, and biotechnological medicines, among others; certificates for their manufacturing process, production, etc. It is even provided that, for the procurement of medicines, the Caja Costarricense del Seguro Social may take its clinical experience with the medicine as a qualification parameter and exempt it from other technical requirements. Regarding the second challenged regulation, issued during session 2011-08 of February 23, 2011, by the Comité Central de Farmacoterapia, in which it proceeded to modify point 6 of the Specific Conditions for the acquisition of medicines called antineoplásicos and other medicines for specific use in oncological and hema-oncological pathologies, issued in agreement CCF-0275-02-09, session 2009-21 published in the month of March 2009, equally technical requirements are imposed for their offer. From the statements of all the experts heard in the oral and public trial, it is concluded that medicines must indeed have three basic elements: quality, safety, and efficacy, which are indispensable for the medicine to produce the effects in patients for which they were produced. The plaintiff, both for the regulation relating to biological, biotechnological, and antineoplásicos medicines, argues on the merits that the reforms introduced in the regulations questioned by the Comité Central de Farmacoterapia of the Caja Costarricense del Seguro Social threaten the health and life of Costa Ricans, as there is no guarantee that said medicines possess the essential elements of quality, safety, and efficacy, presenting in detail a series of questions of a technical nature. From a meticulous review of said regulations, technical requirements are indeed established, or exemptions are made compared to the previous regulation for the purchase of medicines, which are ultimately used to fulfill the public purpose entrusted to the institution, public health. It must not be lost sight of that these provisions, without going into the merits of the case, are directed at regulating the requirements that medicines must contain for their purchase. A large number of people in our country depend on these medicines, not only to protect their health, but to preserve and rescue their lives. This regulation evidently has provisions that must guarantee public health, which necessarily makes the discussion of its rules a matter of public interest. Although the effects of said provisions are initially a parameter for the purchase of medicines, their implicit objective is precisely to safeguard the health of all patients who go to public health centers in our country seeking to improve and preserve their health and their lives. Therefore, the effects of said regulations are not limited to a matter of the Institution's organization, but evidently to a matter of Public Health. General provisions must not only be classified according to the body that issues them, but also according to their effects and to whom they are directed. In the specific case of the challenged regulations, the final objective is the guarantee of the medicines supplied to patients. Therefore, in the opinion of this Collegiate Body, the questioned rules are independent technical regulations, although not executive, due to the effects of their application and compliance. Their interest, therefore, cannot be limited only to organizations or groups, individuals or legal entities engaged in the production, distribution, and commercialization of medicines, but to every person as a guarantee of the fundamental right to health and life, as protected by our Political Constitution. Consequently, it is not possible to accept the position held by the defendant's representation, that being a technical regulation, it does not require the procedure established in the Ley General de la Administración Pública. On the contrary, given the technical matter it regulates, the hearing (audiencia) provided for in Article 361 of the cited law should have been granted for its formation. It cannot be ignored that said hearing (audiencia) aims at the participation (participación) of citizens in public affairs, whenever the matter regulated by said norms, as in those questioned here, is of public interest, as in the present case the right to life and health. Continuing with the analysis of the special procedure for drafting general provisions, other general rules and principles governing the administrative procedure can be cited, an interpretation that is possible in accordance with Article 229, paragraph 1, of the Ley General de la Administración Pública, which reads as follows: "This Book shall govern the procedures of all Administrations, unless a provision opposes it." For its part, Article 223 sets forth that the omission of substantial procedural formalities shall cause the nullity of what has been acted upon. 2. A formality shall be understood as substantial if its correct completion would have prevented or changed the final decision in important aspects, or whose omission caused defenselessness." It must be clear, as indicated supra, what the purpose is of the hearing (audiencia) provided for in Article 361 of the Ley General de la Administración Pública, because for the effects entailed by the questioned regulations, the hearing (audiencia) is essential, not only for organizations like the plaintiff, but also for professional associations, medical and pharmacy professionals who can provide essential information on the quality, safety, and efficacy of the medicines, as well as the technical requirements requested for their procurement, and even more so, administrative bodies, such as the Ministerio de Salud. In this regard, the Ley General de Salud, in its Article 102, states that the importation of medicines and their distribution shall only be permitted to legal entities or individuals registered with the Ministry, upon prior authorization and registration with the Colegio de Farmacéuticos, which reinforces this Court's position on the obligatory nature of said hearing (audiencia). Article 106 of the Ley General de Salud imposes that a medicine can legally be destined for commerce, public use, and consumption when it satisfies the regulatory requirements or those of the pharmacopoeia declared official by the Executive Branch regarding its identity, quality, safety, and efficacy for the purposes for which it is used, consumed, or prescribed, and an additional element: the full knowledge and acceptance of the Caja Costarricense del Seguro Social, which its representative states in the response to the lawsuit (folio 239, final paragraph of the main file) where he states that "that for the purposes of registering biotechnological medicines, despite there being no regulation from the Ministerio de Salud of Costa Rica, the Comité Central de Farmacoterapia, until such regulation is issued by the governing body, has been visionary and in order to maintain the principles of Safety and Efficacy in the medicines recognized in the Supplier Registry of my represented entity," which absolutely confirms the criterion of this Collegiate Body on the obligatory nature of granting the prior hearing (audiencia) to the issuance of the challenged regulations. Since it is known that the governing body in the matter had not issued the specific regulation regarding the sanitary registration of said medicines, the legal hearing (audiencia) was necessary, timely, and convenient so that the governing public body in the matter could pronounce itself. It should be noted that the reforms made in 2010 to the Regulations with Requirements for the Registration of Suppliers for Biotechnological and Biological Medicines, and in early 2011 to the Specific Conditions for the acquisition of medicines called antineoplásicos and other medicines for specific use in oncological and hema-oncological pathologies, are very close to the year 2011 when Decreto Ejecutivo 37006-S was issued, regulating the Registration and Control of Biological Medicines. This means that at those dates, the technical regulation that the defendant misses from the governing body in the matter was being drafted. When the challenged regulations were issued, there is no doubt, then, that granting the hearing (audiencia) is a substantial formality, because such action could result in a modification of the final act. Precisely, the hearing (audiencia) aims to provide the opportunity for the entity or affected party to influence the will of the Administration, before the latter acts in accordance with its regulatory powers. Non-compliance with the hearing (audiencia) process, which is not discretionary but mandatory, is necessarily linked to the validity of the general provision issued (as the culmination of the procedure) and, consequently, its omission can cause invalidity, therefore, determining the nullity of everything acted upon by the Administration in relation to the issuance of the questioned regulatory provisions. Consequently, the omission of the hearing (audiencia) by the defendant in the adoption of the challenged regulations constitutes a substantial defect in the procedure for issuing them. In the present case, it is not feasible to make any distinction regarding the validity of parts of the challenged acts, as the defect, being of a procedural nature, affects the integrity of the acts. Consequently, the absolute nullity is declared of the following general acts: 1- Agreement CCF- 3376-11-10, session 2010-44 issued on November 17, 2010, by the Comité Central de Farmacoterapia of the Caja Costarricense del Seguro Social, published in the Diario Oficial La Gaceta number 10 of January 14, 2011, and 2- Agreement taken during session 2011-08, held on February 23, 2011, by the Comité Central de Farmacoterapia, through which it amends point 6 of the Specific Conditions for the acquisition of medicines called antineoplásicos and other medicines for specific use in oncological and hema-oncological pathologies, for lacking a formal prerequisite of validity.

It should be noted that although the plaintiff</span><span style=\"line-height:150%; font-family:'Century Gothic'; font-size:11pt\">&#xa0;</span><span style=\"line-height:150%; font-family:'Century Gothic'; font-size:11pt\"> presents an extensive argument for the nullity of these rules on different grounds, since one has been upheld, it is completely unnecessary to expressly rule on the remaining ones; however, it is appropriate to advise the public entity that it must be clear about which competencies are its own with respect to those reserved for the Ministry of Health as the governing body in this area. Thus, both agencies must coordinate the fulfillment of their public purposes, but without one encroaching upon the other.</span><span style=\"line-height:150%; font-family:'Century Gothic'; font-size:11pt\">&#xa0;</span><span style=\"line-height:150%; font-family:'Century Gothic'; font-size:11pt\"> In this regard, we draw attention to the fact that matters concerning the sanitary registration and its exception fall under the Ministry's purview, a topic that must not be lost sight of.</span></p><p style=\"margin-top:0pt; margin-bottom:0pt; line-height:150%\"><span>&#xa0;</span></p><p style=\"margin-top:0pt; margin-bottom:0pt; line-height:150%; font-size:11pt\"><span style=\"font-family:'Century Gothic'; font-weight:bold\">X. REGARDING THE REMAINING CLAIMS</span></p><p style=\"margin-top:0pt; margin-bottom:0pt; line-height:150%\"><span style=\"line-height:150%; font-family:'Century Gothic'; font-size:11pt\">The plaintiff requests that “</span><span> </span><span style=\"line-height:150%; font-family:'Century Gothic'; font-size:11pt; color:#010101\">Since the challenged agreements are null, we require restoring the validity of the previous agreements; </span><span style=\"line-height:150%; font-family:'Century Gothic'; font-size:11pt; font-style:italic; color:#010101\">Normativa con Requisitos de Oferentes para Medicamentos Biotecnológicos y Biológicos</span><span style=\"line-height:150%; font-family:'Century Gothic'; font-size:11pt; font-style:italic; color:#010101\">&#xa0;</span><span style=\"line-height:150%; font-family:'Century Gothic'; font-size:11pt; color:#010101\">of 2009 and that in its place, the </span><span style=\"line-height:150%; font-family:'Century Gothic'; font-size:11pt; font-style:italic; color:#010101\">Normativa con Requisitos para el Registro de Oferentes para Medicamentos Biotecnológicos y Biológicos</span><span style=\"line-height:150%; font-family:'Century Gothic'; font-size:11pt; color:#010101\">of 2009 be applied, which corresponds to the version prior to the reform published in the Official Gazette La Gaceta No. 10 of January 14, 2011, regarding the agreement of the Logistics Management of the Caja Costarricense del Seguro Social (CCSS) taken in session No. 2010-44 of the Central Pharmacotherapy Committee (agreement number CCF 3376-11-10) and the Agreement Denominated \"Requisitos de los medicamentos antineoplásicos y otros de uso específico en patologías oncológicas y hematológicas\" published in La Gaceta No. 47 of March 9, 2010, which corresponds to the version prior to the introductory reform in session 2011-08 held on February 23, 2011, by the CCSS's Central Pharmacotherapy Committee, published in La Gaceta No. 58 of March 23, 2011, and \"that the Caja Costarricense del Seguro Social apply the content of Decreto 37006-S published in the Official Gazette La Gaceta Number 59 of March 22, 2012, named Reglamento de Inscripción y Control de Medicamentos Biológicos, which conforms to the prior regulation of the Caja Costarricense del Seguro Social, whose validity we request be restored in point 3 of the lawsuit's claims.\"</span><span style=\"line-height:150%; font-family:'Century Gothic'; font-size:11pt; color:#010101\">&#xa0;</span><span style=\"line-height:150%; font-family:'Century Gothic'; font-size:11pt; color:#010101\"> In this regard, it is important to highlight that although the first two claims, regarding restoring the validity of the previous regulations, the </span><span style=\"line-height:150%; font-family:'Century Gothic'; font-size:11pt; font-style:italic; color:#010101\">Normativa con Requisitos para el Registro de Oferentes para Medicamentos Biotecnológicos y Biológicos</span><span style=\"line-height:150%; font-family:'Century Gothic'; font-size:11pt; color:#010101\">of 2009 and the Agreement Denominated \"</span><span style=\"line-height:150%; font-family:'Century Gothic'; font-size:11pt; font-style:italic; color:#010101\">Requisitos de los medicamentos antineoplásicos y otros de uso específico en patologías oncológicas y hematológicas</span><span style=\"line-height:150%; font-family:'Century Gothic'; font-size:11pt; color:#010101\">” published in La Gaceta No. 47 of March 9, 2010, which corresponds to the version prior to the introductory reform, were outlined by the plaintiff from the outset of her lawsuit, and subsequently when the issuance of executive decree 37006-S occurred (alleged as a new fact), and she requests the application of the latter, it is evident that for the Caja Costarricense del Seguro Social, the circumstances have changed, specifically regarding the matter it regulated due to the absence of technical regulation by the governing body, the Ministry of Health. For this reason, it is the Caja Costarricense del Seguro Social that must determine which regulation it must apply, always in fulfillment of its purposes and the exercise of its competence, taking into consideration the existence and validity of executive decree 37006-S. What is sought by the plaintiff cannot be declared; it is rejected, due to the variation in circumstances that she herself brought forward as a new fact. To subordinate the Caja Costarricense del Seguro Social to the application of a regulation issued by the Central Pharmacology Committee under other, now non-prevailing circumstances, would therefore, as indicated above, be an invasion of the regulatory power (Potestad reglamentaria) of the autonomous Institution. Thus, it will be the institution that defines which regulation best suits the fulfillment of its purposes, within its competence, and respecting the competencies of the governing body</span><span style=\"line-height:150%; font-family:'Century Gothic'; font-size:11pt; color:#010101\">&#xa0;</span><span style=\"line-height:150%; font-family:'Century Gothic'; font-size:11pt; color:#010101\">in health matters, the Ministry of Health.</span><span style=\"line-height:150%; font-family:'Century Gothic'; font-size:11pt\"> In application of Article 131 of the Código Procesal Contencioso Administrativo, it is clarified that the retroactive effects of this declaration of absolute nullity shall not affect third parties who, as of the date this judgment becomes final, have subjective rights acquired in good faith or consolidated legal situations derived from the aforementioned rule. Additionally, in application of precept 130, section 3) of the CPCA, the full publication of this judgment in the official gazette La Gaceta must be ordered at the expense of the Caja Costarricense del Seguro Social.</span></p><p style=\"margin-top:0pt; margin-bottom:7.05pt; line-height:150%\"><span>&#xa0;</span></p><p style=\"margin-top:0pt; margin-bottom:7.05pt; line-height:150%; font-size:11pt\"><span style=\"font-family:'Century Gothic'; font-weight:bold; color:#010101\">XI- REGARDING THE RAISED DEFENSES.</span></p><p style=\"margin-top:0pt; margin-bottom:7.05pt; line-height:150%; font-size:11pt\"><span style=\"font-family:'Century Gothic'; color:#010101\">The defendant raises a Lack of Standing (Falta de Legitimación) of the plaintiff, arguing that Fedefarma does not seek to assert the rights of the community regarding the use of medications, but rather that its underlying strategy is directed at a commercial interest, and therefore it lacks standing to sue the Caja Costarricense del Seguro Social. For her part, the plaintiff affirms that her interest is that of the patients, which justifies the defense of collective rights, and that the action seeks to enforce quality and safety provisions introduced into the legal system by the Ministry of Health and which are recommended by the World Health Organization. That it is not, as the defendant claims, a commercial matter, but rather ensuring that the population has safe and effective medications, which is why they defend the rights of the community. Therefore, her represented party has standing to file</span><span style=\"font-family:'Century Gothic'; color:#010101\">&#xa0;</span><span style=\"font-family:'Century Gothic'; color:#010101\">the action.</span><span style=\"font-family:'Century Gothic'; color:#010101\">&#xa0;</span><span style=\"font-family:'Century Gothic'; color:#010101\"> Regarding Standing, it is the necessary correlation between the defendant and the holder of the right or legitimate interest claimed. It is an essential prerequisite of the procedural legal relationship, indispensable for a favorable judgment. Numeral 10, subsection b of the Código Procesal Contencioso, establishes that the following have standing to bring an action: “</span><span style=\"font-family:'Century Gothic'; font-style:italic; color:#010101\">b) Entities, corporations, and public law institutions, and any others that hold the representation and defense of interests or rights of a general, guild, or corporate nature, insofar as such interests or rights are affected, and groups governed by any statute while they defend collective interests</span><span style=\"font-family:'Century Gothic'; color:#010101\">.” The second paragraph of said numeral stipulates that those who hold, with respect to regulatory provisions, any legitimate interest, individual or collective, or any subjective right, may directly challenge such provisions, without requiring an individual application act. It is necessary to mention that the rule establishes two different prerequisites: subsection 1.B for specific acts or actions, and subsection 2 for the challenge of regulatory</span><span style=\"font-family:'Century Gothic'; color:#010101\">&#xa0;</span><span style=\"font-family:'Century Gothic'; color:#010101\">provisions, as in the specific case, and in this prerequisite, it grants standing to act in defense of collective rights. Therefore, it is essential to determine if the plaintiff, even though she mentions it, truly appears representing collective interests. The national jurist Manrique Jiménez Meza defined collective interests as \"</span><span style=\"font-family:'Century Gothic'; font-style:italic; color:#010101\">typical group or minor collective interests, attributable to organized collectivity, whether through legal entities or through groups not incorporated into such entities, for the protection of the interests embedded in each category of belonging (...) collective interests are category interests and, as such, constitute a partial treatment in the context of the broad impersonal, anonymous, and indeterminate collective, but this does not make them any less vitally important in the social context. Consequently, collective interests are attributable to the subjects representing such interests, whether through associations, organizations, various entities, or even through groups organized by virtue of shared interests against common threats or harms.\"</span><span style=\"font-family:'Century Gothic'; font-style:italic; color:#010101\">&#xa0;</span><span style=\"font-family:'Century Gothic'; font-style:italic; color:#010101\"> </span><span style=\"font-family:'Century Gothic'; color:#010101\">(Jiménez Meza Manrique, El Nuevo Proceso Contencioso Administrativo, San José. Poder Judicial. Departamento de Artes Gráficas, 2006, page 89.) Professor Jinesta Lobo defines them as \"</span><span style=\"font-family:'Century Gothic'; color:#010101\">&#xa0;</span><span style=\"font-family:'Century Gothic'; font-style:italic; color:#010101\">those of a group or category, which are subdivided, in turn, into corporate and diffuse. Consequently, collective interests are a species of the genus, whose holder is an organized or unorganized, personified or not, group, different from the national collectivity, within a larger one that can be considered total or general. Such category or group can be identified by a characteristic or common trait of social relevance (hobby, occupation, line of business, consumers or users of certain goods or public services, etc.)</span><span style=\"font-family:'Century Gothic'; color:#010101\"> JINESTA LOBO, Ernesto. Tratado de Derecho Administrativo Tomo III. 1st Edition. Editorial Jurídica Continental. San José, 2007, p.</span><span style=\"font-family:'Century Gothic'; color:#010101\">&#xa0;</span><span style=\"font-family:'Century Gothic'; color:#010101\">243.</span><span style=\"font-family:'Century Gothic'; color:#010101\">&#xa0;</span><span style=\"font-family:'Century Gothic'\"> The plaintiff, from her lawsuit (folio 2), informs that \"FEDEFARMA is a civil organization constituted in accordance with the laws of the Republic of Guatemala, which represents the research and development pharmaceutical companies operating in the Central American Isthmus and the Caribbean area (…) it groups fourteen multinational research pharmaceutical companies.\" From the review of the evidence provided by the plaintiff in response to the prevention issued by this Tribunal regarding her legal capacity, the articles of incorporation of said Federation were reviewed, specifically at folio 483, the said articles state \"</span><span style=\"font-family:'Century Gothic'; font-style:italic\">ARTICLE 3. The Federation is an entity foreign to all profit and religious purposes. Completely apolitical, created to promote the development and improvement of pharmaceutical activity, defend and coordinate the interests of its associates, and represent them in their relations with other public or private entities and with private individuals</span><span style=\"font-family:'Century Gothic'\">\". In analyzing the lawsuit, it is extracted that the plaintiff, within her arguments, has mentioned that her interest is in defense of the quality of the medications supplied to patients, repeatedly stating that she demands the protection of the right to health of the patients who are ultimately</span><span style=\"font-family:'Century Gothic'\">&#xa0;</span><span style=\"font-family:'Century Gothic'\">the users of the medications that the Caja Costarricense del Seguro Social acquires to meet health needs. Notwithstanding the above, from the same lawsuit it is also evident that the plaintiff always informed that she represents a group of multinational research pharmaceutical companies, and from the articles of its constitution, its objective is indeed to promote the development and improvement of pharmaceutical activity. Therefore, in application of the second paragraph of numeral 10</span><span style=\"font-family:'Century Gothic'\">&#xa0;</span><span style=\"font-family:'Century Gothic'\">of the Código Procesal Contencioso, the plaintiff indeed has standing to appear in defense of the collective interests that Fedefarma represents, coupled with the fact that from her own arguments, the questioning of the quality of the medications that may be distributed and consumed in our country is obtained.</span><span style=\"font-family:'Century Gothic'\">&#xa0;</span><span style=\"font-family:'Century Gothic'\">Thus, the core that unites the pharmaceutical companies to form the Federation serves as the basis in the present process; hence the regulatory prerequisite is satisfied. Even though this argument is not developed in the best manner in the lawsuit writing, as already indicated, this can be inferred without major questioning. Note that even though the cited second paragraph limits, for the purpose of challenging regulatory provisions, to legitimate interests, individual and collective, but not diffuse, the plaintiff meets the legal prerequisite to act on behalf of those they represent, a Federation composed of pharmaceutical companies, with the purpose of promoting and protecting the activities of pharmaceutical laboratories. In addition to the above, as expressed by this Chamber, the effects of the challenged regulations are ultimately directed at a Public Health issue, and since the protection of life and the health of individuals is a fundamental right, standing in this matter cannot be restrictive. Consequently, the defense of lack of active standing raised by the defendant's representation must be rejected. Furthermore, it should be noted that doctrine has pointed out a series of topics where standing is open to any inhabitant (almost like an actio popularis) due to the level of social relevance, among which tax matters and environmental matters are located; and some doctrine accepts health topics within this list. The logic that would prevail according to this reasoning is that in areas where the impact on health is the substance of the discussion, any natural or legal person would have standing. A position which, while not embraced by the Tribunal at this moment, is nonetheless not without its due support and legal logic. Regarding the Lack of Right (Falta de Derecho), it is rejected insofar as the ruling effectively ordered the nullity of the challenged regulatory provisions, the plaintiff being correct in her arguments, it being understood as upheld in the remaining claims. Thus, the right invoked by the defendant lacks its corresponding support, and the scales of justice lean in another direction, implying the rejection of the preliminary defense.</span></p><p style=\"margin-top:0pt; margin-bottom:7.05pt; line-height:150%\"><span>&#xa0;</span></p><p style=\"margin-top:0pt; margin-bottom:7.05pt; line-height:150%; font-size:11pt\"><span style=\"font-family:'Century Gothic'; font-weight:bold; color:#010101\">XII.- REGARDING COSTS</span><span style=\"font-family:'Century Gothic'; color:#010101\">. Regarding costs, pursuant to numeral 193 of the Código Procesal Contencioso Administrativo, the costs of the proceeding are to be borne by the defendant.</span><span style=\"font-family:'Century Gothic'; color:#010101\">&#xa0;</span><span style=\"font-family:'Century Gothic'; color:#010101\"> The foregoing, as the plaintiff has had to resort to this venue to assert her right, which determines that failing to charge the public entity would result in unjust enrichment for the plaintiff.</span></p><p style=\"margin-top:0pt; margin-bottom:7.05pt; text-align:center; line-height:150%; font-size:11pt\"><span style=\"font-family:'Century Gothic'; font-weight:bold; color:#010101\">THEREFORE:</span></p><p style=\"margin-top:0pt; margin-bottom:0pt; line-height:150%\"><span style=\"line-height:150%; font-family:'Century Gothic'; font-size:11pt; color:#010101\">The new facts presented by the plaintiff are admitted. The defenses of Lack of Active Standing and Lack of Right raised by the defendant are declared without merit, the latter as to what was granted, it being understood as admitted as to the remainder. The lawsuit is partially upheld, and denied as to what is not expressly granted; consequently, the absolute nullity of the following administrative acts is declared: 1- Agreement CCF- 3376-11-10, session 2010-44 issued on November 17, 2010, by the Central Pharmacotherapy Committee of the Caja Costarricense del Seguro Social,</span><span style=\"line-height:150%; font-family:'Century Gothic'; font-size:11pt; color:#010101\">&#xa0;</span><span style=\"line-height:150%; font-family:'Century Gothic'; font-size:11pt; color:#010101\">published in the Official Gazette La Gaceta number 10 of January 14, 2011, in which the 2009 Normativa con Requisitos de Oferentes para Medicamentos Biotecnológicos y Biológicos is modified. 2- Agreement taken in session 20011-08, held on February 23, 2011, by the Central Pharmacotherapy Committee, by which point 6 of the Specific Conditions for the Acquisition of Medications Called Antineoplastic and Other Medications for Specific Use in Oncological and Hema-Oncological Pathologies is reformed, published in La Gaceta 58. The Caja Costarricense del Seguro Social takes note of what is set forth in the recitals of this judgment. Both costs of the proceeding are to be borne by the losing party.</span><span style=\"line-height:150%; font-family:'Century Gothic'; font-size:11pt; font-weight:bold; color:#010101\"> Notify.</span><span style=\"font-family:Arial; color:#010101\"> </span></p><p style=\"margin-top:0pt; margin-bottom:7.05pt; line-height:150%\"><span>&#xa0;</span></p><p style=\"margin-top:0pt; margin-bottom:0pt; text-align:center; line-height:150%; font-size:11pt\"><span style=\"font-family:'Century Gothic'; font-weight:bold\">Grace Emilia Loaiza Sánchez</span></p><p style=\"margin-top:0pt; margin-bottom:0pt; text-align:center; line-height:150%\"><span>&#xa0;</span></p><p style=\"margin-top:0pt; margin-bottom:0pt; text-align:center; line-height:150%; font-size:11pt\"><span style=\"font-family:'Century Gothic'; font-weight:bold\">&#xa0;</span></p><p style=\"margin-top:0pt; margin-bottom:0pt; text-align:center; line-height:150%\"><span>&#xa0;</span></p><p style=\"margin-top:0pt; margin-bottom:0pt; text-align:center; line-height:150%\"><span>&#xa0;</span></p><p style=\"margin-top:0pt; margin-bottom:0pt; text-align:center; line-height:150%\"><span>&#xa0;</span></p><p style=\"margin-top:0pt; margin-bottom:0pt; text-align:center; line-height:150%; font-size:11pt\"><span style=\"font-family:'Century Gothic'; font-weight:bold\">Ricardo Ant. Madrigal Jiménez</span><span style=\"font-family:'Century Gothic'; font-weight:bold\">&#xa0;</span><span style=\"font-family:'Century Gothic'; font-weight:bold\">&#xa0;</span><span style=\"font-family:'Century Gothic'; font-weight:bold\">&#xa0;</span><span style=\"font-family:'Century Gothic'; font-weight:bold\">&#xa0;</span><span style=\"font-family:'Century Gothic'; font-weight:bold\">&#xa0;</span><span style=\"font-family:'Century Gothic'; font-weight:bold\">&#xa0;</span><span style=\"font-family:'Century Gothic'; font-weight:bold\">&#xa0;</span><span style=\"font-family:'Century Gothic'; font-weight:bold\">&#xa0;</span><span style=\"font-family:'Century Gothic'; font-weight:bold\">&#xa0;</span><span style=\"font-family:'Century Gothic'; font-weight:bold\">&#xa0;</span><span style=\"font-family:'Century Gothic'; font-weight:bold\">&#xa0;</span><span style=\"font-family:'Century Gothic'; font-weight:bold\">&#xa0;</span><span style=\"font-family:'Century Gothic'; font-weight:bold\">&#xa0;</span><span style=\"font-family:'Century Gothic'; font-weight:bold\">&#xa0;</span><span style=\"font-family:'Century Gothic'; font-weight:bold\">&#xa0;</span><span style=\"font-family:'Century Gothic'; font-weight:bold\">&#xa0;</span><span style=\"font-family:'Century Gothic'; font-weight:bold\">&#xa0;</span><span style=\"font-family:'Century Gothic'; font-weight:bold\">&#xa0;</span><span style=\"font-family:'Century Gothic'; font-weight:bold\">&#xa0;</span><span style=\"font-family:'Century Gothic'; font-weight:bold\">&#xa0;</span><span style=\"font-family:'Century Gothic'; font-weight:bold\">&#xa0;</span><span style=\"font-family:'Century Gothic'; font-weight:bold\">&#xa0;</span><span style=\"font-family:'Century Gothic'; font-weight:bold\">&#xa0;</span><span style=\"font-family:'Century Gothic'; font-weight:bold\">&#xa0;</span><span style=\"font-family:'Century Gothic'; font-weight:bold\">&#xa0;</span><span style=\"font-family:'Century Gothic'; font-weight:bold\">&#xa0;</span><span style=\"font-family:'Century Gothic'; font-weight:bold\">&#xa0;</span><span style=\"font-family:'Century Gothic'; font-weight:bold\">&#xa0;</span><span style=\"font-family:'Century Gothic'; font-weight:bold\">&#xa0;</span><span style=\"font-family:'Century Gothic'; font-weight:bold\">&#xa0;</span><span style=\"font-family:'Century Gothic'; font-weight:bold\">&#xa0;</span><span style=\"font-family:'Century Gothic'; font-weight:bold\">&#xa0;</span><span style=\"font-family:'Century Gothic'; font-weight:bold\">&#xa0;</span><span style=\"font-family:'Century Gothic'; font-weight:bold\"> Carlos Enrique Espinoza Salas</span></p><p style=\"margin-top:0pt; margin-bottom:0pt; text-align:center; line-height:150%\"><span>&#xa0;</span></p><p style=\"margin-top:0pt; margin-bottom:0pt; text-align:center; line-height:150%; font-size:11pt\"><span style=\"font-family:'Century Gothic'; font-weight:bold\">Trial Judges</span></p><p style=\"margin-top:0pt; margin-bottom:0pt; text-align:center; line-height:150%; font-size:11pt\"><span style=\"font-family:'Century Gothic'; font-weight:bold\">Fourth Section</span></p><p style=\"margin-top:0pt; margin-bottom:0pt; text-align:center\"><span>&#xa0;</span></p><p style=\"margin-top:0pt; margin-bottom:0pt\"><span>&#xa0;</span></p><p style=\"margin-top:0pt; margin-bottom:0pt\"><span>&#xa0;</span></p><p style=\"margin-top:0pt; margin-right:28.35pt; margin-bottom:0pt; line-height:150%\"><span>&#xa0;</span></p><p style=\"margin-top:0pt; margin-right:28.35pt; margin-bottom:0pt; line-height:150%\"><span>&#xa0;</span></p><p style=\"margin-top:0pt; margin-right:28.35pt; margin-bottom:0pt; line-height:150%\"><span>&#xa0;</span></p><p style=\"margin-top:0pt; margin-bottom:0pt; text-align:center; line-height:150%\"><span>&#xa0;</span></p><p style=\"margin-top:0pt; margin-bottom:0pt; text-align:center; line-height:150%\"><span>&#xa0;</span></p><p style=\"margin-top:0pt; margin-bottom:0pt; text-align:center; line-height:150%\"><span>&#xa0;</span></p><p style=\"margin-top:0pt; margin-bottom:0pt\"><span>&#xa0;</span><span>&#xa0;</span></p><p style=\"margin-top:0pt; margin-bottom:0pt\"><span style=\"font-family:Arial; color:#010101\">&#xa0;</span></p> Reglamento de Inscripción y Control de Medicamentos Biológicos||1", Reglamento a la Ley de Promoción de la Competencia y Defensa Efectiva del Consumidor N° 7472||6", Reglamento a la Ley de Promoción de la Competencia y Defensa Efectiva del Consumidor N° 7472||8", Reglamento a la Ley de Promoción de la Competencia y Defensa Efectiva del Consumidor N° 7472||24", Reglamento a la Ley de Promoción de la Competencia y Defensa Efectiva del Consumidor N° 7472||41", Reglamento a la Ley de Promoción de la Competencia y Defensa Efectiva del Consumidor N° 7472||43", Pacto Internacional de Derechos Civiles y Políticos||6", Pacto Internacional de Derechos Civiles y Políticos||7", Pacto Internacional de Derechos Económicos, Sociales y Culturales||9", Pacto Internacional de Derechos Económicos, Sociales y Culturales||10", Pacto Internacional de Derechos Económicos, Sociales y Culturales||11", Pacto Internacional de Derechos Económicos, Sociales y Culturales||12", Convención Americana sobre Derechos Humanos (Pacto de San José)||1", Convención Americana sobre Derechos Humanos (Pacto de San José)||5", Ley General de Salud||102", Ley General de Salud||103", Ley General de Salud||104", Ley General de Salud||105", Ley General de Salud||106", Ley General de Salud||107", Ley General de Salud||108", Ley General de Salud||112", Ley General de Salud||113", Ley General de Salud||114", Ley General de Salud||115", Ley General de Salud||116", Ley General de Salud||117", Ley General de la Administración Pública||229", Ley General de la Administración Pública||361", Código Civil||46", Convención sobre los Derechos del Niño||24", Ley General de Arrendamientos Urbanos y Suburbanos (Inquilinato)||5", Ley General de Arrendamientos Urbanos y Suburbanos (Inquilinato)||22", Ley General de Arrendamientos Urbanos y Suburbanos (Inquilinato)||93", Ley General de Arrendamientos Urbanos y Suburbanos (Inquilinato)||94", Ley General de Arrendamientos Urbanos y Suburbanos (Inquilinato)||97", Ley General de Arrendamientos Urbanos y Suburbanos (Inquilinato)||98", Ley General de Arrendamientos Urbanos y Suburbanos (Inquilinato)||135", Ley contra la Violencia Doméstica||2", Ley de Protección Fitosanitaria||2", Ley de Protección Fitosanitaria||30", Ley de Protección Fitosanitaria||31", Ley de Protección Fitosanitaria||32", Ley de Protección Fitosanitaria||42", Ley de Protección Fitosanitaria||45", Código de la Niñez y la Adolescencia||19", Código de la Niñez y la Adolescencia||20", Código de la Niñez y la Adolescencia||42", Código de la Niñez y la Adolescencia||43", Código de la Niñez y la Adolescencia||45", Código de la Niñez y la Adolescencia||46", Código de la Niñez y la Adolescencia||50", Código de la Niñez y la Adolescencia||54", Código de la Niñez y la Adolescencia||78", Código de la Niñez y la Adolescencia||97", Código de la Niñez y la Adolescencia||121", Ley sobre estupefacientes, sustancias psicotrópicas, drogas de uso No Autorizado, actividades Conexas, legitimación de capitales y financiamiento al terrorismo||1", Ley sobre estupefacientes, sustancias psicotrópicas, drogas de uso No Autorizado, actividades Conexas, legitimación de capitales y financiamiento al terrorismo||3", Ley sobre estupefacientes, sustancias psicotrópicas, drogas de uso No Autorizado, actividades Conexas, legitimación de capitales y financiamiento al terrorismo||6", Ley sobre estupefacientes, sustancias psicotrópicas, drogas de uso No Autorizado, actividades Conexas, legitimación de capitales y financiamiento al terrorismo||47", Ley Nacional de Emergencia||2", Ley Nacional de Emergencia||11" **Disclaimer: The following translation is an informative service and does not replace the official published text.** **Case Law and Constitutional Chamber Precedent:** In relation to the nature of the right to health, this Chamber in ruling No. 4654-2003 of 10:09 hrs. of May 28, 2003, indicated that:

> "IV.- ... As for the right to health, this Chamber has extensively elaborated the matter, establishing that health is a fundamental right of the human being, and as such, it is part of the Block of Constitutionality. It is an individual and, simultaneously, a collective right to public health, for which reason the State and the Administrations in charge of the health sector are obliged to guarantee it and, furthermore, to oversee that other public and private agents do not violate it, which is why it is considered an erga omnes right and a diffuse interest." It has also considered that life and health are values that constitutionally guide the interpretation of all other fundamental rights, since, without them, the enjoyment of the rest would be impossible. In this line, national and international regulations highlight the prevalence of these rights, resulting from the analysis of Articles 21 of the Political Constitution (right to life) and the international instruments ratified by the country, among which is the International Covenant on Civil and Political Rights (Law No. 4229 of December 11, 1968), specifically its articles 6 and 7. Likewise, Article 12 of the International Covenant on Economic, Social and Cultural Rights (Law No. 4229 of December 11, 1968) indicates that States must recognize the right of every person to the enjoyment of the highest attainable standard of physical and mental health and should adopt measures to ensure, among other aspects, the healthy development of children. In this same line, it is worth mentioning Article 10 of the aforementioned legal instrument, in relation to the protection of the family and, especially, mothers and minor children. The latter instruments, together with the Convention on the Rights of the Child (Law No. 7184 of July 18, 1990), Article 24, impose obligations on the State that are directly related to the enjoyment of the highest level of health. In the national context, the Political Constitution establishes, as an obligation and fundamental task of the State, to ensure the defense of the right to health (Article 21), and as a duty of all persons to ensure its conservation (Article 46 of the Civil Code). In accordance with the above, the Political Charter, in Article 50, recognizes the right to a healthy and ecologically balanced environment. Along the same lines, Article 89 of the political text recognizes the social aims of health, among which is the protection of minor children and the family. In harmony with the normative framework described, the General Health Law (Law No. 5395 of October 30, 1973) details health actions at the general and specific levels, from articles 102 to 108, but the field of protection of the family and minors is widely provided for in articles 112 to 117 of that legal body. The preceding provisions, together with the stipulations of the Childhood and Adolescence Code (Law No. 7739 of January 6, 1998), article 42, set forth obligations for the State in terms of the care of minor children and their protection. In this regard, the Childhood and Adolescence Code, within the framework of the special protection granted by Law 7739, compels the State to guarantee national policies against any violation of human rights that affects minor persons (articles 19 and 20, 43, 45, 46, 50 and 54, in relation to article 121 of the same instrument). Furthermore, Articles 19 and 78 of the Childhood and Adolescence Code include a reinforced protection of the right to health and the quality of life expressed in access to medical-pharmacological services afforded to the minor population. Certainly, Article 97 of this same body of law defines public and private health services as basic services, for which reason they cannot be interrupted under any circumstances. At the infra-constitutional level, the political text, in ordinal 50, broadly provides for the right of every person to a healthy and ecologically balanced environment, consecrating the obligation of the State to guarantee, defend, and preserve that right. Thus, law 5395 of October 30, 1973 (Ley General de Salud), in articles 102, 103, 104, 106 and 107, establishes the general provisions regarding the right to health protection, namely: "The right to health protection is irrenounceable" (article 102), "All persons must ensure the conservation of their health and will be subject to the health provisions of this law and other pertinent legal provisions" (article 103), "The health of the inhabitants of the Nation is a public good" (article 104), "Any act or omission by natural or juridical persons contrary to general health is unlawful" (article 106), and "Everyone is obliged to provide their cooperation in regard to general health, and the authorities may require the compulsory compliance of this provision" (article 107). Finally, it is appropriate to note that, in relation to the specific provisions according to the matter, apart from the norms cited, Chapter II of Section III (articles 113 to 117) specifically includes the protection of the child and the family. In the same sense, the regulations for the protection of health considered in other normative frameworks such as the domestic violence law, Law No. 7586, law against sexual exploitation, the Phytosanitary Protection Law, Law No. 7664 of April 8, 1997, articles 2, 30, 31, 32, 42 and 45, Law 7786 on narcotics, psychotropic substances, drugs of unauthorized use, related activities, money laundering, and financing of terrorism, articles 1, 3, 6, 47, and the National Emergency Law, Law 7914, articles 2 and 11, among many other regulatory provisions.

The substantive and normative basis of the preceding paragraph is complemented by the development carried out in the administrative sphere by the Caja Costarricense de Seguro Social (CCSS). Indeed, this Institution, in use of the powers granted by numeral 73 of the Political Constitution and its Constitutive Law, has the legal obligation to provide the services contemplated in articles 1 and 2 of its Constitutive Law, also possessing the authority to manage its own resources and create the necessary regulations for the proper provision of the health services under its charge, including those related to the medicinal formulary that is the subject of challenge in this case. In accordance with this generic attribution, the Institution dictates the necessary regulations for the creation and operation of the official list of medications, the procedure for its modification, and everything related to the administrative review of these decisions, which constitutes the regulatory framework governing the case under examination, which consists of the "Regulations for the Official List of Medications" (agreement of the Board of Directors of the CCSS number 1445 of June 10, 2009, and its reform), and the "Regulation for the Evaluation of Medications and Application of Pharmacoeconomics" (agreement of March 9, 2010, published in gazette number 47 of March 9, 2010, approved through agreement CCF-0275-02-10 (session 2010-05) of the Central Pharmacotherapy Committee). From the analysis of this regulatory body, it is determined that there is a rigid procedure that must be followed in advance of any elimination or modification of the official list of medications. This procedure, at the administrative level, is a guarantee of respect for the right to health and life of the administered parties. Indeed, the administrative act by which a medication is excluded from the official list can only be issued if it complies with the procedural steps, especially a scientific, medical, and pharmacoeconomic analysis that ensures that the decision adopted does not compromise the right to health and the lives of the users, in the understanding that this power of the Administration conferred by the legal system cannot be exercised arbitrarily or capriciously. The contrary would imply a flagrant violation of the Principle of Rationality cited in article 229 of the General Law of Public Administration, a regulatory provision that is cited as violated as a parameter of constitutionality by the appellants. In summary, direct violations of the Political Constitution and international human rights instruments are clearly and unequivocally accredited if a medication is excluded from the official list without following the legally established procedure, affecting the rights of an especially vulnerable population, which requires the immediate provisional remedy. The foregoing is in accordance with repeated jurisprudence of this Chamber (see in this regard the vote of the Constitutional Chamber, No. 4654-2003 and No. 2007-0196).

**III.- On the rights to life, health, and housing: General aspects.** The right to health has currently been understood as part of second-generation human rights, or economic, social, and cultural rights, whose protection entails a series of positive obligations on the part of the State; that is, actions and services that the State must provide directly or indirectly. In reality, life and health, more than being constitutionally protected rights, constitute values that constitutionally guide the interpretation of all other fundamental rights, since, without them, the enjoyment of the rest would be impossible (Ernesto Jinesta Lobo. Treatise on Administrative Law).

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VI- REGULATORY FRAMEWORK FOR MEDICINES AND COMPETENCIES OF THE CAJA COSTARRICENSE DE SEGURO SOCIAL REGARDING THE PURCHASE OF MEDICINES: The hospital medical care service is a proper public service to the extent that it is executed by a Hospital Center, or a Health Care Center (clinic, EBAIS, etc.) under the purview of the Caja Costarricense de Seguro Social. This Entity, by constitutional mandate, is responsible for overseeing (planning, developing, executing, etc.), among other things, everything related to Social Security (Seguridad Social), which encompasses the health care service. Thus, Article 75 of our Political Constitution (Constitución Política) states in the relevant part: "Social insurance is established for the benefit of manual and intellectual workers, regulated by a system of compulsory contributions from the State, employers, and workers, in order to protect them against the risks of illness, disability, old age, death, and other contingencies determined by law. The administration and governance of the social insurance system shall be the responsibility of an autonomous institution, called the Caja Costarricense de Seguro Social...". In this way, social security, which naturally includes the area of health care, is elevated to a constitutional rank, thereby constituting an unavoidable mandate that requires the State, through the aforementioned Institution – CAJA COSTARRICENSE DE SEGURO SOCIAL – to procure, in the most efficient manner possible, the care and treatment of this important sector of social security, that is, the area of health.

It is not superfluous to highlight from the outset the preponderance that the Costa Rican Social Security Fund (Caja Costarricense de Seguro Social) acquires in this aspect, as the Entity expressly entrusted by constitutional provision to carry out, as previously discussed, the administration and governance of social insurance; this point has been addressed by our Constitutional Chamber (Sala Constitucional), thus in vote number 6256-94, it established, in what is relevant to us: ". . .b) the norm grants exclusively to the Costa Rican Social Security Fund the administration and governance of social insurance, a degree of autonomy that is, of course, different from and superior to that defined generally in article 188 ibid..." Furthermore, it is worth saying that this right to health can now be defined from a legal perspective as: "the set of mandatory precepts that recognize individuals' rights concerning their health and that regulate their conduct regarding all those matters in which the health of the person and the group comes into play." Health as such can be defined as established in the preamble of the Constitution of the World Health Organization (WHO): "Health is a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity." Despite its transcendental importance, that right is not expressly enshrined in our Political Constitution, as we shall see next. We consider it indispensable to link the aforementioned article 73 of the Constitution, due to its fundamental content, with a norm that allows it to be complemented, from the perspective that interests us in this study, namely numeral 21 of the cited Constitution; said norm provides: "Article 21.- Human life is inviolable. " By speaking here of "Human life", reference is not made exclusively to the right to life in a strict sense, but rather reference is also made to its "health" dimension, that is, the norm does not refer literally to protecting only human life in a restricted sense, but in a broad sense, to the state of "health", as a basic prerequisite of life itself, which is inherent to life as such, so that given their consubstantial relationship, that "right to health" is understood to be included in this norm; in that sense it has been said: " V- Human life is only possible in solidarity with the nature that sustains us and supports us, not only for physical nourishment, but also for psychological well-being; it constitutes the right that all citizens have to live in an environment free of contamination, which is the basis of a just and productive society. It is thus that article 21 of the Political Constitution states: "Human life is inviolable"; and continues; "It is from this constitutional principle that the right to health, to physical, mental and social well-being, undeniably derives, a human right that is indissolubly linked to the right to health and to the State's obligation to protect human life." (Votes Number 3705-93, 3341-96. Constitutional Chamber, Supreme Court of Justice). On the other hand, and given that transcendence of the right we analyze, the Constitutional Chamber itself has expressly recognized the State's responsibility in ensuring the due protection of that right: " Modernly, the determining role that the State must play is undeniable, and in the case that concerns us, the State of Costa Rica, represented by the Ministry of Health in this field, regarding the establishment of programs for the protection of that fundamental value of all citizens." (Vote number 2522-97, of the Constitutional Chamber of the Supreme Court of Justice). Equally, and as a corollary, we indicate that the Constitutional Chamber has established that this right to life, constitutionally protected, as we have seen, must be supported and protected through the protection that the Costa Rican Social Security Fund provides to the population, through health plans, patient care, and the supply of medications, among other functions, given that the state responsibility to determine the suitable and safe practices of the service has been delegated to it. With the foregoing, it is clear that the right to health is a right of constitutional roots, projected as a power-duty charged to the corresponding authorities, in this case the Costa Rican Social Security Fund, and therefore under that context, the provision of that service has an eminent public character.

Naturally, matters concerning the right to health have not escaped regulation by international instruments, which bind as such the actions of the affiliated States based on that right; thus we find the following regulations: Universal Declaration of Human Rights, in its article 25, in what interests us, establishes: "Everyone has the right to a standard of living adequate for the health and well-being of himself and of his family, including food, clothing, housing and medical care and necessary social services, and the right to security in the event of unemployment...". For its part, the American Convention on Human Rights, specifically in its articles 1 and 5, in the relevant parts state: "Article 1. Every person has the right to have his life respected...", which as we already said, the right to health derives from it.... "Article 5.1. Every person has the right to have his physical, mental, and moral integrity respected." The Convention on the Rights of the Child, Article 24: "States Parties recognize the right of the child to the enjoyment of the highest attainable standard of health and to facilities for the treatment of illness and rehabilitation of health". The Convention on the Elimination of All Forms of Discrimination against Women: "Article 12. States Parties shall take all appropriate measures to eliminate discrimination against women in the field of health care in order to ensure, on a basis of equality of men and women, access to health care services, including those related to family planning." We also allow ourselves to merely mention other instruments such as the International Covenant on Economic, Social and Cultural Rights, in its numerals 9, 10, 11, and 12; the International Covenant on Civil and Political Rights, 6 and 7; the American Declaration of the Rights and Duties of Man, in its numeral 1; the Convention on the Elimination of All Forms of Racial Discrimination, article 5, subsection e). In relation to our legal regulations, it is certainly exhaustive in focusing on the recognition of such right, denoting its public character, just to cite some examples: Civil Code, article 46: "Every person may refuse to be subjected to a medical or surgical examination or treatment, with the exception of cases of mandatory vaccination, or other measures related to public health..."; Childhood and Adolescence Code, article 19: "Minors shall have the right to seek refuge, aid and guidance when the threat to their rights entails serious danger to their physical or spiritual health; likewise, to obtain, in accordance with the law, adequate and timely assistance and protection from the competent institutions.", 20, "Minors shall have the right to obtain information, regardless of its source and mode of expression, especially that which promotes their spiritual and emotional well-being, as well as their physical and mental health", 42, 43, 45, 46, 50, 54, 78, 97, and 121, which are not transcribed for obvious reasons; Domestic Violence Law, article 2; Law on Narcotics, Psychotropic Substances, Drugs of Unauthorized Use, articles 1, 3, 6, 47; Phytosanitary Protection Law, 2, 30, 31, 32, 42, 45, 73; Urban and Suburban Leases Law, articles 5, 22, 93, 94, 97, 98, 135; of course the Constitutive Law of the Costa Rican Social Security Fund; The General Health Law, and the Organic Law of the Ministry of Health, without citing others that also highlight the right at hand, and that denote its public character. In that sense, there are also a great number of Regulations that protect that right, we cite as an example the National Emergencies Regulation articles 2 and 11; the Autonomous Regulation of Organization of the Ombudsman's Office article 21; the Regulation of the General Customs Law, articles 12, 34, 246, 287, and 386; Regulation of the Law for the Promotion of Competition and Effective Consumer Protection, articles 6, 8, 24, 41, 43; Regulation of the Regulatory Law on Smoking, articles 1 and 5; Law on Equal Opportunities for Persons with Disabilities, articles 92 and 94, among others. Returning to the competencies of the Costa Rican Social Security Fund, the Political Constitution in article 73, indicates that the Fund is an autonomous institution in charge of the administration and governance of social insurance, this is so with the object of protecting workers against the risks of illness, disability, maternity, old age, and death. For the fulfillment of its purposes, the Constitutive Law of the Costa Rican Social Security Fund, number 17 of October 22, 1943, provides in its ordinal 71, that said entity is authorized to import, clear customs, manufacture, buy, sell, and export, directly, medications included in the National Formulary, reagents and biologicals, as well as raw materials and packaging and conditioning materials, required in the elaboration of those. It is equally authorized to supply these same articles to public and private institutions that provide health services. In that sense, numeral 72 of the aforementioned law expresses that such purchases and negotiations may be carried out, as long as the following requirements are met: a) Establish and maintain updated a supplier registry (registro de oferentes) of the products, based on their generic name, for such purposes the Comptroller General of the Republic (Contraloría General de la República) and the Audit Office of the Costa Rican Social Security Fund shall have a copy of this registry. The Office in charge of purchases shall freely request quotations from national and foreign companies, registered in the supplier registry, and their responses shall be considered formal offers if they meet the requirements of the case. To have the right to be considered, such responses must be given by the suppliers within three business days following the receipt of the quotation request. b) The Comptroller General of the Republic must resolve the purchase authorizations within a period no longer than five business days. c) In special cases of urgency, purchases may be made with the sole approval of the Fund's Audit Office, but, in any case, the Comptroller must be informed of the actions taken within the following twenty-four hours. ch) The officials in charge of carrying out the purchases must make them under the best conditions of quality and price, and shall be responsible for their acts and for the damages that may eventually be caused, in accordance with the law. For its part, numeral 73 of the ibid regulations indicates that the Costa Rican Social Security Fund may export medications, reagents and biologicals, provided that national needs are satisfied. It may also exchange medications with state or private organizations from other countries for the purpose of satisfying social needs. The norms and authorizations contained in this article shall be applicable equally to the Ministry of Health. In turn, numeral 102 of the General Health Law, number 5395 of October 30, 1973, expresses that the importation of medications and their distribution shall only be permitted to legal entities or individuals registered with the Ministry, upon prior authorization and registration with the College of Pharmacists, in accordance with the corresponding legal and regulatory provisions. In any case, the Central Government and public institutions with health functions may, directly import, elaborate, handle, store, sell or supply medications, raw materials or medical-surgical materials, when the fulfillment of their programs or emergency situations require it, with the sole approval of the Ministry, pursuant to the respective Regulation (ordinal 103 of Law 5395). It being understood by medication any substance or natural, synthetic or semi-synthetic products and any mixture of those substances or products that are used for the diagnosis, prevention, treatment and relief of diseases or abnormal physical states, or of the symptoms thereof and for the reestablishment or modification of organic functions in persons or animals. Included in the same denomination and for the same purposes are dietetic foods and foods and cosmetics that have been added with medicinal substances. The substances referred to in the first paragraph are not considered medications when they are used for chemical and clinical-chemical analyses, or when used as raw material in industrial processes. Every medication must conform to the particular regulatory requirements that, by their nature, are exclusively applicable to them, in addition to the general ones established for every medication in Law 5395 (article 104). Medications may be presented for their use, commerce, distribution and supply under a generic name or under a registered name. Medications under a generic name are those pure medications, presented in a pharmaceutical formula or singly, designated with a general technical name recognized by official pharmacopoeias or by technical works of recognized authority. The generic name medication may be simple or may be a formula constituted by two or more generic name medications. Medications under a registered name are those that are delivered to commerce and use under a particular invented name and under a registered trademark (numeral 105 of Law 5395). It is considered that a medication may, legally, be destined for commerce, public use and consumption, when it satisfies the regulatory requirements, or those of the pharmacopoeia declared official by the Executive Branch regarding its identity and qualities, safety and efficacy for the purposes for which it is used, consumed or prescribed and in terms of the natural or legal persons responsible who are involved in its importation, commerce, handling, distribution and prescription, having complied with the legal and regulatory requirements pertinent to each of these actions (numeral 106 of Law 5395). The importation, elaboration, commerce, distribution or supply under any title, handling, use, consumption and possession for commerce, of deteriorated, adulterated or falsified medications is prohibited (ordinal 107 of Law 5395). The importation, commerce, use or supply of medications that are in an experimental process is prohibited, except under the conditions and circumstances and for the time that the Ministry authorizes it (numeral 108 of Law 5395). Furthermore, every natural or legal person may only import, manufacture, handle, trade or use medications registered with the Ministry and whose registration has satisfied the regulatory requirements, especially those related to: the nature and quantity of the information required about the medication or product submitted for registration; the delivery of samples necessary to perform the analyses that may be needed, to those pertinent to the name with which the product will be identified; the content of the labeling; the type of containers or wrappers that will be used and the payment of the fees indicated by the pertinent tariff (article 112 of Law 5395). The registration of every medication shall be made before the Ministry where the inscription will be carried out when it proceeds according to the corresponding regulatory provisions. Said inscription shall be in charge of a Technical Body whose integration and functions shall be determined by the Organic Law of the Ministry and the respective Regulation (article 113 of Law 5395). The registration of every medication shall last five years, unless the infractions in the elaboration, commerce or use incurred by its holder, or experiences demonstrating that the product is unsafe or ineffective under the terms in which it was authorized and registered, make its cancellation or the corresponding modification appropriate (numeral 114 of Law 5395). Any modification in the name of a medication, in its formula, in the form of its dosage, in the container and content of the labeling that accompanies it, or in the advertising, shall require prior permission from the Ministry (numeral 115 ibid). Medications under a registered name, for the purposes of their importation, commerce and distribution in the country, require for their inscription proof of sanitary registration in the country of origin and proof of analysis corresponding to the product, issued by a national or foreign laboratory, that, in the judgment of the Ministry, guarantees its identity and its quality, according to the official pharmacopoeia or technical texts of recognized authority; this latter proof may also be issued by the quality control laboratory of chemical and pharmaceutical products of the manufacturing company itself. Medications under a generic name require for their inscription and for the same purposes indicated in the preceding paragraph, proof of analysis that guarantees their identity and quality, according to the official pharmacopoeia or technical texts of recognized authority, this proof being issued in the same form and conditions indicated in the preceding paragraph. The Ministry may exempt from the tests cited above, when it concerns a known product and that by its own nature makes those requirements unnecessary; or, in the case of medications not described in the official pharmacopoeia or technical texts of recognized authority, whether they are trademarked pharmaceutical products or generic name medications, it may demand the tests that are necessary for the verification of identity, quality, and therapeutic and biopharmaceutical efficacy of the product (article 116 ibid). For its part, ordinal 117 ibid, expresses that the Ministry of Health, the Costa Rican Social Security Fund and any other state entity, with public health or social security functions, may acquire unregistered medications, at any time or circumstance and that in case of urgency or public necessity, that Ministry may authorize the importation of unregistered medications, in addition to the fact that for exclusive research purposes, the importation, production and use of unregistered medications may be authorized, in accordance with the corresponding regulatory provisions. Up to here, it is convenient to be clear about one aspect: the governing body in health matters is the Ministry of Public Health and the Costa Rican Social Security Fund is the administering entity of public insurance. These are, in effect, competencies that interrelate with each other, but some correspond to the Ministry and others to the public entity. Regarding the Sanitary Registration, it is clear that the balance tilts in favor of the Ministry and not the Fund, with the natural obligation of coordination in the field of common competencies.

VII- ON THE REQUIREMENTS THAT MUST BE MET TO FORM THE SUPPLIER REGISTRY OF THE COSTA RICAN SOCIAL SECURITY FUND TO OFFER BIOTECHNOLOGICAL, BIOLOGICAL, ANTINEOPLASTIC MEDICATIONS AND OTHER MEDICATIONS FOR SPECIFIC USE IN ONCOLOGICAL AND HEMATOLOGICAL PATHOLOGIES: Through an agreement dated April 28, 2009, issued by the Costa Rican Social Security Fund, published in La Gaceta 89 of May 11, 2009, and approved by the Central Pharmacotherapy Committee in agreement CCF-0908-04-09 (Session 2009-13), the requirements for the supplier registry applicable to biological medications are established, and specific conditions for the acquisition of medications called antineoplastics and other medications for specific use in oncological and hemato-oncological pathologies. Stating that registered suppliers and suppliers to be registered in the CCSS Supplier Registry for medications of biological origin from Group 1 and/or Group 2, must comply with a series of requirements stipulated below for each group. It is indicated in turn, that these requirements are also mandatory for those suppliers that participate in the Fund with medications that do not have a Sanitary Registration of the Medication and where the importation of the medication must proceed by article 117 of the General Health Law of Costa Rica or with medications with an in-transit code. In the first group are located medications of biological origin, which in their manufacturing process do not use raw material derived from human blood products (blood products (hemoderivados)) (for example human plasma), establishing as requirements, the following: 1. Certificate of the Sanitary Registration of the Medication issued by the Ministry of Health of Costa Rica. 2. Attach the complete qualitative-quantitative formula with the excipients used and the permitted ranges of related substances (if applicable in this specific case). 3. Those biological medications from Group 1 that contain in their formulation, and corroborated in their qualitative-quantitative formula, excipients of human plasma origin (blood products) must also comply with the requirements for Group 2. 4. Medications that do not have a sanitary registration issued by the Ministry of Health of CR must also present the duly certified clinical studies that correspond to those that gave rise to their registration in their country of origin, for the same official indications of use and safety in reference to the innovator. 5. In the event of offers that are under equal conditions, the administration clearly establishes a tie-breaking mechanism, which is to give priority to the biological product that is registered and consumed in the mentioned countries: United States (FDA) and/or countries of the European Economic Community (EMEA), and/or Canada and/or Japan and/or Switzerland. It is important to note that the manufacturing laboratories of the medication must present the certificate of free sale of their product in the United States and/or Canada and/or European Economic Community and/or Japan and/or Switzerland in the event that offers under equal conditions are presented and it is necessary to apply the tie-breaking mechanism. This document must be issued by the corresponding regulatory authority of the respective country. 6. Every biological medication, whether a new drug or not, that has the approval of at least the FDA and/or EMEA and/or Canada and/or Japan and/or Switzerland shall be exempt from the requirements referred to in point 3, if they present the official documentation from the FDA and/or EMEA and/or from the regulatory authorities of Japan and/or Switzerland that accredits the product for its commercialization in these countries. 7. Biological medications that do not have a sanitary registration issued by the Ministry of Health of CR must also comply with point 5. 8. All requested documents must be authenticated via our country's consular route and ratified by the Ministry of Foreign Affairs. In group 2, are located medications of biological origin, that use in their manufacturing process, raw material derived from human blood products (for example human plasma), requiring them to provide: 1. Certificate of the Sanitary Registration of the Medication issued by the Ministry of Health of Costa Rica. 2. Attach the complete qualitative-quantitative formula with the excipients used and the permitted ranges of related substances (if applicable in this specific case). 3. Must comply with the Quality Specifications specified in each corresponding technical data sheet. 4. Must comply with all the regulations requested by the Ministry of Health of CR and everything requested by the Laboratory of Standards and Quality of Medications of the CCSS regarding blood products. 5. Those biological medications from Group 1 that contain in their formulation, and corroborated in their qualitative-quantitative formula, excipients of human plasma origin (blood products) must also comply with the requirements for Group 2. 6.

Medications that do not have a sanitary registration (registro sanitario) issued by the Ministry of Health of CR must also present duly certified clinical studies corresponding to those that gave rise to their registration in their country of origin, in the same official indications for use and safety in reference to the innovator. 7. In the event of bids that are in equal conditions, the administration clearly establishes a tie-breaking mechanism, which is to give priority to the biological product that is registered and consumed in the mentioned countries: United States (FDA) and/or countries of the European Economic Community (EMEA), and/or Canada and/or Japan and/or Switzerland. It is important to note that the laboratories manufacturing the medication must present the certificate of free sale of their product in the United States and/or Canada and/or the European Economic Community and/or Japan and/or Switzerland in the event that bids are submitted under equal conditions and it is necessary to apply the tie-breaking mechanism. This document must be issued by the corresponding regulatory authority of the respective country. 8. All requested documents must be authenticated via our country's consular channel and ratified by the Ministry of Foreign Affairs. 9. The manufacturing laboratory must guarantee that the human plasma used as raw material in the manufacture of each of the biological medications must come from healthy human beings, and be entirely free of viruses or other pathogens. <b>In turn, the Central Pharmacotherapy Committee (Comité Central de Farmacoterapia), in agreement CCF-0944-04-09 (Session 2009-13) and ratified by agreement issued in Session 2009-14 of April 22, 2009, agreed to update the regulations for the Specific Conditions for the acquisition of medications called antineoplastics and other medications for specific use in oncological and hemato-oncological pathologies</b>, thus for the purposes of the Medication Registry at the Costa Rican Social Security Fund (Caja Costarricense de Seguro Social), whether or not they are registered with the Ministry of Health of Costa Rica, in point one, the certification issued by the General Medical Directorate (Dirección Médica General) of the General or Oncological Hospital or Cancer Institute of the country of origin of the manufacturing laboratory must be presented, signed by the highest authority in medical oncology and the General Medical Director of the Medical Center, indicating the annual quantity consumed by patients of the medication manufactured by said laboratory, the number of beds in that hospital for adults and the occupancy rate (for parenteral medications), and the number of oncology and onco-hematology consultations (for oral medications). All information must correspond to the same year in which it is registered with the Fund (Caja) or preferably to the year prior to the registration date. When the analysis is carried out by the CCSS, if the drug has consumption in the General or Oncological Hospital or Cancer Institute of the country of origin equal to or greater than 100% of that consumed at the Hospital Nacional San Juan de Dios, it will be determined with a comparative study of defined daily dose (DDD) per 100 hospital beds/day for parenteral medications, and with a comparative study of defined daily dose (DDD) per 1000 consultations/day for oral medications, the supplier approval (aval de oferente) will be given and it will be incorporated into the Registry at the Fund (Caja). In the case of suppliers that are National Laboratories, based on a comparative study of defined daily dose (DDD) per 100 hospital beds/day (parenteral medications) or 1000 consultations/day (oral medications) taking the Hospital San Juan de Dios as a reference, if the result is equal to or greater than the DDD study from the year prior to the medication's registration with the Fund (Caja), the supplier approval (aval de oferente) will be given and it will be incorporated into the Registry at the Fund (Caja). For the case of national laboratories, the information related to consumption at the Hospital will be obtained through the internal information mechanisms available at the institution. In point 2, certification must be presented issued by the Medical Directorate (Dirección Médica) of the General or Oncological Hospital or Cancer Institute of the country of origin of the manufacturing laboratory, signed by the highest authority in medical oncology and the General Medical Director of the Medical Center, presenting the annual consumption in patients corresponding to the same year, efficacy and safety results obtained with the use of the medicinal product in the treatment of patients with hemato-oncological pathology and the type of oncological pathologies treated. The documents must contain, in a complete and concrete manner, the type and percentage of side effects presented by patients who have received treatment with said product for its analysis. In point 3: Certification from the Ministry of Public Health or the equivalent highest public health authority in the country of origin of the manufacturing laboratory presented by its representative, recognizing the General or Oncological Hospital or Cancer Institute requesting to be registered. In point 4: it is mandated that the certification must be presented individually and the information must refer to the most recent previous year closest to the date of its inclusion in the CCSS Supplier Registry for medications included in the Official List of Medications (Lista Oficial de Medicamentos), or correspond to the most recent previous year closest to the tender when it involves medications not included in the Official List of Medications (Lista Oficial de Medicamentos) and are acquired at the Central or local level. These certifications must be updated each time the renewal of registration is requested before the CCSS for medications included in the LOM; if not registered, each time a purchase is made at the Central or local level for non-LOM medications. In point 5: it is stated that the requested documents must have the signatures of health authorities duly authenticated, as required by Costa Rican legislation, in addition to completing the chain of consular legalization of our country and ratified by the Ministry of Foreign Affairs of Costa Rica. In point six, amended by agreement made in session 2011-08 held on February 23, 2011, it is provided that those antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies for parenteral or oral use that have marketing authorization (permiso de comercialización) in any of the following countries are exempt from the requirements stated in points 1, 2, 3, and 4: United States (FDA), Canada (Health Canada), Japan (MHLW), Switzerland (Swissmedic), Germany, England, Sweden, France, Italy, Spain, Belgium, Denmark, Austria, Holland, Finland, Norway, Colombia (INVIMA), Argentina (ANMAT), Brazil (ANVISA), stating that laboratories must present: the certificate of pharmaceutical product (or Certificate of Free Sale plus the Certificate of Good Manufacturing Practices), as support for their registration and marketing authorization in the United States (FDA), Canada, Japan (MHLW), Switzerland (Swissmedic), Germany, England, Sweden, France, Italy, Spain, Belgium, Denmark, Austria, Holland, Finland, Norway, Colombia (INVIMA), Argentina (ANMAT), Brazil (ANVISA). Likewise, it exempts those medications whose origin does not correspond to any of the countries listed above, but which have the Mutual Recognition certificate for their marketing in any of the reference member states (European Union), a certificate that must be issued by the highest competent regulatory authority in public health of the respective country. It is provided that to exempt from the requirements listed in points 1, 2, 3, and 4, it is necessary that the certificates of pharmaceutical product (or Certificate of Free Sale) include the name and address of the manufacturing plant, which must coincide with the address of the manufacturing plant of the medication registered with the Ministry of Health of Costa Rica (provided the medication is registered in the country). The manufacturing plant (name and address) from which the registered medication originates and has marketing authorization in one of the countries listed above must correspond to the same manufacturing plant from which the medication to be delivered to the CCSS will be imported. Point seven establishes that the supplier who is already registered in the CCSS supplier registry can revalidate their registration by presenting the information indicated in the corresponding points above. Said registration will be valid until the expiration of the sanitary registration (registro sanitario) issued by the Ministry of Health of Costa Rica. Point 8 indicates that those suppliers who are registered but prefer to submit their data at the time of the purchase process and not revalidate the registration with the CCSS until its expiration, must present the requirements for antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies for each purchase process. Point nine states that in the case of the acquisition of antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies included in the Official List of Medications (LOM), the Medications and Clinical Therapeutics Area attached to the Pharmacoepidemiology Directorate will be responsible for carrying out the analysis of the data and the corresponding Defined Daily Dose (DDD) study. In point 10, it stipulates that in the case of non-LOM antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies acquired by each center, the analysis of the data and the corresponding Defined Daily Dose (DDD) study will be carried out each time a purchase process is initiated, and will be performed and analyzed by each Pharmacy Service. Point 11 states that once the Executive Decree of the Ministry of Public Health regulating the Medication Registry is published, the specific requirements for molecular target therapy products are contemplated therein; these requirements are based on the ICH recommendations and form part of these conditions. Point 12 indicates that in the event of bids for antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies for parenteral or oral use not included in the Official List of Medications that are acquired, at the Central or local level, and are in equal conditions, as a tie-breaking mechanism, priority will be given to the medication that is registered and consumed in any of the following countries: United States (FDA), Canada, Japan, Switzerland, Germany, England, Sweden, France, Italy, Spain, Belgium, Denmark, Austria, Holland, Finland, Norway. The supplier must present certification issued by the highest regulatory authority of the country confirming that it is registered and consumed in one of the aforementioned countries, and that upon the Cancer Council's request regarding bioequivalence requirements and the requirements for medications called biotechnological-origin antineoplastics, the mechanism established at the Ministry of Health and CCSS is continued. <b>In turn, through agreement number 1445 of June 10, 2009, the Costa Rican Social Security Fund (Caja Costarricense del Seguro Social) established the requirements to be met for the registration of suppliers of biotechnological medications, which was published in La Gaceta 127 of July 2, 2009</b>. In said regulation, regarding the obligations that registered suppliers and suppliers to be registered in the CCSS Supplier Registry must meet for biological-origin medications of Group 1 and/or Group 2, it provides that they must comply with the mandatory requirements for those suppliers participating in the Fund (Caja) with medications that do not have a Sanitary Registration of the Medication (Registro Sanitario del Medicamento) and for which the medication must be imported under Article 117 of the General Health Law of Costa Rica (Ley General de Salud de Costa Rica), or with medications with a transit code. Said groups being, number one corresponding to biological-origin medications, which in their manufacturing process do not use raw material from human blood products (for example, human plasma), with the supplier being required to present the following requirements: 1. Certificate of the sanitary registration (registro sanitario) of the medication issued by the Ministry of Health of Costa Rica. 2. For innovator medications, the complete qualitative-quantitative formula with the excipients used and the permitted ranges of related substances must be attached, as well as the medication characterization studies. 3. For biosimilar medications, the complete qualitative-quantitative formula with the excipients used and the permitted ranges of related substances must be attached, as well as the medication characterization studies; in addition, they must present the characterization studies of the medication compared with the reference medication marketed in Costa Rica. 4. Medications that in their manufacturing process do not use blood product raw material, but whose formulation and qualitative formula confirms that they contain excipients of human plasma such as albumin, must comply with all current guidelines established in the Blood Products Executive Decree No. 19981-S of October 3, 1990. 5. They must comply with the quality specifications established in the official technical data sheet corresponding to each medication. 6. The Supplier Registry of the Laboratory of Standards and Quality of Medications and the Central Pharmacotherapy Committee clearly establishes that only biological products that are or are not registered with the Ministry of Health of Costa Rica, but are consumed in the following countries, are approved: United States (FDA), and/or countries of the European Community (EMEA), and/or Canada, and/or Japan, and/or Switzerland. 7. In the case of innovator medications, the manufacturing laboratories must present Free Sale Certificates of the medication in the country of origin, such as the United States, European Economic Community, Canada, Japan, Switzerland, issued by the regulatory health authority of that country. 8. In the case of biosimilar medications, the manufacturing laboratories must present Free Sale Certificates of the medication in the country of origin, such as the United States, European Economic Community, Canada, Japan, Switzerland, issued by the regulatory health authority of that country, as well as a certificate issued by the same health entity guaranteeing that the medication meets the quality criteria requested for biological medications and that it has the clinical studies of safety and efficacy that gave rise to its sanitary registration (registro sanitario) in the country of origin, that it has clinical studies of immunogenicity, safety, and efficacy, in the same official indications as the reference product marketed in the country, as well as the characterization and comparability studies demonstrating that the product is biosimilar to the reference product marketed in Costa Rica. In addition, the complete qualitative-quantitative formula with the excipients used and the permitted ranges of related substances must be attached, along with the certification from the health authority (EMEA and/or FDA) accrediting it as a biosimilar medication. 9. All documents requested to be issued abroad (other countries) must be consular-processed and presented in Spanish. 10. The Institution, based on the extensive clinical experience acquired over the years with the use of biological medications, reserves the right to determine criteria on some specifications and requirements to be evaluated for the inclusion of new medications sharing the same code in the supplier and unregistered medication registry; and only approves the interchangeability of biological products that have documented proven safety and efficacy through their clinical use in the Institution over the years. And regarding group 2 of biological-origin medications, it is stated that these are those that use in their manufacturing process raw material from human blood products (for example, human plasma), and the supplier must meet the following requirements: 1. Certificate of the Sanitary Registration of the Medication issued by the Ministry of Health of Costa Rica. 2. Attach the complete qualitative-quantitative formula with the excipients used and the permitted ranges of related substances. 3. Must comply with the Quality Specifications specified in each corresponding technical data sheet for each medication. 4. Must comply with all the regulations requested by the Ministry of Health of CR and everything requested by the CCSS Laboratory of Standards and Quality of Medications regarding blood products. 5. The Supplier Registry of the Laboratory of Standards and Quality of Medications and the Central Pharmacotherapy Committee clearly establishes that only biological products that are or are not registered with the Ministry of Health of Costa Rica, but are consumed in the following countries, are approved: United States (FDA), and/or countries of the European Community (EMEA), and/or Canada, and/or Japan, and/or Switzerland. 6. All documents requested to be issued abroad (other countries) must be consular-processed and presented in Spanish. 7. The Institution, based on the extensive clinical experience acquired over the years with the use of biological medications, reserves the right to determine criteria on some specifications and requirements to be evaluated for the inclusion of new medications sharing the same code in the supplier registry; and only approves that it has documented proven safety and efficacy through their clinical use in the Institution over the years. 8. The manufacturing laboratory must guarantee that the human plasma used as raw material in the manufacture of each of the biological medications must come from healthy human beings and be entirely free of viruses or other pathogens; it must comply with the current guidelines established in the Blood Products Executive Decree No. 19981-S of October 3, 1990. <b>Subsequently, by agreement of March nine, 2010, published in La Gaceta number 47 of March 09, 2010, approved by agreement CCF-0275-02-10 (session 2010-05) of the Central Pharmacotherapy Committee</b>, the specific conditions for the acquisition of medications called antineoplastics and other medications for specific use in oncological and hemato-oncological pathologies are reformed, establishing the following points: Point 1: For antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies, the certification issued by the General Medical Directorate (Dirección Médica General) of the General or Oncological Hospital or Cancer Institute of the country of origin of the manufacturing laboratory must be presented, signed by the highest authority in medical oncology and the General Medical Director of the Medical Center, indicating the annual quantity consumed by patients of the medication manufactured by said laboratory, the number of beds in that hospital for adults and the occupancy rate (for parenteral medications), and the number of oncology and onco-hematology consultations (for oral medications). All information must correspond to the same year in which it is registered with the Fund (Caja) or preferably to the year prior to the registration date. When the analysis is carried out by the CCSS, if the drug has consumption in the General or Oncological Hospital or Cancer Institute of the country of origin equal to or greater than 100% of that consumed at the Hospital Nacional San Juan de Dios, it will be determined with a comparative study of defined daily dose (DDD) per 100 hospital beds/day for parenteral medications, and with a comparative study of defined daily dose (DDD) per 1000 consultations/day for oral medications, the supplier approval (aval de oferente) will be given and it will be incorporated into the Registry at the Fund (Caja). In the case of suppliers that are National Laboratories, based on a comparative study of defined daily dose (DDD) per 100 hospital beds/day (parenteral medications) or 1000 consultations/day (oral medications) taking the Hospital San Juan de Dios as a reference, if the result is equal to or greater than the DDD study from the year prior to the medication's registration with the Fund (Caja), the supplier approval (aval de oferente) will be given and it will be incorporated into the Registry at the Fund (Caja). For the case of national laboratories, the information related to consumption at the Hospital San Juan de Dios (national reference hospital) will be obtained through the internal information mechanisms available at the institution. Point 2: The specific medication (oral or parenteral) for which its entry into the Fund's (Caja) supplier registry is requested for its registration, or the medication to be acquired at the Central or Local level, will present certification issued by the Medical Directorate (Dirección Médica) of the General or Oncological Hospital or Cancer Institute of the country of origin of the manufacturing laboratory, signed by the highest authority in medical oncology and the General Medical Director of the Medical Center, presenting the annual consumption in patients corresponding to the same year, efficacy and safety results obtained with the use of the medicinal product in the treatment of patients with hemato-oncological pathology and the type of oncological pathologies treated. The documents must contain, in a complete and concrete manner, the type and percentage of side effects presented by patients who have received treatment with said product for its analysis. Point 3: Certification from the Ministry of Public Health or the equivalent highest public health authority in the country of origin of the manufacturing laboratory presented by its representative, recognizing the General or Oncological Hospital or Cancer Institute requesting to be registered. Point 4: Any certification requested must be presented individually and the information must refer to the most recent previous year closest to the date of its inclusion in the CCSS Supplier Registry for medications included in the Official List of Medications (Lista Oficial de Medicamentos), or correspond to the most recent previous year closest to the tender when it involves medications not included in the Official List of Medications (Lista Oficial de Medicamentos) and are acquired at the Central or local level. These certifications must be updated each time the renewal of registration is requested before the CCSS for medications included in the LOM; if not registered, each time a purchase is made at the Central or local level for non-LOM medications. Point 5: All requested documents must have the signatures of health authorities duly authenticated, as required by Costa Rican legislation, in addition to completing the chain of consular legalization of our country and ratified by the Ministry of Foreign Affairs of Costa Rica. Point 6: Those antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies for parenteral or oral use that are registered and consumed in any of the following countries will be exempted from the requirements stated in points 1, 2, 3, and 4: United States (FDA), Canada (Health Canada), Japan (MHLW), Switzerland (Swissmedic), Germany, England, Sweden, France, Italy, Spain, Belgium, Denmark, Austria, Holland, Finland, Norway. It is important to note that laboratories must present the certificate of free sale of their product in the United States (FDA), Canada, Japan (MHLW), Switzerland (Swissmedic), Germany, England, Sweden, France, Italy, Spain, Belgium, Denmark, Austria, Holland, Finland, Norway; or with registration and marketing in these same countries. Similarly, those medications whose origin does not correspond to any of the countries listed above, but which have the Mutual Recognition certificate issued by the EMEA for their marketing in any of the reference member states of the European Union, will be exempted. That certificate must be issued by the highest competent regulatory authority in public health of the respective country. Point 7: The supplier who is already registered in the CCSS supplier registry can revalidate their registration by presenting the information indicated in the corresponding points above. Said registration will be valid until the expiration of the sanitary registration (registro sanitario) issued by the Ministry of Health of Costa Rica. Point 8: Those suppliers who are registered but prefer to submit their data at the time of the purchase process and not revalidate the registration with the CCSS until its expiration, must present the requirements for antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies for each purchase process. Point 9: In the case of the acquisition of antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies included in the Official List of Medications (LOM), the Medications and Clinical Therapeutics Area attached to the Pharmacoepidemiology Directorate will be responsible for carrying out the analysis of the data and the corresponding Defined Daily Dose (DDD) study. Point 10: In the case of non-LOM antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies acquired by each center, the analysis of the data and the corresponding Defined Daily Dose (DDD) study will be carried out each time a purchase process is initiated, and will be performed and analyzed by each Pharmacy Service. Point 11: Once the Executive Decree of the Ministry of Public Health regulating the Medication Registry is published, the specific requirements for molecular target therapy products are contemplated therein; these requirements are based on the ICH recommendations and form part of these conditions.

Point 12: In the case of bids for antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies for parenteral or oral use not included in the Official List of Medications that are acquired, at the Central or local level, and are under equal conditions, as a tie-breaking mechanism, priority will be given to the medication that is registered and consumed in any of the following countries: United States (FDA), Canada, Japan, Switzerland, Germany, England, Sweden, France, Italy, Spain, Belgium, Denmark, Austria, Holland, Finland, Norway. The bidder must present certification issued by the highest regulatory authority of the country stating that it is registered and consumed in one of the aforementioned countries. In response to the request from the Cancer Council regarding bioequivalence requirements and requirements for medications called biotechnological antineoplastics, the mechanism established by the Ministry of Health and the CCSS shall continue. <b>Subsequently, the Central Pharmacotherapy Committee, in session 2011-08 held on February 23, 2011, analyzed Point 6 of the requirements for medications called antineoplastics and other medications for specific use in oncological and hematological pathologies published in <i>La Gaceta</i> Nº 47 of March 9, 2010</b>, agreeing to modify it, leaving it as follows: " <i>The requirements set forth in points 1, 2, 3, and 4 shall be waived for those antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies for parenteral or oral use, that have marketing authorization in any of the following countries: United States (FDA), Canada (Health Canada), Japan (MHLW), Switzerland (Swissmedic), Germany, England, Sweden, France, Italy, Spain, Belgium, Denmark, Austria, Holland, Finland, Norway, Colombia (INVIMA), Argentina (ANMAT), Brazil (ANVISA). It is important to note that laboratories must present: the certificate of pharmaceutical product (or Certificate of Free Sale plus the Certificate of Good Manufacturing Practices), as support for their registration and marketing authorization in the United States (FDA), Canada, Japan (MHLW), Switzerland (Swissmedic), Germany, England, Sweden, France, Italy, Spain, Belgium, Denmark, Austria, Holland, Finland, Norway, Colombia (INVIMA), Argentina (ANMAT), Brazil (ANVISA). Likewise, those medications whose origin does not correspond to any of the countries listed above, but that have the Mutual Recognition certificate for their marketing in any of the reference member states (European Union), shall be exempted. This certificate must be issued by the highest competent regulatory authority in public health of the respective country. To exempt them from the requirements listed in points 1, 2, 3, and 4, it is necessary that the certificates of pharmaceutical product (or Certificate of Free Sale) include the name and address of the manufacturing plant, which must coincide with the address of the manufacturing plant of the medication registered with the Ministry of Health of Costa Rica (provided that the medication is registered in the country). The manufacturing plant (name and address) from which the registered medication with marketing authorization in one of the countries listed above originates, must correspond to the same manufacturing plant from which the medication to be delivered to the CCSS will be imported</i> ". <b>For its part, the technical regulation called Registration and Control of Biological Medications, number 37006 of November 15, 2011</b>, established that its regulations govern the requirements and procedures necessary for the registration and control of biological medications for human use and apply to all products of this type, whether produced in the national territory or imported (article one). In said regulation, in its fifth article, it was established regarding the sanitary registration (registro sanitario) of biological medications, " <i>that when the presentation of any of the studies or documents mentioned in this Regulation is not scientifically applicable, the applicant must present the justification for its assessment by the Ministry of Health, establishing that for the sanitary registration of biological medications, a dossier must be submitted following the format and content established in article 27 of Decree Nº 28466-S of February 8, 2000 “Regulation for the Registration, Control, Import, and Advertising of Medications”</i>, <i>published in La Gaceta Nº 42 of February 29, 2000, and its amendments or the current sanitary registration regulations. Information on the regulatory status of the product at the international level must be presented: A list of Health Authorities that have registered the product as of the date of the application before the Ministry of Health and those that have conducted inspections in the last two years at the laboratories manufacturing the finished products. In addition to information regarding safety and efficacy for biological medications. The scientific documentation presented, referring to the conclusive reports of clinical studies, must have been prepared in a period not exceeding ten years. In the event that the aforementioned studies were conducted more than 10 years ago, the applicant must present the justification for its assessment by the Ministry of Health. All conclusive reports of clinical studies must refer to the same product and pharmaceutical form that is presented for its sanitary registration. For biological products containing active ingredients not included in the formulation of a product previously registered in Costa Rica: i) In the case of products containing chemical entities not included in the formulation of a previously registered product: • Conclusive reports of the results of preclinical studies (including information on in vivo and in vitro pharmacodynamic parameters). • Conclusive reports of the results of Phase I, II, and III clinical studies (including pharmacokinetic, pharmacodynamic studies, and immunogenicity studies). ii) In the case of pharmaceutical products containing chemical entities included in previously registered products whose active ingredient corresponds to new derivatives, such as pegylated or others, they must submit: • Conclusive reports of the results of Phase I, II, and III clinical studies. For biological medications containing active ingredients included in the formulation of a product previously registered in Costa Rica but that present: i) New fixed combinations of active ingredients: • Conclusive reports of the results of Phase I, II, and III clinical studies. Such reports must compare the existing and new proportion or dose, including bioavailability studies. ii) New pharmaceutical form with an already registered route of administration: • Conclusive reports of the results of bioavailability studies. iii) New pharmaceutical form with a new route of administration: • Conclusive reports of the results of preclinical studies and Phase I, II, and III clinical studies. iv) New pharmaceutical form with a new release form: • Conclusive reports of the results of Phase I, II, and III clinical studies. v) New potencies or concentrations of previously registered active ingredients: • Conclusive reports of the results of bioavailability studies and Phase II and III clinical studies. vi) New routes of administration with an already registered pharmaceutical form: • Conclusive reports of the results of bioavailability and Phase II and III clinical studies. 5.5. In addition to the requirements mentioned in the preceding numeral, for the registration of biological medications, the documents established in the following sections must be attached to the dossier in the order in which they are mentioned. For recombinant DNA or biotechnological medications, the following must be submitted: 5.6.a. Quality information related to the physicochemical, biological, and immunological properties of the active ingredient: i) Description, chemical structure, amino acid sequence, post-translational modifications, physicochemical, biological, and immunological properties. ii) Description of the manufacturing process, in-process controls, cell substrate control, control of critical stages and intermediate products, and process validation. iii) Description of the methodology for characterization, including description of the chemical structure and product-related and process-related impurities and contaminants. iv) Description of the controls for the active ingredient, including specifications, analytical methods, and validation of analytical methods. v) Description of the reference standards or materials. vi) Description of the container-closure system. vii) Description and results of the stability study. 5.6.b. Quality information related to the physicochemical, biological, and immunological properties of the finished product: i) Description of the product and its composition. ii) Description of the manufacturing process, in-process controls, control of critical stages and intermediate products, and process validation. iii) Description of quality control, including specifications, analytical methods, validation of analytical methods, analysis of the results of the lots used for the specifications, characterization of impurities and contaminants, and justification of the specifications that guarantee batch-to-batch uniformity. When more than one manufacturer is involved, indicate at which step each one intervenes. iv) Description of the reference standards or materials. v) Description of the safety assessment against infections by adventitious agents. Details on viral inactivation and elimination. vi) Risk management plan and post-marketing pharmacovigilance (farmacovigilancia). NOTE 1: These requirements apply to the innovator medication, and in the case of biosimilars, they must additionally present the biosimilarity exercise related to quality in comparison with the reference biological medication, to determine that the differences do not have implications for its safety and efficacy. The submitted documentation must specify the name of the medication for which it intends to be a biosimilar and the name of the laboratory that manufactures it. NOTE 2: The biosimilarity exercise must be conducted for both the finished product and the active ingredient, as detailed in numeral 5.12., and for this purpose, the international guidelines of the WHO shall be followed, and in their absence, those issued by the FDA, EMA, or ICH may be used. Notwithstanding the foregoing, the guidelines of other countries may be adopted as official, once the Ministry of Health verifies that they are internationally accepted and they are made official by Administrative Resolution that shall be published in the Official Gazette La Gaceta, along with the instructions, forms, and any other corresponding document, and placed on the web page of the Ministry of Health. 5.7. For blood products (hemoderivados) and vaccines, the manufacturing method must be submitted, which must contain the following information: 5.7.a. Master formula, including batch size. 5.7.b. Description of the starting materials of biological origin such as: strains, cell lines, microorganisms, plasma donations or blood components, cells or cell substrates, and culture media. Including: quality control specifications, validated analysis methods, and methods for the exclusion of adventitious agents. 5.7.c. Description of the manufacturing process: i) Manufacturing flow diagram indicating process controls, and when more than one manufacturer is involved, indicating at which step each one intervenes. ii) Complete description of the entire process, manufacturing methods, and their controls. Information on the fermentation, harvest, and purification steps, if applicable to the product's manufacture, including acceptance and rejection criteria. iii) Process control specifications and analytical methods issued by the manufacturer, which must be validated. iv) Reprocessing criteria for each stage. v) Quality specifications that include the characterization and purity of the product obtained at each stage and the analytical techniques used for its verification. vi) Description of the double viral inactivation processes, agent used, and method to verify the effectiveness of the process, as applicable. vii) Document in which the manufacturer indicates that its manufacturing process achieves, for all manufactured lots, a maximum reduction of prion infectivity, in accordance with the current state of knowledge. 5.7.d. Analytical certificates must contain the quality specifications of the Active Ingredient(s), Auxiliary Substance(s), In-Process Product, Finished Product, and Reference Material(s). The analytical results of the medication components must be expressed in units of weight, or biological activity as appropriate. These certificates must include: i) Name of the substance or product. ii) Manufacturing stage, in the case of in-process products. iii) Date and place of manufacture. iv) Batch number. v) Batch size. vi) Physical, chemical, biological, and microbiological quality parameters with their limits and results. vii) Expiration date, when applicable. viii) Date and place of analysis, name of the person responsible for the analysis, and decision of conformity according to the specifications. ix) Reference to the official method used or indication that the manufacturer's validated method was used. 5.7.e. Risk management plan and post-marketing pharmacovigilance. 5.8. For blood products, in addition to the information from numerals 5.3., 5.4., and 5.7., the following requirements must be submitted: 5.8.a. Certificate of current sanitary registration of the product issued by the FDA, the EMA, or any other competent health authority that performs the Certification of the Plasma Master File (PMF) after the corresponding scientific and technical evaluation has been conducted. 5.8.b. Information on the selection and control of donors. 5.8.c. Description of the procedures used to guarantee the traceability of the finished product back to the donors and vice versa. This description must be accompanied by a detailed diagram. 5.8.d. Results of the tests performed to detect HIV 1 and HIV 2 antibodies, hepatitis C antibodies, and the ELISA or RIA test for hepatitis B that detects 0.5 IU per ml of HBs antigen or less. 5.8.e. Information on the centers where plasma is obtained, location of the plasma collection centers, information on the inspections conducted at said centers, and on the quarantine policy. Detail the type of plasma obtained (donation or plasmapheresis), the type of donation (altruistic or remunerated), seroconversion percentage data for habitual donors, and marker data in the first donation. Also include information on the storage and transport conditions of the plasma established by the manufacturer. 5.9. For vaccines, in addition to the information from numerals 5.3., 5.4., and 5.7., the following must be submitted: 5.9.a. Clinical studies on reactogenicity and immunogenicity and on efficacy. The lack of efficacy studies must be justified. 5.9.b. Information on the Cell Bank Systems: i) Preparation, description, and controls performed on the Master Cell Bank (MCB) and Working Cell Bank (WCB). ii) Description of the controls used to verify the absence of adventitious agents. iii) Description and characterization of stabilizers, adjuvants, and preservatives. iv) Nucleic acid sequence of the strain and its comparative study with other strains, including vaccine strains. 5.10. For combined vaccines, in addition to the information from numerals 5.3., 5.4., and 5.7., the following requirements must be submitted: 5.10.a. Clinical studies on reactogenicity and immunogenicity. 5.10.b. Information on the Cell Bank Systems: i) Preparation, description, and controls performed on the Master Cell Bank (MCB) and Working Cell Bank (WCB). ii) Description of the controls used to verify the absence of adventitious agents. iii) Description and characterization of stabilizers, adjuvants, and preservatives. 5.10.c. Information on the characterization and controls of each individual antigen, which must meet the same requirements established for their use in single vaccines. 5.10.d. Information on the tests performed after the combination to study the possible interaction between the antigens. 5.10.e. Information about the effects of adjuvants and preserving agents on the stability and activity of the finished product. 5.10.f. Studies of reactogenicity and immunogenicity that demonstrate safety in comparison with that of the vaccines administered separately but simultaneously. 5.11. For antivenoms and antitoxins of animal origin, the manufacturing method must be submitted, which must contain the following information: 5.11.a. Master formula, including batch size. 5.11.b. Description of the starting materials of biological origin such as: venoms and plasma or blood components. Including: quality control specifications, validated analysis methods, and methods for the exclusion of adventitious agents. 5.11.c. Information on the control of the venom lots used for the immunization of the donor animal. i) Certification signed by the biological regent of the snake species used in venom extractions for the immunization mixtures, including the scientific and common names of the snakes used. This certification must include a minimum of 10 specimens used per species for each venom lot and the extraction date. ii) Flow diagram describing the handling and storage of the venom mixtures for immunization, including storage conditions. iii) Results of biological and biochemical tests that certify the consistency of the venoms (specifically, HPLC chromatographic profile and LD50 toxicological activity). 5.11.d. Information on the plasma lots obtained from the immunized animals: i) Information on endotoxin tests, neutralizing potency of the plasma mixture for one lot, and protein content. ii) Information on the venoms used in the immunization, bleeding dates, immunization dates, and identification of the horses for a specific lot. iii) Identification profile of the horses participating in a specific plasma lot, with their respective breed, sex, age, and weight. 5.11.e. Description of the manufacturing process: i) Manufacturing flow diagram indicating process controls, and when more than one manufacturer is involved, indicating at which step each one intervenes. ii) Complete description of the entire process, manufacturing methods, and their controls. Information on the purification steps, including acceptance and rejection criteria. iii) Process control specifications and analytical methods issued by the manufacturer, which must be validated. iv) Reprocessing criteria for each stage. v) Quality specifications that include the characterization and purity of the product obtained at each stage and the analytical techniques used for its verification. vi) Description of the double viral inactivation process(es), agent used, and method to verify the effectiveness of the process, as applicable. vii) Document in which the manufacturer indicates that its manufacturing process achieves, for all manufactured lots, a maximum reduction of prion infectivity, in accordance with the current state of knowledge. This applies to those antivenoms or antitoxins derived from animals in which prion infectivity has been demonstrated. 5.11.f. Analytical certificates must contain the quality specifications of the Active Ingredient(s), Auxiliary Substance(s), In-Process Product, Finished Product, and Reference Material(s). The analytical results of the medication components must be expressed in units of weight, or biological activity as appropriate. These certificates must include: i) Name of the substance or product. ii) Manufacturing stage, in the case of in-process products. iii) Date and place of manufacture. iv) Batch number. v) Batch size. vi) Physical, chemical, biological, and microbiological quality parameters with their limits and results. vii) Expiration date, when applicable. viii) Date and place of analysis, name of the person responsible for the analysis, and decision of conformity according to the specifications. ix) Reference to the official method used or indication that the manufacturer's validated method was used. 5.11.g. Risk management plan and post-marketing pharmacovigilance. 5.12. Regarding the information related to safety and efficacy, and for biosimilar medications not previously registered in Costa Rica and for biosimilars already registered, the biosimilarity exercise must be submitted, which includes: 5.12.a. Preclinical studies (in vitro and in vivo) that must be comparative in nature and designed to detect significant differences between the biosimilar and the reference innovator biological. 5.12.b. Comparative clinical studies with the reference biological medication for each of the indications requested. The following must be submitted: i) Pharmacokinetic studies. ii) Pharmacodynamic studies. iii) Clinical efficacy studies. iv) Safety studies. v) Immunogenicity studies. The type and quantity of studies will depend on the knowledge available on the reference biological medication and the therapeutic indications being requested; for this, international guidelines shall be followed, and in their absence, those issued by the FDA, EMA, and ICH may be used on a case-by-case basis. 5.12.c. Letter of approval for the clinical studies indicated in this regulation, issued by the Scientific-Ethical Committee(s), duly legalized or apostilled. Said committees must be recognized by the health authority of the country where these studies were conducted. 5.12.d. Risk management plan and post-marketing pharmacovigilance. Any specific safety monitoring imposed on the reference product must be considered in the risk management plan of the biosimilar product. 5.12.e. Detail on the criterion used to select the reference biological product with which the biosimilarity exercise was conducted. For this, the sequence of criteria from numeral 6 of this Regulation must be used. 6. SELECTION OF THE REFERENCE BIOLOGICAL MEDICATION: The criteria for selecting the reference biological medication in order of priority are as follows: 6.1. The first choice must always be the innovator product manufactured in the first country of origin, which has a complete dossier on its quality, efficacy, and safety, provided that it is the same one registered and marketed in Costa Rica. 6.2. The second choice must always be the innovator product manufactured, registered, and marketed in Costa Rica. 6.3. The third choice must be the innovator product manufactured in an alternate origin, registered, and marketed in Costa Rica. 6.4. The fourth choice, and in the event that the previous conditions are not met, the reference product may be chosen from the innovator product manufactured in the first country of origin or alternate origin, or the reference product suggested in the WHO lists, even if it has not been marketed in Costa Rica. To define the reference product through the application of this numeral, a written consultation must be made with the Directorate of Health Regulation of the Ministry of Health. 6.5. The fifth choice, and in the event that the previous conditions are not met, corresponds to the market-leading product that has demonstrated its quality, efficacy, and safety. To define the reference product through the application of this numeral, a written consultation must be made with the Directorate of Health Regulation of the Ministry of Health. 7. POST-REGISTRATION CHANGES OF BIOLOGICAL MEDICATIONS: For any change associated with the biological medication that is contemplated in the Guide for post-registration changes published on the web page of the Ministry of Health, the specific requirements established in said Guide must be submitted according to the type of change to be made. 8. RENEWAL OF THE SANITARY REGISTRATION 8.1. For the renewal of the sanitary registration of the biological medications described in this regulation, a dossier must be submitted with the requirements established in article 34 of Decree Nº 28466-S Regulation for the Registration, Control, Import, and Advertising of Medications, published in La Gaceta Nº 42 of February 29, 2000, and its amendments or the current sanitary registration regulations, also attaching, in the event they have not been presented in previous registration procedures, the requirements established in this regulation. 8.2. For biosimilar medications that have not presented it in previous procedures, they must submit the biosimilarity exercise that contemplates what is established in this regulation. 9. LOT RELEASE OF BIOLOGICAL PRODUCTS. The Customer Service Directorate (Dirección de Atención al Cliente) will authorize the release of each lot of biological products (with the exception of biotechnological products, which by their nature are not subject to lot-by-lot release) once the correspondence between the documentation of the registration dossier and the following requirements is verified: 9.1. Lot Release Certificate issued by the regulatory authority of the producing country. For national laboratories, the Ministry of Health will review its files to verify compliance with this requirement. 9.2. Summarized manufacturing protocol and certificate of the manufacturer's release test results, and in the case of blood derivatives of human origin or medications that contain them, the certificate must include that the product is free of HIV virus, cytomegalovirus, parvovirus B19, and hepatitis B and C viruses. 9.3. Letter of commitment, from the manufacturer, the product holder, or their legal representative, guaranteeing compliance at all times with the storage conditions established on the labeling of the imported lot, from the manufacturing laboratory to the drugstore (droguería) in Costa Rica. NOTE: The lot release procedure for biological medications by the Customer Service Directorate of the Ministry of Health will be carried out at the importing drugstore or at the national manufacturing laboratory within a period of 5 business days counted from the notification to the Ministry of Health. 10. CONTROL OF BIOLOGICAL MEDICATIONS. 10.1. What is stated in the registration declarations and compliance with the required requirements will be carried out by the Directorate of Health Regulation, through inspection and sampling of the market, at the pharmaceutical laboratory, or at customs, in accordance with the provisions of the General Health Law and the Law for the Promotion of Competition and Effective Consumer Defense.

The first quality control performed on biological medicinal products will be carried out on the first marketing batch, without prejudice to the post-marketing verification and inspection controls that the Directorate of Health Regulation (Dirección de Regulación de la Salud) may eventually order. 10.2. For control purposes, the manufacturer of the biological medicinal product or its holder must submit to the Ministry of Health (Ministerio de Salud) the updates of the reports generated pursuant to the Risk Management and Pharmacovigilance Plans, which will form part of the product file before the Ministry of Health. 10.3. In the event that non-compliance or falsity of what was declared in the registration before the Ministry of Health is demonstrated, the health authority shall detain, seize, or withdraw the respective product from circulation, or cancel its registration, as appropriate, after prior notification to the legal representative, who must assume the costs of the applied health measure. The foregoing is without prejudice to other sanctions established by the Law for the Promotion of Competition and Effective Consumer Defense (Ley de Promoción de la Competencia y Defensa Efectiva del Consumidor). The Ministry of Health shall proceed with the application of these special measures based on the provisions of Article 386 of the General Health Law (Ley General de Salud), without detriment to the civil or criminal liability incurred by the natural or legal persons responsible for such non-compliance and without prejudice to any other sanction that may be applicable in accordance with current legislation. ". For its part, the Regulation for the Registration, Control, Importation, and Advertising of Medicinal Products, number 28466 of February 8, 2000, established the pertinent regulations for the registration, control, importation, and advertising of medicinal products, governing all persons who manufacture, import, and market medicinal products in the national territory (section 2 ibid). Furthermore, this regulation defines Bioavailability as the rate and extent to which the active ingredient or active fraction of a pharmaceutical dosage form is absorbed and becomes available at the site of action, Bioequivalence: as the relationship between two pharmaceutical products that are pharmaceutically equivalent and whose bioavailability, in terms of rate and degree, after being administered at the same molar dose under the same conditions, are similar to such a degree that their effects would be essentially the same, Good Manufacturing Practices: as the set of rules and procedures aimed at guaranteeing the uniform production of batches of pharmaceutical products that meet the quality requirements demanded by user needs, certificate of analysis: as the certificate indicating the specifications and results of the physical, chemical, biological, microbiological, and biopharmaceutical analyses of a pharmaceutical product, issued by a national or foreign laboratory that, in the judgment of the Ministry, guarantees its identity and quality, certificate of Good Manufacturing Practices: as the document issued by the health authority of the country of origin, certifying that the laboratory to which it refers satisfactorily complies with the Good Manufacturing Practices requirements in force in that country for the pharmaceutical dosage form to which the product belongs. These requirements must at a minimum meet WHO standards equivalent to those of the regulations in force in Costa Rica. In the case of beta-lactams, cytotoxics, hormones, and biologicals, the certificate must specifically declare that the manufacturing laboratory is authorized for the manufacture of those pharmaceutical products, Certificate of Free Sale: as the document issued by the regulatory authority or authority responsible for the registration of pharmaceutical products in the country of origin or provenance, duly legalized, certifying that the pharmaceutical product to which the certificate refers has its registration in force and is authorized for sale or distribution in that country. In the case of third-party manufacture, it may be from the country where the holder or party responsible for marketing the product is located, Certificate of a Pharmaceutical Product: the certification proposed by the World Health Organization (WHO) and issued by the Regulatory Authority (Autoridad Reguladora) of the country or region of origin or provenance as part of the certification system for the quality of pharmaceutical products subject to international trade. In the case of third-party manufacture, the certificate of a pharmaceutical product must be issued by the Regulatory Authority (Autoridad Reguladora) of the country of the product holder. For subsidiaries, the certificate of a pharmaceutical product may be issued by the Regulatory Authority (Autoridad Reguladora) of the country of the manufacturer or the holder, and as a Manufacturing Contract: the legal document entered into between the holder of the medicinal product and the manufacturer, establishing the conditions, commitments, and other circumstances for the manufacture of one or more products; and which must indicate at a minimum: 1) The existing contractual relationship between the parties involved. 2) That the contractor complies with Good Manufacturing Practices. 3) That the contractor has from the contracting party all the necessary information to carry out the contracted actions, as well as the processes they must implement for the medicinal product subject to the contract. 4) That the contracting party will conduct periodic audits of the contractor. Also defined is the Pharmaceutical equivalent: A pharmaceutical product containing identical quantities of the same active ingredients as the product to which it is equivalent, for example, the same salt or ester of the active ingredient, in identical pharmaceutical dosage forms, meeting established specifications, but not necessarily containing the same excipients. Consequently, two pharmaceutical equivalents may exhibit different bioavailabilities and pharmacological activities, and Therapeutic equivalence: referring to two pharmaceutical products that are therapeutically equivalent if they are pharmaceutically equivalent and after administration at the same molar dose, their effects regarding efficacy and safety will be the same, as determined by appropriate in vivo bioequivalence, pharmacodynamic, and clinical studies and/or in vitro dissolution studies. The term Biological pharmaceutical product is further conceptualized: as a pharmaceutical product obtained from living organisms or their tissues, and the Sanitary registration (Registro sanitario) as an administrative act through which it is established that the pharmaceutical product to be registered meets the sanitary requirements of current regulations regarding quality, efficacy, and safety and that, therefore, it may be marketed in the country. For its part, section four provides that the functions of the technical body, established in Article 113 of the General Health Law (Ley General de Salud), centralized henceforth in the Directorate of Customer Service (Dirección de Atención al Cliente), shall be the approval or denial of the registration of any product referred to in this Regulation, and the Directorate of Health Regulation (Dirección de Regulación de la Salud) shall be responsible for establishing or approving the technical pharmacological standards governing the evaluation of medicinal products and the list of multi-source pharmaceutical products of sanitary risk. For these purposes, it is provided in section 24 of decree 28466, that the Ministry of Health must publish on its website a list of sanitary registration (registro sanitario) applications in process within a maximum period of 15 working days from the receipt of the application and must publish a list of pharmaceutical products that have been granted a sanitary registration within a maximum period of 15 working days from the issuance of the sanitary registration. Regarding applications for sanitary registration of multi-source pharmaceutical products, the following must be provided: a) An application for which no information on safety and efficacy is submitted must be considered by the Ministry as an application for the registration of a multi-source pharmaceutical product. The Ministry may only grant sanitary registration to a multi-source pharmaceutical product that is a pharmaceutical equivalent: i) Of a pharmaceutical product for which safety and efficacy data have previously been submitted to the Ministry by its applicant and for which a sanitary registration has previously been granted in Costa Rica. ii) Of a pharmaceutical product that meets all of the following conditions: a) That it is not protected by patents, b) That it does not contain protected test data, c) That it contains a chemical entity present in the formulation of a product that has previously obtained a sanitary registration in Costa Rica, d) That the applicant demonstrates, through a document issued by a regulatory authority, that the active ingredient has been authorized for marketing in any country for more than 5 years; and e) That international information exists guaranteeing the safety and efficacy of the pharmaceutical product before the Ministry of Health. The foregoing to guarantee access to medicinal products of sanitary interest. b) Applicants requesting a sanitary registration for a multi-source pharmaceutical product must indicate in the application the name of the pharmaceutical product previously registered in the country with which the applicant's product is a pharmaceutical or therapeutic equivalent, as well as the expiration date of any protected test data and any patent covered by the pharmaceutical product previously registered in the country, in accordance with the information contained in the databases of the Ministry of Health. c) The Ministry shall not, without the consent of the legitimate holder of the test data submitted to the Ministry in support of an application for sanitary registration of a new pharmaceutical product, grant sanitary registration to the applicant of a multi-source pharmaceutical product, based on: i) That test data; or ii) The sanitary registration granted to that new pharmaceutical product, before the expiration of the protection period of said test data. d) The applicant for a sanitary registration of a multi-source pharmaceutical product or its legal representative may request that the Ministry review the test data submitted in support of an application for sanitary registration for a new pharmaceutical product as evidence and support for its sanitary registration application, in the cases established in Chapter XI of this Regulation. In turn, regarding applications for a sanitary registration of a new pharmaceutical product, a sworn statement must be submitted, issued before a notary public, indicating any product or process patent granted and in force in Costa Rica covering the pharmaceutical product, indicating the patent number and its expiration date. Applicants or their legal representative may update this list to include patents granted after the sanitary registration application. However, these updates shall not suspend the processing or granting of the sanitary registration for applications already submitted, nor shall they affect sanitary registrations already granted. The Ministry must publish on its website, for each pharmaceutical product to which a sanitary registration has been granted, the list of product or process patents in force in the country covering said pharmaceutical products, according to the information provided by the applicant or its legal representative. The Ministry must include this information on its website within a maximum period of 15 working days from the receipt of said information. The Ministry shall publish in said list the number and expiration date of each patent submitted by an applicant or its legal representative. In the case of first-time sanitary registration applications for multi-source pharmaceutical products, when the applicant cannot meet any of the requirements established in subparagraphs i) or ii), the applicant or its legal representative must submit a sworn statement issued before a notary public indicating that no patent granted and in force in Costa Rica claims the pharmaceutical product subject to sanitary registration, or, if such patents exist, the expiration or expiry date of the patent or patents claiming it, and indicating that the multi-source pharmaceutical product shall not be marketed until after the expiration date of said patents. The applicant or its legal representative must indicate in its sworn statement issued before a notary public that it has reviewed the Ministry's website for the purpose of verifying this information. In such case, the Ministry shall not issue the sanitary registration to the applicant until after the expiration of the protection period of all patents claiming the multi-source pharmaceutical product for which sanitary registration is sought, according to the information provided by the applicant or its legal representative, or the test data protection period, whichever is later, except as established in Chapter XI of this Regulation. For its part, section 27 stipulates the requirements for obtaining a sanitary registration for the first time, for which a sanitary registration application file shall be opened. Regarding the control of medicinal products, Article 50 ibid states that post-registration verification shall be carried out by the Directorate of Health Regulation (Dirección de Regulación de la Salud), through inspectors designated for this purpose, through inspection and sampling in the market, at the pharmaceutical laboratory, or at customs, in accordance with the provisions of the General Health Law (Ley General de Salud), Law No. 5395 of October 30, 1973; and the Law for the Promotion of Competition and Effective Consumer Defense (Ley de Promoción de la Competencia y Defensa Efectiva del Consumidor), Law No. 7472 of December 20, 1994; and other applicable regulations, and the first quality control performed on pharmaceutical products shall be carried out during the first year of marketing, without prejudice to the controls eventually ordered by the Directorate of Health Regulation (Dirección de Regulación de la Salud).

**VIII- REGARDING THE ALLEGED PROCEDURAL DEFECT OF THE REGULATORY ADMINISTRATIVE ACTS, DUE TO THE ABSENCE OF THE HEARING PROVIDED FOR IN SECTION 361 OF THE GENERAL LAW OF THE PUBLIC ADMINISTRATION (Ley General de la Administración Pública).** As indicated in previous recitals (considerandos), the Constitutive Law (Ley Constitutiva) of the Costa Rican Social Security Fund (Caja Costarricense del Seguro Social) in its section 72 mandates that it must establish and keep updated a registry of product suppliers. Under that norm, the Costa Rican Social Security Fund (Caja Costarricense del Seguro Social) issued, through agreement CCF-1445-06-209, session 2009-21 of June 10, 2009, the Regulation with Requirements for the Registration of Suppliers for Biotechnological Medicinal Products (Normativa con Requisitos para el Registro de Oferentes para Medicamentos Biotecnológicos), published through Gazette 127 of July 2, 2009, which, through agreement 3376-11-10, session 2010-44 of November 17, 2010, the Central Pharmacotherapy Committee (Comité Central de Farmacoterapia) of the Institution proceeded to repeal all previous agreements issued on that regulation, establishing the following Regulation with Requirements for the Registration of Suppliers for Biotechnological and Biological Medicinal Products (Normativa con Requisitos para el Registro de Oferentes para Medicamentos biotecnológicos y biológicos), which was stated to be directed at registered suppliers and suppliers to be registered in the CCSS Supplier Registry for biological medicinal products of Group 1 and Group 2 listed therein, imposing mandatory compliance also for those suppliers participating with the Fund with medicinal products that do not have a Sanitary Registration for the Medicinal Product (Registro sanitario del Medicamento). Likewise, the Central Pharmacotherapy Committee (Comité Central de Farmacoterapia) of the Costa Rican Social Security Fund (Caja Costarricense del Seguro Social), through agreement CCF-0275-02-09, session 2009-21 published in March 2009, issued the Specific Conditions for the Acquisition of Medicinal Products Designated as Antineoplastics and Other Medicinal Products for Specific Use in Oncological and Hemato-Oncological Pathologies, which through session 2011-08 of February 23, 2011, of the Central Pharmacotherapy Committee (Comité Central de Farmacoterapia) proceeded to modify point 6. The plaintiff party first submitted substantive arguments and concluded both its action brief and its conclusions with arguments aimed at highlighting the existence of a formal defect in the regulation in its capacity as an administrative act of a general nature. Therefore, this Panel of Judges clarifies that it is then pertinent, first, to begin the study of the procedural arguments; subsequently, if necessary, in order to fully understand the rest of the plaintiff's claims, substantive considerations will be addressed. Thus, it is established that the plaintiff party alleges the lack of the hearing mandated by section 361 of the General Law of the Public Administration (Ley General de la Administración Pública) for the adoption of provisions of a general nature, which in its view is an element of validity, and its omission implies its absolute nullity. The representation of the defendant maintains that such a requirement is not applicable to the scientific-technical provisions and/or guidelines issued by the Central Pharmacotherapy Committee (Comité Central de Farmacoterapia), since what is provided for in section 361 of the General Law of the Public Administration (Ley General de la Administración Pública) is for the preparation of provisions of a general nature in the strict sense by the Executive Branch that, in the exercise of its executive regulatory power, deems necessary to adopt; that is, such a requirement, in the opinion of its represented party, is not applicable to technical regulations adopted by technical advisory bodies as in this case. In order to address the arguments of both parties, it is important to clarify some concepts. Citizen participation and the doctrine of the glass house in the exercise of public function establish as a maxim that, except in very exceptional situations, the participation of inhabitants must be allowed, both through the display of decisions and through the possibility of challenging them. If public action presents its due basis, the Administration has no reason to fear expressing the proper justifications for its various acts. Now, by Regulation (Reglamento) we must understand any legal provision of a general nature issued by the Public Administration and with a value subordinate to the law; it is one of the manifestations of the exercise of administrative function, through the creation of a normative body of a lower degree and subject to the law, but with the authority to create legal effects. The regulation develops a law upon which its validity depends. The regulation is a norm, hence its dual condition. The regulatory power is founded on the need to generate norms whose approval, repeal, or modification procedure is sufficiently expeditious to ensure agile resolution mechanisms for the ordinary activity inherent to the Administration, while the law, in its approval process, is slower due to the dynamics of parliament and also cannot foresee all the situations that may be faced in each specific case when exercising public competences. Such power results in the issuance of an administrative act of a general nature called a regulation, subject to certain formal and substantial limits. Regarding its classification, the Constitutional Chamber (Sala Constitucional) has ruled in the following terms: " **IV.-** **OF THE AUTONOMOUS REGULATIONS OF SERVICE AND ORGANIZATION.** It is alleged that through regulations, which do not meet the characteristics of an executive regulation, nor of an autonomous service or organization regulation, matters proper to formal law are regulated, by establishing limitations on fundamental rights, concerning the creation of sanctioning administrative bodies and the establishment of sanctions; in addition to not being issued by the respective hierarchical body, but by the provider of the National Bank of Costa Rica. In order to analyze the consulted regulation, it is necessary to recall what this Constitutional Court has previously indicated regarding the different categories or types of regulations that are constitutionally possible: "The categories in which regulations are distinguished are: a.) implementing regulations: which tend to carry out the concrete execution of laws, especially when they are of a rather generic scope; b.) independent or autonomous regulations from any legislative provision, relating to matters under the competence of the Executive Branch not regulated by law, or partially regulated. Among these may figure the so-called organization regulations, which refer to the institution and structure of various public offices. Derived from the foregoing, the proper subject matter of regulations can be defined: **administrative matter** , which includes the organizational aspects of the Public Administration (Administración Pública) -understood as the Executive Branch in the performance of its own functions-. Therefore, there is an impediment to regulate matters referring to the rights and obligations of citizens as such, the limitation of their liberty or their rights -including the regime of taxes, penalties, and fundamental rights- via regulation. These concepts have already been indicated by this Chamber on repeated occasions, through resolution number 1876-90, at sixteen hours on December nineteenth, and number 1635-93, at seventeen hours on November fourteenth, among others." (Judgment number 5227-94, at fifteen hours six minutes on September thirteenth, nineteen ninety-four.) By virtue of the foregoing, the content of independent regulations or autonomous regulations can be clearly differentiated from executive ones, as they are characterized by regulating the own competence of their author –the Administration– and of the lower authorities, as they aim to organize and regulate the activity of their author and subordinates, to achieve better fulfillment of the assigned public purpose. They are of two types: autonomous organization regulations and autonomous service regulations. The former find their basis in the power of self-organization of the administration itself, and the latter have their support in the competence of the administrative head to regulate the provision of the service under their charge, without the need for a prior law on the matter. These are regulations that create special subjection regimes and come to limit the rights of the administered citizens who have entered into a relationship with the Administration." **Vote number 2000-2856 of 15:48 hours on March 29, 2002.** In reality, the autonomous regulatory act is reserved for aspects of organization and operation, where not even the law can establish certain limitations. This led to the generation of the *interna corporis* act doctrine, as the power of self-organization of public powers. The national Constitution clearly develops the subject of the executive regulation and the power of organization regulation. The subordination of the latter to the former is clear, given that the national legal system does not establish matters reserved for regulatory norms. Regarding the procedure for the formation of regulations, the General Law of the Public Administration (Ley General de la Administración Pública), in its section 361, mandates that in the preparation of provisions of a general nature: "1. A hearing shall be granted to decentralized entities regarding draft general provisions that may affect them. 2. Entities representative of general or corporate interests affected by the provision shall be given the opportunity to express their opinion, within a period of ten days, unless reasons of public interest or urgency, duly recorded in the preliminary draft, oppose this. 3. When, in the judgment of the Executive Branch or the Ministry, the nature of the provision so advises, the preliminary draft shall be submitted for public information, during the period specified in each case." . From the study of the second paragraph of said norm, several legal prerequisites that must be met are observed, such as dealing with the process of creating a general norm, affecting general or corporate interests by denying, aggrieving, suppressing, or limiting subjective rights and/or direct legitimate interests, and dealing with entities representative of them. It is not superfluous to indicate that the General Agreement on Tariffs and Trade (GATT) and the Uruguay Round, both legal norms ratified by Costa Rica and having supremacy over domestic laws, consider that any regulatory norm that implicitly or directly implies a restriction on trade conditions (non-tariff barriers) must be consulted prior to its entry into force. This allows for harmony between the legal norm and those established in international regulations. Regarding the first requirement of being a general norm, we must indicate that the administrative act produces individual or concrete effects (resolutions and administrative agreements) and collective or general types (decrees and regulations), by addressing indeterminate subjects.

Regarding the impact on general or corporate interests, these refer to private or public entities that, through their management, represent the community, the population, or a corporation, which constitutes <i>"a duly formed, personified, and organized collective organization that represents and defends the interests of a determinable group or sector of people (e.g., chambers, associations, professional bodies) (...)</i><i>". </i>Jinesta Lobo, Ernesto. Tratado de Derecho administrativo. Tomo tercero, San José, Costa Rica, editorial jurídica Continental, 2007, page 244. Regarding the procedure, the First Chamber of the Supreme Court of Justice, in vote number 10 of 14:20 hours on January 22, 2002, ordered that <i>"IIIº The General Law of Public Administration devised a special procedure for the preparation of provisions of a general nature, which are administrative acts of normative scope. In the specialty adopted by the legislator, lies the answer to the questions raised by the sub judice case, regarding the value that the hearing process has within that special process. A simple reading of the articles regulating that special procedure reveals that it was devised precisely to enshrine the hearing process, in some cases, for entities of the state conglomerate itself (Article 361, paragraph 1), and in others, for entities -it makes no distinction between public and private- representative of interests of a general or corporate nature affected by the provision (Article 361, paragraph 2). From this, the value and significance of the hearing in the procedure for preparing general provisions is indisputable, this being a substantial, unavoidable formality, unless the exceptional circumstances provided for in the same norm occur. This obligation, in the indicated special procedure, constitutes the legislative development of norms that, as general principles, inform the administrative procedure. Articles 217, 218, and 220, in relation to 239 and subsequent articles, of the General Law of Public Administration, provide for the necessary intervention of the administered party in the procedure. In the absence of individualized subjects who could be considered directly interested parties in the adoption of regulatory acts, the legislator provided that in such cases the transfer, the hearing, must be given to entities representative of corporate or general interests.</i>". By virtue thereof, the cited hearing process is recognized as a necessary requirement for unavoidable validity and effectiveness, of legal and supra-legal roots, in the special procedure for creating administrative norms of a general nature. In accordance with the foregoing, the hearing that must be granted is an essential requirement of the procedure, which is founded on constitutional principles not only of due process but also of the citizens' right of participation, as our Constitutional Court has repeatedly established in its rulings: <b><i>II.- </i></b> <b><i>ON CITIZEN PARTICIPATION. The participation of citizens in public decision-making is provided for in Article 9 of the Political Constitution, thereby acquiring the rank and force of a fundamental constitutional right. This is not a deconstitutionalization of the principle of legality of the Public Administration, although it is certainly a more democratic form of government, which broadens the forums for debate on different issues affecting the community, and which, by virtue thereof, are open to citizen intervention and opinion. We are, then, facing an option already widely accepted in the evolution of the concept of democracy, and this amparo offers a magnificent opportunity to give it clear and effective force, so that it does not remain mere discourse. The cited precept, then, embodies the mentioned principle through access to available information and its dissemination, so that decision-making is not limited to a restricted group of interests. In this way, and in accordance with our democratic system, ARESEP is obliged to convene such a hearing, particularly to guarantee the right of defense and access to information that concerns each and every one of our country's inhabitants, so that decisions are not made unexpectedly for the "affected" interested parties. Precisely, in the ARESEP Law and its regulations, the legislator provided for a special administrative procedure, which is the public hearing whose main characteristic is to provide transparency in the decisions of the Regulatory Entity and the possibility of giving participation to consumers and users within the process. Likewise, by providing the opportunity for neighbors, social organizations, the state and private sector, citizen defense institutions, and other government institutions to participate, greater benefit is achieved, which facilitates a better exchange of information among participants, making the hearing a transcendental instrument in decision-making and an instrument of transparency in a democratic system like ours. By virtue of the foregoing, the setting or modification of tariffs must be submitted to a public hearing in which those citizens who present an opposition based on technical criteria may participate, giving the interested party the right to exercise the use of the floor at the holding of the respective act for the purpose of defending their interest in the matter. In this way, the public hearing that the Regulatory Authority of Public Services must conduct in those cases where it processes a study for setting tariffs for public services, is intended to allow the exercise of the community's right to participation in a matter that directly affects them, prior to the making of the administrative decision, and, in that manner, constitutes a manifestation of the democratic principle. This hearing aims to allow interested persons to state whatever they deem appropriate regarding the tariff-setting application under study before the Regulatory Authority, therefore the rigor required for procedures seeking the suppression of a subjective right is not applicable (judgment 2002-08848 of sixteen hours fifty-seven minutes on September ten, two thousand two); however, it is not a simple formal requirement, such that it can be set in a way that nullifies the exercise of the right it intends to protect, by being granted under conditions that prevent or hinder the fulfillment of the objectives it is meant to achieve, in protection of the right to information and citizen participation</span></i></b>…” <b><i>III.- </i></b> <i>In conclusion, it is clear that in order to guarantee the right of citizen participation provided for in Article 9 of the Political Constitution, the public hearing that the Regulatory Authority of Public Services must conduct in those cases where it processes a study for setting tariffs for public services must allow the exercise of the community's right to participation in a matter of its interest and must be given within a reasonable timeframe that allows the community to express itself. As such, the appropriate course of action is to uphold the claim filed for violation of the right of citizen participation and to annul the convocation made by the Regulatory Authority of Public Services to hear a tariff increase proposed by COOPEMORAVIA, to increase the tariff for route 40MB, described as San José-Moravia-Ramales and common corridors of routes 40, 41, 42, and 43 processed in case file ET-29-2010." Ruling: 10708 of June 18, 2010.

**IX- ON THE SPECIFIC CASE.** It remains, then, to establish the type of general provision constituted by the administrative acts challenged herein and whether the hearing, in accordance with numeral 361 of the General Law of Public Administration, had to be granted prior to their adoption. From the foregoing, it is concluded that the Caja Costarricense del Seguro Social effectively issued said regulations under the protection of section 72 of its Constitutive Law, and that the regulations issued are indeed of a technical nature. Given the body that issued them, they do not constitute executive regulations, but rather independent and highly sui generis regulations. Regarding the act issued through agreement 3376-11-10, session 2010-44 of November 17, 2010, the Institution's Central Pharmacotherapy Committee proceeded to repeal all previous agreements issued for that regulation, establishing the following Regulation with Requirements for the Registration of Suppliers for Biotechnological and Biological Medicines, issuing a new regulation. From the review of the content of said regulation, we find that the requirements, in reality, are not for the supplier as such, but rather regarding the product, group 1 medicines of biological origin whose manufacturing process does not use raw material from blood products, and group 2 of biological origin that use blood product raw material in their manufacturing process - understood according to point 4.53 of executive decree 37006, as that obtained by industrial procedures, whose raw material is human blood or plasma, which, according to the experts who testified in the oral and public trial (Julián Cuesta Ramírez, Renato Murillo Masis, and Albín Chávez Matamoros), are highly complex in their production and used for very specific and serious diseases. From the review of this regulation, it is extracted that for both group 1 and group 2 medicines, technical requirements are imposed for innovative, biosimilar, biological, and biotechnological medicines, among others; certificates in their manufacturing and production process, etc. It is even provided that for the procurement of medicines, the Caja Costarricense del Seguro Social may take its clinical experience with the medicine as a qualification parameter and exempt from other technical requirements. Regarding the second challenged regulation, issued by the Central Pharmacotherapy Committee in session 2011-08 of February 23, 2011, in which it proceeded to modify point 6 of the Specific Conditions for the acquisition of medicines called antineoplastic and other medicines for specific use in oncological and hemato-oncological pathologies, issued in agreement CCF-0275-02-09, session 2009-21 published in March 2009, equally technical requirements are imposed for their supply. From the statements of all the experts received in the oral and public trial, it is concluded that medicines must indeed possess three basic elements; quality, safety, and efficacy, which are essential for the medicine to produce the effects in patients for which they were produced. The plaintiff, both for the regulation relating to biological, biotechnological, and antineoplastic medicines, argues on the merits that the reforms introduced in the challenged regulations by the Central Pharmacotherapy Committee of the Caja Costarricense del Seguro Social threaten the health and life of Costa Ricans, as there is no guarantee that said medicines have the essential elements of quality, safety, and efficacy, and they detail a series of technical queries. From the meticulous review of said regulations, technical requirements are indeed established, or they are exempted with respect to the previous regulation for the purchase of medicines, requirements that are ultimately used to fulfill the public purpose entrusted to the institution, public health. It must not be lost sight of that, without entering into the merits of the process, these provisions are aimed at regulating the requirements that medicines must meet for their purchase. These medicines are relied upon by a large number of people in our country to protect not only their health but to preserve and rescue their lives; regulations that evidently contain provisions that must guarantee public health, which inevitably makes the discussion of its rules a matter of public interest, because the effects of said provisions, although initially a parameter for the purchase of medicines, their implicit objective is precisely to safeguard the health of all patients who attend public health centers in our country seeking to improve and preserve their health and their lives, therefore, the effects of these regulations are not subject to a matter of the Institution's internal organization, but clearly to a matter of Public Health. General provisions must not only be classified according to the body that issues them but also according to their effects and to whom they are directed; in the specific case of the challenged regulations, the final objective is the guarantee of the medicines provided to patients. Therefore, in the opinion of this Collegiate Body, the challenged rules are independent technical regulations, although not executive, due to the effects of their application and compliance, meaning their interest cannot only be subject to organizations or groups, natural or legal persons engaged in the production, distribution, and marketing of medicines, but to every person in guarantee of a fundamental right to health and life as also protected by our Political Constitution, thus it is not possible to accept the position held by the defendant's representation that, being a technical regulation, it does not require the procedure established in the General Law of Public Administration. On the contrary, due to the technical matter it regulates, it was required, for its formation, to grant the hearing provided for in numeral 361 of the cited law. It cannot be overlooked that this hearing aims at the participation of citizens in public affairs, provided that the subject matter regulated in such regulations, as in those challenged here, is of public interest, as in the present case the right to life and health. Continuing with the analysis of the special procedure for the elaboration of provisions of a general nature, other norms and general principles that regulate the administrative procedure can be cited, an interpretation that is possible in accordance with Article 229, paragraph 1, of the General Law of Public Administration, which reads as follows: <i>"This Book shall govern the procedures of the entire Administration, except as otherwise provided." For its part, ordinal 223 stipulates that the nullity of the proceedings shall be caused by the omission of substantial formalities of the procedure. 2. A formality shall be understood as substantial if its correct execution would have prevented or changed the final decision in important aspects, or whose omission caused defenselessness." </i> Clarity must be maintained, as indicated above, regarding the purpose of the hearing provided for in numeral 361 of the General Law of Public Administration, because given the effects entailed by the challenged regulations, the hearing is essential, not only for organizations like the plaintiff, but also for professional bodies, medicine and pharmacy professionals who can provide essential information on the quality, safety, and efficacy of medicines, as well as the technical requirements needed for their procurement, and even more so, for administrative bodies, such as the Ministry of Health. In this regard, the General Health Law, in its numeral 102, states that the importation of medicines and their distribution shall only be permitted to legal or natural persons registered with the Ministry, with prior authorization and registration with the College of Pharmacists, which reinforces this Court's position on the mandatory nature of said hearing. Numeral 106 of the General Health Law imposes that a medicine can legally be destined for commerce, public use, and consumption when it meets the regulatory requirements or those of the pharmacopoeia officially declared by the Executive Branch regarding its identity, quality, safety, and efficacy for the purposes for which it is used, consumed, or prescribed, and an additional element, the full knowledge and acceptance of the Caja Costarricense del Seguro Social, which its representative states in the response to the lawsuit (folio 239, final paragraph of the main case file) where it manifestly states “<i>that for the purposes of the registration of biotechnological medicines, even though there is no regulation from the Ministry of Health of Costa Rica, the Central Pharmacotherapy Committee, until the regulation issued by the governing body exists, has been visionary and, in order to maintain the principles of Safety and Efficacy in the medicines recognized in the Suppliers Registry of my client</i>”, which absolutely confirms the opinion of this Collegiate Body on the mandatory nature of granting the hearing prior to the issuance of the challenged regulations, since, knowing that the governing body in the matter had not issued the specific regulation regarding the sanitary registration of said medicines, the legal hearing was necessary, timely, and convenient, so that the public governing body in the matter could issue a pronouncement. Note that the reforms made in 2010 to the Regulation with Requirements for the Registration of Suppliers for Biotechnological and Biological Medicines and in early 2011 to the Specific Conditions for the acquisition of medicines called antineoplastic and other medicines for specific use in oncological and hemato-oncological pathologies, are very close to the year 2011 when Executive Decree 37006-S is issued, which Regulates the Registration and Control of Biological Medicines, which means that on those dates the technical regulation that the defendant misses from the governing body in the matter was being developed. For when the challenged regulations were issued, there is no doubt, then, that granting the hearing is a substantial formality, because a modification of the final act may arise from such action. Precisely, the hearing aims to provide the opportunity for the entity or affected party to influence the will of the Administration, before it acts in accordance with its regulatory powers. Failure to comply with the hearing process, which is not discretionary but mandatory, is necessarily linked to the validity of the general provision issued (as the culmination of the procedure) and, consequently, its omission can cause invalidity, thereby determining the nullity of all actions taken by the Administration in relation to the issuance of the challenged regulatory provisions. Consequently, the omission of the hearing by the defendant in the adoption of the challenged regulations constitutes a substantial defect in the procedure for their issuance, it not being viable in this case to make any distinction regarding the validity of any parts of the challenged acts, as the defect, being of a procedural nature, affects the integrity of the acts. Consequently, the absolute nullity is declared of the following acts of a general nature: 1- Agreement CCF- 3376-11-10, session 2010-44 issued on November 17, 2010, by the Central Pharmacotherapy Committee of the Caja Costarricense del Seguro Social, published in the Official Gazette La Gaceta number 10 of January 14, 2011, and 2- Agreement taken in session 20011-08, held on February 23, 2011, by the Central Pharmacotherapy Committee, by means of which it reforms point 6 of the Specific Conditions for the acquisition of medicines called antineoplastic and other medicines for specific use in oncological and hemato-oncological pathologies, for lacking a formal prerequisite of validity. It should be noted that although the plaintiff makes a prolific argument for the nullity of these norms under different aspects, having upheld one of them, it is devoid of any interest to expressly rule on the remaining ones; however, it is appropriate to advise the public entity that it must be clear about which competencies are its own, with respect to those reserved for the Ministry of Health as the governing body in the matter. So that both agencies must coordinate the fulfillment of their public purposes, but without the invasion of one into the other.

In that regard, we draw attention to how matters pertaining to the sanitary registration, the exception to this, fall under the purview of the Ministry, a topic that must not be lost sight of.

The Institution, based on the extensive clinical experience acquired over the years with the use of biological medications, reserves its judgment on certain specifications and requirements to be evaluated for the inclusion of new medications that share the same code in the registry of suppliers and unregistered medications; and exclusively endorses the interchangeability of biological products that have documented safety and efficacy proven through their clinical use in the Institution over the years." (See folios 224 and 225 of the administrative file); **4-** In the second (2) Group of Medications of biological origin, the supplier had to present the following requirements: "1. Certificate of the Sanitary Registration of the Medication issued by the Ministry of Health of Costa Rica. 2. Attach the complete qualitative-quantitative formula with the excipients used and the permitted ranges of related substances. 3. Must comply with the Quality Specifications specified in each corresponding technical data sheet for each medication. 4. Must comply with all regulations required by the Ministry of Health of CR and everything required by the CCSS Laboratory of Standards and Quality of Medications regarding blood products (hemoderivados). 5. The Supplier Registry of the Laboratory of Standards and Quality of Medications and the Central Pharmacotherapy Committee clearly establishes that only biological products are endorsed, whether or not they are registered with the Ministry of Health of Costa Rica, but which are consumed in the following countries: United States (FDA), and/or countries of the European Community (EMEA), and/or Canada, and/or Japan, and/or Switzerland. 6. All documents requested that are issued abroad (other countries) must be consularized and presented in the Spanish language. 7. The Institution, based on the extensive clinical experience acquired over the years with the use of biological medications, reserves its judgment on certain specifications and requirements to be evaluated for the inclusion of new medications that share the same code in the registry of suppliers; and only endorses that which has documented safety and efficacy proven through its clinical use in the Institution over the years. 8. The manufacturing laboratory must guarantee that the human plasma used as raw material in the manufacture of each of the biological medications must come from healthy human beings and be entirely free of viruses or other pathogens; it must comply with the current guidelines established in the Blood Products Decree No. 19981-S of October 3, 1990." (see folio 226 of the administrative file); **5-** Said agreement was published in the official newspaper La Gaceta number 127 of July 02, 2009 (see folio 222 of the administrative file); **6-** The Central Pharmacotherapy Committee, through session 2010-44, agreement 3376-11-10 of November 17, 2010, proceeded to modify the regulations with requirements to be met for the registration of suppliers of biotechnological and biological medications, issuing new regulations, which were published in gazette number 10 of January 14, 2011 (see folios 230 to 239 and 264 of volume II of the administrative file); **7-** The aforementioned regulations were approved in the following terms: "In this first Group of Medications (Group 1) of biological origin, the supplier must present the following requirements: 1. Certificate of the sanitary registration of the medication issued by the Ministry of Health of Costa Rica. 2. For innovative medications, the complete qualitative-quantitative formula must be attached with the excipients used and the permitted ranges of related substances, as well as the characterization studies of the medication (physicochemical and pharmacological). 3. For biosimilar medications, the complete qualitative-quantitative formula must be attached with the excipients used and the permitted ranges of related substances, as well as the characterization studies of the medication (physicochemical and pharmacological). 4. Medications whose manufacturing process does not use blood product raw materials but whose formulation and qualitative formula prove they contain human plasma excipients such as albumin, must comply with all current guidelines established in the Blood Products Decree No. 19981-8 of October 3, 1990. 5. Must comply with the quality specifications established in the official technical data sheet corresponding to each medication. 6. All suppliers of biological or biotechnological medications who need to prequalify before the Supplier Registry or offer their products to the Institution must present a certificate that such medications are registered and/or marketed in any of the following countries: United States (FDA), Canada (Health Canada), Japan (MHLW), Switzerland (Swissmedic), and member countries of the European Economic Community that are registered with the European Medicines Agency (EMA) or that have Mutual Recognition in any of the reference member states of the European Economic Community. These countries are considered reference countries because they have high standards in medication regulation. 7. All documents requested and issued abroad must be consularized and certified by a notary public, as required by Costa Rican legislation and our country's chain of consular legalization, and ratified by the Ministry of Foreign Affairs. All documents must be presented in the Spanish language, and if in another language, the official translation of the original document into Spanish must be attached. 8. "The Institution, based on the extensive clinical experience acquired over the years with the use of biological medications, reserves its judgment on certain specifications and requirements to be evaluated, not only for the inclusion of new medications that share the same code in the registry of suppliers and unregistered medications, but also for their acquisition, technically endorsing the interchangeability of biological products that have documented safety and efficacy, proven through their clinical use in the Institution over the years. For biological medications (same manufacturing laboratory) that have been historically acquired and consumed at the Institutional Level, with proven experience of use and support for their efficacy and safety, it is permissible to exempt them from the requirements established in point 6, without prejudice to compliance with the rest of the established requirements. Suppliers of biological medications (same manufacturing laboratory) with which there is historical Institutional use experience and that would be exempted from the requirements indicated in point 6 must attach the free sale certificate of the medication in the country of origin of the manufacturing laboratory, complying with what is indicated in point 7". Regarding the second Group of Medications (Group 2) of biological origin, the supplier must present the following requirements: "1. Certificate of the Sanitary Registration of the Medication issued by the Ministry of Health of Costa Rica. 2. Attach the complete qualitative-quantitative formula with the excipients used and the permitted ranges of related substances. 3. Must comply with the Quality Specifications indicated in each corresponding technical data sheet for each medication. 4. Must comply with all regulations required by the Ministry of Health of CR and everything required by the CCSS Laboratory of Standards and Quality of Medications regarding blood products. 5. All suppliers of biological or biotechnological medications who need to prequalify before the Supplier Registry or offer their products to the Institution must present a certificate that such medications are registered and/or marketed in any of the following countries: United States (FDA), Canada (Health Canada), Japan (MHLW), Switzerland (Swissmedic), and member countries of the European Economic Community that are registered with the European Medicines Agency (EMA) or that have Mutual Recognition in any of the reference member states of the European Economic Community. These countries are considered reference countries because they have high standards in medication regulation. 6. All documents requested and issued abroad must be consularized and certified by a notary public, as required by Costa Rican legislation and our country's chain of consular legalization, and ratified by the Ministry of Foreign Affairs. All documents must be presented in the Spanish language, and if in another language, the official translation of the original document into Spanish must be attached. 7. "The Institution, based on the extensive clinical experience acquired over the years with the use of biological medications, reserves its judgment on certain specifications and requirements to be evaluated, not only for the inclusion of new medications that share the same code in the registry of suppliers and unregistered medications, but also for their acquisition, technically endorsing the interchangeability of biological products that have documented safety and efficacy, proven through their clinical use in the Institution over the years. For biological medications (same manufacturing laboratory) that have been historically acquired and consumed at the Institutional Level, with proven experience of use and support for their efficacy and safety, it is permissible to exempt them from the requirements established in point 5, without prejudice to compliance with the rest of the established requirements. Suppliers of biological medications (same manufacturing laboratory) with which there is historical Institutional use experience and that would be exempted from the requirements indicated in point 5 must attach the free sale certificate of the medication in the country of origin of the manufacturing laboratory, complying with what is indicated in point 6". 8. The manufacturing laboratory must guarantee that the human plasma used as raw material in the manufacture of each of the biological medications must come from healthy human beings and be entirely free of viruses or other pathogens; it must comply with the current guidelines established in the Blood Products Decree No. 19981-8 of October 3, 1990. These requirements are mandatory for any new biotechnological or biological medication of group 1 or group 2 that is included in the LOM" (see folios 236 to 239 of the administrative file volume II); **8** - Through agreement CCF-0275-02-09, session 2009-21, the Central Pharmacotherapy Committee of the Caja Costarricense del Seguro Social established the specific conditions for the acquisition of medications called antineoplastics and other medications for specific use in oncological and hemato-oncological pathologies, published in gazette number 47 of March 9, 2010 (see folios 266 and 267 verso of the administrative file); **9-** The cited general act was ordered in the following terms: "Point 1: For antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies, certification must be submitted issued by the General Medical Directorate of the General or Oncological Hospital or Cancer Institute of the country of origin of the manufacturing laboratory, signed by the highest authority in medical oncology and the General Medical Director of the Medical Center, indicating the annual quantity consumed by patients of the medication manufactured by said laboratory, the number of beds in that hospital destined for adults and the occupancy rate (for parenteral use medications), and the number of oncology and onco-hematology consultations (for oral use medications). All information must correspond to the same year in which it is registered with the Caja or preferably to the year prior to the registration date. When the analysis is carried out by the CCSS, if the drug has a consumption in the General or Oncological Hospital or Cancer Institute of the country of origin equal to or greater than 100% of that consumed in the Hospital Nacional San Juan de Dios, it will be determined by a comparative study of defined daily dose (DDD) per 100 hospital beds/day for parenteral use medications, and by a comparative study of defined daily dose (DDD) per 1000 consultations/day for oral use medications, they will be given supplier endorsement and will be incorporated into the Registry with the Caja. In the case of suppliers that are National Laboratories, based on a comparative study of defined daily dose (DDD) per 100 hospital beds/day (parenteral use medications) or 1000 consultations/day (oral use medications) taking as reference the Hospital San Juan de Dios, if the result is equal to or greater than the DDD study of the year prior to the Registration of the medication with the Caja, they will be given supplier endorsement and will be incorporated into the Registry with the Caja. For national laboratories, the information related to consumption at the Hospital San Juan de Dios (national reference hospital) will be obtained through the internal information mechanisms available in the institution. Point 2: The specific medication (oral or parenteral) for which entry into the Caja's supplier registry is requested for its registration, or the medication to be acquired at the Central or Local level, will present certification issued by the Medical Directorate of the General or Oncological Hospital or Cancer Institute of the country of origin of the manufacturing laboratory, signed by the highest authority in medical oncology and the General Medical Director of the Medical Center, presenting the annual consumption in patients corresponding to the same year, results of efficacy and safety that have been obtained with the use of the medicinal product in the treatment of patients with hemato-oncological pathology and the type of oncological pathologies treated. The documents must contain, in a complete and concrete form, the type and percentage of side effects presented by patients who have received treatment with said product for analysis. Point 3: Certification from the Ministry of Public Health or the equivalent highest public health authority in the country of origin of the manufacturing laboratory, presented by its representative, recognizing the General or Oncological Hospital or Cancer Institute that requests to be registered. Point 4: All certification requested must be presented individually, and the information must refer to the most recent previous year closest to the date of its inclusion in the Register of medication suppliers before the CCSS when dealing with medications included in the Official List of Medications (LOM), or correspond to the most recent previous year closest to the tender when dealing with medications not included in the Official List of Medications and are acquired at the Central or local level. These certifications must be updated each time renewal of registration is requested before the CCSS for medications included in the LOM; if not registered, each time a purchase is made at the Central or local level in the case of non-LOM medications. Point 5: All documents requested must have the signatures of health authorities duly authenticated, as required by Costa Rican legislation, in addition to completing our country's chain of consular legalization and being ratified by the Ministry of Foreign Affairs of Costa Rica. Point 6: Exempted from the requirements set forth in points 1, 2, 3, and 4 are those antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies for parenteral or oral use, that are registered and consumed in any of the following countries: United States (FDA), Canada (Health Canada), Japan (MHLW), Switzerland (Swissmedic), Germany, England, Sweden, France, Italy, Spain, Belgium, Denmark, Austria, Holland, Finland, Norway. It is important to note that laboratories must present the certificate of free sale of their product in the United States (FDA), Canada, Japan (MHLW), Switzerland (Swissmedic), Germany, England, Sweden, France, Italy, Spain, Belgium, Denmark, Austria, Holland, Finland, Norway; or with registration and marketing in these same countries. Likewise, those medications will be exempted whose origin does not correspond to any of the countries listed above, but which have the certificate of Mutual Recognition issued by the EMEA for its marketing in any of the reference member states of the European Union. This certificate must be issued by the highest competent regulatory authority in public health of the respective country. Point 7: The supplier already registered in the CCSS supplier registry can revalidate its registration by presenting the information indicated in the corresponding points above. Said registration will be valid until the expiration of the sanitary registration issued by the Ministry of Health of Costa Rica. Point 8: Those suppliers that are registered but prefer to present their data at the time of the purchase process and not revalidate the registration before the CCSS until its expiration must present the requirements for antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies for each purchase process. Point 9: In the case of the acquisition of antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies included in the Official List of Medications (LOM), the Area of Medications and Clinical Therapeutics attached to the Directorate of Pharmacoepidemiology will be responsible for carrying out the data analysis and the corresponding Defined Daily Dose (DDD) study. Point 10: In the case of non-LOM antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies acquired by each center, the data analysis and the corresponding Defined Daily Dose (DDD) study will be carried out each time a purchase procedure is promoted, and will be executed and analyzed by each Pharmacy Service. Point 11: Once the Executive Decree of the Ministry of Public Health that regulates the Registration of Medications is published, which contemplates the specific requirements for molecular target therapy products, these requirements are based on ICH recommendations and form part of these conditions. Point 12: Given offers of antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies for parenteral or oral use not included in the Official List of Medications that are acquired at the Central or local level and are on equal terms, as a tie-breaking mechanism, priority will be given to the medication that is registered and consumed in any of the following countries: United States (FDA), Canada, Japan, Switzerland, Germany, England, Sweden, France, Italy, Spain, Belgium, Denmark, Austria, Holland, Finland, Norway. The supplier must present certification issued by the highest regulatory authority of the country stating that it is registered and consumed in one of the aforementioned countries. Given the request of the Cancer Council regarding the bioequivalence requirements and requirements for medications called antineoplastics of biotechnological origin, the mechanism established in the Ministry of Health and CCSS continues." (see folios 266 and 267 verso of the administrative file); **10-** Through session 2011-08 held on February 23, 2011, by the Central Pharmacotherapy Committee, point 6 was modified in the following terms: "Point 6: Exempted from the requirements set forth in points 1, 2, 3, and 4 are those antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies for parenteral or oral use, that have marketing authorization in any of the following countries: United States (FDA), Canada (Health Canada), Japan (MHLW), Switzerland (Swissmedic), Germany, England, Sweden, France, Italy, Spain, Belgium, Denmark, Austria, Holland, Finland, Norway, Colombia (INVIMA), Argentina (ANMAT), Brazil (ANVISA). It is important to note that laboratories must present: the pharmaceutical product certificate (or Certificate of Free Sale plus the Certificate of Good Manufacturing Practices), as support for their registration and marketing authorization in the United States (FDA), Canada, Japan (MHLW), Switzerland (Swissmedic), Germany, England, Sweden, France, Italy, Spain, Belgium, Denmark, Austria, Holland, Finland, Norway, Colombia (INVIMA), Argentina (ANMAT), Brazil (ANVISA). Likewise, those medications will be exempted whose origin does not correspond to any of the countries listed above, but which have the certificate of Mutual Recognition for their marketing in any of the reference member states (European Union). This certificate must be issued by the highest competent regulatory authority in public health of the respective country. To exempt them from the requirements listed in points 1, 2, 3, and 4, it is necessary that the pharmaceutical product certificates (or Certificate of Free Sale) include the name and address of the manufacturing plant, which must coincide with the address of the manufacturing plant of the medication registered with the Ministry of Health of Costa Rica (provided the medication is registered in the country). The manufacturing plant (name and address) from which the registered medication originates and has marketing authorization in one of the countries listed above must correspond to the same manufacturing plant from which the medication to be delivered to the CCSS will be imported." which was published in gazette number 58 of February 23, 2011 (see folio 310, 311 and 322 of the administrative file); **III- UNPROVEN FACTS** Of relevance for the resolution of this process, the following is considered not demonstrated: **Single**: That the defendant entity followed the procedure regulated in Article 361 of the General Law of Public Administration at the time of issuing the general provisions challenged here, and that this was accepted by the defendant itself *(there is no proof of this in the record).* **IV- REGARDING THE ARGUMENTS OF THE PARTIES** The plaintiff alleges the nullity of the agreement adopted through Session No. 2010-44 of the Central Pharmacotherapy Committee (agreement number CCF 3376-11-10 which has regulatory character), by modifying the regulations already set forth in 2009, as well as the nullity of the agreement issued in session 2011-08 of February 23, 2011, which modifies point 6 of the requirements for medications called antineoplastics and other medications for non-specific use for specific use in oncological and hematological pathologies, and that in its place, the validity of the norms that were modified be restored. To this end, it appears, according to its criteria, under the legitimacy conferred by numeral 10, subsection 2 of the Contentious Administrative Procedure Code, as a collective interest, alleging that the reform carried out by the Central Pharmacotherapy Committee of the Caja Costarricense del Seguro Social, specifically regarding the elimination of the mandatory requirements that any biotechnological or biological medication must meet to be a supplier to the Caja Costarricense del Seguro Social, affects the community and violates principles of the World Health Organization. It claims that the challenged regulations mention biological and biotechnological medications as being of the same typology, when what is intended to be regulated is biotechnological medications exclusively. In addition, the evaluation criteria for said medications are not sufficient to certify their quality. According to the challenged regulations, suppliers are exempted from presenting the characterization studies of the medication, which does not guarantee its quality by making its use more flexible without verifying compliance with the evaluation guidelines issued by recognized "strict" authorities such as the WHO and the EMA among other international organizations, which does not guarantee the safety, effectiveness, and efficacy of the medication that is essential for patients. It adds that for innovative medications, the manufacturing laboratories are exempted from presenting the free sale certificate from the country of origin. It points out that the Caja Costarricense del Seguro Social endorses the interchangeability of the medication, which threatens the health of patients since in medications of biotechnological composition, the interchangeability of chemical synthesis products cannot be compared, which could generate serious implications for the patient's health. As pharmacovigilance has not been satisfactorily and safely developed in the institution, it is not possible to monitor the effects of interchangeability for the benefit of patients' health. It also points out that the regulatory norms regarding pharmacovigilance do not contain risk analysis processes designed to address the nature of the biotechnological product. On the issue of immunogenicity, it alleges that as the pharmacovigilance process is absent, it is not possible to determine the immunogenicity of the medications, placing patients at risk. It argues the nullity of the administrative acts due to flaws in their formation by not having been consulted as established by the General Law of Public Administration for acts of general scope such as those challenged here.

At the trial hearing, it raised new facts, based on a regulation subsequently issued by the Ministry of Health, noting that the challenged acts contradict those provided for in the aforementioned act of general scope. The representation of the Caja Costarricense del Seguro Social rejects the claim. First, it questions the legal standing (legitimación) with which the plaintiff appears in the proceedings, alleging an interest on behalf of the entire community, highlighting that in its own claim it accepts that its primary interest is the impact on all the companies represented by Fedefarma, insofar as the requirements for being suppliers (oferentes) are made more flexible. Regarding the 2010 regulations for the registration of suppliers (oferentes) for biotechnological and biological medicines, the Comité Central de Farmacodependencia, in the absence of specific regulations from the Ministry of Health, is the body that must impose the requirements for suppliers (oferentes) in the medicine procurement process. Concerning medicines called antineoplastics, and other medicines for specific use in oncological and hematological pathologies, the modification refers to the incorporation of countries such as Argentina, Brazil, and Colombia, motivated by the fact that they were classified as Level IV regional reference regulatory authorities by PAHO/WHO, in the performance of their functions, and that based on the certificates from said regulatory authorities, they would be exempted from the requirements established in points 1, 2, 3, and 4. All of the foregoing was the product of a study and technical motivation by the Comité Central de Farmacoterapia, and therefore does not entail any risk to public health, since the efficacy and safety of the treatments used for cancer patients are not compromised; on the contrary, it is supported by higher standards established by PAHO/WHO. Regarding the interchangeable use of the terms biological and biotechnological, the regulations establish the requirements for supplier (oferente) registration for both. Likewise, biotechnological medicines must also have immunogenicity and pharmacovigilance studies. It is also established in the regulations under discussion that biosimilar medicines must attach the complete qualitative-quantitative formula with the excipients used and the permitted ranges of related substances, as well as medicine characterization studies. Regarding the issue of immunogenicity, it alleges that the country does not have the capacity to carry out this type of studies; however, it has an active pharmacovigilance program of spontaneous notifications. It argues that internationally there is no real consensus on the interchangeability of biotechnological products; however, the Social Security institution has extensive clinical experience in the use of biotechnological medicines, where the therapeutic benefit in the management of various pathologies has been documented. Regarding the procedural defect (vicio procedimental) pointed out by the plaintiff, concerning the absence of the hearing provided for in numeral 361 of the Ley General de la Administración Pública, it states that the formal defect is not applicable, because it pertains to acts of a general nature issued by the Executive Branch, not by autonomous Institutions such as the defendant here, coupled with the fact that the general provisions issued are technical regulations adopted by technical advisory bodies such as the Comité de Farmacoterapia of the Caja Costarricense del Seguro Social in its capacity as a technical advisor. It raises the defense of Lack of Active Legal Standing (Falta de Legitimación Activa), accusing the plaintiff of fundamentally having a commercial interest, and not seeking to enforce the rights of the community, and Lack of Right (Falta de Derecho). It requests that the claim be declared without merit.

V- ON THE REPRESENTATION OF THE PLAINTIFF PARTY IN THE PROCEEDINGS.

By resolution issued at thirteen hours and fifteen minutes on October third, two thousand thirteen, this Collegiate Body, in accordance with numerals 66 subsection b and 92 subsection 1 of the Código Procesal Contencioso, warned the plaintiff to provide to the proceedings the legal capacity (personería) of the Federación Centroamericana de Laboratorios Farmacéuticos (FEDEFARMA), to indicate if it is registered in the papis, its validity, and if not, to present duly legalized documents proving its constitution, existence, validity, and representation. The foregoing was due to the fact that from the review carried out by this Panel of Judges, only the document on page 40, the registry inscription of a power of attorney of Mr. Rodolfo Antonio Lambour Chocano as legal representative of the plaintiff, was found to have been contributed to the proceedings. The plaintiff contributed to the proceedings the documents found on pages 482 to 528 and 566 to 572, in which the constitution and inscription of the plaintiff in the Republic of Guatemala are indeed recorded, as well as the appointment of Mr. Rodolfo Antonio Lambour Chocano as legal representative of the plaintiff, a person who effectively registered his representation and power of attorney for the aforementioned Federation in our country, who in turn granted special judicial power of attorney to attorneys Carlos Ubico Durán and Alejandra Castro Bonilla, who have been conducting the proceedings. This being the case, let the procedural defect be considered corrected and the plaintiff be considered duly represented in the proceedings.

VI- REGULATIONS GOVERNING MEDICINES AND POWERS OF THE CAJA COSTARRICENSE DEL SEGURO SOCIAL IN THE MATTER OF MEDICINE PROCUREMENT: Hospital medical care service is a proper public service insofar as it is executed by a Hospital Center or a Health Care Center (clinic, evais, etc.); those that are under the dependence of the Caja Costarricense de Seguro Social. This Entity, by constitutional provision, is responsible for ensuring (planning, developing, executing, etc.), among other things, everything related to Social Security, and included within it, the health care service. Thus, ordinal 75 of our Constitución Política states in the relevant part: "Social insurance is established for the benefit of manual and intellectual workers, regulated by a system of mandatory contributions from the State, employers, and workers, in order to protect them against the risks of illness, disability, old age, death, and other contingencies that the law determines. The administration and governance of social insurance shall be in charge of an autonomous institution, called Caja Costarricense de Seguro Social...". In such a way that social security is elevated to constitutional rank, which naturally includes the field of health care, thereby constituting an unavoidable mandate that requires the State, through the aforementioned Institution -CAJA COSTARRICENSE DE SEGURO SOCIAL-, to procure in the most efficient manner possible the care and treatment of that important sector of social security, that is, the field of health. It is worth emphasizing from the outset the preponderance that the Caja Costarricense de Seguro Social acquires in this aspect, as the Entity expressly entrusted by constitutional provision to carry out, as previously commented, the administration and governance of social insurance; this point has been the subject of treatment by our Sala Constitucional, thus in vote number 6256-94, in what interests us it established: ". .b) the norm exclusively grants the Caja Costarricense de Seguro Social the administration and governance of social insurance, a degree of autonomy that is, of course, different and superior to that defined generally in article 188 ibid..." On the other hand, it is worth saying that this right to health, today we can define it from a legal perspective as: " the set of mandatory precepts that recognize individuals' rights concerning their health and that regulate their conduct regarding all those matters in which the health of the person and the group comes into play". Health as such can be defined as established in the preamble of the Constitution of the World Health Organization (WHO): "Health is a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity." Notwithstanding its transcendental importance, this right is not expressly enshrined in our Constitución Política, as we will see below. We consider it essential to link the aforementioned constitutional article 73, due to its fundamental content, with a norm that allows it to be complemented, from the perspective that interests us in this study, namely numeral 21 of the cited Constitution; said norm provides: "Article 21.- Human life is inviolable." When speaking here of "Human life", reference is not made exclusively to the right to life in the strict sense, but reference is also made to its "health" dimension, meaning the norm does not literally refer to protecting only human life in a restricted sense, but in a broad sense, to the state of "health", as a basic presupposition of life itself, which is inherent to life as such, therefore, given its consubstantial relationship, this "right to health" is understood to be included in this norm; in that sense it has been said: "V- Human life is only possible in solidarity with the nature that sustains us and holds us, not only for physical nourishment, but also for psychological well-being; it constitutes the right that all citizens have to live in an environment free of contamination, which is the basis of a just and productive society. It is thus that article 21 of the Constitución Política states: 'Human life is inviolable'; and it continues; 'It is from this constitutional principle that the right to health, to physical, mental, and social well-being undeniably emerges, a human right that is indissolubly linked to the right to health and to the State's obligation to protect human life.'" (Votes Number 3705-93, 3341-96. Sala Constitucional, Corte Suprema de Justicia). On the other hand, and given this transcendence of the right we are analyzing, the Sala Constitucional itself has expressly recognized the responsibility of the State in ensuring the due protection of that right: “Nowadays, the determining role that the State must play is undeniable, and in the case at hand, the State of Costa Rica, represented by the Ministry of Health in this field, regarding the establishment of programs for the protection of that fundamental value of all citizens.” (Vote number 2522-97, of the Sala Constitucional of the Corte Suprema de Justicia). Likewise, and by way of corollary, we indicate that the Sala Constitucional has established that this right to life, constitutionally protected, as we have seen, must be supported and protected through the protection that the Caja Costarricense de Seguro Social provides to the population, by means of health plans, patient care, and supply of medicines, among other functions, given that it has been delegated the state responsibility to determine the suitable and safe practices of the service. With the foregoing, it is made clear that the right to health is a right of constitutional roots, projected as a power-duty in charge of the corresponding authorities, in this case the Caja Costarricense de Seguro Social, and therefore under that context, the provision of that service has an imminent public character. Naturally, matters pertaining to the right to health have not escaped regulation by international instruments, which bind as such the actions of the subscribing States based on that right; thus we find the following regulations: the Universal Declaration of Human Rights, in its article 25, in what interests us, establishes: " Everyone has the right to a standard of living adequate for the health and well-being of himself and of his family, including food, clothing, housing and medical care and necessary social services, and the right to security in the event of unemployment...". For its part, the American Convention on Human Rights, specifically in its articles 1 and 5, in the pertinent parts state: " Article 1. Every person has the right to have his life respected...", which, as we have already said, the right to health derives from it.... "Article 5.1. Every person has the right to have his physical, mental, and moral integrity respected." The Convention on the Rights of the Child, Article 24: "States Parties recognize the right of the child to the enjoyment of the highest attainable standard of health and to facilities for the treatment of illness and rehabilitation of health". The Convention on the Elimination of All Forms of Discrimination against Women: " Article 12. States Parties shall take all appropriate measures to eliminate discrimination against women in the field of health care in order to ensure, on a basis of equality of men and women, access to health care services, including those related to family planning." We also allow ourselves to merely mention other instruments such as the International Covenant on Economic, Social and Cultural Rights, in its numerals 9, 10, 11, and 12; the International Covenant on Civil and Political Rights, 6 and 7; the American Declaration of the Rights and Duties of Man, in its numeral 1; the Convention on the Elimination of All Forms of Racial Discrimination, article 5, subsection e). In relation to our national legislation, it is certainly exhaustive in terms of focusing on the recognition of such right, denoting its public character, just to cite some examples: Civil Code, article 46: "Every person may refuse to be subjected to a medical or surgical examination or treatment, with the exception of cases of mandatory vaccination, or other measures relating to public health..."; Código de la Niñez y la Adolescencia, article 19: "Minors shall have the right to seek refuge, assistance, and guidance when the threat to their rights entails serious danger to their physical or spiritual health; likewise, to obtain, in accordance with the law, adequate and timely assistance and protection from the competent institutions.", 20, "Minors shall have the right to obtain information, regardless of its source and mode of expression, especially that which promotes their spiritual and emotional well-being, as well as their physical and mental health", 42, 43, 45, 46, 50, 54, 78, 97, and 121, which are not transcribed for obvious reasons; Ley de Violencia Doméstica, article 2; Ley sobre Estupefacientes, Sustancias Psicotrópicas, Drogas de Uso no Autorizado, articles 1, 3, 6, 47; Ley de Protección Fitosanitaria, Placa19473; Ley de Arrendamientos Urbanos y Suburbanos, articles 5, 22, 93, 94, 97, 98, 135; of course the Ley Constitutiva de la Caja Costarricense de Seguro Social; the Ley General de Salud, and the Ley Orgánica del Ministerio de Salud, without citing others that also highlight the right at hand, and denote its public character. In that sense, there are also a large number of Regulations that protect this right; we cite by way of example Reglamento de Emergencias Nacionales articles 2 and 11; the Reglamento Autónomo de Organización de la Defensoría de los Habitantes article 21; the Reglamento de la Ley General de Aduanas, articles 12, 34, 246, 287, and 386; Reglamento de la Ley de Promoción de la Competencia y Defensa Efectiva del Consumidor, articles 6, 8, 24, 41, 43; Reglamento de la Ley Reguladora del Fumado, articles 1 and 5; Ley de Igualdad de Oportunidades para Personas con Discapacidad, articles 92 and 94, among others. Returning to the powers of the Caja Costarricense del Seguro Social, the Constitución Política in article 73 indicates that the Caja is an autonomous institution in charge of the administration and governance of social insurance, this being so in order to protect workers against the risks of illness, disability, maternity, old age, and death. For the fulfillment of its purposes, the Ley Constitutiva de la Caja Costarricense del Seguro Social, number 17 of October 22, 1943, in its ordinal 71, provides that said entity is authorized to import, release from customs, manufacture, buy, sell, and export, directly, medicines included in the National Formulary, reagents and biologicals, as well as raw materials and conditioning and packaging materials, required in the elaboration thereof. It is equally authorized to supply these same articles to public and private institutions that provide health services. In that sense, numeral 72 of the aforementioned law expresses that such purchases and negotiations may be carried out, as long as and insofar as the following requirements are met: a) Establish and maintain an updated registry of suppliers (oferentes) of the products, based on their generic name; for such purposes, the Contraloría General de la República and the Auditoría of the Caja Costarricense de Seguro Social shall have a copy of this registry. The Office in charge of purchases shall freely request quotations from national and foreign companies, registered in the registry of suppliers (oferentes), and their responses shall be considered formal offers if they meet the requirements of the case. To have the right to be considered, such responses must be given by the suppliers (oferentes) within the three business days following receipt of the quotation request. b) The Contraloría General de la República must resolve purchase authorizations within a period not exceeding five business days. c) In special cases of urgency, purchases may be made with the sole approval of the Auditoría of the Caja, but, in any case, the Contraloría must be informed of the actions taken within the following twenty-four hours. ch) The officials responsible for carrying out the purchases must make them under the best conditions of quality and price, and shall be responsible for their acts and for the damages and losses that they may eventually cause, in accordance with the law. For its part, numeral 73 of the same regulations indicates that the Caja Costarricense de Seguro Social may export medicines, reagents and biologicals, provided that national needs are satisfied. It may also exchange medicines with state or private organizations of other countries in order to satisfy social needs. The norms and authorizations contained in this article shall be equally applicable to the Ministry of Health. In turn, numeral 102 of the Ley General de Salud, number 5395 of October 30, 1973, states that the importation of medicines and their distribution shall only be permitted to legal entities or individuals registered with the Ministry, upon prior authorization and registration with the Colegio de Farmacéuticos, in accordance with the corresponding legal and regulatory provisions. In any case, the Central Government and public institutions with health functions may directly import, elaborate, handle, store, sell, or supply medicines, raw materials, or medical-surgical materials, when the fulfillment of their programs or emergency situations so require, with the sole approval of the Ministry, pursuant to the respective Regulations (ordinal 103 of Ley 5395). Medicine shall be understood to mean any substance or natural, synthetic, or semi-synthetic products and any mixture of those substances or products used for the diagnosis, prevention, treatment, and relief of diseases or abnormal physical states, or the symptoms thereof, and for the restoration or modification of organic functions in persons or animals. Included under the same name and for the same effects are dietary foods and foods and cosmetics that have been added with medicinal substances. The substances referred to in the first paragraph are not considered medicines when used for chemical and clinical-chemical analysis, or when used as raw materials in industrial processes.

Every medication must comply with the specific regulatory requirements that, by their nature, are exclusively applicable to them, in addition to the general requirements established for all medications in Ley 5395 (article 104). Medications may be presented for use, trade, distribution, and supply under a generic name or a registered name. Those pure medications, presented in a pharmaceutical formula or singly, designated by a general technical name recognized by official pharmacopoeias or by technical works of recognized authority, are of a generic name. A generic-name medication may be simple or may be a formula constituted by two or more generic-name medications. Registered-name medications are those delivered to commerce and use under a particular invented name and under a registered trademark (numeral 105 of Ley 5395). A medication is considered to be legally eligible for trade and public use and consumption when it satisfies regulatory requirements, or those of the pharmacopoeia declared official by the Executive Branch, regarding its identity and qualities, safety, and efficacy for the purposes for which it is used, consumed, or prescribed, and provided that the responsible natural or legal persons involved in its importation, trade, handling, distribution, and prescription have fulfilled the legal and regulatory requirements pertinent to each of these actions (numeral 106 of Ley 5395). The importation, manufacture, trade, distribution, or supply under any title, handling, use, consumption, and possession for trade of deteriorated, adulterated, or falsified medications is prohibited (ordinal 107 of Ley 5395). The importation, trade, use, or supply of medications that are in the experimental phase is prohibited, except under the conditions, circumstances, and for the time authorized by the Ministry (numeral 108 of Ley 5395). Furthermore, any natural or legal person may only import, manufacture, handle, trade, or use medications registered with the Ministry, the registration of which has satisfied the regulatory requirements, especially those relating to: the nature and quantity of the information required about the medication or product submitted for registration; the delivery of samples necessary to perform the analyses that may be required; those pertinent to the name by which the product will be identified; the content of the labeling; the type of containers or wrappers to be used; and the payment of the fees indicated by the relevant tariff (article 112 of Ley 5395). The registration of every medication shall be made before the Ministry, where the inscription will be carried out when appropriate according to the corresponding regulatory provisions. Said inscription will be the responsibility of a Technical Body, whose composition and functions will be determined by the Organic Law of the Ministry and the respective Regulation (article 113 of Ley 5395). The registration of every medication shall last five years, unless infractions in the manufacture, trade, or use incurred by its holder, or demonstrative experiences that the product is unsafe or ineffective under the terms in which it was authorized and registered, make its cancellation or the corresponding modification appropriate (numeral 114 of Ley 5395). Any modification in the name of a medication, its formula, the form of its dosage, the container and content of the accompanying labeling, or the advertising, will require prior permission from the Ministry (numeral 115 ibid). Registered-name medications, for the purposes of their importation, trade, and distribution in the country, require for their inscription proof of sanitary registration in the country of origin and proof of analysis corresponding to the product, issued by a national or foreign laboratory that, in the judgment of the Ministry, guarantees its identity and quality, according to the official pharmacopoeia or technical texts of recognized authority; this latter proof may also be issued by the chemical and pharmaceutical product control laboratory of the manufacturing company itself. Generic-name medications require for their inscription and for the same effects indicated in the preceding paragraph, proof of analysis that guarantees their identity and quality, according to the official pharmacopoeia or technical texts of recognized authority, this proof being issued in the same manner and conditions indicated in the preceding paragraph. The Ministry may exempt from the aforementioned tests when it involves a known product and its own nature makes those requirements unnecessary; or, in the case of medications not described in the official pharmacopoeia or technical texts of recognized authority, be they trademarked pharmaceutical products or generic-name medications, it may require the tests necessary for the verification of identity, quality, and therapeutic and biopharmaceutical efficacy of the product (article 116 ibid). For its part, ordinal 117 ibid expresses that the Ministry of Health, the Costa Rican Social Security Fund (Caja Costarricense de Seguro Social), and any other state entity with public health or social security functions may acquire unregistered medications at any time or circumstance, and that in cases of urgency or public need, that Ministry may authorize the importation of unregistered medications, in addition to the fact that for exclusive research purposes, the importation, production, and use of unregistered medications may be authorized, in accordance with the corresponding regulatory provisions. Up to this point, it is necessary to be clear on one aspect: the governing body in health matters is the Ministry of Public Health, and the Costa Rican Social Security Fund (Caja Costarricense del Seguro Social) is the administering entity of public insurance. These are indeed competencies that interrelate with each other, but some correspond to the Ministry and others to the public entity. Regarding Sanitary Registration, it is clear that the balance tilts in favor of the Ministry and not the Fund (Caja), with the natural obligation of coordination in the field of common competencies.

**VII- ON THE REQUIREMENTS THAT MUST BE MET TO FORM THE SUPPLIER REGISTRY OF THE COSTA RICAN SOCIAL SECURITY FUND (CAJA COSTARRICENSE DEL SEGURO SOCIAL) FOR OFFERING BIOTECHNOLOGICAL, BIOLOGICAL, ANTINEOPLASTIC MEDICATIONS AND OTHER MEDICATIONS FOR SPECIFIC USE IN ONCOLOGICAL AND HEMATOLOGICAL PATHOLOGIES:** By agreement of April 28, 2009, issued by the Costa Rican Social Security Fund (Caja Costarricense del Seguro Social), published in Gazette 89 of May 11, 2009, and approved by the Central Pharmacotherapy Committee (Comité Central de Farmacoterapia) in agreement CCF-0908-04-09 (Session 2009-13), the requirements are established for the supplier registration applicable to biological medications, and specific conditions for the acquisition of medications called antineoplastics and other medications for specific use in oncological and hemato-oncological pathologies. It provides that registered suppliers and suppliers to be registered in the CCSS Supplier Registry (Registro de Oferentes de la CCSS) for medications of biological origin from Group 1 and/or Group 2 must comply with a series of requirements stipulated below for each group. It is indicated, in turn, that these requirements are of mandatory observance also for those suppliers that participate in the Fund (Caja) with medications that do not have a Medication Sanitary Registration and that the medication must be imported under article 117 of the General Health Law of Costa Rica (Ley General de Salud de Costa Rica) or with medications with an in-transit code. In the first group are located medications of biological origin that, in their manufacturing process, do not use raw material coming from human blood products (for example, human plasma), establishing as requirements the following: 1. Certificate of the Medication Sanitary Registration issued by the Ministry of Health of Costa Rica. 2. Attach the complete qualitative-quantitative formula with the excipients used and the permitted ranges of related substances (if applicable in this specific case). 3. Those biological medications from Group 1 that contain in their formulation, and corroborated in their qualitative-quantitative formula, excipients of human plasma origin (blood products) must also comply with the requirements for Group 2. 4. Medications that do not have a sanitary registration issued by the Ministry of Health of CR must also present the duly certified clinical studies that correspond to those that gave rise to their registration in their country of origin, for the same official indications for use and safety in reference to the innovator. 5. In the event of bids that are in equal conditions, the administration clearly establishes a tie-breaking mechanism, which is to give priority to the biological product that is registered and consumed in the mentioned countries: United States (FDA) and/or countries of the European Economic Community (EMEA), and/or Canada, and/or Japan, and/or Switzerland. It is important to note that the medication manufacturing laboratories must present the certificate of free sale of their product in the United States and/or Canada and/or European Economic Community and/or Japan and/or Switzerland in the event that bids are presented in equal conditions and it is necessary to apply the tie-breaking mechanism. This document must be issued by the corresponding regulatory authority of the respective country. 6. Every biological medication, whether a new drug or not, that has the approval of at least the FDA and/or EMEA and/or Canada and/or Japan and/or Switzerland will be exempt from the requirements referred to in point 3, if they present the official documentation from the FDA and/or EMEA and/or from the regulatory authorities of Japan and/or Switzerland that accredits the product for its commercialization in these countries. 7. Biological medications that do not have a sanitary registration issued by the Ministry of Health of CR must also comply with point 5. 8. All requested documents must be authenticated via the consulate of our country and ratified by the Ministry of Foreign Affairs. In group 2, medications of biological origin are located that use, in their manufacturing process, raw material coming from human blood products (for example, human plasma), requiring from them that they provide: 1. Certificate of the Medication Sanitary Registration issued by the Ministry of Health of Costa Rica. 2. Attach the complete qualitative-quantitative formula with the excipients used and the permitted ranges of related substances (if applicable in this specific case). 3. Must comply with the Quality Specifications specified in each corresponding technical data sheet. 4. Must comply with all the regulations requested by the Ministry of Health of CR and everything requested by the Laboratory of Drug Standards and Quality of the CCSS (Laboratorio de Normas y Calidad de Medicamentos de la CCSS) regarding blood products. 5. Those biological medications from Group 1 that contain in their formulation, and corroborated in their qualitative-quantitative formula, excipients of human plasma origin (blood products) must also comply with the requirements for Group 2. 6. Medications that do not have a sanitary registration issued by the Ministry of Health of CR must also present the duly certified clinical studies that correspond to those that gave rise to their registration in their country of origin, for the same official indications for use and safety in reference to the innovator. 7. In the event of bids that are in equal conditions, the administration clearly establishes a tie-breaking mechanism, which is to give priority to the biological product that is registered and consumed in the mentioned countries: United States (FDA) and/or countries of the European Economic Community (EMEA), and/or Canada, and/or Japan, and/or Switzerland. It is important to note that the medication manufacturing laboratories must present the certificate of free sale of their product in the United States and/or Canada and/or European Economic Community and/or Japan and/or Switzerland in the event that bids are presented in equal conditions and it is necessary to apply the tie-breaking mechanism. This document must be issued by the corresponding regulatory authority of the respective country. 8. All requested documents must be authenticated via the consulate of our country and ratified by the Ministry of Foreign Affairs. 9. The manufacturing laboratory must guarantee that the human plasma used as raw material in the manufacture of each of the biological medications must come from healthy human beings, and the same must be entirely free of viruses or other pathogens.

For its part, the Central Pharmacotherapy Committee (Comité Central de Farmacoterapia) in agreement CCF-0944-04-09 (Session 2009-13) and ratified by agreement issued in Session 2009-14 of April 22, 2009, agreed to update the regulations for the Specific conditions for the acquisition of medications called antineoplastics and other medications for specific use in oncological and Hemato-Oncological pathologies, for purposes of Medication Registration with the Costa Rican Social Security Fund (Caja Costarricense de Seguro Social), whether registered or not with the Ministry of Health of Costa Rica. In point one, certification must be presented issued by the General Medical Directorate of the General or Oncological Hospital or Cancer Institute of the country of origin of the manufacturing laboratory, signed by the highest authority in medical oncology and the General Medical Director of the Medical Center, indicating the annual quantity consumed by patients of the medication manufactured by said laboratory, the number of beds in that hospital allocated to adults and the occupancy rate (for parenteral-use medications), and the number of oncology and onco-hematology consultations (for oral-use medications). All information must correspond to the same year in which it is registered with the Fund (Caja) or preferably to the year prior to the registration date. When the analysis is carried out by the CCSS, if the drug has a consumption in the General or Oncological Hospital or Cancer Institute of the country of origin equal to or greater than 100% of that consumed in the Hospital Nacional San Juan de Dios, it will be determined by a comparative study of defined daily dose (DDD) per 100 hospital beds/day for parenteral-use medications, and by a comparative study of defined daily dose (DDD) per 1000 consultations/day for oral-use medications; they will be given the supplier endorsement and will be incorporated into the Registry in the Fund (Caja). In the case of suppliers that are National Laboratories, based on a comparative study of defined daily dose (DDD) per 100 hospital beds/day (parenteral-use medications) or 1000 consultations/day (oral-use medications) taking as a reference the Hospital San Juan de Dios, if the result is equal to or greater than the DDD study from the year prior to the Registration of the medication in the Fund (Caja), they will be given the supplier endorsement and will be incorporated into the Registry in the Fund (Caja). For the case of national laboratories, the information related to the consumption in the Hospital San Juan de Dios (national reference hospital) will be obtained through the internal information mechanisms available in the institution. In point 2, certification issued by the Medical Directorate of the General or Oncological Hospital or Cancer Institute of the country of origin of the manufacturing laboratory must be presented, signed by the highest authority in medical oncology and the General Medical Director of the Medical Center, presenting the annual consumption in patients corresponding to a same year, efficacy and safety results obtained with the use of the medicinal product in the treatment of patients with hemato-oncological pathology and the type of oncological pathologies treated. The documents must fully and concretely contain the type and percentage of side effects presented by patients who have received treatment with said product for its analysis. In point 3: Certification from the Ministry of Public Health or the highest equivalent Public Health authority in the country of origin of the manufacturing laboratory presented by its representative, recognizing the General or Oncological Hospital or Cancer Institute requesting registration. In point 4: it is mandatory that the certification be presented individually and the information must refer to the nearest previous year to the date of its inclusion in the CCSS Supplier Registry of Medications when dealing with medications included in the Official List of Medications (Lista Oficial de Medicamentos, LOM), or correspond to the nearest previous year to the bidding process when dealing with medications not included in the Official List of Medications and are acquired at the Central or local level. These certifications must be updated each time the renewal of registration with the CCSS is requested for medications included in the LOM; if not registered, each time a purchase is made at the Central or local level in the case of non-LOM medications. In point 5: it is expressed that the requested documents must bear the signatures of health authorities duly authenticated, as required by Costa Rican legislation, in addition to completing the chain of consular legalization of our country and ratified by the Ministry of Foreign Affairs of Costa Rica. In point six, amended by agreement taken in session 2011-08 held on February 23, 2011, it is provided that those antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies for parenteral or oral use are exempt from the requirements stated in points 1, 2, 3, and 4, provided they have marketing authorization in any of the following countries: United States (FDA), Canada (Health Canada), Japan (MHLW), Switzerland (Swissmedic), Germany, England, Sweden, France, Italy, Spain, Belgium, Denmark, Austria, Netherlands, Finland, Norway, Colombia (INVIMA), Argentina (ANMAT), Brazil (ANVISA), expressing that the laboratories must present: the pharmaceutical product certificate (or Certificate of Free Sale plus the Certificate of Good Manufacturing Practices), as backing for its registration and marketing authorization in the United States (FDA), Canada, Japan (MHLW), Switzerland (Swissmedic), Germany, England, Sweden, France, Italy, Spain, Belgium, Denmark, Austria, Netherlands, Finland, Norway, Colombia (INVIMA), Argentina (ANMAT), Brazil (ANVISA). Likewise, it exempts those medications whose origin does not correspond to any of the countries listed above, but that have the Mutual Recognition certificate for their commercialization in any of the reference member states (European Union), a certificate that must be issued by the highest competent regulatory authority in public health of the respective country. It is provided that to exempt from the requirements listed in points 1, 2, 3, and 4, it is necessary that the pharmaceutical product certificates (or Certificate of Free Sale) include the name and address of the manufacturing plant, which must match the address of the manufacturing plant of the medication registered with the Ministry of Health of Costa Rica (whenever the medication is registered in the country). The manufacturing plant (name and address) from which the registered medication originates and has marketing authorization in one of the countries listed above, must correspond to the same manufacturing plant from which the medication to be delivered to the CCSS will be imported. Point seven establishes that the supplier already registered in the CCSS supplier registry can revalidate their registration by presenting the information indicated in the corresponding points above. Said registration will be valid until the expiration of the sanitary registration issued by the Ministry of Health of Costa Rica. Point 8 indicates that those suppliers who are registered but prefer to present their data at the time of the purchase process and not revalidate the registration with the CCSS until its expiration, must present the requirements for antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies for each purchase process. Point nine expresses that in the case of the acquisition of antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies included in the Official List of Medications (LOM), it will be the Area of Medications and Clinical Therapeutics (Área de Medicamentos y Terapéutica Clínica) attached to the Directorate of Pharmacoepidemiology (Dirección de Farmacoepidemiología) in charge of carrying out the data analysis and the corresponding Defined Daily Dose (DDD) study. In point 10, it stipulates that in the case of NON-LOM antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies acquired by each center, the data analysis and the corresponding Defined Daily Dose (DDD) study will be carried out each time a purchase process is initiated, and will be carried out and analyzed by each Pharmacy Service. Point 11 expresses that once the Executive Decree of the Ministry of Public Health that regulates the Medication Registry is published, the specific requirements for molecular target therapy products are contemplated therein; these requirements are based on ICH recommendations and form part of these conditions. Point 12 indicates that for bids of antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies for parenteral or oral use not included in the Official List of Medications that are acquired, at the Central or local level, and are in equal conditions, as a tie-breaking mechanism, priority will be given to the medication that is registered and consumed in any of the following countries: United States (FDA), Canada, Japan, Switzerland, Germany, England, Sweden, France, Italy, Spain, Belgium, Denmark, Austria, Netherlands, Finland, Norway. The supplier must present certification issued by the highest regulatory authority of the country stating that it is registered and consumed in one of the aforementioned countries, and that at the request of the Cancer Council (Consejo de Cáncer) regarding the bioequivalence requirements and requirements for medications called antineoplastics of biotechnological origin, the mechanism established in the Ministry of Health and CCSS is continued.

In turn, by agreement number 1445 of June 10, 2009, the Costa Rican Social Security Fund (Caja Costarricense del Seguro Social) established the requirements to be met for the registration of suppliers of biotechnological medications, which was published in Gazette 127 of July 2, 2009. This rule provides, regarding the obligations that must be met by registered suppliers and suppliers to be registered in the CCSS Supplier Registry for medications of biological origin from Group 1 and/or Group 2, that they must comply with the requirements of mandatory observance for those suppliers that participate in the Fund (Caja) with medications that do not have a Medication Sanitary Registration and that the medication must be imported under article 117 of the General Health Law of Costa Rica (Ley General de Salud de Costa Rica) or with medications with an in-transit code. These groups being, number one corresponding to medications of biological origin, that in their manufacturing process do not use raw material coming from human blood products (for example, human plasma), the supplier must present the following requirements: 1. Certificate of the medication's sanitary registration issued by the Ministry of Health of Costa Rica. 2. For innovator medications, the complete qualitative-quantitative formula with the excipients used and the permitted ranges of related substances must be attached, as well as the medication characterization studies. 3. For biosimilar medications, the complete qualitative-quantitative formula with the excipients used and the permitted ranges of related substances must be attached, as well as the medication characterization studies; in addition, they must present the characterization studies of the medication compared with the reference medication that is commercialized in Costa Rica. 4. Medications that in their manufacturing process do not use raw materials that are blood products but that in their formulation, and through their qualitative formula, are corroborated to present excipients from human plasma such as albumin, must comply with all the current guidelines established in the Blood Products Decree No. 19981-S of October 3, 1990. 5. Must comply with the quality specifications established in the official technical data sheet corresponding to each medication. 6. The Supplier Registry of the Laboratory of Drug Standards and Quality (Laboratorio de Normas y Calidad de Medicamentos) and the Central Pharmacotherapy Committee (Comité Central de Farmacoterapia) clearly establish that only biological products are endorsed that are registered or not with the Ministry of Health of Costa Rica, but that are consumed in the following countries: United States (FDA), and/or countries of the European Community (EMEA), and/or Canada, and/or Japan, and/or Switzerland. 7. In the case of innovator medications, manufacturing laboratories must present Certificates of free sale of the medication in the country of origin such as the United States, European Economic Community, Canada, Japan, Switzerland, issued by the regulatory health authority of that country. 8. In the case of biosimilar medications, manufacturing laboratories must present Certificates of free sale of the medication in the country of origin such as the United States, European Economic Community, Canada, Japan, Switzerland, issued by the regulatory health authority of that country, as well as a certificate issued by the same health entity guaranteeing that the medication meets the quality criteria requested for biological medications and that it has the clinical safety and efficacy studies that gave rise to its sanitary registration in the country of origin, that it has clinical studies of immunogenicity, safety, and efficacy, in the same official indications as the reference product commercialized in the country, as well as the characterization and comparability studies demonstrating that the product is biosimilar to the reference product commercialized in Costa Rica. Furthermore, the complete qualitative-quantitative formula with the excipients used and the permitted ranges of related substances must be attached, along with the certification from the Health Authority (EMEA and/or FDA) that accredits it as a biosimilar medication. 9. All documents requested that are issued abroad (other countries) must be consularized and presented in the Spanish language. 10. The Institution, based on the extensive clinical experience acquired over the years with the use of biological medications, reserves the right to judge certain specifications and requirements to be evaluated for the inclusion of new medications that share the same code, in the supplier registry and unregistered medications; and only endorses the interchangeability of biological products that have documented safety and efficacy proven through their clinical use in the Institution over the years. And regarding group 2 of medications of biological origin, it is expressed that these are those that use, in their manufacturing process, raw material coming from human blood products (for example, human plasma), and the supplier must meet the following requirements: 1. Certificate of the Medication Sanitary Registration issued by the Ministry of Health of Costa Rica. 2. Attach the complete qualitative-quantitative formula with the excipients used and the permitted ranges of related substances.

Must comply with the Quality Specifications specified in each corresponding technical data sheet for each medication. 4. Must comply with all regulations required by the Ministry of Health of CR and everything required by the CCSS Laboratory of Drug Standards and Quality regarding blood products (hemoderivados). 5. The Supplier Registry of the Laboratory of Drug Standards and Quality and the Central Pharmacotherapy Committee (Comité Central de Farmacoterapia) clearly establishes that only biological products are endorsed that are registered or not with the Ministry of Health of Costa Rica, but that are consumed in the following countries: United States (FDA), and/or countries of the European Community (EMEA), and/or Canada, and/or Japan, and/or Switzerland. 6. All documents requested that are issued abroad (other countries) must be consularized and submitted in the Spanish language. 7. The Institution, based on the extensive clinical experience acquired over the years with the use of biological medications, reserves the right to exercise its judgment regarding certain specifications and requirements to be evaluated for the inclusion of new medications that share the same code in the supplier registry; and only endorses those for which proven safety and efficacy have been documented through their clinical use in the Institution over the years. 8. The manufacturing laboratory must guarantee that the human plasma used as raw material in the manufacture of each of the biological medications must come from healthy human beings and be entirely free of viruses or other pathogens, and must comply with the current guidelines established in the Blood Products Decree (Decreto de Hemoderivados) Nº 19981-S of October 3, 1990. Subsequently, by agreement of March ninth, 2010, published in Gazette number 47 of March 09, 2010, approved by agreement CCF-0275-02-10 (session 2010-05) of the Central Pharmacotherapy Committee, the specific conditions for the acquisition of medications called antineoplastic and other medications for specific use in oncological and hemato-oncological pathologies were reformed, establishing the following points: Point 1: For antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies, certification must be submitted issued by the General Medical Directorate of the General or Oncological Hospital or Cancer Institute of the country of origin of the manufacturing laboratory, signed by the highest authority in medical oncology and the General Medical Director of the Medical Center, indicating the annual quantity consumed by patients of the medication manufactured by said laboratory, the number of beds in that hospital designated for adults and the occupancy rate (for parenteral-use medications), and the number of oncology and onco-hematology consultations (for oral-use medications). All information must correspond to the same year in which it is registered with the Caja or preferably the year prior to the registration date. When the analysis is carried out by the CCSS, if the drug has a consumption level in the General or Oncological Hospital or Cancer Institute of the country of origin equal to or greater than 100% of that consumed at the Hospital Nacional San Juan de Dios, a comparative study of defined daily dose (DDD) per 100 hospital beds/day for parenteral-use medications, and a comparative study of defined daily dose (DDD) per 1000 consultations/day for oral-use medications will be conducted; they will be granted the supplier endorsement and will be incorporated into the Registry at the Caja. In the case of suppliers that are National Laboratories, based on a comparative study of defined daily dose (DDD) per 100 hospital beds/day (parenteral-use medications) or 1000 consultations/day (oral-use medications) taking the Hospital San Juan de Dios as a reference, if the result is equal to or greater than the DDD study from the year prior to the medication's registration with the Caja, they will be granted the supplier endorsement and will be incorporated into the Registry at the Caja. In the case of national laboratories, the information related to consumption at the Hospital San Juan de Dios (National reference hospital) will be obtained through the internal information mechanisms available at the institution. Point 2: The specific medication (oral or parenteral) for which entry into the Caja's supplier registry is requested for registration, or the medication to be acquired at the Central or Local level, will submit certification issued by the Medical Directorate of the General or Oncological Hospital or Cancer Institute of the country of origin of the manufacturing laboratory, signed by the highest authority in medical oncology and the General Medical Director of the Medical Center, presenting the annual consumption in patients corresponding to a same year, efficacy and safety results obtained with the use of the medicinal product in the treatment of patients with hemato-oncological pathology, and the type of oncological pathologies treated. The documents must completely and concretely contain the type and percentage of side effects presented by patients who have received treatment with said product for analysis. Point 3: Certification from the Ministry of Public Health or the highest equivalent Public Health authority in the country of origin of the manufacturing laboratory, presented by its representative, recognizing the General or Oncological Hospital or Cancer Institute requesting to be registered. Point 4: All requested certifications must be submitted individually and the information must refer to the closest previous year to the date of its inclusion in the CCSS Supplier Registry of Medications when dealing with medications included in the Official List of Medications (Lista Oficial de Medicamentos, LOM), or correspond to the closest previous year to the tender when dealing with medications not included in the Official List of Medications and are acquired at the Central or local level. These certifications must be updated each time a renewal of the registration with the CCSS is requested for medications included in the LOM; if not registered, each time a purchase is made at the Central or local level in the case of non-LOM medications. Point 5: All requested documents must have the signatures of health authorities duly authenticated, as required by Costa Rican legislation, in addition to completing the chain of consular legalization from our country and ratified by the Ministry of Foreign Affairs of Costa Rica. Point 6: Exempted from the requirements set forth in points 1, 2, 3, and 4 are those antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies for parenteral or oral use, which are registered and consumed in any of the following countries: United States (FDA), Canada (Health Canada), Japan (MHLW), Switzerland (Swissmedic), Germany, England, Sweden, France, Italy, Spain, Belgium, Denmark, Austria, the Netherlands, Finland, Norway. It is important to note that laboratories must present the certificate of free sale of their product in the United States (FDA), Canada, Japan (MHLW), Switzerland (Swissmedic), Germany, England, Sweden, France, Italy, Spain, Belgium, Denmark, Austria, the Netherlands, Finland, Norway; or with registration and commercialization in these same countries. Likewise, exempt will be those medications whose origin does not correspond to any of the countries listed above, but which have the Mutual Recognition certificate issued by the EMEA for commercialization in any of the reference member states of the European Union. This certificate must be issued by the highest competent regulatory authority in public health of the respective country. Point 7: The supplier already registered in the CCSS supplier registry can revalidate their registration by submitting the information indicated in the corresponding points above. Said registration will be valid until the expiration of the health registration (registro sanitario) issued by the Ministry of Health of Costa Rica. Point 8: Those suppliers who are registered but who prefer to present their data at the time of the purchase process and not revalidate the registration with the CCSS until its expiration, must submit the requirements for antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies for each purchase process. Point 9: In the case of the acquisition of antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies included in the Official List of Medications (LOM), the Area of Medications and Clinical Therapeutics attached to the Directorate of Pharmacoepidemiology will be responsible for carrying out the data analysis and the corresponding Defined Daily Dose (DDD) study. Point 10: In the case of NON-LOM antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies acquired by each center, the data analysis and the corresponding Defined Daily Dose (DDD) study will be carried out each time a purchase procedure is promoted, and will be performed and analyzed by each Pharmacy Service. Point 11: Once the Executive Decree of the Ministry of Public Health that regulates the Medication Registry is published, which contemplates the specific requirements for molecular target therapy products, these requirements are based on the ICH recommendations and form part of these conditions. Point 12: Faced with offers of parenteral or oral antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies not included in the Official List of Medications that are acquired at the Central or local level, and that are in equal conditions, as a tie-breaking mechanism, priority will be given to the medication that is registered and consumed in any of the following countries: United States (FDA), Canada, Japan, Switzerland, Germany, England, Sweden, France, Italy, Spain, Belgium, Denmark, Austria, the Netherlands, Finland, Norway. The supplier must present certification issued by the highest regulatory authority of the country indicating that it is registered and consumed in one of the aforementioned countries. Regarding the Cancer Council's request concerning bioequivalence requirements and requirements for medications called antineoplastics of biotechnological origin, the mechanism established by the Ministry of Health and CCSS is continued. Subsequently, the Central Pharmacotherapy Committee in session 2011-08 held on February 23, 2011, analyzed Point 6 of the requirements for medications called antineoplastics and other medications for specific use in oncological and hematological pathologies published in La Gaceta Nº 47 of March 09, 2010, agreeing to modify it, resulting as follows: "Exempted from the requirements set forth in points 1, 2, 3, and 4 are those antineoplastic medications and other medications for specific use in oncological and hemato-oncological pathologies for parenteral or oral use, which have a marketing authorization in any of the following countries: United States (FDA), Canada (Health Canada), Japan (MHLW), Switzerland (Swissmedic), Germany, England, Sweden, France, Italy, Spain, Belgium, Denmark, Austria, the Netherlands, Finland, Norway, Colombia (INVIMA), Argentina (ANMAT), Brazil (ANVISA). It is important to note that laboratories must present: the certificate of pharmaceutical product (or Certificate of Free Sale plus the Certificate of Good Manufacturing Practices), as supporting evidence of their registration and marketing authorization in the United States (FDA), Canada, Japan (MHLW), Switzerland (Swissmedic), Germany, England, Sweden, France, Italy, Spain, Belgium, Denmark, Austria, the Netherlands, Finland, Norway, Colombia (INVIMA), Argentina (ANMAT), Brazil (ANVISA). Likewise, exempt will be those medications whose origin does not correspond to any of the countries listed above, but which have the Mutual Recognition certificate for their commercialization in any of the reference member states (European Union). This certificate must be issued by the highest competent regulatory authority in public health of the respective country. To exempt them from the requirements listed in points 1, 2, 3, and 4, it is necessary that the certificates of pharmaceutical product (or Certificate of Free Sale) include the name and address of the manufacturing plant, which must match the address of the manufacturing plant of the medication registered with the Ministry of Health of Costa Rica (whenever the medication is registered in the country). The manufacturing plant (name and address) from which the medication registered and with a marketing authorization in one of the countries listed above originates, must correspond to the same manufacturing plant from which the medication to be delivered to the CCSS will be imported". In turn, the technical regulation called Registration and Control of Biological Medications, number 37006 of November 15, 2011, established that its regulations govern the requirements and necessary procedures for the registration and control of biological medications for human use and applies to all products of this type, whether produced in the national territory or imported (first article). In said regulation, in its fifth clause, it was established regarding the health registration of biological medications, "that when the submission of any of the studies or documents mentioned in this Regulation is not scientifically appropriate, the applicant must submit the justification for its evaluation by the Ministry of Health, establishing that for the health registration of biological medications, a dossier must be submitted following the format and content established in Article 27 of Decree Nº 28466-S of February 8, 2000 "Regulation for the Registration, Control, Importation, and Advertising of Medications", published in La Gaceta Nº 42 of February 29, 2000, and its amendments or the current health registration regulations. Information on the international regulatory status of the product must be submitted: List of Health Authorities that have the product registered as of the date of the procedure before the Ministry of Health and those that have conducted inspections in the last two years at the laboratories manufacturing the finished products. In addition to information regarding safety and efficacy for biological medications. The scientific documentation submitted, referring to the conclusive reports of the clinical studies, must have been prepared within a period not exceeding ten years. In the event that the aforementioned studies were conducted more than 10 years ago, the applicant must submit the justification for its evaluation by the Ministry of Health. All conclusive reports of the clinical studies must refer to the same product and pharmaceutical form that is submitted for its health registration. For biological products containing active ingredients not included in the formulation of a product previously registered in Costa Rica: it is required i) In the case of products containing chemical entities not included in the formulation of a previously registered product: • Conclusive reports of the results of the preclinical studies (including information on in vivo and in vitro pharmacodynamic parameters). • Conclusive reports of the results of Phase I, II, and III clinical studies (including pharmacokinetic, pharmacodynamic studies, clinical studies, and immunogenicity studies). ii) In the case of pharmaceutical products containing chemical entities included in previously registered products whose active ingredient corresponds to new derivatives, such as pegylated ones or others, they must submit: • Conclusive reports of the results of Phase I, II, and III clinical studies. For biological medications containing active ingredients included in the formulation of a product previously registered in Costa Rica but which present: i) New fixed combinations of active ingredients: • Conclusive reports of the results of Phase I, II, and III clinical studies. Such reports must compare the existing and new proportions or doses, including bioavailability studies. ii) New pharmaceutical form with an already registered route of administration: • Conclusive reports of the results of bioavailability studies. iii) New pharmaceutical form with a new route of administration: • Conclusive reports of the results of preclinical studies and Phase I, II, and III clinical studies. iv) New pharmaceutical form with a new form of release: • Conclusive reports of the results of Phase I, II, and III clinical studies. v) New potencies or concentrations of previously registered active ingredients: • Conclusive reports of the results of bioavailability studies and Phase II and III clinical studies. vi) New routes of administration with an already registered pharmaceutical form: • Conclusive reports of the results of bioavailability and Phase II and III clinical studies. 5.5. In addition to the requirements mentioned in the preceding numeral, for the registration of biological medications, the documents established in the following sections must be attached to the dossier in the order mentioned. For recombinant DNA or biotechnological medications, the following must be submitted: 5.6.a. Quality information related to the physicochemical, biological, and immunological properties of the active ingredient: i) Description, chemical structure, amino acid sequence, post-translational modifications, physicochemical, biological, and immunological properties. ii) Description of the manufacturing process, in-process controls, cell substrate control, control of critical stages and intermediate products, and process validation. iii) Description of the characterization methodology, including the description of the chemical structure and product-related and process-related impurities and contaminants. iv) Description of the active ingredient controls, including specifications, analytical methods, and validation of analytical methods. v) Description of reference standards or materials. vi) Description of the container-closure system. vii) Description and results of the stability study. 5.6.b. Quality information related to the physicochemical, biological, and immunological properties of the finished product: i) Description of the product and its composition. ii) Description of the manufacturing process, in-process controls, control of critical stages and intermediate products, and process validation. iii) Description of quality control, including specifications, analytical methods, validation of analytical methods, analysis of lot results used for specifications, characterization of impurities and contaminants, and justification of the specifications guaranteeing lot-to-lot uniformity. When more than one manufacturer is involved, indicate at which step each one intervenes. iv) Description of reference standards or materials. v) Description of the safety assessment against infections by adventitious agents. Details on viral inactivation and elimination. vi) Risk management and post-marketing pharmacovigilance plan. NOTE 1: These requirements apply to the innovator medication, and in the case of biosimilars, they must additionally present the biosimilarity exercise related to quality compared to the reference biological medication, to determine that the differences do not have implications for its safety and efficacy. In the documentation provided, the name of the medication to which it intends to be biosimilar and the name of the laboratory that manufactures it must be specified. NOTE 2: The biosimilarity exercise must be performed for both the finished product and the active ingredient, as detailed in numeral 5.12., and for this purpose, the international guidelines of the WHO will be followed, and in their absence, those issued by the FDA, EMA, or ICH may be used. Notwithstanding the foregoing, the guidelines of other countries may be adopted as official once the Ministry of Health verifies that they are internationally accepted and they are formalized through an Administrative Resolution to be published in the Official Gazette La Gaceta together with the instructions, forms, and any other corresponding document, and placed on the Ministry of Health's website. 5.7. For blood products (productos hemoderivados) and vaccines, the manufacturing method must be submitted, containing the following information: 5.7.a. Master formula, including batch size. 5.7.b. Description of starting materials of biological origin, such as: strains, cell lines, microorganisms, plasma or blood component donations, cells or cell substrates, and culture media. Including: quality control specifications, validated analytical methods, and methods for the exclusion of adventitious agents. 5.7.c. Description of the manufacturing process: i) Manufacturing flow diagram indicating process controls and, when more than one manufacturer participates, indicating at which step each one intervenes. ii) Complete description of the entire process, manufacturing methods, and their controls. Information on the fermentation, harvest, and purification steps, if applicable to the product's manufacture, including acceptance and rejection criteria. iii) Process control specifications and analytical methods issued by the manufacturer, which must be validated. iv) Reprocessing criteria for each stage. v) Quality specifications including the characterization and purity of the product obtained at each stage and the analytical techniques used for its verification. vi) Description of the double viral inactivation processes, agent used, and method to verify the effectiveness of the process, as applicable. vii) Document in which the manufacturer states that its manufacturing process achieves, for all manufactured batches, a maximum reduction of prion infectivity, in accordance with the current state of knowledge. 5.7.d. Analytical certificates must contain the quality specifications of Active Ingredient(s), Excipient(s), In-process Product, Finished Product, and Reference Material(s). The analytical results of the medication components must be expressed in units of weight or biological activity, as appropriate. These certificates must include: i) Name of the substance or product. ii) Processing stage in the case of in-process products. iii) Date and place of manufacture. iv) Batch number. v) Batch size. vi) Physical, chemical, biological, and microbiological quality parameters with their limits and results. vii) Expiration date when applicable. viii) Date and place of analysis, name of the person responsible for the analysis, and conformity decision in accordance with the specifications. ix) Reference to the official method used or indication that the manufacturer's validated method was used. 5.7.e. Risk management and post-marketing pharmacovigilance plan. 5.8. For blood products, in addition to the information from numerals 5.3., 5.4, and 5.7., the following requirements must be submitted: 5.8.a. Certificate of current health registration of the product issued by the FDA, the EMA, or any other competent health authority that performs the Plasma Master File (PMF) Certification after conducting the corresponding scientific and technical evaluation. 5.8.b. Information on donor selection and control. 5.8.c. Description of the procedures used to ensure traceability from the finished product to the donors and vice versa. This description must be accompanied by a detailed Diagram. 5.8.d. Results of the tests performed to detect HIV 1 and HIV 2 antibodies, Hepatitis C antibodies, and the ELISA or RIA test for Hepatitis B that detects 0.5 IU per ml of HBsAg or less. 5.8.e. Information on the centers where the plasma is obtained, location of the plasma collection centers, information on inspections conducted at said Centers, and on the Quarantine Policy. Detail the type of plasma obtained (donation or plasmapheresis), the type of donation (altruistic or compensated), data on the seroconversion percentage of regular donors, and data on markers from first-time donations. Also include information on the plasma storage and transport conditions established by the manufacturer. 5.9. For vaccines, in addition to the information from numerals 5.3., 5.4, and 5.7., the following must be submitted: 5.9.a. Clinical studies of reactogenicity, immunogenicity, and efficacy. The absence of efficacy studies must be justified. 5.9.b. Information on the Cell Bank Systems: i) Preparation, description, and controls performed on the Master Cell Bank (BCM) and Working Cell Bank (BCT). ii) Description of the controls used to verify the absence of adventitious agents. iii) Description and characterization of stabilizers, adjuvants, and preservatives. iv) Nucleic acid sequence of the strain and its comparative study with other strains, including vaccine strains. 5.10. For combined vaccines, in addition to the information from numerals 5.3., 5.4., and 5.7., the following requirements must be submitted: 5.10.a. Clinical studies of reactogenicity and immunogenicity. 5.10.b. Information on the Cell Bank Systems: i) Preparation, description, and controls performed on the Master Cell Bank (BCM) and Working Cell Bank (BCT). ii) Description of the controls used to verify the absence of adventitious agents. iii) Description and characterization of stabilizers, adjuvants, and preservatives. 5.10.c. Information on the characterization and controls of each individual antigen, which must meet the same requirements established for their use in single vaccines. 5.10.d.

Information on tests conducted after combination with a view to studying the possible interaction between the antigens. 5.10.e. Information on the effects of adjuvants and preservatives on the stability and activity of the finished product. 5.10.f. Reactogenicity and immunogenicity studies demonstrating safety compared to the vaccines administered separately but simultaneously. 5.11. For antivenoms and antitoxins of animal origin, the manufacturing method must be submitted, which must contain the following information: 5.11.a. Master formula, including batch size. 5.11.b. Description of starting materials of biological origin such as: venoms and plasma or blood components. Including: quality control specifications, validated analytical methods, and methods for the exclusion of adventitious agents. 5.11.c. Information on the control of venom batches used for the immunization of the donor animal. i) Certification signed by the biological director of the snake species used in venom extractions for immunization mixtures, including the scientific and common names of the snakes used: This certification must include a minimum of 10 specimens used per species for each venom batch and the extraction date. ii) Flow chart describing the handling and storage of venom mixtures for immunization, including storage conditions. iii) Results of biological and biochemical tests certifying venom consistency (specifically HPLC chromatographic profile and LD50 toxicological activity). 5.11.d. Information on plasma batches obtained from immunized animals: i) Information on endotoxin tests, neutralizing potency of the plasma mixture for a batch, and protein content. ii) Information on the venoms used in immunization, bleeding dates, immunization dates, and identification of horses for a specific batch. iii) Identification profile of the horses participating in a specific plasma batch, with their respective breed, sex, age, and weight. 5.11.e. Description of the manufacturing process: i) Manufacturing flow chart indicating process controls and, when more than one manufacturer is involved, indicating at which step each one intervenes. ii) Complete description of the entire process, manufacturing methods, and their controls. Information on purification steps, including acceptance and rejection criteria. iii) Process control specifications and analytical methods issued by the manufacturer, which must be validated. iv) Reprocessing criteria for each stage. v) Quality specifications including the characterization and purity of the product obtained at each stage and the analytical techniques used for its verification. vi) Description of the double viral inactivation process(es), agent used, and method for verifying the effectiveness of the process, as applicable. vii) Document in which the manufacturer indicates that its manufacturing process achieves, for all manufactured batches, a maximum reduction of prion infectivity, in accordance with the current state of knowledge. This applies to those antivenoms or antitoxins derived from animals in which prion infectivity has been demonstrated. 5.11.f. Analytical certificates, must contain the quality specifications of Active Principle(s), Auxiliary Substance(s), In-Process Product, Finished Product, and Reference Material(s). The analytical results of the drug components must be expressed in units of weight, or biological activity as appropriate. These certificates must include: i) Name of the substance or product. ii) Manufacturing stage in the case of in-process products. iii) Date and place of manufacture. iv) Batch number. v) Batch size. vi) Physical, chemical, biological, and microbiological quality parameters with their limits and results. vii) Expiration date when applicable. viii) Date and place of analysis, name of the person responsible for the analysis, and conformity decision according to specifications. ix) Reference to the official method used or indication that the manufacturer's validated method was used. 5.11.g. Risk management plan and post-marketing pharmacovigilance. 5.12. Regarding information concerning safety and efficacy for biosimilar medicines not previously registered in Costa Rica and for biosimilars already registered, the biosimilarity exercise must be submitted, including: 5.12.a. Pre-clinical studies (in vitro and in vivo) that must be comparative in nature and designed to detect significant differences between the biosimilar and the reference innovative biological. 5.12.b. Comparative clinical studies with the reference biological medicine for each of the indications requested. Must submit: i) Pharmacokinetic studies. ii) Pharmacodynamic studies. iii) Clinical efficacy studies. iv) Safety studies. v) Immunogenicity studies. The type and amount of studies will depend on the knowledge available about the reference biological medicine and the therapeutic indications being requested; for this, international guidelines will be followed and, in their absence, those issued by the FDA, EMA, and ICH may be used on a case-by-case basis. 5.12.c. Approval letter for the clinical studies indicated in this regulation, issued by the Ethical-Scientific Committee(s), duly legalized or apostilled. Said committees must be recognized by the health authority of the country where these studies were conducted. 5.12.d. Risk management plan and post-marketing pharmacovigilance. Any specific safety monitoring imposed on the reference product must be considered in the risk management plan of the biosimilar product. 5.12.e. Detail on the criterion used to select the reference biological product with which the biosimilarity exercise was conducted. For this, the sequence of criteria from numeral 6 of this Regulation must be used. 6. SELECTION OF THE REFERENCE BIOLOGICAL MEDICINE: The criteria for selecting the reference biological medicine in order of priority are the following: 6.1. The first choice must always be the innovative product manufactured in the first country of origin, which has a complete dossier on its quality, efficacy, and safety, provided that it is the same one registered and marketed in Costa Rica. 6.2. The second choice must always be the innovative product manufactured, registered, and marketed in Costa Rica. 6.3. The third choice must be the innovative product manufactured in an alternate origin, registered and marketed in Costa Rica. 6.4. The fourth choice, in case the previous conditions are not met, may be the innovative product manufactured in the first country of origin or alternate origin, or the reference product suggested in the WHO lists, even if it has not been marketed in Costa Rica. To define the reference product through the application of this numeral, a written consultation must be made with the Dirección de Regulación de la Salud of the Ministry of Health. 6.5. The fifth choice, in case the previous conditions are not met, corresponds to the leading market product that has demonstrated its quality, efficacy, and safety. To define the reference product through the application of this numeral, a written consultation must be made with the Dirección de Regulación de la Salud of the Ministry of Health. 7. POST-REGISTRATION CHANGES TO BIOLOGICAL MEDICINES: For any change associated with a biological medicine that is contemplated in the Guide on post-registration changes published on the Ministry of Health website, the specific requirements established in said Guide must be submitted according to the type of change to be made. 8. RENEWAL OF THE SANITARY REGISTRATION 8.1. For the renewal of the sanitary registration of the biological medicines described in this regulation, a dossier must be submitted with the requirements established in Article 34 of Decreto Nº 28466-S, Reglamento de Inscripción, Control, Importación y Publicidad de Medicamentos, published in La Gaceta Nº 42 of February 29, 2000, and its amendments or the current sanitary registration regulations, also attaching, in case they have not been submitted in previous registration procedures, the requirements established in this regulation. 8.2. For biosimilar medicines that have not submitted it in previous procedures, they must submit the biosimilarity exercise that contemplates the provisions of this regulation. 9. LOT RELEASE OF BIOLOGICAL PRODUCTS. The Dirección de Atención al Cliente will authorize the release of each lot of biological products (with the exception of biotechnological products which, due to their nature, are not subject to lot-by-lot release) once it verifies the correspondence between the documentation of the registration dossier and the following requirements: 9.1. Lot Release Certificate issued by the regulatory authority of the producing country. For national laboratories, the Ministry of Health will review its files to verify compliance with this requirement. 9.2. Summarized manufacturing protocol and certificate of the manufacturer's release test results, and in the case of blood derivatives of human origin or medicines containing them, the certificate must include that the product is free of HIV, cytomegalovirus, parvovirus B19, and hepatitis B and C viruses. 9.3. Letter of commitment, from the manufacturer, the product holder, or its legal representative, guaranteeing compliance at all times with the storage conditions established on the labeling of the imported lot, from the manufacturing laboratory to the drugstore in Costa Rica. NOTE: The lot release procedure for biological medicines by the Dirección de Atención al Cliente of the Ministry of Health will be carried out at the importing drugstore or at the national manufacturing laboratory within a period of 5 working days counted from the notification to the Ministry of Health. 10. CONTROL OF BIOLOGICAL MEDICINES. 10.1. What is stated in the registration declarations and compliance with the required requirements will be carried out by the Dirección de Regulación de la Salud, through inspection and sampling in the market, at the pharmaceutical laboratory, or at customs, in accordance with the provisions of the Ley General de Salud and the Ley de Promoción de la Competencia y Defensa Efectiva del Consumidor. The first quality control carried out on biological medicines will be performed on the first marketing lot, without diminishing the post-marketing verification and inspection controls that the Dirección de Regulación de la Salud may eventually order. 10.2. For control purposes, the manufacturer of the biological medicine or its holder must submit to the Ministry of Health the updates of the reports generated by the Risk Management and Pharmacovigilance Plans, which will form part of the product's dossier before the Ministry of Health. 10.3. In the event of demonstrating non-compliance or falsity of what was declared in the registration before the Ministry of Health, the sanitary authority will stop, seize, or withdraw the respective product from circulation, or cancel its registration as appropriate, after prior notification to the legal representative, who must assume the costs of the applied sanitary measure. The foregoing is without prejudice to other sanctions established by the Ley de Promoción de la Competencia y Defensa Efectiva del Consumidor. The Ministry of Health will proceed to apply these special measures based on the provisions of Article 386 of the Ley General de Salud, without prejudice to the civil or criminal liability incurred by the natural or legal persons responsible for such non-compliance and without prejudice to any other sanction that may proceed in accordance with current legislation." For its part, the Reglamento de Inscripción, Control, Importación y Publicidad de Medicamentos, number 28466 of February 8, 2000, established the pertinent regulations for the registration, control, importation, and advertising of medicines, applying to all persons who manufacture, import, and market medicines in the national territory (numeral 2 ibid). Furthermore, in this regulation, Bioavailability is defined as the rate and extent to which the active ingredient or active moiety is absorbed from a pharmaceutical form and becomes available at the site of action; Bioequivalence: as the relationship between two pharmaceutical products that are pharmaceutically equivalent and whose bioavailability, in terms of rate and extent, after being administered at the same molar dose, under the same conditions, are similar to such a degree that their effects would be essentially the same; Good manufacturing practices: as the set of norms and procedures aimed at guaranteeing the uniform production of batches of pharmaceutical products that meet the quality requirements demanded by user needs; certificate of analysis: as the certificate indicating the specifications and results of the physical, chemical, biological, microbiological, and biopharmaceutical analyses of a pharmaceutical product, issued by a national or foreign laboratory that, in the judgment of the Ministry, guarantees its identity and quality; Certificate of Good Manufacturing Practices: as the document issued by the sanitary authority of the country of origin, certifying that the laboratory to which it refers satisfactorily complies with the Good Manufacturing Practices requirements in force in that country for the pharmaceutical form to which the product belongs. Said requirements must at least comply with the WHO standards equivalent to those of the regulations in force in Costa Rica. In the case of beta-lactams, cytotoxics, hormonals, and biologicals, the certificate must specifically declare that the manufacturing laboratory is authorized for the manufacture of those pharmaceutical products; Certificate of Free Sale: as the document issued by the regulatory authority or body responsible for the registration of pharmaceutical products of the country of origin or provenance, duly legalized, certifying that the pharmaceutical product to which the certificate refers has its registration in force and is authorized for sale or distribution in that country. In case of manufacturing by third parties, it may be from the country where the holder or party responsible for the commercialization of the product is located; Certificate of Pharmaceutical Product: the certification proposed by the World Health Organization (WHO) and issued by the Regulatory Authority of the country or region of origin or provenance as part of the certification system for the quality of pharmaceutical products subject to international trade. In case of manufacturing by third parties, the certificate of pharmaceutical product must be issued by the Regulatory Authority of the country of the product holder. For subsidiaries, the certificate of pharmaceutical product may be issued by the Regulatory Authority of the manufacturer's or holder's country; and as Manufacturing contract: The legal document concluded between the medicine holder and the manufacturer establishing the conditions, commitments, and other circumstances for the manufacture of one or more products; and which must indicate at minimum: 1) The existing contractual link between the parties involved. 2) That the contractor complies with Good Manufacturing Practices. 3) That the contractor has from the contracting party all the necessary information to carry out the contracted actions, as well as the processes it must implement for the medicine subject to the contract. 4) That the contracting party will conduct periodic audits of the contractor. Pharmaceutical equivalent is also defined: Pharmaceutical product containing identical amounts of the same active principles as the product to which it is equivalent, for example, the same salt or ester of the active principle, in identical pharmaceutical forms, that meet the established specifications, but do not necessarily contain the same excipients. Consequently, two pharmaceutical equivalents may show different bioavailability and pharmacological activities; and Therapeutic equivalence: referring to two pharmaceutical products that are therapeutically equivalent if they are pharmaceutically equivalent and after their administration in the same molar dose, their effects regarding efficacy and safety will be the same, determined by appropriate in vivo bioequivalence, pharmacodynamic, and clinical studies and/or in vitro dissolution studies. The term Biological pharmaceutical product is also conceptualized: as a pharmaceutical product obtained from living organisms or their tissues; and Sanitary registration as an administrative act by which it is established that the pharmaceutical product to be registered complies with the sanitary requirements of current regulations relating to quality, efficacy, and safety and that, therefore, it may be marketed in the country. For its part, numeral four provides that the functions of the technical body, established in Article 113 of the Ley General de Salud, centralized subsequently in the Dirección de Atención al Cliente, will be the approval or denial of the registration of any product referred to in this Regulation, and the Dirección de Regulación de la Salud will be responsible for establishing or approving the pharmacological technical norms governing the evaluation of medicines and the list of multi-source pharmaceutical products of sanitary risk. For these purposes, numeral 24 of decree 28466 provides that the Ministry of Health must publish on its website a list of applications for sanitary registration in process within a maximum period of 15 working days from the receipt of the application and must publish a list of pharmaceutical products that have been granted a sanitary registration within a maximum period of 15 working days counted from the issuance of the sanitary registration. Regarding applications for sanitary registration of multi-source pharmaceutical products, the following must be provided: a) An application for which no information on safety and efficacy is submitted must be considered by the Ministry as an application for the registration of a multi-source pharmaceutical product. The Ministry may only grant sanitary registration to a multi-source pharmaceutical product that is a pharmaceutical equivalent: i) Of a pharmaceutical product for which safety and efficacy data have been previously submitted to the Ministry by its applicant and for which a sanitary registration has been previously granted in Costa Rica. ii) Of a pharmaceutical product that meets all of the following conditions: a) That it is not protected by patents, b) That it does not contain protected test data, c) That it contains a chemical entity present in the formulation of a product that has previously obtained a sanitary registration in Costa Rica, d) That the applicant demonstrates, through a document issued by a regulatory authority, that the active principle has been authorized for marketing in any country for more than 5 years; and e) That international information exists guaranteeing the safety and efficacy of the pharmaceutical product before the Ministry of Health. The foregoing is to guarantee access to medicines of sanitary interest. b) Applicants requesting a sanitary registration for a multi-source pharmaceutical product must indicate in the application the name of the pharmaceutical product previously registered in the country with which the applicant's product is a pharmaceutical or therapeutic equivalent, as well as the expiration date of any protected test data and any patent covering the pharmaceutical product previously registered in the country, in accordance with the information contained in the Ministry of Health databases. c) The Ministry must not, without the consent of the legitimate holder of the test data submitted to the Ministry in support of an application for sanitary registration of a new pharmaceutical product, grant sanitary registration to the applicant for a multi-source pharmaceutical product, on the basis of: i) That test data; or ii) The sanitary registration granted to that new pharmaceutical product, before the expiration of the protection period for said test data. d) The applicant for a sanitary registration of a multi-source pharmaceutical product or its legal representative may request that the Ministry review the test data submitted in support of an application for sanitary registration for a new pharmaceutical product as evidence and support for its sanitary registration application, under the circumstances established in Chapter XI of this Regulation. In turn, regarding applications for a sanitary registration of a new pharmaceutical product, a sworn statement issued before a notary public must be submitted indicating any product or process patent granted and in force in Costa Rica that covers the pharmaceutical product, indicating the patent number and its expiration date. Applicants or their legal representative may update this list to include patents granted after the application for sanitary registration. However, these updates will not suspend the processing or granting of the sanitary registration for applications already submitted, nor will they affect sanitary registrations already granted. The Ministry must publish on its website, for each pharmaceutical product for which a sanitary registration has been granted, the list of product or process patents in force in the country that cover said pharmaceutical products, according to the information provided by the applicant or its legal representative. The Ministry must include this information on its website within a maximum period of 15 working days counted from the receipt of said information. The Ministry will publish in said list, the number and expiration date of each patent submitted by an applicant or its legal representative. In the case of applications for sanitary registration for the first time of multi-source pharmaceutical products, when the applicant cannot meet any of the requirements established in subparagraphs i) or ii), the applicant or its legal representative must submit a sworn statement issued before a notary public indicating that there is no patent granted and in force in Costa Rica claiming the pharmaceutical product subject to sanitary registration or, when such patents exist, the expiration or expiry date of the patent(s) claiming it, and indicating that the multi-source pharmaceutical product will not be marketed until after the expiration date of said patents. The applicant or its legal representative must indicate in their sworn statement issued before a notary public that they have reviewed the Ministry's website for the purpose of verifying this information. In such case, the Ministry will not issue the sanitary registration to the applicant until after the expiration of the protection period for all patents claiming the multi-source pharmaceutical product for which sanitary registration is requested, according to the information provided by the applicant or its legal representative, or the test data protection period, whichever is later, except as established in Chapter XI of this Regulation. For its part, numeral 27 stipulates the requirements to obtain a sanitary registration for the first time, for which a sanitary registration application dossier will be opened. Regarding the control of medicines, Article 50 ibid states that post-registration verification will be carried out by the Dirección de Regulación de la Salud, through inspectors designated for this purpose, by means of inspection and sampling in the market, at the pharmaceutical laboratory, or at customs, in accordance with the provisions of the Ley General de Salud, Law No. 5395 of October 30, 1973; and the Ley de Promoción de la Competencia y Defensa Efectiva del Consumidor, Law No. 7472 of December 20, 1994; and other applicable regulations, and the first quality control carried out on pharmaceutical products will be performed during the first year of marketing, without diminishing the controls eventually ordered by the Dirección de Regulación de la Salud.

VIII- ON THE ALLEGED PROCEDURAL DEFECT OF THE REGULATORY ADMINISTRATIVE ACTS, DUE TO THE ABSENCE OF THE HEARING PROVIDED FOR IN NUMERAL 361 OF THE LEY GENERAL DE LA ADMINISTRACION PÚBLICA.

As indicated in previous recitals, the Ley Constitutiva de la Caja Costarricense del Seguro Social in its numeral 72 mandates that it must establish and keep updated a registry of product suppliers. Under the protection of that norm, the Caja Costarricense del Seguro Social issued, by agreement CCF-1445-06-209, session 2009-21 of June 10, 2009, the Normativa con Requisitos para el Registro de Oferentes para Medicamentos Biotecnológicos, published in Gaceta 127 of July 2, 2009, which by agreement 3376-11-10, session 2010-44 of November 17, 2010, the Comité Central de Farmacoterapia of the Institution proceeded to annul all previous agreements issued on that regulation, establishing the following Normativa con Requisitos para el Registro de Oferentes para Medicamentos biotecnológicos y biológicos, which was stated to be directed at registered suppliers and suppliers to be registered in the CCSS Registry of Suppliers for biological medicines of Group 1 and Group 2 as stated, also imposing mandatory compliance for those suppliers participating with the Caja with medicines that do not have a Sanitary Registration of the Medicine. Similarly, the Comité Central de Farmacoterapia of the Caja Costarricense del Seguro Social, by agreement CCF-0275-02-09, session 2009-21 published in March 2009, issued the Condiciones específicas para la adquisición de medicamentos denominados antineoplásicos y otros medicamentos de uso específico en patologías oncológicas y hemato-oncológicas, which by session 2011-08 of February 23, 2011, of the Comité Central de Farmacoterapia, proceeded to modify point 6.

The claimant first presented substantive arguments and concluded both its statement of claim and its closing arguments with arguments tending to highlight the existence of a formal defect in the regulation in its capacity as an administrative act of a general nature. In view of the foregoing, this Panel of Judges clarifies that it is therefore pertinent, first, to begin the study of the procedural arguments, and subsequently, if necessary, in order to fully address the rest of the claimant's claims, to enter into substantive considerations. Thus, it is noted that the claimant alleges the absence of the hearing imposed by Article 361 of the General Law on Public Administration (Ley General de la Administración Pública) for the adoption of provisions of a general nature, which in its judgment constitutes an element of validity and its omission implies absolute nullity. The respondent's representation argues that such a requirement is not applicable to the scientific-technical provisions and/or guidelines issued by the Central Pharmacotherapy Committee (Comité Central de Farmacoterapia), since what is provided for in Article 361 of the General Law on Public Administration is for the drafting of provisions of a general nature in the strict sense by the Executive Branch which, in the exercise of its executive regulatory power (potestad reglamentaria ejecutiva), deems necessary to adopt; that is, in its represented party's judgment, such a requirement is not applicable to technical regulations adopted by advisory Technical Bodies as in this case. In order to address the arguments of both parties, it is important to clarify some concepts. Citizen participation and the "glass house" doctrine in the exercise of public function establish as a maxim that, except in very exceptional situations, the participation of the inhabitants must be allowed, both through the exhibition of decisions and the possibility of challenging them. If the public action presents its due foundation, the Administration should have no fear in expressing the proper justifications based on its different acts. Now, by Regulation (Reglamento) we must understand any legal provision of a general nature issued by the public Administration and with value subordinate to the law; it is one of the manifestations of the exercise of the administrative function, through the creation of a normative body of a lower rank and subject to the law, but with the authority to create legal effects. The regulation develops a law upon which its validity depends. The regulation is a norm, hence its dual condition. The regulatory power (potestad reglamentaria) is based on the need to generate norms whose procedure for approval, repeal, or modification is sufficiently expeditious to ensure agile resolution mechanisms for the ordinary activity inherent to the Administration, while the law, in its approval process, is slower due to the dynamics of parliament and, furthermore, cannot foresee all the scenarios that may be faced in each particular case when exercising public competences. Such power results in the issuance of an administrative act of a general nature called a regulation, subject to certain formal and substantial limits. Regarding its classification, the Constitutional Chamber (Sala Constitucional) has ruled in the following terms: "*IV.- ON AUTONOMOUS SERVICE AND ORGANIZATION REGULATIONS. (DE LOS REGLAMENTOS AUTÓNOMOS DE SERVICIO Y DE ORGANIZACIÓN.) It is alleged that through regulations, which do not meet the characteristics of an executive regulation (reglamento ejecutivo) or an autonomous service or organization regulation (reglamento autónomo de servicio o de organización), matters proper to formal law are regulated, by establishing limitations on fundamental rights, regarding the creation of sanctioning administrative bodies and the establishment of sanctions; in addition to the fact that it was not issued by the respective hierarchical body, but by the supplier of the Banco Nacional de Costa Rica. In order to analyze the consulted regulation, it is necessary to recall what this Constitutional Court has previously indicated regarding the different categories or types of regulations that are constitutionally possible: 'The categories into which regulations are distinguished are: a.) executive regulations (reglamentos de ejecución): which tend to carry out the concrete execution of laws, especially when these are of a rather generic scope; b.) independent or autonomous regulations (reglamentos independientes o autónomos) from any legislative provision, and related to matters within the competence of the Executive Branch not regulated by law, or partially regulated. Among these may be included the so-called organization regulations (reglamentos de organización), which refer to the institution and structure of the various public offices. Derived from the foregoing, the proper subject matter of regulations can be defined: *administrative matters*, which comprise the organizational aspects of the Public Administration - meaning the Executive Branch in the performance of its own functions. Therefore, there is an impediment to regulating by regulatory means matters referring to the rights and obligations of citizens as such, the limitation of their freedom or their rights - including the regime of taxes, penalties, and fundamental rights. These concepts have already been indicated by this Chamber on repeated occasions, through resolution number 1876-90, at sixteen hours on the nineteenth of December, and number 1635-93, at seventeen hours on the fourteenth of November, among others.' (Judgment number 5227-94, at fifteen hours six minutes on the thirteenth of September, nineteen ninety-four.) By virtue of the foregoing, the content of independent regulations or autonomous regulations can be clearly differentiated from executive ones, since they are characterized by regulating the own competence of their author -the Administration- and of the lower authorities, insofar as they aim to organize and regulate the activity of their author and subordinates, to achieve better fulfillment of the assigned public purpose. They are of two types: autonomous organization regulations (reglamentos autónomos de organización) and autonomous service regulations (reglamentos autónomos de servicio). The former find their basis in the power of self-organization of the administration itself, and the latter have their support in the competence of the administrative head to regulate the provision of the service under their charge, without the need for a prior law on the matter. These are regulations that create special subjection regimes and that come to limit the rights of the administered citizens who have entered into a relationship with the Administration." **vote number 2000-2856 of 15:48 hours on March 29, 2002.** In reality, the autonomous regulatory act is reserved for aspects of organization and functioning, where not even the law can establish certain limitations. That led to the generation of the doctrine of the interna corporis act, as the power of the public powers to self-organize. The national Constitution clearly develops the issue of the executive regulation and the power of the organization regulation. The submission of the latter to the former is clear, since the national legal system does not establish matters reserved for regulatory norms. Regarding the procedure for the formation of regulations, the General Law on Public Administration, in its Article 361, imposes that in the drafting of provisions of a general nature: *"1. A hearing shall be granted to the decentralized entities on the projects of general provisions that may affect them. 2. The representative entities of general or corporate interests affected by the provision shall be granted the opportunity to state their opinion, within a period of ten days, unless reasons of public interest or urgency duly stated in the preliminary draft oppose it. 3. When, in the judgment of the Executive Branch or the Ministry, the nature of the provision so advises, the preliminary draft shall be submitted to public information, during the period indicated in each case."*. From a study of the second paragraph of said norm, several legal prerequisites that must be met are observed, such as dealing with the process of creating a general norm, affecting interests of a general or corporate nature by denying, aggrieving, eliminating, or limiting subjective rights and/or legitimate and direct interests, and dealing with representative entities of the same. It is not superfluous to indicate that the General Agreement on Tariffs and Trade (GATT) and the Uruguay Round, both legal norms ratified by Costa Rica and having supremacy over legal norms, consider that any regulatory norm that implicitly, directly or indirectly, implies a restriction on trade conditions (non-tariff barriers) must be consulted prior to its entry into force. This allows an echo between the legal norm and that established in international regulations. Regarding the first requirement of dealing with a general norm, we must indicate that the administrative act produces individual or concrete effects (administrative resolutions and agreements) and collective or general effects, such as decrees and regulations, when directed at indeterminate subjects. As for the affectation of general or corporate interests, these refer to private or public entities that represent the community, the population, through their management, or deal with a corporation, which constitutes *"a duly constituted, personified, and organized collective organization that represents and defends the interests of a determinable group or sector of people (e.g., chambers, associations, professional bodies) (...)"*. Jinesta Lobo, Ernesto. Tratado de Derecho administrativo. Volume Three, San José, Costa Rica, editorial jurídica Continental, 2007, page 244. Regarding the procedure, the First Chamber (Sala Primera) of the Supreme Court of Justice (Corte Suprema de Justicia), in vote number 10 of 14:20 hours on January 22, 2002, provided that *"III ° The General Law on Public Administration devised a special procedure for the drafting of provisions of a general nature, which are administrative acts of normative scope. In the specialty that the legislator adopted, the answer lies to the questions raised in the sub judice, regarding the value that the hearing procedure has within that special process. A simple reading of the articles that regulate this special procedure reveals that it was devised with the precise object of enshrining the hearing procedure, in some cases, for entities of the state conglomerate itself (Article 361, paragraph 1), in others, for entities -it makes no distinction between public and private- representative of general or corporate interests, affected by the provision (Article 361, paragraph 2). From this, the value and transcendence of the hearing in the procedure for drafting general provisions is indisputable, this being a substantial, unavoidable formality, unless the concurrence of the exception assumptions that the same norm provides exists. This obligation, in the indicated special procedure, constitutes the legislative development of norms that, as a general principle, inform the administrative procedure. Articles 217, 218, and 220, in relation to 239 and following, of the General Law on Public Administration provide for the necessary intervention of the administered party in the procedure. As there are no individualized subjects in the adoption of regulatory acts who can be considered direct interested parties, the legislator provided that in such cases the transfer, the hearing, should be made to entities representative of corporate or general interests."*. By virtue of this, the cited hearing procedure is recognized as a necessary, unavoidable requirement of validity and efficacy, with legal and supra-legal roots, of the special procedure for creating administrative norms of a general nature. Pursuant to the foregoing, the hearing that must be granted is an essential requirement of the procedure, which has its foundation in constitutional principles not only of due process but also the right of citizens to participate, as our Constitutional Court has repeatedly provided in its rulings: **II .-ON CITIZEN PARTICIPATION. (SOBRE LA PARTICIPACION CIUDADANA.)** *The participation of citizens in public decision-making is provided for in Article 9 of the Political Constitution, therefore acquiring the rank and force of a fundamental constitutional right. It is not a matter of deconstitutionalizing the principle of legality of the Public Administration, although it is, of course, a more democratic form of government, which expands the forums for debate on different issues that affect the community, and by virtue of this, they are open to citizen intervention and opinion. We are, then, facing an option already widely accepted in the evolution of the concept of democracy, and this amparo offers a magnificent opportunity to give it clear and effective validity, so that it does not remain mere discourse. The aforementioned provision, then, embraces the cited principle through access to the available information and its dissemination, so that decision-making is not limited to a restricted group of interests. In this way, and in accordance with our democratic system, the ARESEP is obliged to convene such a hearing, particularly to guarantee the right of defense and access to information that concerns each and every one of the inhabitants of our country, so that decisions are not taken by surprise for the "affected" interested parties. Precisely, in the Law of the ARESEP and its regulation, the legislator provided a special administrative procedure, which is the public hearing whose main characteristic is to give transparency to the decisions of the Regulatory Entity and the possibility of giving participation to consumers and users within the process. Likewise, by giving the opportunity for neighbors, social organizations, the state and private sector, citizen defense institutions, and other government institutions to participate in it, a greater benefit is achieved, which facilitates a better exchange of information among the participants, making the hearing a transcendental instrument in decision-making and an instrument of transparency in a democratic system like ours. By virtue of the foregoing, the setting or modification of rates must be submitted to a public hearing in which those citizens who present an opposition based on technical criteria may participate, giving the interested party the right to exercise the use of the floor during the celebration of the respective act in order to defend their interest in the matter. In this way, the public hearing that the Regulatory Authority of Public Services (Autoridad Reguladora de los Servicios Públicos) must hold in those cases where it processes a study for setting public service rates, has the purpose of allowing the exercise of the right to community participation in a matter that directly affects it, prior to the making of the administrative decision and, in this way, constitutes a manifestation of the democratic principle. This hearing intends for interested persons to state what they deem appropriate regarding the rate-setting request under study before the Regulatory Authority, therefore the rigor required for proceedings intended to suppress a subjective right is not applied to it (judgment 2002-08848 at sixteen hours fifty-seven minutes on September ten, two thousand two); however, it is not a simple formal requirement, such that it can be set in a way that nullifies the exercise of the right it aims to protect, by being granted under conditions that prevent or hinder the fulfillment of the objectives it is called upon to achieve, in protection of the right to information and citizen participation…*" **III .-** *In conclusion, it is clear that in order to guarantee the right to citizen participation provided for in Article 9 of the Political Constitution, the public hearing that the Regulatory Authority of Public Services must hold in those cases where it processes a study for setting public service rates, must allow the exercise of the right to community participation in a matter of its interest and must be held within a reasonable period that allows the community to express itself. Thus, it is appropriate to accept the claim raised for violation of the right to citizen participation and annul the call made by the Regulatory Authority of Public Services to hear the rate increase proposed by COOPEMORAVIA, to increase the rate for route 40MB, described as San José-Moravia-Ramales and common corridors of routes 40, 41, 42, and 43 processed in case file ET-29-2010."* Judgment: 10708 of June 18, 2010.

**IX- ON THE SPECIFIC CASE. (SOBRE EL CASO CONCRETO.)** It remains then to establish the type of provision of a general nature that the administrative acts challenged here constitute and whether the hearing should have been granted in accordance with Article 361 of the General Law on Public Administration prior to their adoption.

From the foregoing, it is concluded that the Caja Costarricense del Seguro Social effectively issued said regulations under the protection of Article 72 of its Constitutive Law, and that the regulations issued are indeed of a technical nature. Given the body that issued them, they do not constitute executive regulations (reglamentos ejecutivos), but rather independent and highly sui generis regulations. Regarding the act issued by means of agreement 3376-11-10, session 2010-44 of November 17, 2010, the Institution's Central Pharmacotherapy Committee (Comité Central de Farmacoterapia) proceeded to render void all previous agreements issued under that regulation, establishing the following Regulation with Requirements for the Registration of Suppliers for Biotechnological and Biological Medicines (Normativa con Requisitos para el Registro de Oferentes para Medicamentos biotecnológicos y biológicos), thereby issuing a new regulation. From the review of the content of said regulation, we find that the requirements, in reality, are not for the supplier as such, but rather regarding the product: group 1, medicines of biological origin whose manufacturing process does not use raw material derived from blood products, and group 2, of biological origin whose manufacturing process uses raw material from blood products – the latter being understood according to point 4.53 of Decreto Ejecutivo 37006, as that obtained by industrial procedures, whose raw material is human blood or plasma, which, according to the experts who testified at the oral and public trial (Julián Cuesta Ramírez, Renato Murillo Masis and Albín Chávez Matamoros), are of high complexity in their production and are used for very specific and serious diseases. From the review of said regulation, it is extracted that for both group 1 and group 2 medicines, technical requirements are imposed for innovative, biosimilar, biological, and biotechnological medicines, among others; certificates in their manufacturing process, production, etc. It is even provided that, for the procurement of medicines, the Caja Costarricense del Seguro Social may take its clinical experience with the medicine as a qualification parameter and exempt from other technical requirements. Regarding the second challenged regulation, issued during session 2011-08 of February 23, 2011, by the Central Pharmacotherapy Committee, in which it proceeded to modify point 6 of the Specific Conditions for the acquisition of medicines called antineoplastic and other medicines for specific use in oncological and hema-oncological pathologies (Condiciones Específicas para la adquisición de medicamentos denominados antineoplásicos y otros medicamentos de uso específico en patologías oncológicas y hema-oncológicas), issued in agreement CCF-0275-02-09, session 2009-21 published in March 2009, equally technical requirements are imposed for their supply. From the statements of all the experts received at the oral and public trial, it is concluded that medicines must indeed possess three basic elements: quality, safety, and efficacy, which are indispensable for the medicine to produce the effects in the patients for which they were produced. The plaintiff, for both the regulation relative to biological, biotechnological, and antineoplastic medicines, argues on the merits that the reforms introduced in the regulations challenged by the Central Pharmacotherapy Committee of the Caja Costarricense del Seguro Social threaten the health and life of Costa Ricans, since there is no guarantee that said medicines possess the essential elements of quality, safety, and efficacy; it raises, in a detailed manner, a series of questions of a technical nature. From the meticulous review of said regulations, technical requirements are indeed established, or exemptions are made from the previous regulation for the purchase of medicines, which are ultimately used to fulfill the public purpose entrusted to the institution: public health. One must not lose sight of the fact that these provisions, without entering into the merits of the process, are indeed aimed at regulating the requirements that medicines must meet for their purchase. Medicines upon which a large number of people in our country depend, not only to protect their health but to preserve and rescue their lives; regulations that evidently contain provisions that must guarantee public health, which inevitably makes the discussion of their norms a matter of public interest, because the effects of said provisions, although they are initially a parameter for the purchase of medicines, their implicit objective is precisely to safeguard the health of all patients who attend public health centers in our country seeking to improve and preserve their health and their life. Therefore, the effects of said regulations are not limited to a matter of the Institution's organization, but are evidently a matter of Public Health. General provisions must not only be classified according to the body that issues them but also according to their effects and to whom they are directed. In the specific case of the challenged regulations, the final objective is the guarantee of the medicines supplied to patients. Therefore, in the opinion of this Collegiate Body, the challenged norms are independent technical regulations (Reglamentos técnicos independientes), albeit not executive, due to the effects of their application and compliance. Consequently, their interest cannot be limited only to organizations or groups, or to natural or legal persons dedicated to the production, distribution, and commercialization of medicines, but rather to every person in guarantee of a fundamental right to health and life as protected by our Political Constitution (Constitución Política). For this reason, it is not possible to accept the position maintained by the defendant's representation that, being a technical regulation, it does not require the procedure established in the Ley General de la Administración Pública. On the contrary, due to the technical matter it regulates, it should have, for its formation, granted the hearing (audiencia) established by Article 361 of the cited law. It cannot be overlooked that said hearing aims at the participation of citizens in public affairs, provided that the matter regulated in said regulations, as in those challenged here, is of public interest, as in the present case the right to life and health. Continuing with the analysis of the special procedure for the drafting of general provisions, other norms and general principles regulating the administrative procedure can be cited, an interpretation that is possible in accordance with Article 229, paragraph 1, of the Ley General de la Administración Pública, which reads as follows: "The present Book shall govern the procedures of all Administrations, unless a provision opposes it." For its part, Article 223 imposes that the omission of substantial formalities of the procedure shall cause the nullity of the proceedings. "2. A formality shall be understood as substantial if its correct fulfillment would have prevented or changed the final decision in important aspects, or whose omission caused defenselessness." It must be clear, as indicated above, the purpose of the hearing provided in Article 361 of the Ley General de la Administración Púbica, because for the effects that the challenged regulations entail, the hearing is essential, not only for organizations like the plaintiff, but for professional associations (colegios profesionales), medical and pharmacy professionals who can provide essential information on the quality, safety, and efficacy of medicines, as well as on the technical requirements requested for their procurement, and even more so, for administrative bodies such as the Ministry of Health (Ministerio de Salud). In this regard, the Ley General de Salud, in its Article 102, states that the importation of medicines and their distribution shall only be permitted to legal or natural persons registered with the Ministry, with prior authorization and registration with the Colegio de Farmacéuticos. This reinforces this Court's position regarding the mandatory nature of said hearing. Article 106 of the Ley General de Salud establishes that a medicine can legally be destined for commerce, public use, and consumption when it satisfies the regulatory requirements or those of the pharmacopoeia officially declared by the Executive Branch regarding its identity, quality, safety, and efficacy for the purposes for which it is used, consumed, or prescribed. An additional element is the full knowledge and acceptance of the Caja Costarricense del Seguro Social, which its representative expressed in the response to the complaint (folio 239, final paragraph of the main court file) where it states "that for the purposes of registering biotechnological medicines, although there is no regulation from the Ministry of Health of Costa Rica, the Central Pharmacotherapy Committee, until the regulation issued by the governing body exists, has been visionary and, in order to maintain the principles of Safety and Efficacy in the medicines recognized in my represented party's Supplier Registry…" This absolutely confirms this Collegiate Body's criterion on the mandatory nature of granting a prior hearing for the issuance of the challenged regulations, because knowing that the governing body in the matter had not issued the specific regulation regarding the sanitary registration (registro sanitario) of said medicines, the hearing established by law was necessary, timely, and convenient, so that the public governing body in the matter could rule. Note that the reforms made in 2010 to the Regulation with Requirements for the Registration of Suppliers for Biotechnological and Biological Medicines and, at the beginning of 2011, the Specific Conditions for the acquisition of medicines called antineoplastic and other medicines for specific use in oncological and hema-oncological pathologies, are very close to the year 2011 when Decreto Ejecutivo 37006-S is issued, which Regulates the Registration and Control of Biological Medicines (Reglamento de Inscripción y Control de Medicamentos Biológicos). This means that on those dates, the technical regulation that the defendant claims was lacking from the governing body in the matter was being developed. When the challenged regulations were issued, there is no doubt then that granting the hearing is a substantial formality, because a modification of the final act can arise from such an action. Precisely, the hearing aims to provide the opportunity for the entity or affected party to influence the will of the Administration before it acts in accordance with its regulatory powers. Failure to comply with the hearing process, which is not discretionary but mandatory, is necessarily linked to the validity of the general provision issued (as the culmination of the procedure) and, consequently, its omission can cause invalidity, therefore, it determines the nullity of all actions taken by the Administration in relation to the issuance of the challenged regulatory provisions. Consequently, the omission of the hearing by the defendant in the adoption of the challenged regulations constitutes a substantial defect (vicio sustancial) in the procedure for their issuance. It is not viable in the present case to make any distinction regarding the validity of parts of the challenged acts, insofar as the defect, being of a procedural nature, affects the entirety of the acts. Consequently, the absolute nullity of the following acts of a general nature is declared: 1- Agreement CCF-3376-11-10, session 2010-44 issued on November 17, 2010, by the Central Pharmacotherapy Committee of the Caja Costarricense del Seguro Social, published in the official newspaper La Gaceta number 10 of January 14, 2011, and 2- Agreement taken during session 20011-08, held on February 23, 2011, by the Central Pharmacotherapy Committee, by means of which it reforms point 6 of the Specific Conditions for the acquisition of medicines called antineoplastic and other medicines for specific use in oncological and hema-oncological pathologies, for lacking a formal prerequisite for validity. It should be noted that although the plaintiff makes a prolific argument for the nullity of these norms in different aspects, having upheld one renders it lacking all interest to expressly rule on the remaining ones. However, it is advisable to warn the public entity that it must be clear about which competencies belong to it with respect to those reserved for the Ministry of Health as the governing body in the matter. So that both dependencies must coordinate the fulfillment of their public purposes, but without the invasion of one into the other. In that aspect, we draw attention to the fact that matters referring to sanitary registration and its exception are the purview of the Ministry, a topic that must not be lost sight of.

X. REGARDING THE REMAINING CLAIMS

The plaintiff requests that “Since the challenged agreements are null, we require the restoration of the validity of the previous agreements; the 2009 Regulation with Requirements for Suppliers for Biotechnological and Biological Medicines (Normativa con Requisitos de Oferentes para Medicamentos Biotecnológicos y Biológicos) and in its place, that the 2009 Regulation with Requirements for the Registration of Suppliers for Biotechnological and Biological Medicines (Normativa con Requisitos para el Registro de Oferentes para Medicamentos Biotecnológicos y Biológicos) be applied, which corresponds to the previous version of the reform published in the official newspaper La Gaceta No. 10 of January 14, 2011, relating to the agreement of the Logistics Management of the Caja Costarricense del Seguro Social (CCSS) taken in session No. 2010-44 of the Central Pharmacotherapy Committee (agreement number CCF 3376-11-10) and the Agreement Called 'Requirements for antineoplastic medicines and others for specific use in oncological and hematological pathologies' published in La Gaceta No. 47 of March 9, 2010, which corresponds to the previous version of the introductory reform of session 2011-08 held on February 23, 2011, by the Central Pharmacotherapy Committee of the CCSS, published in La Gaceta No. 58 of March 23, 2011, and 'that the Caja Costarricense del Seguro Social apply the content of Decreto 37006-S published in the official newspaper La Gaceta Number 59 of March 22, 2012, called Regulation for the Registration and Control of Biological Medicines (Reglamento de Inscripción y Control de Medicamentos Biológicos), which is in accordance with the previous regulation of the Caja Costarricense del Seguro Social, whose validity we request be restored in point 3 of the claims of the lawsuit.'” In this regard, it is important to highlight that although the first two claims, regarding restoring the validity of the previous regulations, the 2009 Regulation with Requirements for the Registration of Suppliers for Biotechnological and Biological Medicines and the Agreement Called "Requirements for antineoplastic medicines and others for specific use in oncological and hematological pathologies” published in La Gaceta No. 47 of March 9, 2010, which corresponds to the previous version of the introductory reform, were outlined by the plaintiff from the beginning of their lawsuit, and subsequently, upon the occurrence of the issuance of Decreto Ejecutivo 37006-S (alleged as a new fact), they request the application of the latter. The circumstances evidently vary for the Caja Costarricense del Seguro Social, specifically regarding the matter it regulated due to the absence of technical regulation by the governing body, the Ministry of Health. Because of the above, it is the Caja Costarricense del Seguro Social that must determine which regulation is appropriate to apply, always in fulfillment of its purposes and the exercise of its competence, taking into consideration the existence and validity of Decreto Ejecutivo 37006-S. What is sought by the plaintiff cannot be declared; it is rejected, due to the variation in circumstances that it itself introduced as a new fact. To subject the Caja Costarricense del Seguro Social to the application of a regulation issued by the Central Pharmacology Committee under other circumstances and not those currently prevailing, as indicated above, would be to invade the regulatory power (Potestad reglamentaria) of the autonomous Institution. Therefore, it shall be the institution that defines which regulation best suits the fulfillment of its purposes, within its competence and in respect of the competencies of the governing body in the matter of health, the Ministry of Health. In application of Article 131 of the Código Procesal Contencioso Administrativo, it is clarified that the retroactive effects of this present declaration of absolute nullity shall not affect third parties who, as of the date of the finality of this judgment, have subjective rights acquired in good faith or consolidated legal situations derived from the aforementioned norm. Additionally, in application of Article 130, subsection 3) of the CPCA, the full publication of this judgment in the official newspaper La Gaceta must be ordered, at the expense of the Caja Costarricense del Seguro Social.

XI- REGARDING THE ALLEGED DEFENSES.

The defendant alleges a Lack of Standing (Falta de Legitimación) on the part of the plaintiff, asserting that Fedefarma does not seek to enforce the rights of the community regarding the use of medicines, but rather its underlying strategy is aimed at a commercial interest, which is why it lacks standing to sue the Caja Costarricense del Seguro Social. For its part, the plaintiff states that its interest is that of the patients, which justifies the defense of collective rights, and the action seeks to ensure compliance with quality and safety provisions introduced into the legal system by the Ministry of Health, which are recommended by the World Health Organization. That it is not, as the defendant claims, a commercial matter, but rather ensuring that the population has safe and effective medicines, which is why they defend the rights of the community. Therefore, its represented party has standing to file the action. Regarding Standing, it is the necessary correspondence between the defendant and the holder of the right or legitimate interest claimed. It is an essential prerequisite of the procedural legal relationship, indispensable for a favorable judgment. Article 10, subsection b of the Código Procesal Contencioso establishes that the following have standing to bring an action: “b) Entities, corporations, and institutions of Public Law and those representing and defending interests or rights of a general, union, or corporate nature, insofar as such interests or rights are affected, and groups governed by some statute as long as they defend collective interests.” The second subsection of the cited article establishes that those who hold, with respect to regulatory provisions, some legitimate interest, whether individual or collective, or some subjective right, may directly challenge them, without requiring an individual application act. It is necessary to mention that the norm establishes two different prerequisites: subsection 1.B for specific acts or concrete actions, and subsection 2 for the challenging of regulatory provisions, as in the specific case, and this prerequisite grants standing to act in defense of collective rights. Therefore, it is essential to determine if the plaintiff, even if it mentions so, is truly acting in representation of collective interests. The national jurist Manrique Jiménez Meza defined collective interests as "typical interests of a group or smaller collectivities, attributable to the organized collectivity, whether through legal entities or through groups not incorporated into such entities, for the protection of the interests embedded in each category of belonging (...) collective interests are category interests and, as such, constitute a partial treatment in the context of the broad impersonal, anonymous, and indeterminate collective, but they are no less of vital importance in the social context for that. Consequently, collective interests are attributable to the subjects representing such interests, whether through associations, organizations, various entities, or even through groups organized by virtue of shared interests in the face of common threats or harms." (Jiménez Meza Manrique, The New Administrative Litigation Process, San José. Judicial Branch. Department of Graphic Arts, 2006, page 89.) Professor Jinesta Lobo defines them as "those belonging to a group or a category, which are subdivided, in turn, into corporate and diffuse. Consequently, collective interests are a species of the genre, whose holder is an organized or unorganized group, incorporated or not, different from the national community, within another of greater magnitude that can be considered total or general. Such a category or group can be identified by a characteristic or common feature of social relevance (hobby, occupation, line of business, consumers or users of certain public goods or services, etc.)." JINESTA LOBO, Ernesto. Tratado de Derecho Administrativo Tomo III. 1st Edition. Editorial Jurídica Continental. San José, 2007, p. 243. The plaintiff, from its lawsuit (folio 2), informs that "FEDEFARMA is a civil organization constituted in accordance with the laws of the Republic of Guatemala, which represents research and development pharmaceutical companies operating in the Central American Isthmus and the Caribbean area (…) it groups fourteen multinational research pharmaceutical companies." From the review of the evidence provided by the plaintiff in response to the preliminary order issued by this Court regarding its legal standing (personería), the articles of incorporation of said Federation were reviewed, and specifically at folio 483, the said articles establish: "ARTICLE 3. The Federation is an entity foreign to all profit and religious purposes. Completely apolitical, created to promote the development and improvement of the pharmaceutical activity, to defend and coordinate the interests of its associates and to represent them in their relations with other public or private entities and with private individuals." In analyzing the complaint, it is evident that the plaintiff, within her arguments, has mentioned that her interest lies in defending the quality of the medications supplied to patients, repeatedly alleging that she demands the protection of the right to health of the patients who are ultimately the users of the medications acquired by the Caja Costarricense del Seguro Social to meet health needs. Notwithstanding the foregoing, the same complaint also demonstrates that the plaintiff always stated that she represents a group of multinational research pharmaceutical companies, and from the articles of her incorporation, her objective is indeed to promote the development and improvement of pharmaceutical activity; therefore, in application of the second paragraph of numeral 10 of the Código Procesal Contencioso, the plaintiff does have standing (legitimada) to appear in defense of the collective interests that Fedefarma represents, coupled with the fact that her own arguments present a challenge to the quality of the medications that may be distributed and consumed in our country. Thus, the core that unites the pharmaceutical companies to form the Federation serves as the basis in the process at hand; so the normative requirement is satisfied. Although this argument is not developed in the best manner in the complaint, as already indicated, this is inferred without major questions. Note that although the cited second paragraph limits, for purposes of challenging regulatory provisions, legitimate, individual, and collective interests—but not diffuse interests—the plaintiff does meet the legal requirement to bring an action on behalf of those she represents, a Federation composed of pharmaceutical houses, with the purpose of promoting and protecting the activities of pharmaceutical laboratories. Added to the above, as expressed by this Chamber, the effects of the challenged regulations are ultimately directed at a matter of Public Health, and since the protection of life and health of individuals is a fundamental right, standing in this matter cannot be restrictive. Consequently, the defense of lack of standing to sue (falta de legitimación activa) alleged by the defendant's representative must be rejected. For greater abundance, it should be noted that doctrine has identified a series of topics where standing is open to any inhabitant (almost like actio popularis) due to the level of social relevance, among which are tax matters and environmental matters; some doctrine further accepts health topics within this list. The logic that would prevail according to this reasoning is that in those matters where the impact on health is the core of the discussion, any natural or legal person would have standing. A position that, although not embraced by the Tribunal at this moment, does not lack its due support and legal logic. Regarding the Lack of Right (Falta de Derecho), this is rejected insofar as the ruling indeed declared the nullity of the challenged regulatory provisions, and the plaintiff is correct in her arguments, being understood as accepted in the remaining claims. Thus, the right invoked by the defendant lacks its corresponding support; instead, the scales of justice lean in another direction, implying the rejection of the preliminary defense.

XII.- REGARDING COSTS. Regarding costs, in accordance with numeral 193 of the Código Procesal Contencioso Administrativo, the costs of the process are the responsibility of the defendant. The foregoing is because the plaintiff has had to resort to this avenue to enforce her right, which determines that if not charged to the public entity, it would result in unjust enrichment for the plaintiff.

POR TANTO:

The new facts presented by the plaintiff are admitted. The defenses of Lack of Standing (Falta de Legitimación activa) and Lack of Right (Falta de Derecho) raised by the defendant are dismissed, the latter in what was granted, understood as admitted in the remainder. The complaint is partially granted, understood as denied in what is not expressly granted; consequently, the absolute nullity of the following administrative acts is declared: 1- Acuerdo CCF- 3376-11-10, session 2010-44 issued on November 17, 2010, issued by the Comité Central de Farmacoterapia of the Caja Costarricense del Seguro Social, published in the Diario Oficial la Gaceta number 10 of January 14, 2011, in which the Normativa con Requisitos de Oferentes para Medicamentos Biotecnológicos y Biológicos of 2009 is modified. 2- Acuerdo taken during session 20011-08, held on February 23, 2011, by the Comité central de Farmacoterapia, whereby point 6 of the Condiciones específicas para la adquisición de medicamentos denominados antineoplásicos y otros medicamentos de uso específico en patologías oncológicas y hema-oncológicas, published in Gaceta 58, is amended. The Caja Costarricense del Seguro Social takes note of what is set forth in the recitals of this ruling. Both costs of the process are the responsibility of the losing party. Notifìquese.

Grace Emilia Loaiza Sánchez Ricardo Ant. Madrigal Jiménez Carlos Enrique Espinoza Salas Jueces de juicio Sección Cuarta

SENTENCIA 120-2013 TRIBUNAL CONTENCIOSO ADMINISTRATIVO Y CIVIL DE HACIENDA, SEGUNDO CIRCUITO JUDICIAL DE SAN JOSÉ, ANEXO A, SECCIÓN CUARTA, a las quince horas con treinta minutos del veinte de diciembre de dos mil trece.

Proceso de conocimiento tramitado bajo el número de expediente 11-5719-1027-CA, incoado por FEDERACIÓN CENTROAMERICANA DE LABORATORIOS FARMACÉUTICOS (en adelante FEDEFARMA ), cédula jurídica CED87542, representada por su Apoderado Generalísimo sin límite de suma Álvaro Soto Monge, mayor, casado, vecino de Moravia, cédula de identidad CED87543 en contra de la CAJA COSTARRICENSE DEL SEGURO SOCIAL, la primera representada en el proceso por los licenciados Carlos Ubico Durán, soltero, cédula de identidad CED87544, vecino de San José y Alejandra Castro Bonilla, casada, vecina de Moravia, cédula de identidad CED87545, ambos mayores y abogados, y la segunda por su Apoderado General Judicial, licenciado Eder José Ramírez Segura, mayor abogado. Expediente número xxxxxx.

RESULTANDO

1- Con base en la demanda interpuesta (folios 1 a 49) , se ordene en sentencia: "(...) 2- Que se declaren absolutamente nulos, por ser disconformes con el ordenamiento jurídico, y por ende se proceda a la anulación total de: // i) el acuerdo tomado en sesión N° 2010-44 del Comité Central de Farmacoterapia (acuerdo número CCF 3376-11-10) publicado en el Diario Oficial de la Gaceta de N° 10 del 14 de enero de 2011 por la Gerencia de Logística de la Caja Costarricense del Seguro Social, en virtud del cual se modifica la Normativa con Requisitos de Oferentes para Medicamentos Biotecnológicos y Biológicos del 2009 y en su lugar se aplique la Normativa con Requisitos para el Registro de Oferentes para Medicamentos Biotecnológicos y Biológicos del 2009 y // ii) el acuerdo tomado por el Comité Central de Farmacoterapia de la Caja Costarricense del Seguro Social en sesión 2011-08 celebrada el 23 de febrero del 2011 en el cuál modificó el Punto 6 de los requisitos de los medicamentos denominados antineoplásicos y otros medicamentos de uso específico en patologías oncológicas y hematológicas publicado en la Gaceta N° 58 del 23 de marzo de 2011 y en su lugar se aplica la disposición anterior publicada en La Gaceta N° 47 del 9 de marzo de 2010. // 3- Al ser nulos los acuerdos impugnados requerimos restaurar la vigencia de los siguientes acuerdos: // a-Normativa con Requisitos de Oferentes para Medicamentos Biotecnológicos y Biológicos del 2009 y en su lugar se aplique la Normativa con Requisitos para el Registro de Oferentes para Medicamentos Biotecnológicos y Biológicos del 2009 y que corresponde a la versión anterior de la reforma publicada en el Diario Oficial La Gaceta N° 10 del 14 de enero de 2011 relativa al acuerdo de la gerencia de Logística de la Caja Costarricense del Seguro Social (CCSS) tomando en sesión N° 2010-44 del Comité Central de Farmacoterapia (acuerdo número CCF 3376-11-10). // b- Acuerdo Denominado "Requisitos de los medicamentos antineoplásicos y otros de uso específico en patologías oncológicas y hematológicas publicada en la Gaceta N° 47 del 9 de marzo de 2010, que corresponde a la versión anterior de la reforma introductoria sesión del 2011-08 celebrada el 23 de febrero de 2011 por parte del Comité Central de Farmacoterapia de la CCSS, publicada en Gaceta N° 58 del 23 de marzo de 2011. // 4- Se condene al demandado al pago de las costas procesales y personales de este proceso." 2- En la apertura del juicio oral y Público, se formularon hechos nuevos y se realizaron ajustes en las pretensiones, adicionando (folio 451): " Que la Caja Costarricense del Seguro Social aplique el contenido del Decreto 37006-S publicado en Diario oficial La Gaceta Número 59 del 22 de marzo del 2012, denominado Reglamento de Inscripción y Control de Medicamentos Biológicos, el cual es conforme a la normativa anterior de la Caja Costarricense del Seguro Social, que en el punto 3 de las pretensiones de la demanda solicitamos se restaure su vigencia." 3- La representación de la demandada contestó negativamente la demanda opuso las excepciones de Falta de Legitimación activa y Falta de Derecho 4- El juicio oral y público se celebró en la primera y segunda audiencia del 20 y 21 de agosto, primera del 22 y 23 de agosto y 17 de setiembre, segundas del 29 de octubre y 26 de noviembre todas de 2013, a las cuales asistieron ambas partes.

5- El señor Juez Ricardo Madrigal Jiménez, miembro del Tribunal estuvo incapacitado del 9 al 13 de setiembre de 2013 (folios 459, 460, 462 y 463) 6- En fecha de tres de octubre de 2013, de conformidad con el numeral 110 del Código Procesal Contencioso se ordenó reabrir el debate, y se previno a la parte accionante la presentación de su personería (folio 465), la audiencia de reapertura de se llevó a cabo el 29 de octubre de 2013, a la cual asistieron ambas partes.

7- La jueza Loaiza Sánchez miembro del Tribunal estuvo incapacitada del 4 al 8 de noviembre de 2013 (folio 564) 8- En fecha 21 de noviembre de 2013, se ordenó de conformidad con el numeral 110 del Código Procesal Contencioso Administrativo la reapertura del debate a fin de someter a discusión prueba para mejor resolver ofrecida en la etapa de deliberación por la parte accionada, la cual fue admitida por el Tribunal (folio 573) La audiencia de reapertura se llevó a cabo el 26 de noviembre de 2013 (folio 576) 9- La Juez Loaiza Sánchez estuvo incapacitada del 29 de noviembre al 6 de diciembre de 2013 (ver folio 577 y 578) 10- Durante el Juicio oral y público se ordenó prueba para mejor resolver, la cual fue puesta en conocimiento de las partes y discutida en la reapertura de juicio.

11- En los procedimientos se han seguido las prescripciones legales, no existen defectos capaces de producir nulidad y se dicta esta resolución dentro del término establecido en el numeral 111 del Código Procesal Contencioso Administrativo, para los procesos de trámite complejo, previa deliberación y por unanimidad:

Redacta la Juez Loaiza Sánchez;

CONSIDERANDO:

I- HECHOS NUEVOS: Se formularon como tales en la audiencia de juicio oral y público, por la parte actora, en los siguientes términos: "HECHO VIGESIMO SEGUNDO: Que en la Gaceta 59 del 22 de marzo de3 2012, se aprobó el Decreto Ejecutivo N° 37006-s, Reglamento de Inscripción y Control de Medicamentos Biológicos y Biotecnológicos, que regula los requisitos para inscripción de medicamentos de origen biológico, es decir, medicamentos biológicos y biotecnológicos. HECHO VIGESIMO TERCERO: Que el acuerdo tomado en sesión N° 2010-44 del Comité Central de Farmacoterapia (acuerdo Número CCF- 3376-11-10), publicado en el Diario Oficial La Gaceta de No 10 del 14 de enero de 2011 por la Gerencia de Logística de la Caja Costarricense del Seguro Social, en virtud del cual se modifica la Normativa con Requisitos para el registro de Oferentes para Medicamentos Biotecnológicos y Biológicos del 2009, presenta importantes contradicciones con respecto al Decreto Ejecutivo N° 37006-S, que detallamos seguidamente: //1. En el Artículo 5.6 del Decreto Ejecutivo N° 37006-S el Ministerio de Salud exige que se deberá de presentar el ejercicio de biosimilitud relacionado con la calidad en comparación del medicamento biotecnológico de referencia, esto para determinar que no tiene implicaciones adicionales de seguridad y eficacia para lo cual el reglamento detalla una serie de estudios relacionados con la estructura del medicamento, entre otros. Del mismo modo el artículo 5.12 detalla la información sobre seguridad y eficacia que se debe aportar dentro de lo que se incluye estudios pre clínicos (in vivo e in vitro) así como estudios clínicos comparativos con el medicamento original de referencia. Los requisitos detallados en estos artículos del reglamento, no son exigidos por la CCSS quien solo pide la fórmula cuali-cuantiativa del medicamento (ver normas que contradicen el decreto 37006-S: Grupo 1, punto 3; Grupo 2, punto 2 de la norma impugnada. // 2. El Reglamento emitido por el Ministerio de Salud establece en el artículo 5.12 que la experiencia en productos biosimilares se medirá de acuerdo a lo que establece la Organización Mundial de la Salud, para lo cual pide estudios pre clínicos y clínicos así como el detalle requerido por las guías de las autoridades estrictas (FDA, EMA e ICH) y el detalle de los estudios de biosimilitud aplicados. Dichas Pruebas no son requeridas por la normativa de la CCSS quien por contrario, pide como única experiencia del producto biotecnológico que el producto posea "amplia experiencia clínica" en la CCSS. Por ende, la normativa de la CCSS (ver normas que contradicen el decreto 37006-S: Grupo 1, punto 8; Grupo 2, punto 7 de la norma impugnada) contradice la normativa emitida por el Ministerio de Salud. // 3. En la nota 2 del artículo 5 del Decreto Ejecutivo n° 37006-S, el Ministerio de Salud exige para todos los estudios de biosimilitud que deben utilizarse las guías de la OMS (aportadas en autos a folios 41 a 91 del expediente de la medida cautelar) o bien las normas emitidas por autoridades estrictas (FDA, EMA e ICH). Sin embargo, la normativa de la CCSS permite a la CCSS prescindir incluso de esos estudios, pese que el Ministerio de Salud no establece ninguna excepción para dejar de pedirlos (Normas que contradicen el decreto 37006-S: Grupo 1, punto 8; Grupo 2, punto 7 de la norma impugnada). // 4. El artículo 5.3 del Decreto N° 37006-S, establece como requisitos para el registro sanitario de los medicamentos biológicos la información sobre el estatus regulatorio del producto a nivel internacional así como las inspecciones a los laboratorios internacionales. Esta información asegura que los productos biotecnológicos que se introducen al mercado tengan experiencia en otros mercados y por ende se prueba su efectiva experiencia, seguridad y eficacia en el momento del registro así como que el medicamento ha tenido efectos positivos o negativos en una determinada población. No obstante, la normativa de la CCSS exclusivamente pide experiencia del producto de la misma CCSS, no así a nivel regulatorio internacional (ver normas que contradicen el decreto 37006-S; Grupo 1, punto 8; Grupo 2, punto 7 de la norma impugnada). // 5. El artículo 10 del Decreto 37006-S, exige reportes de los Planes de manejo de Riesgo y de Farmacovigilancia que la CCSS no requiere en su normativa y que resultan indispensables para vigilar la inmunogenicidad de un medicamento biotecnológico. // 6. El Ministerio de Salud no avala la intercambialidad de medicamentos biotecnológicos mientras que la CCSS si permite sin restricciones tal intercambiabilidad (ver normas que contradicen el decreto 37006-S: Grupo 1, punto 8; Gripo 2, punto 7 de la norma impugnada). La consecuencia de esta contradicción radica en que si la CCSS está avalando productos en virtud de su "amplia experiencia clínica" demostrada en la CCSS, no es posible probar dicha experiencia clínica exitosa por medio de la farmacovigilancia, por cuanto si se avala la intercambialidad, se hace imposible seguir el comportamiento de una solución terapéutica con respecto a la otra y por ende imposible de verificar cual es la experiencia del producto; sobre todo cuando estamos ante medicamento de estrecho margen terapéutico que atiende padecimiento gravísimos. HECHO VIGESINO CUARTO: El Decreto Ejecutivo N° 37006-S, es el único que cumple con las estipulaciones de la Organización Mundial de la Salud, pues a diferencia de la normativa de la CCSS, exige que para el permiso de comercialización de un biotecnológico se cumpla con la presentación de una serie de requisitos indispensables que exige la OMS, por medio del "Procedimiento para la precalificación de productos farmacéuticos emitida por la Organización Mundial de la Salud" (folio 54-41 medida cautelar) y de las "Directrices en la evaluación de productos bioterapéuticos similares emitida por la Organización Mundial de la Salud" (Folio 91-55 medida cautelar). Es de suma importancia mantener dichos requisitos exigidos para el registro sanitario de medicamentos biotecnológicos así como los detallados en el reglamento del Ministerio de Salud, considerando sobre todo que la CCSS puede y de hecho compra medicamentos que no poseen registro sanitario en Costa Rica, podrían adquirir productos que solo cumplan con los escasos requisitos de la CCSS y no con los Ministerio de Salud ". Conforme el numeral 68 del Código Procesal Contencioso Administrativo, habiéndose opuesto los anteriores hechos dentro de la etapa procesal dispuesta, este Tribunal procede a admitirlos como hechos nuevos, que se incorporan a la demanda inicial, y procederá en los siguientes considerandos a su análisis. Téngase a la vista que corresponde a situaciones fácticas ocurridas después de presentada la demanda, y con intima relación con el proceso que nos ocupa; de esa manera se satisfacen los presupuestos normativos que nos ocupan.

II- HECHOS PROBADOS. SE TIENEN POR DEMOSTRADOS LOS SIGUIENTES:

1- Mediante decreto ejecutivo 28466 del 08 de febrero de 2000, se dictó Reglamento de Inscripción, Control, Importación y Publicidad de Medicamentos Datos generales: con el objetivo de establecer los requisitos y trámites necesarios para inscripción, control, importación y publicidad de medicamentos, de aplicación para todas las personas que fabrican, importan y comercializan medicamentos en el territorio Nacional (documento de acceso público); 2- Mediante acuerdo CCF-1445-06-09, sesión 2009-21 del 10 de junio de 2009, el Comité Central de Farmacoterapia de la Caja Costarricense del Seguro Social, se establecieron los requisitos a cumplir para el registro de oferentes en medicamentos biotecnológicos, Tanto del grupo 1, medicamentos de origen biológico, que en su proceso de manufactura no utilizan como materia prima proveniente de hemoderivados (plasma humano), como del grupo 2, medicamentos de origen biológico que utilizan en su proceso de manufactura, materia prima proveniente de hemoderivados (plasma humano) (ver folios 222 a 226 del expediente administrativo tomo I y 117 del tomo 2); 3- En el primer (1) Grupo de Medicamentos de origen biológico el oferente debía presentar los siguientes requisitos: "1. Certificado del registro sanitario del medicamento emitido por el Ministerio de Salud de Costa Rica. 2. Para los medicamentos innovadores se debe adjuntar la fórmula cualitativa-cuantitativa completa con los excipientes usados y los rangos permitidos de sustancias relacionadas, asimismo los estudios de caracterización del medicamento. 3. Para los medicamentos biosimilares se debe adjuntar la fórmula cualitativa-cuantitativa completa con los excipientes usados y los rangos permitidos de sustancias relacionadas, asimismo los estudios de caracterización del medicamento; además, deben presentar los estudios de caracterización del medicamento comparado con el medicamento de referencia que se comercializa en Costa Rica. 4. Los medicamentos que en su proceso de manufactura no utilizan materia prima hemoderivados pero que en su formulación y mediante su fórmula cualitativa se corrobora que presentan excipientes del plasma humano como albúmina, deben cumplir con todos los lineamientos vigentes establecidos en el Decreto de Hemoderivados Nº 19981-S del 3 de octubre de 1990. 5. Deben cumplir con las especificaciones de calidad establecidas en la ficha técnica oficial correspondiente a cada medicamento. 6. El Registro de Oferentes del Laboratorio de Normas y Calidad de Medicamentos y el Comité Central de Farmacoterapia deja bien establecido que se avalan únicamente productos biológicos que se encuentren o no inscritos en el Ministerio de Salud de Costa Rica, pero que se consuman en los siguientes países: Estados Unidos (FDA), y /o países de la Comunidad Europea (EMEA), y/o Canadá, y/o Japón, y/o Suiza. 7. En el caso de los medicamentos innovadores, los laboratorios fabricantes deben presentar Certificados de libre venta del medicamento en el país de origen como Estados Unidos, Comunidad Económica Europea, Canadá, Japón, Suiza por la instancia sanitaria regulatoria de ese país. 8. En el caso de los medicamentos biosimilares, los laboratorios fabricantes deben presentar Certificados de libre venta del medicamento en el país de origen como Estados Unidos, Comunidad Económica Europea, Canadá, Japón, Suiza por la instancia sanitaria regulatoria de ese país, asimismo que un certificado emitido por la misma entidad sanitaria, que garantice que el medicamento cumple con los criterios de calidad solicitados para medicamentos biológicos y que cuenta con los estudios clínicos de seguridad y eficacia que dieron origen a su registro sanitario en el país de origen, que cuenta con estudios clínicos de inmunogenicidad (aplicable solo para los medicamentos marcados con *****), seguridad y eficacia, en las mismas indicaciones oficiales que el producto de referencia que se comercializa en el país, al igual que de los estudios de caracterización y comparabilidad que demuestran que el producto es biosimilar al de referencia que se comercializa en Costa Rica. Además se debe adjuntar la fórmula cualitativa-cuantitativa completa con los excipientes usados y los rangos permitidos de sustancias relacionadas, y la certificación de la Instancia sanitaria (EMEA y/o FDA) que lo acredita como medicamento biosimilar. 9. Todos los documentos que se solicitan que sean emitidos en el exterior (otros países), deben ser consularizados y presentados en idioma español. 10. La Institución, con base en la amplia experiencia clínica adquirida a través de los años con el uso de medicamentos biológicos, se reserva el criterio sobre algunas especificaciones y requisitos a evaluar para la inclusión de nuevos medicamentos que comparten el mismo código, en el registro de oferentes y medicamentos no registrados; y avala únicamente la intercambiabilidad de productos biológicos que han documentado seguridad y eficacia comprobada mediante su uso clínico en la Institución a través de los años." (Ver folios 224 y 225 del expediente administrativo); 4- En el segundo (2) Grupo de Medicamentos de origen biológico el oferente debía presentar los siguientes requisitos: "1. Certificado del Registro Sanitario del Medicamento emitido por el Ministerio de Salud de Costa Rica. 2. Adjuntar la fórmula cualitativa-cuantitativa completa con los excipientes usados y los rangos permitidos de sustancias relacionadas. 3. Debe cumplir con las Especificaciones de Calidad especificadas en cada ficha técnica correspondiente de cada medicamento. 4. Deben cumplir con toda la reglamentación solicitada por el Ministerio de Salud de CR y todo lo solicitado por el Laboratorio de Normas y Calidad de Medicamentos de la CCSS en materia de hemoderivados. 5. El Registro de Oferentes del Laboratorio de Normas y Calidad de Medicamentos y el Comité Central de Farmacoterapia deja bien establecido que se avalan únicamente productos biológicos que se encuentren o no inscritos en el Ministerio de Salud de Costa Rica, pero que se consuman en los siguientes países: Estados Unidos (FDA), y /o países de la Comunidad Europea (EMEA), y/o Canadá, y/o Japón, y/o Suiza. 6. Todos los documentos que se solicitan que sean emitidos en el exterior (otros países), deben ser consularizados y presentados en idioma español. 7. La Institución con base en la amplia experiencia clínica adquirida a través de los años con el uso de medicamentos biológicos, se reserva el criterio sobre algunas especificaciones y requisitos a evaluar para la inclusión de nuevos medicamentos que comparten el mismo código, en el registro de oferentes; y avala únicamente que ha documentado seguridad y eficacia comprobada mediante su uso clínico en la Institución a través de los años. 8. El laboratorio fabricante debe garantizar que el plasma humano utilizado como materia prima en la manufactura de cada uno de los medicamentos biológicos, debe proceder de seres humanos sanos y el mismo exento en su totalidad de virus o de otros patógenos, debe cumplir con los lineamientos vigentes establecidos en el Decreto de Hemoderivados Nº 19981-S del 3 de octubre de 1990." (ver folio 226 del expediente administrativo); 5- Dicho acuerdo fue publicado en el diario oficial La Gaceta número 127 del 02 de julio de 2009 (ver folio 222 del expediente administrativo); 6- El Comité Central de Farmacoterapia mediante sesión 2010-44, acuerdo 3376-11-10 del 17 de noviembre de 2010, procedió a modificar la normativa con requisitos a cumplir para el registro de oferentes en medicamentos biotecnológicos y biológicos, dictando una nueva normativa, lo que se publicó en gaceta número 10 del 14 de enero de 2011 (ver folios 230 a 239 y 264 del tomo II del expediente administrativo); 7- La citada normativa se aprobó en los siguientes términos: "En este primer Grupo de Medicamentos (Grupo 1) de origen biológico, el oferente debe presentar los siguientes requisitos: 1. Certificado del registro sanitario del medicamento emitido por el Ministerio de Salud de Costa Rica. 2. Para los medicamentos innovadores se debe adjuntar la fórmula cualitativa-cuantitativa completa con los excipientes usados y los rangos permitidos de sustancias relacionadas, asimismo los estudios de caracterización del medicamento (fisicoquímica y farmacológica). 3. Para los medicamentos biosimilares se debe adjuntar la fórmula cualitativa-cuantitativa completa con los excipientes usados y los rangos permitidos de sustancias relacionadas, asimismo los estudios de caracterización del medicamento (fisicoquímica y farmacológica). 4. Los medicamentos que en su proceso de manufactura no utilizan materia prima hemoderivados pero que en su formulación y mediante su fórmula cualitativa se corrobora que presentan excipientes del plasma humano como albúmina, deben cumplir con todos los lineamientos vigentes establecidos en el Decreto de Hemoderivados N° 19981-8 del 3 de octubre de 1990. 5. Deberá cumplir con las especificaciones de calidad establecidas en la ficha técnica oficial correspondiente a cada medicamento. 6. Todos aquellos proveedores de medicamentos biológicos o biotecnológicos que requieran precalificarse ante el Registro de Proveedores u ofertar sus productos a la Institución, deberán presentar certificado de que dichos medicamentos se encuentran registrados y/o se comercialicen en cualquiera de los siguientes países: Estados Unidos (FDA), Canadá (Health Canadá), Japón (MHLW), Suiza (Swissmedic), y países miembros de la Comunidad Económica Europea que se encuentran registrados ante la Agencia Europea de Medicamentos (EMA) o que cuentan con Reconocimiento Mutuo en alguno de los estados miembros de referencia de la Comunidad Económica Europea. Estos países se consideran como de referencia debido a que tienen altos estándares en la regulación de medicamentos. 7. Todos los documentos que se solicitan y que sean emitidos en el exterior. Deben estar consularizados y certificados por notario público, según lo exige la legislación costarricense y la cadena de legalización consular de nuestro país y ratificadas por el Ministerio de Relaciones exteriores. Todo documento debe presentarse en idioma español y si está en otro idioma debe adjuntarse la traducción oficial del documento original al español. 8. "La Institución, con base en la amplia experiencia clínica adquirida a través de los años con el uso de medicamentos biológicos, se reserva el criterio sobre algunas especificaciones y requisitos a evaluar, no solo para la inclusión de nuevos medicamentos que comparten el mismo código en el registro de oferentes y de los medicamentos no registrados, sino que también para su adquisición, avalando técnicamente la intercambiabilidad de productos biológicos que han documentado la seguridad y eficacia, comprobada mediante su uso clínico en la Institución a través de los años. Para el caso de medicamentos biológicos (mismo laboratorio fabricante) que han sido adquiridos y consumidos históricamente a Nivel Institucional, con comprobada experiencia de uso y respaldo de su eficacia y seguridad, es permisible se les exima de los requisitos establecidos en el punto 6, sin menoscabo del cumplimiento del resto de requisitos establecidos. Los oferentes de medicamentos biológicos (mismo laboratorio fabricante) con los que se cuenta con experiencia histórica de uso Institucional y que se les estaría eximiendo de los requisitos indicados en el punto 6 deben adjuntar la certificación de libre venta del medicamento en el país de origen del laboratorio fabricante, cumpliendo con lo señalado en el punto 7". Respecto al segundo Grupo de Medicamentos (Grupo 2) de origen biológico, el oferente debe presentar los siguientes requisitos: "1. Certificado del Registro Sanitario del Medicamento emitido por el Ministerio de Salud de Costa Rica. 2, Adjuntar la fórmula cualitativa-cuantitativa completa con los excipientes usados y los rangos permitidos de sustancias relacionadas. 3. Debe cumplir con las Especificaciones de Calidad indicadas en cada ficha técnica correspondiente de cada medicamento. 4. Deben cumplir con toda la reglamentación solicitada por el Ministerio de Salud de CR y todo lo solicitado por el Laboratorio de Normas y Calidad de Medicamentos de la CCSS en materia de hemoderivados. 5. Todos aquellos proveedores de medicamentos biológicos o biotecnológicos que requieran precalificarse ante el Registro de Proveedores u ofertar sus productos a la Institución, deberán presentar certificado de que dichos medicamentos se encuentran registrados y/o se comercialicen en cualquiera de los siguientes países: Estados Unidos (FDA), Canadá (Health Canadá), Japón (MHLW), Suiza (Swissmedic), y países miembros de la Comunidad Económica Europea que se encuentran registrados ante la Agencia Europea de Medicamentos (EMA) o que cuentan con Reconocimiento Mutuo en alguno de los estados miembros de referencia de la Comunidad Económica Europea. Estos países se consideran de referencia debido a que tienen altos estándares en la regulación de medicamentos. 6. Todos los documentos que se solicitan y que sean emitidos en el exterior, deben estar consularizados y certificados por notario público, según lo exige la legislación costarricense y la cadena de legalización consular de nuestro país y ratificadas por el Ministerio de Relaciones Exteriores. Todo documento debe presentarse en idioma español y si está en otro idioma debe adjuntarse la traducción oficial del documento original al español. 7. "La Institución, con base en la amplia experiencia clínica adquirida a través de los años con el uso de medicamentos biológicos, se reserva el criterio sobre algunas especificaciones y requisitos a evaluar, no solo para la inclusión de nuevos medicamentos que comparten el mismo código en el registro de oferentes y de los medicamento no registrados, sino que también para su adquisición, avalando técnicamente la intercambiabilidad de productos biológicos que han documentado la seguridad y eficacia, comprobada mediante su uso clínico en la Institución a través de los años. Para el caso de medicamentos biológicos (mismo laboratorio fabricante) que han sido adquiridos y consumidos históricamente a Nivel Institucional, con comprobada experiencia de uso y respaldo de su eficacia y seguridad, es permisible se les exima de los requisitos establecidos en el punto 5, sin menoscabo del cumplimiento del resto de requisitos establecidos. Los oferentes de medicamentos biológicos (mismo laboratorio fabricante) con los que se cuenta con experiencia histórica de uso Institucional y que se les estaría eximiendo de los requisitos indicados en el punto 5 deben adjuntar la certificación de libre venta del medicamento en el país de origen del laboratorio fabricante, cumpliendo con lo señalado en el punto 6". 8. El laboratorio fabricante debe garantizar que el plasma humano utilizado como materia prima en la manufactura de cada uno de los medicamentos biológicos, debe proceder de seres humanos sanos y el mismo exento en su totalidad de virus o de otros patógenos, debe cumplir con los lineamientos vigentes establecidos en el Decreto de Hemoderivados N° 19981-8 del 3 de octubre de 1990. Estos requisitos son de acatamiento obligatorio para cualquier nuevo medicamento biotecnológico o biológico del grupo 1 o del grupo 2 que se incluya en la LOM" (ver folios 236 a 239 del expediente administrativo tomo II); 8 - Mediante acuerdo CCF-0275-02-09, sesión 2009-21 el Comité Central de Farmacoterapia de la Caja Costarricense del Seguro Social, se establecieron las Condiciones específicas para la adquisición de medicamentos denominaos antineoplásicos y otros medicamentos de uso específico en patologías oncológicas y hemato- oncológicas, publicado en gaceta número 47 del 9 de marzo de 2010 (ver folios 266 y 267 vuelto del expediente administrativo); 9- El citado acto general, se dispuso en los siguientes términos: "Punto 1: Para los medicamentos antineoplásicos y otros medicamentos de uso específico en patologías oncológicas y hemato-oncológicas se debe presentar la certificación emitida por la Dirección Médica General del Hospital General u Oncológico o Instituto del Cáncer del país de origen del laboratorio fabricante, firmada por la máxima autoridad en oncología médica y el Director Médico General del Centro Médico, en la que se indique la cantidad anual consumida por pacientes del medicamento fabricado por dicho laboratorio, el número de camas de ese hospital destinado a adultos y el índice ocupacional (para medicamentos de uso parenteral), y el número de consultas en oncología y onco-hematología (para medicamentos de uso oral). Toda la información debe corresponder al mismo año en que se registra en la Caja o preferiblemente al año anterior a la fecha del registro. Al realizarse el análisis por la CCSS si el fármaco tiene un consumo en el Hospital General u Oncológico o Instituto del Cáncer del país de origen, igual o mayor al 100% al consumido en el Hospital Nacional San Juan de Dios, se determinará con un estudio comparativo de dosis diaria definida ( DDD ) por 100 camas hospital / día para los medicamentos de uso parenteral, y con un estudio comparativo de dosis diaria definida ( DDD ) por 1000 consultas/día para los medicamentos de uso oral, se les dará el aval de oferente y se incorporará en el Registro en la Caja. En el caso de oferentes que sean Laboratorios Nacionales, con base a un estudio comparativo de dosis diaria definida ( DDD ) por 100 camas hospital / día (medicamentos de uso parenteral) o 1000 consultas/día (medicamentos de uso oral) tomando como referencia al Hospital San Juan de Dios, si el resultado es igual o superior al estudio de DDD del año anterior al Registro del medicamento en la Caja, se les dará el aval de oferente y se incorporará en el Registro en la Caja. Para el caso de los laboratorios nacionales la información relacionada con los consumos en el Hospital San Juan de Dios (Hospital nacional de referencia) se obtendrá a través de los mecanismos internos de información disponibles en la institución. Punto 2: El medicamento específico (oral o parenteral) al que se le solicite su ingreso al registro de oferentes de la Caja para su registro o el medicamento que se adquirirá a nivel Central o Local presentara certificación emitida por la Dirección Médica del Hospital General u Oncológico o Instituto del Cáncer del país de origen del laboratorio fabricante, firmada por la máxima autoridad en oncología médica y el Director Médico General del Centro Médico, en la que se presente el consumo anual en pacientes que corresponda a un mismo año , resultados de eficacia y seguridad que han obtenido con el uso del producto medicamentoso en el tratamiento de pacientes con patología hemato-oncológica y el tipo de patologías oncológicas tratadas. Los documentos deben contener en forma completa y concreta, el tipo y porcentaje de efectos secundarios presentados por los pacientes que han recibido el tratamiento con dicho producto para su análisis. Punto 3: Certificación del Ministerio de Salud Pública o de la máxima autoridad en Salud Pública equivalente en el país de origen del Laboratorio fabricante presentada por su representante, que reconozca el Hospital General u Oncológico o Instituto del Cáncer, que solicita ser registrado. Punto 4: Toda certificación que se solicita debe ser presentada en forma individual y la información debe referirse al año anterior más cercano a la fecha de su inclusión en el Registro de oferentes de medicamentos ante la CCSS cuando se trata de medicamentos incluidos en la Lista Oficial de Medicamentos, o corresponder al año anterior más cercano al concurso cuando se trata de medicamentos no incluidos en la Lista Oficial de Medicamentos y son adquiridos a nivel Central o local. Estas certificaciones deben ser actualizadas cada vez que se solicite la renovación del registro ante la CCSS para los medicamentos incluidos en la LOM, de no estar registrados cada vez que se haga una compra a nivel Central o local en el caso de los medicamentos no LOM. Punto 5: Todos los documentos solicitados deben tener las firmas de autoridades en salud debidamente autenticadas, según lo exige la legislación costarricense, además de completar cadena de legalización consular de nuestro país y ratificadas por el Ministerio de Relaciones Exteriores de Costa Rica. Punto 6: Se eximirá de los requisitos enunciados en el punto 1, 2, 3 y 4 aquellos medicamentos antineoplásicos y otros medicamentos de uso específico en patologías oncológicas y hemato-oncológicas de uso parenteral u oral, que se encuentren inscritos y se consuman en cualquiera de los siguientes países: Estados Unidos (FDA), Canadá (Health Canadá), Japón (MHLW), Suiza (Swissmedic), Alemania, Inglaterra, Suecia, Francia, Italia, España, Bélgica, Dinamarca, Austria, Holanda, Finlandia, Noruega. Es importante señalar que los laboratorios deben presentar el certificado de libre venta de su producto en los Estados Unidos (FDA), Canadá, Japón (MHLW), Suiza (Swissmedic), Alemania, Inglaterra, Suecia, Francia, Italia, España, Bélgica, Dinamarca, Austria, Holanda, Finlandia, Noruega; o con registro y comercialización de estos mismos países. De igual forma, serán eximidos aquellos medicamentos cuya procedencia no corresponda a ninguno de los países antes enlistados, pero que cuenten con el certificado de Reconocimiento Mutuo emitido por la EMEA para su comercialización en alguno de los estados miembros de referencia la Unión Europea. Ese certificado debe ser emitido por la máxima autoridad regulatoria competente en salud pública del respectivo país. Punto 7: El oferente que ya se encuentre registrado en el registro de oferentes de la CCSS puede revalidar su registro, presentando la información señalada en los puntos arriba correspondientes. Dicho registro será válido hasta el vencimiento del registro sanitario emitido por el Ministerio de Salud de Costa Rica. Punto 8: Aquellos oferentes que se encuentren registrados pero que prefieran presentar sus datos al momento del proceso de compra y no revalidar el registro ante la CCSS sino hasta su vencimiento, deberán presentar los requisitos para los medicamentos antineoplásicos y otros medicamentos de uso específico en patologías oncológicas y hemato-oncológicas por cada proceso de compra. Punto 9: En el caso de la adquisición de medicamentos antineoplásicos y otros medicamentos de uso específico en patologías oncológicas y hemato-oncológicas incluidos en la Lista Oficial de Medicamentos (LOM), será el Área de Medicamentos y Terapéutica Clínica adscrita a la Dirección de Farmacoepidemiología la encargada de efectuar el análisis de los datos y el correspondiente estudio de Dosis Diaria Definida (DDD). Punto 10: En el caso de medicamentos antineoplásicos y otros medicamentos de uso específico en patologías oncológicas y hemato-oncológicas NO LOM adquiridos por cada centro, el análisis de los datos y el correspondiente estudio Dosis Diaria Definida ( DDD ) será realizado cada vez que se promueva un trámite de compra, y será efectuado y analizado por cada Servicio de Farmacia. Punto 11: Una vez que se publique el Decreto Ejecutivo del Ministerio de Salud Pública que regula el Registro de Medicamentos, en el mismo se contemplan los requisitos específicos para productos de terapia de blanco molecular, estos requisitos se basan en las recomendaciones ICH y forman parte de estas condiciones. Punto 12: Ante las ofertas de medicamentos antineoplásicos y otros medicamentos de uso específico en patologías oncológicas y hemato-oncológicas de uso parenteral u oral no incluidos en la Lista Oficial de Medicamentos que son adquiridos, a nivel Central o local, y se encuentren en igualdad de condiciones , como mecanismo de desempate, se tomará el dar prioridad al medicamento que se encuentre inscrito y se consuma en alguno de los siguientes países: Estados Unidos (FDA), Canadá, Japón, Suiza, Alemania, Inglaterra, Suecia, Francia, Italia, España, Bélgica, Dinamarca, Austria, Holanda, Finlandia, Noruega. El oferente debe presentar certificación emitida por la máxima autoridad regulatoria del país que s hale que el mismo se encuentra inscrito y se consume en uno de los países antes citados. Ante la solicitud del Consejo de Cáncer sobre los requisitos de bioequivalencia y requisitos para los medicamentos denominados antineoplásicos de origen biotecnológicos se continúa con el mecanismo establecido en el Ministerio de Salud y CCSS." (ver folios 266 y 267 vuelto del expediente administrativo); 10- Mediante sesión 2011-08 celebrado el 23 de febrero de 2011 por el Comité Central de Farmacoterapia se procedió a modificar el punto 6, en los siguientes términos: "Punto 6: Se eximirá de los requisitos enunciados en el punto 1, 2, 3 y 4 aquellos medicamentos antineoplásicos y otros medicamentos de uso específico en patologías oncológicas y hemato-oncológicas de uso parenteral u oral, que cuenten con permiso de comercialización en cualquiera de los siguientes países: Estados Unidos (FDA), Canadá (Health Canadá), Japón (MHLW), Suiza (Swissmedic), Alemania, Inglaterra, Suecia, Francia, Italia, España, Bélgica, Dinamarca, Austria, Holanda, Finlandia, Noruega, Colombia (INVIMA), Argentina (ANMAT), Brasil (ANVISA). Es importante señalar que los laboratorios deben presentar: el certificado de producto farmacéutico (o Certificado de Libre Venta más el Certificado de Buenas Prácticas de Manufactura), como respaldo de su registro y permiso de comercialización en los Estados Unidos (FDA), Canadá, Japón (MHLW), Suiza (Swissmedic), Alemania, Inglaterra, Suecia, Francia, Italia, España, Bélgica, Dinamarca, Austria, Holanda, Finlandia, Noruega, Colombia (INVIMA), Argentina (ANMAT), Brasil (ANVISA). De igual forma, serán eximidos aquellos medicamentos cuya procedencia no corresponda a ninguno de los países antes enlistados, pero que cuenten con el certificado de Reconocimiento Mutuo para su comercialización en alguno de los estados miembros de referencia (Unión Europea). Ese certificado debe ser emitido por la máxima autoridad regulatoria competente en salud pública del respectivo país. Para eximirles de los requisitos enlistados en los puntos 1, 2, 3 y 4 es necesario que en los certificados de producto farmacéutico (o Certificado de libre Venta) se incluya el nombre y la dirección de la planta de fabricación, la cual debe coincidir con la dirección de la planta de fabricación del medicamento registrado en el Ministerio de Salud de Costa Rica (toda vez que el medicamento se encuentre registrado en el país). La planta de fabricación (nombre y dirección) de la cual proviene el medicamento registrado y con permiso de comercialización en uno de los países antes enlistados, debe corresponder a la misma planta de fabricación de la cual será importado el medicamento a entregar a la CCSS. " mismo que fue publicado en la gaceta número 58 del 23 de febrero de 2011 (ver folio 310, 311 y 322 del expediente administrativo); III- HECHOS NO PROBADOS De relevancia para la resolución del presente proceso se tiene como no demostrado el siguiente: Único: Que la entidad demandada haya seguido el procedimiento regulado en el artículo 361 de la Ley General de la Administración Pública al momento de la emisión de las disposiciones generales que aquí se impugnan, y que fuera aceptado por la propia accionada (no hay prueba de ello en autos).

IV- SOBRE LOS ARGUMENTOS DE LAS PARTES Alega la parte actora la nulidad del acuerdo adoptado mediante sesión N° 2010-44 del Comité Central de Farmacoterapia (acuerdo número CCF 3376-11-10 que tiene carácter reglamentario), al modificar la normativa ya dispuesta en el año 2009, así como la nulidad del acuerdo dictado en sesión 2011-08 del 23 de febrero de 2011, que modifica el punto 6 de los requisitos de los medicamentos denominados antineoplásicos y otros medicamentos de uso no específico de uso específico en patologías oncológicas y hematológicas, y en su lugar se restaure la vigencia de las normas que se modificaron. Para lo cual se presenta conforme su criterio bajo la legitimación que le confiere el numeral 10 inciso 2 del Código Procesal Contencioso Administrativo, un interés colectivo, alegando que la reforma realizada por el Comité Central de Farmacoterapia de la Caja Costarricense del Seguro Social, concretamente sobre la eliminación de los requisitos de acatamiento obligatorio que debe cumplir cualquier medicamento biotecnológico o biológico para ser oferente en la Caja Costarricense del Seguro Social, afectan a la colectividad, y violentan principios de la Organización Mundial de la Salud. Reclama que la normativa impugnada menciona los medicamentos biológicos y biotecnológicos como de una misma tipología, cuando lo que se pretende regular son los medicamentos biotecnológicos exclusivamente. Aunado que los criterios de evaluación de dichos medicamentos no bastan para certifican su calidad. Conforme a la normativa impugnada se exime a los oferentes de presentar los estudios de caracterización del medicamento, lo cual no garantiza la calidad del mismo al flexibilizar su uso sin que se verifique el cumplimiento de las directrices de evaluación dictadas por autoridades reconocidas "estrictas" tales como OMS y la EMA entre otros organismos internacionales, lo cual no garantiza la seguridad, efectividad y eficacia del medicamento que resulta indispensable para los pacientes. Agrega sobre los medicamentos innovadores se le exime a los Laboratorios fabricantes de la presentación del certificado de libre venta del país de origen. Señala que la Caja Costarricense del Seguro Social avala la intercambiabilidad del medicamento, lo cual atenta contra la salud de los pacientes ya que en los medicamentos de composición biotecnológica no puede compararse la intercambialidad de los productos de síntesis química, lo cual podría generar implicaciones serias en la salud del paciente, al no haberse desarrollado en la institución de forma satisfactoria y segura la farmacovigilancia no es posible monitorear los efectos de la intercambiabilidad en pro de la salud de los pacientes. Señala además que la normativa reglamentaria respecto a la farmacovigilancia no contiene procesos de análisis de riesgo diseñado para atender la naturaleza del producto biotecnológico. Sobre el tema de inmunogenicidad, alega que al encontrarse ausente el proceso de farmacovigilancia no es posible determinar la inmunogenicidad de los medicamentos, colocando en riesgo a los pacientes. Argumenta la nulidad de los actos administrativos, por tener vicios en su formación al no haber sido consultados conforme lo establece la Ley General de la Administración Pública para actos de alcance general como los aquí impugnados. En la audiencia de juicio, formuló hechos nuevos, fundamentados en un reglamento dictado posteriormente por el Ministerio de Salud, señalando que los actos impugnados se contradicen con los dispuestos con el citado acto de alcance general. La representación de la Caja Costarricense del Seguro Social rechaza la demanda. En primer orden cuestiona la legitimación con la que se presenta la actora al proceso, alegando un interés de toda la colectividad, resaltando que en su misma demanda acepta que su primer interés, es la afectación de todas las empresas representadas por Fedefarma, en el tanto se flexibilizan los requerimientos para ser oferentes. Respecto a la normativa para el registro de oferentes para medicamentos biotecnológicos y biológicos del 2010, el Comité Central de Farmacodependencia al no existir reglamentación específica del Ministerio de Salud, es quien debe imponer los requisitos para los oferentes, en el proceso de la adquisición de los medicamentos. Referente a los medicamentos denominados antineoplásicos, y otros medicamentos de uso específico en patologías oncológicas y hematológicas, la modificación refiere a la incorporación de como países como Argentina, Brasil y Colombia, se motivo en que los mismos fueron clasificados como autoridades regulatorios de referencia regional de Nivel IV por la OPS/OMS, en el desempeño de sus funciones, y que a partir de los certificados de dichas autoridades regulatorios, se les estaría eximiendo de los requisitos establecidos en el los puntos 1, 2, 3 y 4. Todo lo anterior fue producto de un estudio y una motivación técnica del Comité Central de Farmacoterapia, por lo que no conlleva un riesgo alguno para la salud pública, ya que no se compromete la eficacia y seguridad de los tratamientos que con utilizados para los pacientes con cáncer, por el contrario se sustenta en mayores estándares establecidos por OPS/OMS. Sobre el uso indistinto de los términos biológicos y biotecnológicos, la normativa establece los requisitos para el registro de oferente, tanto para unos como para otros. Asimismo los medicamentos biotecnológicos deben además contar con estudios de inmunogenicidad y farmacovigilancia. Se establece además en la normativa en discusión que los medicamentos biosimilares deben adjuntar la fórmula cualitativa-cuantitativa completos con los excipientes usados y los rangos permitidos de sustancias relacionadas, así como estudios de caracterización del medicamento. Respecto al tema de inmunogenicidad alega que el país no tiene la capacidad para realizar este tipo de estudios, no obstante se cuenta con un programa de farmacovigilancia activa de notificaciones espontáneas. Argumenta que a nivel internacional no se tiene consenso real sobre la intercambiabilidad de productos biotecnológicos, sin embargo la institución de Seguridad Social cuenta con amplia experiencia clínico en el uso de medicamentos biotecnológicos, donde se ha documentado el beneficio terapéutico en el manejo de diversas patologías. Sobre el vicio procedimental apuntado por la actora, respecto a la ausencia de la audiencia prevista en el numeral 361 de la Ley General de la Administraciòn Pùblica, expresa que no resulta de aplicación el defecto formal, pues el mismo obedece a los actos de carácter general emitidos por el Poder Ejecutivo, no de Instituciones autónomas como la aquí demandada, aunado a que las disposiciones generales emitidas son regulaciones técnicas adoptadas por Órganos técnicos asesores como el Comité de Farmacoterapia de la Cajaostarricense del Seguro Social en su condición de asesor técnico. Opone la defensa de Falta de Legitimación Activa, acusando de la actora en el fondo un interés comercial, y no pretende hacer valer derechos de la colectividad y la Falta de Derecho. Solicita se declare sin lugar la demanda.

V- SOBRE LA REPRESENTACIÓN DE LA PARTE ACTORA EN EL PROCESO.

Mediante resolución de las trece horas con quince minutos del tres de octubre de dos mil trece, éste Órgano Colegiado, conforme a lo numerales 66 inciso b y 92 inciso 1 del Código Procesal Contencioso, previno a la actora a fin de que aportará al proceso la personería de la Federación Centroamericana de Laboratorios Farmacéuticos (FEDEFARMA), que indicara si encuentra inscrita en el papis, su vigencia y de no ser así presentar los documentos debidamente legalizados que demuestren su constitución, existencia, vigencia y representación. Lo anterior obedeció que de la revisión realizada por este Colegio de Jueces, se encontró únicamente aportado al proceso el documento de folio 40, la inscripción registral de un poder del señor Rodolfo Antonio Lambour Chocano como representante legal de la actora. La actora aportó al proceso los documentos que constan de folios 482 a 528 y 566 a 572, en los cuales efectivamente consta la constitución, e inscripción de la accionante en la República de Guatemala, así como el nombramiento del señor Rodolfo Antonio Lambour Chocano como representante legal de la actora, persona que efectivamente inscribió su representación y poder en nuestro país de la citada Federación, quien a su vez otorgó poder especial judicial a los abogados Carlos Ubico Durán y Alejandra Castro Bonilla, quienes han venido accionando el proceso. Así las cosas, téngase por corregido el defecto procesal y por bien representada la accionante en el proceso.

VI- NORMATIVA REGULADORA DE LOS MEDICAMENTOS Y COMPETENCIAS DE LA CAJA COSTARRICENSE DEL SEGURO SOCIAL EN MATERIA DE COMPRA DE MEDICAMENTOS: El servicio de atención médica hospitalaria es un servicio público propio en la medida en que sea ejecutada por algún Centro Hospitalario, o un Centro de Atención a la Salud (clínica, evais, etc.); de los que se encuentran bajo la dependencia de la Caja Costarricense de Seguro Social. Esta Entidad, por disposición constitucional es la encargada de velar (planificar, desarrollar, ejecutar, etcétera), entre otras cosas, todo lo relacionado con la Seguridad Social, y comprendida dentro de ella, el servicio de atención a la salud. Así el ordinal 75 de la Constitución Política nuestra reza en lo correspondiente: "Se establecen los seguros sociales en beneficio de los trabajadores manuales e intelectuales, regulados por el sistema de contribución forzosa del Estado, patronos y trabajadores, a fin de proteger a éstos contra los riesgos de enfermedad, invalidez, vejez, muerte, y demás contingencias que la ley determine. La administración y el gobierno de los seguros sociales estarán a cargo de una institución autónoma, denominada Caja Costarricense de Seguro Social...". De tal forma que se eleva al rango constitucional la seguridad social, que comprende naturalmente al ámbito de la atención a la salud, con lo que se constituye en un mandato insoslayable que exige al Estado, mediante la Institución aludida -CAJA COSTARRICENSE DE SEGURO SOCIAL-, el procurar de la forma más eficiente posible la atención y tratamiento de ese importante sector de la seguridad social, sea ámbito de la salud. No está de más resaltar desde ya la preponderancia que en este aspecto adquiere la Caja Costarricense de Seguro Social, como el Ente expresamente encomendado por disposición constitucional para llevar a cabo, conforme se comentó antes, la administración y el gobierno de los seguros sociales; este punto ha sido motivo de tratamiento por nuestra Sala Constitucional, así en el voto número 6256-94, en lo que nos interesa estableció: ".. .b) la norma le concede en forma exclusiva a la Caja Costarricense de Seguro Social, la administración y el gobierno de los seguros sociales, grado de autonomía que es, desde luego, distinto y superior al que se define en forma general en el artículo 188 idem..." Por otra parte vale decir que ese derecho a la salud, hoy lo podemos definir desde la perspectiva jurídica como: " el conjunto de preceptos obligatorios que reconocen a los individuos derechos concernientes a su salud y que regulan su conducta respecto de todos aquellos asuntos en los que entra en juego la salud de la persona y del grupo". La salud como tal podemos definirla como se establece en el preámbulo de la Constitución de la Organización Mundial de la Salud (OMS): "La salud es un estado completo de bienestar físico, mental y social, y no solamente la ausencia de afecciones o enfermedades." No obstante su trascendental importancia, ese derecho no se encuentra expresamente consagrado en nuestra Constitución Política, como de seguido lo veremos. Consideramos indispensable enlazar, el citado artículo 73 constitucional, por su fundamental contenido, con una norma que permite complementarlo, desde la perspectiva que nos interesa en este estudio, a saber el numeral 21 de la citada Constitución, dispone dicha norma: "Artículo 21.- La vida humana es inviolable. " Al hablársenos aquí de "La vida humana", no se hace alusión exclusivamente al derecho a la vida en sentido estricto, sino que se hace alusión también a su dimensión "salud", o sea la norma no se refiere literalmente a que se protege sólo la vida humana en sentido restringido, sino de forma amplia, al estado de "salud", como presupuesto básico de la vida misma, que es un inherente a la vida como tal, por lo que dada su consustancial relación se entiende comprendido ese "derecho a la salud" en esta norma; en ese sentido se ha dicho: "V- La vida humana sólo es posible en solidaridad con la naturaleza que nos sustenta y nos sostiene, no sólo para alimento físico, sino también como bienestar psíquico; constituye el derecho que todas (sic) los ciudadanos tenemos a vivir en un ambiente libre de contaminación, que es la base de una sociedad justa y productiva. Es así como el artículo 21 de la Constitución Política señala: "La vida humana es inviolable"; y continúa; "Es de este principio constitucional de donde innegablemente se desprende el derecho a la salud, al bienestar físico, mental y social, derecho humano que se encuentra indisolublemente ligado al derecho de la salud y a la obligación del Estado de proteger la vida humana. " (Votos Número 3705-93, 3341-96. Sala Constitucional, Corte Suprema de Justicia). Por otra parte y dada esa trascendencia del derecho que analizamos, la propia Sala Constitucional expresamente ha reconocido la responsabilidad del Estado en velar por la debida protección de ese derecho: “Modernamente es innegable el papel determinante que debe jugar el Estado, y en el caso que nos ocupa, el Estado de Costa Rica, representado por el Ministerio de Salud en este campo, en cuanto al establecimiento de programas para la protección de ese valor fundamental de todos los ciudadanos.” (Voto número 2522-97, de la Sala Constitucional del la Corte Suprema de Justicia). Igualmente y a manera de corolario indicamos que la Sala Constitucional ha establecido que ese derecho a la vida, amparado constitucionalmente, según vimos, debe estar respaldado y protegido mediante la protección que a la población brinde la Caja Costarricense de Seguro Social, mediante plantes de salud, atención de pacientes, y suministro de medicamentos, entre otras funciones, dado que se le ha delgado la responsabilidad estatal para determinar las prácticas idóneas y seguras del servicio. Con lo anterior se deja claro que el derecho a la salud, es un derecho de raigambre constitucional, proyectado como una potestad-deber a cargo de las autoridades correspondientes, en este caso la Caja Costarricense de Seguro Social, y por lo tanto bajo ese contexto, la prestación de ese servicio tiene un inminente carácter público. Naturalmente lo atinente al derecho a la salud no ha escapado a la regulación por instrumentos internacionales, que vinculan como tales la actuación de los Estados adscritos en función de tal derecho, así encontramos las siguientes regulaciones: Declaración Universal de Derechos Humanos, en su artículo 25, en lo que nos interesa establece: " Toda persona tiene derecho a un nivel de vida adecuado que le asegure, así como a su familia, la salud y el bienestar, y en especial la alimentación, y el vestido, la vivienda, la asistencia médica, y los servicios necesarios; tiene asimismo derecho a los seguros en caso de desempleo...". Por su parte la Convención Americana de Derechos Humanos, propiamente en sus artículos 1 y 5, en lo conducente dicen: " Artículo 1. Toda persona tiene derecho a que se respete su vida...", que como ya dijimos, de ella deriva el derecho a la salud.... "Artículo 5.1. Toda persona tiene derecho a que se le respete su integridad física, psíquica y moral." La Convención sobre los Derechos de los Niños, Artículo 24: "Los Estados Partes reconocen el derecho del niño al disfrute del más alto nivel posible de salud y a servicios para el tratamiento de las enfermedades y la rehabilitación de la salud". La Convención sobre Eliminación de toda Forma de discriminación de la mujer: " Artículo 12. Los Estados Partes adoptarán todas las medidas apropiadas para eliminar la discriminación contra la mujer en la esfera de atención médica a fin de asegurar, en condiciones de igualdad entre hombres y mujeres, el acceso a servicios de atención médica, inclusive los que se refieren a la planificación de la familia." Nos permitos, además tan sólo mencionar otros instrumentos como lo son El Pacto Internacional de Derechos Económicos, Sociales y Culturales, en sus numerales 9,10,11, y 12; el Pacto Internacional de Derechos Civiles y Políticos, 6 y 7; la Declaración Americana de los Derechos y Deberes del Hombre, en su numeral 1; la Convención Sobre la Eliminación de todas las Formas de Discriminación Racial, artículo 5, inciso e). En lo relacionado con nuestra normativa legal, ciertamente es exaustiva en cuanto a enfocar el reconocimiento de tal derecho, denotando su carácter público, sólo para citar algunos ejemplos: Código Civil, artículo 46: "Toda persona puede negarse a ser sometida a un examen o tratamiento médico o quirúrgico, con excepción de los casos de vacunación obligatoria, o de otras medidas relativas a la salud pública..."; Código de la Niñez y la Adolescencia, artículo 19: "Las personas menores de edad tendrán derecho de buscar refugio, auxilio y orientación cuando la amenaza de sus derechos conlleve grave peligro para su salud física o espiritual; asimismo, de obtener, de acuerdo con la ley, la asistencia y protección adecuadas y oportunas de las instituciones competentes.", 20, "Las personas menores de edad tendrán el derecho de obtener información, sin importar su fuente y modo de expresión, en especial la que promueve su bienestar espiritual y emocional, así como su salud física y mental", 42, 43, 45, 46, 50, 54, 78, 97, y 121, los que no se transcriben por razones obvias; Ley de Violencia Doméstica, artículo 2; Ley sobre Estupefacientes, Sustancias Psicotrópicas, Drogas de Uso no Autorizado, artículos 1,3,6,47; Ley de Protección Fitosanitaria, Placa19473; Ley de Arrendamientos Urbanos y Suburbanos, artículos 5,22,93,94,97,98,135; por supuesto la Ley Constitutiva de la Caja Costarricense de Seguro Social; La Ley General de Salud, y la Ley Orgánica del Ministerio de Salud, sin citar otras más que también resaltan el derecho que nos ocupa, y que denota su carácter público. En tal sentido, también existen gran cantidad de Reglamentos que protegen ese derecho, citamos a manera de ejemplo Reglamento de Emergencias Nacionales artículos 2 y 11; el Reglamento Autónomo de Organización de la Defensoría de los Habitantes artículo 21; el Reglamento de la Ley General de Aduanas, artículos 12,34,246,287, y 386; Reglamento de la Ley de Promoción de la Competencia y Defensa Efectiva del Consumidor, artículos 6,8,24,41,43; Reglamento de la Ley Reguladora del Fumado, artículos 1 y 5; Ley de igualdad de Oportunidades para Personas con Discapacidad, artículos 92 y 94, entres otros. Retomando las competencias de la Caja Costarricense del Seguro Social, la Constitución Política en el artículo 73, señala que la Caja es una institución autónoma a cuyo cargo se encuentra la administración y el gobierno de los seguros sociales, esto así con el objeto de proteger a los trabajadores contra los riegos de enfermedad, invalidez, maternidad, vejez y muerte. Para el cumplimiento de sus fines, dispone la Ley Constitutiva de la Caja Costarricense del Seguro Social, número 17 del 22 de octubre de 1943, en su ordinal 71, que dicha entidad se encuentra autorizada para importar, desalmacenar, fabricar, comprar, vender y exportar, directamente, medicamentos incluidos en el Formulario Nacional, reactivos y biológicos, así como materias primas y materiales de acondicionamiento y empaque, requeridos en la elaboración de aquellos. Igualmente queda autorizada para suplir estos mismos artículos a las instituciones públicas y privadas que presten servicios de salud. En ese sentido expresa el numeral 72 de la ley supracitada, que tales compras y negociaciones se podrán realizar, en el tanto y cuanto se cumplan con los siguientes requisitos: a) Establecer y mantener actualizado un registro de oferentes de los productos, con base en su nombre genérico, para tales efectos la Contraloría General de la República y la Auditoría de la Caja Costarricense de Seguro Social tendrán una copia de este registro. La Oficina encargada de las compras pedirá libremente las cotizaciones a las empresas nacionales y extranjeras, inscritas en el registro de oferentes, y sus respuestas serán consideradas ofertas formales si llenan los requisitos del caso. Para tener derecho a ser consideradas, tales respuestas deberán se dadas por los oferentes dentro de los tres días hábiles siguientes al recibo de la solicitud de cotización. b) La Contraloría General de la República deberá resolver las autorizaciones de compra en un plazo no mayor de cinco días hábiles. c) En casos especiales de urgencia, las compras podrán realizarse con la sola aprobación de la Auditoría de la Caja, pero, en todo caso, la Contraloría deberá ser informada de lo actuado dentro de las veinticuatro horas siguientes. ch) Los funcionarios encargados de la realización de las compras, deberán realizarlas en las mejores condiciones de calidad y precio, y responderán por sus actos y por los daños y perjuicios que eventualmente puedan causar, de conformidad con la ley. Por su parte el numeral 73 de la normativa ibid, indica que la Caja Costarricense de Seguro Social podrá exportar medicamentos, reactivos y biológicos, siempre que estén satisfechas las necesidades nacionales. También podrá intercambiar medicamentos con organismos estatales o privados de otros países con el fin de satisfacer necesidades sociales. Las normas y autorizaciones contenidas en este artículo serán aplicables igualmente al Ministerio de Salud. A su vez el numeral 102 de la Ley General de Salud, número 5395 del 30 de octubre de 1973, expresa que la importación de medicamentos y su distribución sólo serán permitidas a las personas jurídicas o físicas inscritas en el Ministerio, previa autorización y registro en el Colegio de Farmacéuticos, de conformidad con las disposiciones legales y reglamentarias correspondientes. En todo caso, el Gobierno Central y las instituciones públicas con funciones de salud podrán, directamente importar, elaborar, manipular, almacenar, vender o suministrar medicamentos, materias primas o materiales médico-quirúrgicos, cuando el cumplimiento de sus programas o situaciones de emergencia lo requieran, con la sola aprobación del Ministerio, conforme al Reglamento respectivo (ordinal 103 de la Ley 5395). Debiendo entenderse por medicamento toda sustancia o productos naturales, sintéticos o semi-sintéticos y toda mezcla de esas sustancias o productos que se utilicen para el diagnóstico, prevención, tratamiento y alivio de las enfermedades o estados físicos anormales, o de los síntomas de los mismos y para el restablecimiento o modificación de funciones orgánicas en las personas o en los animales. Se incluyen en la misma denominación y para los mismos efectos los alimentos dietéticos y los alimentos y cosméticos que hayan sido adicionados con sustancias medicinales. No se consideran medicamentos las sustancias referidas en el párrafo primero cuando se utilizaren para análisis químicos y químico-clínicos, o cuando sean usadas como materia prima en procesos industriales. Todo medicamento deberá ajustarse a las exigencias reglamentarias particulares que por su naturaleza les son exclusivamente aplicables, además de las generales que se establecen para todo medicamento en la ley 5395 (artículo 104). Los medicamentos pueden ser presentados para su uso, comercio, distribución y suministro con nombre genérico o con nombre registrado. Son de nombre genérico aquellos medicamentos puros, presentados en fórmula farmacéutica o singularmente, designados con un nombre técnico general reconocido por las farmacopeas oficiales o por obras técnicas de reconocida autoridad. El medicamento de nombre genérico puede ser simple o puede ser una fórmula constituida por dos o más medicamentos de nombre genérico. Son medicamentos de nombre registrado aquellos que se entregan al comercio y uso bajo un nombre particular de invención y bajo marca de fábrica registrada (numeral 105 de la ley 5395). Se considera que un medicamento puede, legalmente, ser destinado al comercio, al uso y consumo públicos, cuando satisfaga las exigencias reglamentarias, o de la farmacopea declarada oficial por el Poder Ejecutivo en cuanto a su identidad y calidades, seguridad y eficacia para los fines que se lo use, consuma o prescriba y en cuanto a que las personas naturales o jurídicas responsables que se ocupan de su importación, comercio, manipulación, distribución y prescripción, hayan cumplido con los requisitos legales y reglamentarios pertinentes a cada una de estas acciones (numeral 106 de la ley 5395). Queda prohibido la importación, elaboración, comercio, distribución o suministro a cualquier título, manipulación, uso, consumo y tenencia para comerciar, de medicamentos deteriorados, adulterados o falsificados (ordinal 107 de la ley 5395). Quedando prohibido la importación, comercio, uso o suministro de medicamentos que se encuentran en proceso de experimentación, salvo en las condiciones y circunstancias y por el tiempo que el Ministerio lo autorice (numeral 108 de la ley 5395). Además, toda persona física o jurídica sólo podrá importar, fabricar, manipular, comerciar o usar medicamentos registrados en el Ministerio y cuyo registro haya satisfecho las exigencias reglamentarias, en especial las relativas a: la naturaleza y cantidad de la información requerida sobre el medicamento o producto sometido a registro; la entrega de muestras necesarias para practicar los análisis que haya menester, a las pertinentes al nombre con que se identificará el producto; al contenido de la rotulación; al tipo de envases o envolturas que se usarán y al pago de las tasas que indique el arancel pertinente (artículo 112 de la Ley 5395). El registro de todo medicamento se hará ante el Ministerio donde se practicará la inscripción cuando proceda según las disposiciones reglamentarias correspondientes. Dicha inscripción estará a cargo de un Organismo Técnico cuya integración y funciones serán determinadas por la Ley Orgánica del Ministerio y el Reglamento respectivo (artículo 113 de la Ley 5395). El registro de todo medicamento durará cinco años, salvo que las infracciones en la elaboración, comercio o uso en que haya incurrido su titular, o experiencias demostrativas de que el productores inseguro o ineficaz en los términos en que fue autorizado y registrado, hagan procedente su cancelación o la modificación que corresponda (numeral 114 de la ley 5395). Toda modificación en el nombre de un medicamento, en su fórmula, en la forma de su dosificación, en el envase y contenido de la rotulación que le acompaña, o en la publicidad, requerirá de permiso previo del Ministerio (numeral 115 ibid). Los medicamentos de nombre registrado, para los efectos de su importación, comercio y distribución en el país, requieren para su inscripción comprobante de registro sanitario en el país de origen y comprobante de análisis correspondientes al producto, extendido por un laboratorio nacional o extranjero, que a juicio del Ministerio, garantice su identidad y su calidad, de acuerdo a la farmacopea oficial o textos técnicos de reconocida autoridad; este último comprobante puede ser también extendido por el laboratorio de control de productos químicos y farmacéuticos de la propia casa fabricante. Los medicamentos de nombre genérico requieren para su inscripción y para los mismos efectos señalados en el párrafo anterior, comprobante de análisis que garantice su identidad y calidad, de acuerdo a la farmacopea oficial o textos técnicos de reconocida autoridad, extendido este comprobante en la misma forma y condiciones indicadas en el párrafo anterior. El Ministerio podrá exonerar de las pruebas citadas anteriormente, cuando se trate de un producto conocido y que por su propia naturaleza haga innecesario aquellos requisitos; o bien, en el caso de medicamentos no descritos en la farmacopea oficial o textos técnicos de reconocida autoridad, sean productos farmacéuticos de marca registrada o medicamentos de nombre genérico, podrá exigir las pruebas que sean necesarias para la comprobación de identidad, de la calidad y de la eficacia terapéutica y biofarmacéutica del producto (artículo 116 ibid). Por su parte, el ordinal 117 ibid, expresa que el Ministerio de Salud, la Caja Costarricense de Seguro Social y cualquier otra entidad estatal, con funciones de salud pública o seguridad social, podrán adquirir medicamentos no registrados, en cualquier momento o circunstancia y que en caso de urgencia o de necesidad pública, ese Ministerio podrá autorizar la importación de medicamentos no registrados, además de que para fines exclusivos de investigación, podrá autorizarse la importación, producción y uso de medicamentos no registrados, de conformidad con las disposiciones reglamentarias correspondientes. Hasta aquí conviene tener claridad en un aspecto, el órgano rector en materia de salud es el Ministerio de Salud Pública y a la Caja Costarricense del Seguro Social es el ente administrador de los seguros públicos. Se trata en efecto de competencias que se interrelacionan entre sí, pero una corresponden al Ministerio y otras al ente público. En lo que refiere el Registro sanitario es claro que la balanza se inclina a favor del Ministerio y no de la Caja, con la natural obligación de coordinación en el ámbito de las competencias comunes.

VII- SOBRE LOS REQUISITOS QUE DEBEN CUMPLIRSE PARA CONFORMAR EL REGISTRO DE OFERENTES DE LA CAJA COSTARRICENSE DEL SEGURO SOCIAL PARA OFERTAR MEDICAMENTOS BIOTECNOLOGICOS, BIOLOGICOS, ANTINEOPLÁSICOS Y OTROS MEDICAMENTOS DE USO ESPECÍFICO EN PATOLOGÍAS ONCOLÓGICAS Y HEMATOLÓGICAS: Mediante acuerdo del 28 de abril del 2009, dictado por la Caja Costarricense del Seguro Social, publicado en la gaceta 89 del 11 de mayo del 2009, y aprobado por el Comité Central de Farmacoterapia en acuerdo CCF-0908-04-09 (Sesión 2009-13), se establecen los requisitos para el registro de oferentes aplicables a medicamentos biológicos, y condiciones específicas para la adquisición de medicamentos denominados antineoplásicos y otros medicamentos de uso específico en patologías oncológicas y hemato-oncológicas. Disponiendo que los oferentes registrados y oferentes a registrarse en el Registro de Oferentes de la CCSS en los medicamentos de origen biológico del Grupo 1 y/o Grupo 2, deben cumplir con una serie de requisitos estipulados a continuación para cada grupo. Se indica a su vez, que estos requisitos son de acatamiento obligatorio también para aquellos oferentes que participen en la Caja con medicamentos que no cuenten con Registro Sanitario del Medicamento y que se debe proceder a la importación del medicamento por el artículo 117 de la Ley General de Salud de Costa Rica o con medicamentos con código en tránsito En el primer grupo se ubican los medicamentos de origen biológico, que en su proceso de manufactura no utilizan como materia prima proveniente de hemoderivados (por ejemplo el plasma humano) humanos, estableciéndose como requisitos, los siguientes: el 1. Certificado del Registro Sanitario del Medicamento emitido por el Ministerio de Salud de Costa Rica. 2. Adjuntar la fórmula cualitativa-cuantitativa completa con los excipientes usados y los rangos permitidos de sustancias relacionadas (si en este caso específico aplica). 3. Aquellos medicamentos biológicos del Grupo 1 que contienen en su formulación, y corroborada en su fórmula cualitativa-cuantitativa, excipientes de origen de plasma humano (hemoderivados) deben cumplir, además, con los requisitos para el Grupo 2. 4. Los medicamentos que no cuenten con registro sanitario emitido por el Ministerio de Salud de CR, además deben presentar los estudios clínicos debidamente certificados que corresponden a los que dieron origen a su registro en su país de origen, en las mismas indicaciones oficiales de uso y seguridad en referencia al innovador. 5. Ante ofertas que se encuentren en igualdad de condiciones, la administración deja bien establecido un mecanismo de desempate, que es el de dar prioridad al producto biológico que se encuentre inscrito y se consuma en los países mencionados: Estados Unidos (FDA) y/o países de la Comunidad Económica Europea (EMEA), y/o Canadá y/o Japón y/o Suiza. Es importante señalar que los laboratorios fabricantes del medicamento deben presentar el certificado de libre venta de su producto en Estados Unidos y/o Canadá y/o Comunidad Económica Europea y/o Japón y/o Suiza ante la eventualidad que se presenten ofertas en igualdad de condiciones y sea necesario aplicar el mecanismo de desempate. Este documento debe ser emitido por la autoridad regulatoria correspondiente del país respectivo. 6. Todo medicamento biológico, sea droga nueva o no, que cuente con el visto bueno de al menos la FDA y/o EMEA y/o Canadá y/o Japón y/o Suiza será eximido de los requisitos que refiere el punto 3, si presentan la documentación oficial de la FDA y/o EMEA y/o de las autoridades regulatorias de Japón y/o Suiza que acredita el producto para su comercialización en estos países. 7. Los medicamentos biológicos que no cuenten con registro sanitario emitido por el Ministerio de Salud de CR además, deben cumplir con el punto 5. 8. Todos los documentos solicitados deben ser autenticados vía consular de nuestro país y ratificados por el Ministerio de Relaciones Exteriores. En el grupo 2, se ubican los medicamentos de origen biológico, que utilizan en su proceso de manufactura, materia prima proveniente de hemoderivados (por ejemplo el plasma humano) humanos, requiriéndose de ellos el que aporten 1. Certificado del Registro Sanitario del Medicamento emitido por el Ministerio de Salud de Costa Rica. 2. Adjuntar la fórmula cualitativa-cuantitativa completa con los excipientes usados y los rangos permitidos de sustancias relacionadas (si en este caso específico aplica). 3. Debe cumplir con las Especificaciones de Calidad especificadas en cada ficha técnica correspondiente. 4. Deben cumplir con toda la reglamentación solicitada por el Ministerio de Salud de CR y todo lo solicitado por el Laboratorio de Normas y Calidad de Medicamentos de la CCSS en materia de hemoderivados. 5. Aquellos medicamentos biológicos del Grupo 1 que contienen en su formulación, y corroborada en su fórmula cualitativa-cuantitativa, excipientes de origen de plasma humano (hemoderivados) deben además cumplir con los requisitos para el Grupo 2. 6. Los medicamentos que no cuenten con registro sanitario emitido por el Ministerio de Salud de CR, además deben presentar los estudios clínicos debidamente certificados que corresponden a los que dieron origen a su registro en su país de origen, en las mismas indicaciones oficiales de uso y seguridad en referencia al innovador. 7. Ante ofertas que se encuentren en igualdad de condiciones, la administración deja bien establecido un mecanismo de desempate, que es el de dar prioridad al producto biológico que se encuentre inscrito y se consuma en los países mencionados: Estados Unidos (FDA) y/o países de la Comunidad Económica Europea (EMEA), y/o Canadá y/o Japón y/o Suiza. Es importante señalar que los laboratorios fabricantes del medicamento deben presentar el certificado de libre venta de su producto en Estados Unidos y/o Canadá y/o Comunidad Económica Europea y/o Japón y/o Suiza ante la eventualidad que se presenten ofertas en igualdad de condiciones y sea necesario aplicar el mecanismo de desempate. Este documento debe ser emitido por la autoridad regulatoria correspondiente del país respectivo. 8. Todos los documentos solicitados deben ser autenticados vía consular de nuestro país y ratificados por el Ministerio de Relaciones Exteriores. 9. El laboratorio fabricante debe garantizar que el plasma humano usado como materia prima en la manufactura de cada uno de los medicamentos biológicos debe proceder de seres humanos sanos, y el mismo exento en su totalidad de virus o de otros patógenos. Por su parte el Comité Central de Farmacoterapia en acuerdo CCF-0944-04-09 (Sesión 2009-13) y ratificado mediante acuerdo dictado en Sesión 2009-14 del 22 de abril de 2009, acordó actualizar la normativa para las Condiciones específicas para la adquisición de medicamentos denominados antineoplásicos y otros medicamentos de uso específico en patologías oncológicas y Hemato-Oncológicas, ello así para efectos de Registro de Medicamentos en la Caja Costarricense de Seguro Social, que estén registrados o no ante el Ministerio de Salud de Costa Rica, en el punto uno se debe presentar la certificación emitida por la Dirección Médica General del Hospital General u Oncológico o Instituto del Cáncer del país de origen del laboratorio fabricante, firmada por la máxima autoridad en oncología médica y el Director Médico General del Centro Médico, en la que se indique la cantidad anual consumida por pacientes del medicamento fabricado por dicho laboratorio, el número de camas de ese hospital destinado a adultos y el índice ocupacional (para medicamentos de uso parenteral), y el número de consultas en oncología y onco-hematología (para medicamentos de uso oral). Toda la información debe corresponder al mismo año en que se registra en la Caja o preferiblemente al año anterior a la fecha del registro. Al realizarse el análisis por la CCSS si el fármaco tiene un consumo en el Hospital General u Oncológico o Instituto del Cáncer del país de origen, igual o mayor al 100% al consumido en el Hospital Nacional San Juan de Dios, se determinará con un estudio comparativo de dosis diaria definida (DDD) por 100 camas hospital / día para los medicamentos de uso parenteral, y con un estudio comparativo de dosis diaria definida (DDD) por 1000 consultas/día para los medicamentos de uso oral, se les dará el aval de oferente y se incorporará en el Registro en la Caja. En el caso de oferentes que sean Laboratorios Nacionales, con base a un estudio comparativo de dosis diaria definida ( DDD ) por 100 camas hospital / día (medicamentos de uso parenteral) o 1000 consultas/día (medicamentos de uso oral) tomando como referencia al Hospital San Juan de Dios, si el resultado es igual o superior al estudio de DDD del año anterior al Registro del medicamento en la Caja, se les dará el aval de oferente y se incorporará en el Registro en la Caja. Para el caso de los laboratorios nacionales la información relacionada con los consumos en el Hospital internos de información disponibles en la institución. En el punto 2, debe presentarse certificación emitida por la Dirección Médica del Hospital General u Oncológico o Instituto del Cáncer del país de origen del laboratorio fabricante, firmada San Juan de Dios (Hospital nacional de referencia) se obtendrá a través de los mecanismos por la máxima autoridad en oncología médica y el Director Médico General del Centro Médico, en la que se presente el consumo anual en pacientes que corresponda a un mismo año, resultados de eficacia y seguridad que han obtenido con el uso del producto medicamentoso en el tratamiento de pacientes con patología hemato-oncológica y el tipo de patologías oncológicas tratadas. Los documentos deben contener en forma completa y concreta, el tipo y porcentaje de efectos secundarios presentados por los pacientes que han recibido el tratamiento con dicho producto para su análisis. En el punto 3: Certificación del Ministerio de Salud Pública o de la máxima autoridad en Salud Pública equivalente en el país de origen del Laboratorio fabricante presentada por su representante, que reconozca el Hospital General u Oncológico o Instituto del Cáncer, que solicita ser registrado. En el punto 4: se obliga a que la certificación debe ser presentada en forma individual y la información debe referirse al año anterior más cercano a la fecha de su inclusión en el Registro de oferentes de medicamentos ante la CCSS cuando se trata de medicamentos incluidos en la Lista Oficial de Medicamentos, o corresponder al año anterior más cercano al concurso cuando se trata de medicamentos no incluidos en la Lista Oficial de Medicamentos y son adquiridos a nivel Central o local. Estas certificaciones deben ser actualizadas cada vez que se solicite la renovación del registro ante la CCSS para los medicamentos incluidos en la LOM, de no estar registrados cada vez que se haga una compra a nivel Central o local en el caso de los medicamentos no LOM. En el punto 5: se expresa que los documentos solicitados deben tener las firmas de autoridades en salud debidamente autenticadas, según lo exige la legislación costarricense, además de completar cadena de legalización consular de nuestro país y ratificadas por el Ministerio de Relaciones Exteriores de Costa Rica. En el punto seis reformado mediante acuerdo tomado en sesión 2011-08 celebrada el 23 de febrero del 2011, se dispone que se exime de los requisitos enunciados en el punto 1, 2, 3 y 4 aquellos medicamentos antineoplásicos y otros medicamentos de uso específico en patologías oncológicas y hemato-oncológicas de uso parenteral u oral, que cuenten con permiso de comercialización en cualquiera de los siguientes países: Estados Unidos (FDA), Canadá (Health Canadá), Japón (MHLW), Suiza (Swissmedic), Alemania, Inglaterra, Suecia, Francia, Italia, España, Bélgica, Dinamarca, Austria, Holanda, Finlandia, Noruega, Colombia (INVIMA), Argentina (ANMAT), Brasil (ANVISA), expresándose que los laboratorios deben presentar: el certificado de producto farmacéutico (o Certificado de Libre Venta más el Certificado de Buenas Prácticas de Manufactura), como respaldo de su registro y permiso de comercialización en los Estados Unidos (FDA), Canadá, Japón (MHLW), Suiza (Swissmedic), Alemania, Inglaterra, Suecia, Francia, Italia, España, Bélgica, Dinamarca, Austria, Holanda, Finlandia, Noruega, Colombia (INVIMA), Argentina (ANMAT), Brasil (ANVISA). Asimismo, exime aquellos medicamentos cuya procedencia no corresponda a ninguno de los países antes enlistados, pero que cuenten con el certificado de Reconocimiento Mutuo para su comercialización en alguno de los estados miembros de referencia (Unión Europea), certificado que debe ser emitido por la máxima autoridad regulatoria competente en salud pública del respectivo país. Disponiéndose que para eximir de los requisitos enlistados en los puntos 1, 2, 3 y 4 es necesario que en los certificados de producto farmacéutico (o Certificado de libre Venta) se incluya el nombre y la dirección de la planta de fabricación, la cual debe coincidir con la dirección de la planta de fabricación del medicamento registrado en el Ministerio de Salud de Costa Rica (toda vez que el medicamento se encuentre registrado en el país). La planta de fabricación (nombre y dirección) de la cual proviene el medicamento registrado y con permiso de comercialización en uno de los países antes enlistados, debe corresponder a la misma planta de fabricación de la cual será importado el medicamento a entregar a la CCSS. El punto siete establece que el oferente que ya se encuentre registrado en el registro de oferentes de la CCSS puede revalidar su registro, presentando la información señalada en los puntos arriba correspondientes. Dicho registro será válido hasta el vencimiento del registro sanitario emitido por el Ministerio de Salud de Costa Rica. El punto 8 indica que aquellos oferentes que se encuentren registrados pero que prefieran presentar sus datos al momento del proceso de compra y no revalidar el registro ante la CCSS sino hasta su vencimiento, deberán presentar los requisitos para los medicamentos antineoplásicos y otros medicamentos de uso específico en patologías oncológicas y hemato-oncológicas por cada proceso de compra. El punto nueve expresa que en el caso de la adquisición de medicamentos antineoplásicos y otros medicamentos de uso específico en patologías oncológicas y hemato-oncológicas incluidos en la Lista Oficial de Medicamentos (LOM), será el Área de Medicamentos y Terapéutica Clínica adscrita a la Dirección de Farmacoepidemiología la encargada de efectuar el análisis de los datos y el correspondiente estudio de Dosis Diaria Definida (DDD). En punto 10, estipula que en el caso de medicamentos antineoplásicos y otros medicamentos de uso específico en patologías oncológicas y hemato-oncológicas NO LOM adquiridos por cada centro, el análisis de los datos y el correspondiente estudio Dosis Diaria Definida (DDD) será realizado cada vez que se promueva un trámite de compra, y será efectuado y analizado por cada Servicio de Farmacia. El punto 11 expresa que una vez que se publique el Decreto Ejecutivo del Ministerio de Salud Pública que regula el Registro de Medicamentos, en el mismo se contemplan los requisitos específicos para productos de terapia de blanco molecular, estos requisitos se basan en las recomendaciones ICH y forman parte de estas condiciones. El punto 12 indica que ante las ofertas de medicamentos antineoplásicos y otros medicamentos de uso específico en patologías oncológicas y hemato-oncológicas de uso parenteral u oral no incluidos en la Lista Oficial de Medicamentos que son adquiridos, a nivel Central o local, y se encuentren en igualdad de condiciones , como mecanismo de desempate, se tomará el dar prioridad al medicamento que se encuentre inscrito y se consuma en alguno de los siguientes países: Estados Unidos (FDA), Canadá, Japón, Suiza, Alemania, Inglaterra, Suecia, Francia, Italia, España, Bélgica, Dinamarca, Austria, Holanda, Finlandia, Noruega. El oferente debe presentar certificación emitida por la máxima autoridad regulatoria del país que el mismo se encuentra inscrito y se consume en uno de los países antes citados y que ante la solicitud del Consejo de Cáncer sobre los requisitos de bioequivalencia y requisitos para los medicamentos denominados antineoplásicos de origen biotecnológicos se continúa con el mecanismo establecido en el Ministerio de Salud y CCSS. A su vez, mediante acuerdo número 1445 del 10 de junio del año 2009, la Caja Costarricense del Seguro Social estableció los requisitos a cumplir para el registro de oferentes de medicamentos biotecnológicos, el cual se publicó en la Gaceta 127 del 02 de julio de 2009. En dicha norma se dispone en cuanto a las obligaciones que deben cumplir los oferentes registrados y oferentes a registrarse en el Registro de Oferentes de la CCSS en los medicamentos de origen biológico del Grupo 1 y/o Grupo 2, que deben cumplir con los requisitos de acatamiento obligatorio para aquellos oferentes que participen en la Caja con medicamentos que no cuenten con Registro Sanitario del Medicamento y que se debe proceder a la importación del medicamento por el artículo 117 de la Ley General de Salud de Costa Rica o con medicamentos con código en tránsito. Siendo dichos grupos, el número de uno correspondiente a medicamentos de origen biológico, que en su proceso de manufactura no utilizan como materia prima proveniente de hemoderivados (por ejemplo el plasma humano) humanos, debiendo presentar el oferente los siguientes requisitos: 1. Certificado del registro sanitario del medicamento emitido por el Ministerio de Salud de Costa Rica. 2. Para los medicamentos innovadores se debe adjuntar la fórmula cualitativa-cuantitativa completa con los excipientes usados y los rangos permitidos de sustancias relacionadas, asimismo los estudios de caracterización del medicamento. 3. Para los medicamentos biosimilares se debe adjuntar la fórmula cualitativa-cuantitativa completa con los excipientes usados y los rangos permitidos de sustancias relacionadas, asimismo los estudios de caracterización del medicamento; además, deben presentar los estudios de caracterización del medicamento comparado con el medicamento de referencia que se comercializa en Costa Rica. 4. Los medicamentos que en su proceso de manufactura no utilizan materia prima hemoderivados pero que en su formulación y mediante su fórmula cualitativa se corrobora que presentan excipientes del plasma humano como albúmina, deben cumplir con todos los lineamientos vigentes establecidos en el Decreto de Hemoderivados Nº 19981-S del 3 de octubre de 1990. 5. Deben cumplir con las especificaciones de calidad establecidas en la ficha técnica oficial correspondiente a cada medicamento. 6. El Registro de Oferentes del Laboratorio de Normas y Calidad de Medicamentos y el Comité Central de Farmacoterapia deja bien establecido que se avalan únicamente productos biológicos que se encuentren o no inscritos en el Ministerio de Salud de Costa Rica, pero que se consuman en los siguientes países: Estados Unidos (FDA), y /o países de la Comunidad Europea (EMEA), y/o Canadá, y/o Japón, y/o Suiza. 7. En el caso de los medicamentos innovadores, los laboratorios fabricantes deben presentar Certificados de libre venta del medicamento en el país de origen como Estados Unidos, Comunidad Económica Europea, Canadá, Japón, Suiza por la instancia sanitaria regulatoria de ese país. 8. En el caso de los medicamentos biosimilares, los laboratorios fabricantes deben presentar Certificados de libre venta del medicamento en el país de origen como Estados Unidos, Comunidad Económica Europea, Canadá, Japón, Suiza por la instancia sanitaria regulatoria de ese país, asimismo que un certificado emitido por la misma entidad sanitaria, que garantice que el medicamento cumple con los criterios de calidad solicitados para medicamentos biológicos y que cuenta con los estudios clínicos de seguridad y eficacia que dieron origen a su registro sanitario en el país de origen, que cuenta con estudios clínicos de inmunogenicidad, seguridad y eficacia, en las mismas indicaciones oficiales que el producto de referencia que se comercializa en el país, al igual que de los estudios de caracterización y comparabilidad que demuestran que el producto es biosimilar al de referencia que se comercializa en Costa Rica. Además se debe adjuntar la fórmula cualitativa-cuantitativa completa con los excipientes usados y los rangos permitidos de sustancias relacionadas, y la certificación de la Instancia sanitaria (EMEA y/o FDA) que lo acredita como medicamento biosimilar. 9. Todos los documentos que se solicitan que sean emitidos en el exterior (otros países), deben ser consularizados y presentados en idioma español. 10. La Institución, con base en la amplia experiencia clínica adquirida a través de los años con el uso de medicamentos biológicos, se reserva el criterio sobre algunas especificaciones y requisitos a evaluar para la inclusión de nuevos medicamentos que comparten el mismo código, en el registro de oferentes y medicamentos no registrados; y avala únicamente la intercambiabilidad de productos biológicos que han documentado seguridad y eficacia comprobada mediante su uso clínico en la Institución a través de los años. Y sobre el grupo 2 de medicamentos de origen biológico se expresa que son aquellos que se utilizan en su proceso de manufactura, materia prima proveniente de hemoderivados (por ejemplo el plasma humano) humanos, que debe el oferente cumplir con los siguientes requisitos: 1. Certificado del Registro Sanitario del Medicamento emitido por el Ministerio de Salud de Costa Rica. 2. Adjuntar la fórmula cualitativa-cuantitativa completa con los excipientes usados y los rangos permitidos de sustancias relacionadas. 3. Debe cumplir con las Especificaciones de Calidad especificadas en cada ficha técnica correspondiente de cada medicamento. 4. Deben cumplir con toda la reglamentación solicitada por el Ministerio de Salud de CR y todo lo solicitado por el Laboratorio de Normas y Calidad de Medicamentos de la CCSS en materia de hemoderivados. 5. El Registro de Oferentes del Laboratorio de Normas y Calidad de Medicamentos y el Comité Central de Farmacoterapia deja bien establecido que se avalan únicamente productos biológicos que se encuentren o no inscritos en el Ministerio de Salud de Costa Rica, pero que se consuman en los siguientes países: Estados Unidos (FDA), y /o países de la Comunidad Europea (EMEA), y/o Canadá, y/o Japón, y/o Suiza. 6. Todos los documentos que se solicitan que sean emitidos en el exterior (otros países), deben ser consularizados y presentados en idioma español. 7. La Institución con base en la amplia experiencia clínica adquirida a través de los años con el uso de medicamentos biológicos, se reserva el criterio sobre algunas especificaciones y requisitos a evaluar para la inclusión de nuevos medicamentos que comparten el mismo código, en el registro de oferentes; y avala únicamente que ha documentado seguridad y eficacia comprobada mediante su uso clínico en la Institución a través de los años. 8. El laboratorio fabricante debe garantizar que el plasma humano utilizado como materia prima en la manufactura de cada uno de los medicamentos biológicos, debe proceder de seres humanos sanos y el mismo exento en su totalidad de virus o de otros patógenos, debe cumplir con los lineamientos vigentes establecidos en el Decreto de Hemoderivados Nº 19981-S del 3 de octubre de 1990. Posteriormente, mediante acuerdo del nueve de marzo del 2010, publicado en la gaceta número 47 del 09 de marzo del 2010, aprobado mediante acuerdo CCF-0275-02-10 (sesión 2010-05) del Comité Central de Farmacoterapia, se reforman las condiciones específicas para la adquisición de medicamentos denominados antineoplásicos y otros medicamentos de uso específico en patologías oncológicas y hemato-oncológicas, estableciéndose los siguientes puntos: Punto 1: Para los medicamentos antineoplásicos y otros medicamentos de uso específico en patologías oncológicas y hemato-oncológicas se debe presentar la certificación emitida por la Dirección Médica General del Hospital General u Oncológico o Instituto del Cáncer del país de origen del laboratorio fabricante, firmada por la máxima autoridad en oncología médica y el Director Médico General del Centro Médico, en la que se indique la cantidad anual consumida por pacientes del medicamento fabricado por dicho laboratorio, el número de camas de ese hospital destinado a adultos y el índice ocupacional (para medicamentos de uso parenteral), y el número de consultas en oncología y onco-hematología (para medicamentos de uso oral). Toda la información debe corresponder al mismo año en que se registra en la Caja o preferiblemente al año anterior a la fecha del registro. Al realizarse el análisis por la CCSS si el fármaco tiene un consumo en el Hospital General u Oncológico o Instituto del Cáncer del país de origen, igual o mayor al 100% al consumido en el Hospital Nacional San Juan de Dios, se determinará con un estudio comparativo de dosis diaria definida (DDD) por 100 camas hospital / día para los medicamentos de uso parenteral, y con un estudio comparativo de dosis diaria definida (DDD) por 1000 consultas/día para los medicamentos de uso oral, se les dará el aval de oferente y se incorporará en el Registro en la Caja. En el caso de oferentes que sean Laboratorios Nacionales, con base a un estudio comparativo de dosis diaria definida (DDD) por 100 camas hospital / día (medicamentos de uso parenteral) o 1000 consultas/día (medicamentos de uso oral) tomando como referencia al Hospital San Juan de Dios, si el resultado es igual o superior al estudio de DDD del año anterior al Registro del medicamento en la Caja, se les dará el aval de oferente y se incorporará en el Registro en la Caja. Para el caso de los laboratorios nacionales la información relacionada con los consumos en el Hospital San Juan de Dios (Hospital nacional de referencia) se obtendrá a través de los mecanismos internos de información disponibles en la institución. Punto 2: El medicamento específico (oral o parenteral) al que se le solicite su ingreso al registro de oferentes de la Caja para su registro o el medicamento que se adquirirá a nivel Central o Local presentara certificación emitida por la Dirección Médica del Hospital General u Oncológico o Instituto del Cáncer del país de origen del laboratorio fabricante, firmada por la máxima autoridad en oncología médica y el Director Médico General del Centro Médico, en la que se presente el consumo anual en pacientes que corresponda a un mismo año, resultados de eficacia y seguridad que han obtenido con el uso del producto medicamentoso en el tratamiento de pacientes con patología hemato-oncológica y el tipo de patologías oncológicas tratadas. Los documentos deben contener en forma completa y concreta, el tipo y porcentaje de efectos secundarios presentados por los pacientes que han recibido el tratamiento con dicho producto para su análisis. Punto 3: Certificación del Ministerio de Salud Pública o de la máxima autoridad en Salud Pública equivalente en el país de origen del Laboratorio fabricante presentada por su representante, que reconozca el Hospital General u Oncológico o Instituto del Cáncer, que solicita ser registrado. Punto 4: Toda certificación que se solicita debe ser presentada en forma individual y la información debe referirse al año anterior más cercano a la fecha de su inclusión en el Registro de oferentes de medicamentos ante la CCSS cuando se trata de medicamentos incluidos en la Lista Oficial de Medicamentos, o corresponder al año anterior más cercano al concurso cuando se trata de medicamentos no incluidos en la Lista Oficial de Medicamentos y son adquiridos a nivel Central o local. Estas certificaciones deben ser actualizadas cada vez que se solicite la renovación del registro ante la CCSS para los medicamentos incluidos en la LOM, de no estar registrados cada vez que se haga una compra a nivel Central o local en el caso de los medicamentos no LOM. Punto 5: Todos los documentos solicitados deben tener las firmas de autoridades en salud debidamente autenticadas, según lo exige la legislación costarricense, además de completar cadena de legalización consular de nuestro país y ratificadas por el Ministerio de Relaciones Exteriores de Costa Rica. Punto 6: Se eximirá de los requisitos enunciados en el punto 1, 2, 3 y 4 aquellos medicamentos antineoplásicos y otros medicamentos de uso específico en patologías oncológicas y hemato-oncológicas de uso parenteral u oral, que se encuentren inscritos y se consuman en cualquiera de los siguientes países: Estados Unidos (FDA), Canadá (Health Canadá), Japón (MHLW), Suiza (Swissmedic), Alemania, Inglaterra, Suecia, Francia, Italia, España, Bélgica, Dinamarca, Austria, Holanda, Finlandia, Noruega. Es importante señalar que los laboratorios deben presentar el certificado de libre venta de su producto en los Estados Unidos (FDA), Canadá, Japón (MHLW), Suiza (Swissmedic), Alemania, Inglaterra, Suecia, Francia, Italia, España, Bélgica, Dinamarca, Austria, Holanda, Finlandia, Noruega; o con registro y comercialización de estos mismos países. De igual forma, serán eximidos aquellos medicamentos cuya procedencia no corresponda a ninguno de los países antes enlistados, pero que cuenten con el certificado de Reconocimiento Mutuo emitido por la EMEA para su comercialización en alguno de los estados miembros de referencia la Unión Europea. Ese certificado debe ser emitido por la máxima autoridad regulatoria competente en salud pública del respectivo país. Punto 7: El oferente que ya se encuentre registrado en el registro de oferentes de la CCSS puede revalidar su registro, presentando la información señalada en los puntos arriba correspondientes. Dicho registro será válido hasta el vencimiento del registro sanitario emitido por el Ministerio de Salud de Costa Rica. Punto 8: Aquellos oferentes que se encuentren registrados pero que prefieran presentar sus datos al momento del proceso de compra y no revalidar el registro ante la CCSS sino hasta su vencimiento, deberán presentar los requisitos para los medicamentos antineoplásicos y otros medicamentos de uso específico en patologías oncológicas y hemato-oncológicas por cada proceso de compra. Punto 9: En el caso de la adquisición de medicamentos antineoplásicos y otros medicamentos de uso específico en patologías oncológicas y hemato-oncológicas incluidos en la Lista Oficial de Medicamentos (LOM), será el Área de Medicamentos y Terapéutica Clínica adscrita a la Dirección de Farmacoepidemiología la encargada de efectuar el análisis de los datos y el correspondiente estudio de Dosis Diaria Definida (DDD). Punto 10: En el caso de medicamentos antineoplásicos y otros medicamentos de uso específico en patologías oncológicas y hemato-oncológicas NO LOM adquiridos por cada centro, el análisis de los datos y el correspondiente estudio Dosis Diaria Definida (DDD) será realizado cada vez que se promueva un trámite de compra, y será efectuado y analizado por cada Servicio de Farmacia. Punto 11: Una vez que se publique el Decreto Ejecutivo del Ministerio de Salud Pública que regula el Registro de Medicamentos, en el mismo se contemplan los requisitos específicos para productos de terapia de blanco molecular, estos requisitos se basan en las recomendaciones ICH y forman parte de estas condiciones. Punto 12: Ante las ofertas de medicamentos antineoplásicos y otros medicamentos de uso específico en patologías oncológicas y hemato-oncológicas de uso parenteral u oral no incluidos en la Lista Oficial de Medicamentos que son adquiridos, a nivel Central o local, y se encuentren en igualdad de condiciones , como mecanismo de desempate, se tomará el dar prioridad al medicamento que se encuentre inscrito y se consuma en alguno de los siguientes países: Estados Unidos (FDA), Canadá, Japón, Suiza, Alemania, Inglaterra, Suecia, Francia, Italia, España, Bélgica, Dinamarca, Austria, Holanda, Finlandia, Noruega. El oferente debe presentar certificación emitida por la máxima autoridad regulatoria del país que s hale que el mismo se encuentra inscrito y se consume en uno de los países antes citados. Ante la solicitud del Consejo de Cáncer sobre los requisitos de bioequivalencia y requisitos para los medicamentos denominados antineoplásicos de origen biotecnológicos se continúa con el mecanismo establecido en el Ministerio de Salud y CCSS. Posteriormente, el Comité Central de Farmacoterapia en sesión 2011-08 celebrada el 23 de febrero del 2011, analizó el Punto 6 de los requisitos de los medicamentos denominados antineoplásicos y otros medicamentos de uso específico en patologías oncológicas y hematológicas publicadas en La Gaceta Nº 47 del 09 de marzo del 2010, acordando modificarlo quedando de la siguiente forma: " Se eximirá de los requisitos enunciados en el punto 1, 2, 3 y 4 aquellos medicamentos antineoplásicos y otros medicamentos de uso específico en patologías oncológicas y hemato-oncológicas de uso parenteral u oral, que cuenten con permiso de comercialización en cualquiera de los siguientes países: Estados Unidos (FDA), Canadá (Health Canadá), Japón (MHLW), Suiza (Swissmedic), Alemania, Inglaterra, Suecia, Francia, Italia, España, Bélgica, Dinamarca, Austria, Holanda, Finlandia, Noruega, Colombia (INVIMA), Argentina (ANMAT), Brasil (ANVISA). Es importante señalar que los laboratorios deben presentar: el certificado de producto farmacéutico (o Certificado de Libre Venta más el Certificado de Buenas Prácticas de Manufactura), como respaldo de su registro y permiso de comercialización en los Estados Unidos (FDA), Canadá, Japón (MHLW), Suiza (Swissmedic), Alemania, Inglaterra, Suecia, Francia, Italia, España, Bélgica, Dinamarca, Austria, Holanda, Finlandia, Noruega, Colombia (INVIMA), Argentina (ANMAT), Brasil (ANVISA). De igual forma, serán eximidos aquellos medicamentos cuya procedencia no corresponda a ninguno de los países antes enlistados, pero que cuenten con el certificado de Reconocimiento Mutuo para su comercialización en alguno de los estados miembros de referencia (Unión Europea). Ese certificado debe ser emitido por la máxima autoridad regulatoria competente en salud pública del respectivo país. Para eximirles de los requisitos enlistados en los puntos 1, 2, 3 y 4 es necesario que en los certificados de producto farmacéutico (o Certificado de libre Venta) se incluya el nombre y la dirección de la planta de fabricación, la cual debe coincidir con la dirección de la planta de fabricación del medicamento registrado en el Ministerio de Salud de Costa Rica (toda vez que el medicamento se encuentre registrado en el país). La planta de fabricación (nombre y dirección) de la cual proviene el medicamento registrado y con permiso de comercialización en uno de los países antes enlistados, debe corresponder a la misma planta de fabricación de la cual será importado el medicamento a entregar a la CCSS”. Por su parte el Reglamento técnico denominado de Inscripción y Control de medicamentos Biológicos, número 37006 del 15 de noviembre del año 2011, estableció que en su normativa se regulan los requisitos y trámites necesarios para la inscripción y control de medicamentos biológicos de uso humano y aplica a todos los productos de este tipo, sean producidos en el territorio nacional o importados (artículo primero). En dicha normativa, en su ordinal quinto, se estableció respecto al registro sanitario de los medicamentos biológicos, " que cuando científicamente no proceda la presentación de alguno de los estudios o documentos mencionados en el presente Reglamento, el solicitante deberá presentar la justificación para su valoración por parte del Ministerio de Salud, estableciendo que para el registro sanitario de los medicamentos biológicos se debe presentar un expediente siguiendo el formato y el contenido establecido en el artículo 27 del Decreto Nº 28466-S de 8 de febrero de 2000 “Reglamento de Inscripción, Control, Importación y Publicidad de Medicamentos”, publicado en La Gaceta Nº 42 del 29 de febrero del 2000 y sus reformas o la normativa de registro sanitario vigente. Debe presentarse la información sobre el estatus regulatorio del producto a nivel internacional: Listado de Autoridades Sanitarias que tienen registrado el producto a la fecha del trámite ante el Ministerio de Salud y de las que han realizado inspecciones en los últimos dos años a los laboratorios fabricantes de los productos terminados. Además de información relativa a seguridad y eficacia para los medicamentos biológicos. La documentación científica presentada, referida a los informes concluyentes de los estudios clínicos, debe haber sido elaborada en un período no mayor a diez años. En caso de que los estudios mencionados anteriormente, se hayan realizado hace más de 10 años, el solicitante deberá presentar la justificación para su valoración por parte del Ministerio de Salud. Todos los informes concluyentes de los estudios clínicos deben referirse al mismo producto y forma farmacéutica que se presenta para su registro sanitario. Para productos biológicos que contienen principios activos no comprendidos en la formulación de un producto registrado previamente en Costa Rica: se requiere i) En caso de productos que contengan entidades químicas no comprendidas en la formulación de un producto previamente registrado: • Informes concluyentes de los resultados de los estudios pre clínicos (incluyendo la información de parámetros farmacodinámicos in vivo e in Vitro). • Informes concluyentes de los resultados de los estudios clínicos fases I, II y III (incluyendo estudios farmacocinéticos, farmacodinámicos y estudios clínicos y estudios de inmunogenicidad). ii) En caso de productos farmacéuticos que contienen entidades químicas incluidas en productos previamente registrados cuyo principio activo corresponde a nuevos derivados, tales como los pegilados u otros, deberán presentar: • Informes concluyentes de los resultados de los estudios clínicos fases I, II y III. Para medicamentos biológicos que contienen principios activos comprendidos en la formulación de un producto previamente registrado en Costa Rica pero que presentan: i) Nuevas combinaciones fijas de principios activos: • Informes concluyentes de los resultados de los estudios clínicos fases I, II y III. Tales informes deben comparar la proporción o dosis existente y la nueva, incluyendo estudios de biodisponibilidad. ii) Nueva forma farmacéutica con una vía de administración ya registrada: • Informes concluyentes de los resultados de estudios de biodisponibilidad. iii) Nueva forma farmacéutica con una nueva vía de administración: • Informes concluyentes de los resultados de estudios pre clínicos y estudios clínicos fases I, II y III. iv) Nueva forma farmacéutica con una nueva forma de liberación: • Informes concluyentes de los resultados de estudios clínicos fases I, II y III. v) Nuevas potencias o concentraciones de principios activos previamente registrados: • Informes concluyentes de los resultados de estudios de biodisponibilidad y estudios clínicos fases II y III. vi) Nuevas vías de administración con una forma farmacéutica ya registrada: • Informes concluyentes de los resultados de estudios de biodisponibilidad y clínicos fases II y III. 5.5. Además de los requisitos mencionados en el numeral anterior, para el registro de los medicamentos biológicos, se deberán adjuntar al expediente los documentos establecidos en los apartados siguientes en el orden en que se mencionan. Para los medicamentos ADN recombinantes o biotecnológicos se debe presentar: 5.6.a. Información de calidad relacionada a las propiedades fisicoquímicas, biológicas e inmunológicas del principio activo: i) Descripción, estructura química, secuencia de aminoácidos, modificaciones postraduccionales, propiedades fisicoquímicas, biológicas e inmunológicas. ii) Descripción del proceso de fabricación, de los controles durante el proceso, del control del sustrato celular, del control de las etapas críticas y de los productos intermedios y de la validación de los procesos. iii) Descripción de la metodología para la caracterización, incluyendo la descripción de la estructura química y las impurezas relacionadas con el producto y el proceso y contaminantes. iv) Descripción de los controles del principio activo, incluyendo especificaciones, métodos analíticos y validación de los métodos analíticos. v) Descripción de los patrones o materiales de referencia. vi) Descripción del sistema cierre-envase. vii) Descripción y resultados del estudio de estabilidad. 5.6.b. Información de calidad relacionada a las propiedades fisicoquímicas, biológicas e inmunológicas del producto terminado :i) Descripción del producto y de su composición. ii) Descripción del proceso de fabricación, de los controles durante el proceso, del control de las etapas críticas y de los productos intermedios y de la validación de los procesos. iii) Descripción del control de calidad, incluyendo especificaciones, métodos analíticos, validación de los métodos analíticos, análisis de los resultados de los lotes utilizados para las especificaciones, caracterización de impurezas y contaminantes y justificación de las especificaciones que garanticen la uniformidad lote a lote. Cuando está involucrado más de un fabricante indicar en que paso interviene cada uno. iv) Descripción de los patrones o materiales de referencia. v) Descripción de la evaluación de la seguridad frente a infecciones por agentes adventicios. Detalles sobre la inactivación y eliminación viral. vi) Plan de manejo de riesgos y de farmacovigilancia post-comercialización. NOTA 1: Estos requisitos aplican para el medicamento innovador y en el caso de biosimilares deberán presentar además, el ejercicio de biosimilitud relacionado a la calidad en comparación al medicamento biológico de referencia, para determinar que las diferencias no tienen implicaciones en su seguridad y eficacia. En la documentación aportada debe quedar especificado el nombre del medicamento al que se pretende ser biosimilar y el nombre del laboratorio que lo fabrica. NOTA 2: El ejercicio de biosimilitud deberá hacerse tanto para el producto terminado como para el principio activo, tal como se detalla en el numeral 5.12. y para ello se seguirán las guías internacionales de la OMS y en ausencia de éstas, se podrán utilizar las emitidas por la FDA, EMA o ICH. No obstante lo anterior, se podrán adoptar como oficiales las guías de otros países, una vez que el Ministerio de Salud compruebe que son de aceptación internacional y sean oficializadas mediante Resolución Administrativa que se deberá publicar en el Diario Oficial La Gaceta junto con los instructivos, formularios y cualquier otro documento que corresponda y colocadas en la página Web del Ministerio de Salud. 5.7. Para los productos hemoderivados y las vacunas se debe presentar el método de fabricación que debe contener la siguiente información: 5.7.a. Fórmula maestra, incluyendo el tamaño de lote. 5.7.b. Descripción de los materiales de partida de origen biológico tales como: cepas, líneas celulares, microorganismos, donaciones de plasma o componentes de sangre, células o sustratos celulares y medios de cultivo. Incluyendo: especificaciones de control de calidad, métodos de análisis validados y métodos para la exclusión de agentes adventicios. 5.7.c. Descripción del proceso de fabricación: i) Diagrama del flujo de fabricación señalando los controles del proceso y cuando participe más de un fabricante, indicar en qué paso interviene cada uno. ii) Descripción completa de todo el proceso, métodos de fabricación y sus controles. Información sobre los pasos de fermentación, cosecha y purificación, si la fabricación del producto los aplica, incluyendo los criterios de aceptación y rechazo. iii) Especificaciones de control del proceso y los métodos analíticos emitidos por el fabricante, los cuales deben estar validados. iv) Criterios de reproceso para cada etapa. v) Especificaciones de calidad que incluyan la caracterización y pureza del producto obtenido en cada etapa y las técnicas analíticas utilizadas para su comprobación. vi) Descripción de los procesos de doble inactivación viral, agente empleado y método para verificar la efectividad del proceso, según aplique. vii) Documento en el que el fabricante indique que su proceso de manufactura logra para todos los lotes fabricados, una reducción máxima de la inefectividad por priones, de acuerdo con el estado actual del conocimiento. 5.7.d. Certificados analíticos, deben contener las especificaciones de calidad de Principio(s) activo(s), Sustancia(s) auxiliar(es), Producto en proceso, Producto terminado y Material(es) de referencia. Los resultados analíticos de los componentes del medicamento se deben expresar en unidades de peso, o de actividad biológica según proceda. Estos certificados deben incluir: i) Nombre de la sustancia o producto. ii) Etapa de elaboración en caso de productos en proceso. iii) Fecha y lugar de fabricación. iv) Número del lote. v) Tamaño del lote. vi) Parámetros de calidad físicos, químicos, biológicos y microbiológicos con sus límites y resultados. vii) Fecha de vencimiento cuando proceda. viii) Fecha y lugar de análisis, nombre del responsable del análisis y decisión de conformidad de acuerdo con las especificaciones. ix) Referencia del método oficial utilizado o indicación de que se utilizó el método validado del fabricante. 5.7.e. Plan de manejo de riesgos y de farmacovigilancia post-comercialización. 5.8. Para los productos hemoderivados se debe presentar además de la información de los numerales 5.3., 5.4 y 5.7. los siguientes requisitos: 5.8.a. Certificado de registro sanitario vigente del producto emitido por la FDA, la EMA o cualquier otra autoridad sanitaria competente que realice la Certificación del Archivo Principal del Plasma (Plasma Master File o PMF por sus siglas en inglés) posterior a la realización de la correspondiente evaluación científica y técnica. 5.8.b. Información sobre la selección y control de los donantes. 5.8.c. Descripción de los procedimientos utilizados para garantizar la trazabilidad del producto terminado hasta los donantes y viceversa. Esta descripción debe acompañarse de un Diagrama detallado. 5.8.d. Resultado de las pruebas realizadas para detectar anticuerpos de VIH 1 y VIH 2, anticuerpos para hepatitis C y la prueba de ELISA o RIA para hepatitis B que detecte 0.5 UI por ml de antígeno HBs o menos. 5.8.e. Información sobre los centros en los que se obtiene el plasma, localización de los centros de obtención del plasma, información sobre las inspecciones realizadas en dichos Centros y sobre la Política de cuarentena. Detallar el tipo de plasma obtenido (donación o plasmaféresis), el tipo de donación (altruista o retribuida), datos del porcentaje de seroconversión de los donantes habituales y datos de marcadores en primera donación. Incluir además información sobre las condiciones de almacenamiento y de transporte del plasma establecidas por el fabricante. 5.9. Para las vacunas se debe presentar además de la información de los numerales 5.3., 5.4 y 5.7.: 5.9.a. Estudios clínicos de reactogenicidad e inmunogenicidad y de eficacia. La falta de estudios de eficacia deberá justificarse. 5.9.b. Información sobre los Sistemas de Bancos de Células: i) Preparación, descripción y controles realizados al Banco de Células Maestro (BCM) y Banco de Células de Trabajo (BCT). ii) Descripción de los controles utilizados para verificar la ausencia de agentes adventicios. iii) Descripción y caracterización de estabilizadores, adyuvantes y conservantes. iv) Secuencia del ácido nucleído de la cepa y su estudio comparado con otras cepas, incluidas las cepas vacúnales. 5.10. Para las vacunas combinadas se debe presentar adicionalmente de la información de los numerales 5.3., 5.4. y 5.7. los siguientes requisitos: 5.10.a. Estudios clínicos de reactogenicidad e inmunogenicidad. 5.10.b. Información sobre los Sistemas de Bancos de Células: i) Preparación, descripción y controles realizados al Banco de Células Maestro (BCM) y Banco de Células de Trabajo (BCT). ii) Descripción de los controles utilizados para verificar la ausencia de agentes adventicios. iii) Descripción y caracterización de estabilizadores, adyuvantes y preservantes. 5.10.c. Información sobre la caracterización y controles de cada antígeno individual, los que deben cumplir los mismos requisitos que se establecen para su empleo en vacunas simples. 5.10.d. Información sobre las pruebas realizadas después de la combinación con vistas a estudiar la posible interacción entre los antígenos. 5.10.e. Información acerca de los efectos de los adyuvantes y los agentes conservadores sobre la estabilidad y la actividad del producto terminado. 5.10.f. Estudios de reactogenicidad e inmunogenicidad que demuestren la seguridad en comparación con la de las vacunas por separado, pero administradas simultáneamente. 5.11. Para los antivenenos y antitoxinas de origen animal se debe presentar el método de fabricación que debe contener la siguiente información: 5.11.a. Fórmula maestra, incluyendo el tamaño de lote. 5.11.b. Descripción de los materiales de partida de origen biológico tales como: venenos y plasma o componentes de sangre. Incluyendo: especificaciones de control de calidad, métodos de análisis validados y métodos para la exclusión de agentes adventicios. 5.11.c. Información sobre el control de los lotes de veneno utilizados para la inmunización del animal donador. i) Certificación firmada por el regente biológico de la o las especies de serpientes utilizadas en las extracciones de veneno para las mezclas de inmunización, que incluyan los nombres científicos y comunes de las serpientes empleadas: Esta certificación debe incluir un mínimo de 10 ejemplares utilizados por especie para cada lote de veneno y la fecha de extracción. ii) Diagrama de flujo que describa la manipulación y almacenamiento de las mezclas de veneno para inmunización, incluyendo las condiciones de almacenamiento. iii) Resultados de pruebas biológicas y bioquímicas que certifiquen la consistencia de los venenos (perfil cromatográfico HPLC y actividad toxicológica DL50 específicamente). 5.11.d. Información de los lotes de plasma obtenidos de los animales inmunizados: i) Información de pruebas de endotoxinas, potencia neutralizante de la mezcla de plasma para un lote y contenido de proteínas. ii) Información de los venenos empleados en la inmunización, fechas de sangría, fechas de inmunización e identificación de los caballos para un lote específico. iii) Perfil de identificación de los caballos participantes de un lote específico de plasma, con su respectiva raza, sexo, edad y peso. 5.11.e. Descripción del proceso de fabricación: i) Diagrama del flujo de fabricación señalando los controles del proceso y cuando participe más de un fabricante, indicar en qué paso interviene cada uno. ii) Descripción completa de todo el proceso, métodos de fabricación y sus controles. Información sobre los pasos de purificación, incluyendo los criterios de aceptación y rechazo. iii) Especificaciones de control del proceso y los métodos analíticos emitidos por el fabricante, los cuales deben estar validados. iv) Criterios de reproceso para cada etapa. v) Especificaciones de calidad que incluyan la caracterización y pureza del producto obtenido en cada etapa y las técnicas analíticas utilizadas para su comprobación. vi) Descripción de o los procesos de doble inactivación viral, agente empleado y método para verificar la efectividad del proceso, según aplique. vii) Documento en el que el fabricante indique que su proceso de manufactura logra para todos los lotes fabricados, una reducción máxima de la infectividad por priones, de acuerdo con el estado actual del conocimiento. Esto aplica para aquellos antivenenos o antitoxinas derivados de animales en los que se ha demostrado la infectividad por priones. 5.11.f. Certificados analíticos, deben contener las especificaciones de calidad de Principio(s) activo(s), Sustancia(s) auxiliar(es), Producto en proceso, Producto terminado y Material(es) de referencia. Los resultados analíticos de los componentes del medicamento se deben expresar en unidades de peso, o de actividad biológica según proceda. Estos certificados deben incluir: i) Nombre de la sustancia o producto. ii) Etapa de elaboración en caso de productos en proceso. iii) Fecha y lugar de fabricación. iv) Número del lote. v) Tamaño del lote. vi) Parámetros de calidad físicos, químicos, biológicos y microbiológicos con sus límites y resultados. vii) Fecha de vencimiento cuando proceda. viii) Fecha y lugar de análisis, nombre del responsable del análisis y decisión de conformidad de acuerdo con las especificaciones. ix) Referencia del método oficial utilizado o indicación de que se utilizó el método validado del fabricante. 5.11.g. Plan de manejo de riesgos y de farmacovigilancia post-comercialización. 5.12. En cuanto a la Información relativa a seguridad y eficacia y para medicamentos biosimilares no registrados previamente en Costa Rica y para los biosimilares ya registrados, se debe presentar el ejercicio de biosimilitud que incluya: 5.12.a. Estudios pre clínicos (in vitro e in vivo) que deben ser de naturaleza comparativa y diseñados para detectar diferencias significativas entre el biosimilar y el biológico innovador de referencia. 5.12.b. Estudios clínicos comparativos con el medicamento biológico de referencia para cada una de las indicaciones que solicita. Deberá presentar: i) Estudios farmacocinéticos. ii) Estudios farmacodinámicos. iii) Estudios de eficacia clínica. iv) Estudios de seguridad. v) Estudios de inmunogenicidad. El tipo y la cantidad de estudios dependerán del conocimiento que se tenga del medicamento biológico de referencia y las indicaciones terapéuticas que se estén solicitando, para esto se seguirán las guías internacionales y en ausencia de estas, se podrán utilizar las emitidas por la FDA, EMA e ICH caso por caso. 5.12.c. Carta de aprobación de los estudios clínicos indicados en este reglamento emitida por el o los Comités ético-científicos debidamente legalizada o apostillada. Dichos comités deberán estar reconocidos por la autoridad sanitaria del país donde se realizaron estos estudios. 5.12.d. Plan de manejo de riesgos y de farmacovigilancia post-comercialización. Todo monitoreo específico de seguridad impuesto al producto de referencia deberá considerarse en el plan de manejo de riesgo del producto biosimilar. 5.12.e. Detalle sobre el criterio empleado para seleccionar el producto biológico de referencia con el cual se hizo el ejercicio de biosimilitud. Para ello debe utilizarse la secuencia de criterios del numeral 6 del presente Reglamento. 6. SELECCIÓN DEL MEDICAMENTO BIOLÓGICO DE REFERENCIA: Los criterios para seleccionar el medicamento biológico de referencia en orden de prioridad son los siguientes: 6.1. La primera elección deberá ser siempre el producto innovador fabricado en el primer país de origen, el cual cuenta con un expediente completo sobre su calidad, eficacia y seguridad, siempre que éste sea el mismo registrado y comercializado en Costa Rica. 6.2. La segunda elección deberá ser siempre el producto innovador fabricado, registrado y comercializado en Costa Rica. 6.3. La tercera elección deberá ser el producto innovador fabricado en origen alterno, registrado y comercializado en Costa Rica. 6.4. La cuarta elección y en caso de que no se cumplan las condiciones anteriores, se podrá elegir como producto de referencia el producto innovador fabricado en el primer país de origen u origen alterno, o bien el producto de referencia sugerido en las listas de la OMS, aunque no haya sido comercializado en Costa Rica. Para definir el producto de referencia mediante la aplicación del presente numeral, se deberá consultar por escrito con la Dirección de Regulación de la Salud del Ministerio de Salud. 6.5. La quinta elección y en caso de que no se cumplan las condiciones anteriores, corresponde al producto líder del mercado que haya demostrado su calidad, eficacia y seguridad. Para definir el producto de referencia mediante la aplicación del presente numeral, se deberá consultar por escrito con la Dirección de Regulación de la Salud del Ministerio de Salud. 7. CAMBIOS POSTREGISTRO DE MEDICAMENTOS BIOLÓGICOS: Para todo cambio asociado al medicamento biológico que esté contemplado en la Guía de cambios post registro publicada en la página web del Ministerio de Salud, se deberá presentar los requisitos específicos establecidos en dicha Guía según el tipo de cambio a realizar. 8. RENOVACIÓN DEL REGISTRO SANITARIO 8.1. Para la renovación del registro sanitario de los medicamentos biológicos descritos en el presente reglamento, se debe presentar un expediente con los requisitos establecidos en el artículo 34 del Decreto Nº 28466-S Reglamento de Inscripción, Control, Importación y Publicidad de Medicamentos, publicado en La Gaceta Nº 42 del 29 de febrero del 2000 y sus reformas o la normativa de registro sanitario vigente, adjuntando además y en caso de que no se hayan presentado en trámites de registros previos, los requisitos establecidos en este reglamento. 8.2. Para medicamentos biosimilares que en trámites anteriores no lo hayan presentado, deberán presentar el Ejercicio de biosimilitud que contemple lo establecido en el presente reglamento. 9. LIBERACIÓN DE LOTES DE PRODUCTOS BIOLÓGICOS. La Dirección de Atención al Cliente autorizará la liberación de cada lote de los productos biológicos (a excepción de los productos biotecnológicos que por su naturaleza no se les aplica la liberación lote a lote) una vez que constate la correspondencia entre la documentación del expediente de registro con los siguientes requisitos: 9.1. Certificado de Liberación de Lote emitido por la autoridad reguladora del país productor. Para los laboratorios nacionales, el Ministerio de Salud revisará sus archivos para verificar el cumplimiento de este requisito. 9.2. Protocolo resumido de fabricación y certificado de los resultados de la prueba de liberación del fabricante y en caso de derivados sanguíneos de origen humano o de medicamentos que los contengan, se debe incluir en el certificado que el producto está libre de virus VIH, citomegalovirus, parvovirus B19 y virus de la hepatitis B y C. 9.3. Carta de compromiso, proveniente del fabricante, el titular del producto o su representante legal , en la que se garantice el cumplimiento en todo momento de las condiciones de almacenamiento establecidas en el etiquetado del lote importado, desde el laboratorio fabricante hasta la droguería en Costa Rica. NOTA: El trámite de liberación de los lotes para medicamentos biológicos por parte de la Dirección de Atención al Cliente del Ministerio de Salud, se realizará en la droguería importadora o en el laboratorio fabricante nacional en un periodo de 5 días hábiles contados a partir de la notificación al Ministerio de Salud. 10. CONTROL DE LOS MEDICAMENTOS BIOLÓGICOS. 10.1. Lo consignado en las declaraciones de registro y el cumplimiento de los requisitos exigidos, lo realizará la Dirección de Regulación de la Salud, mediante inspección y toma de muestras en el mercado, en el laboratorio farmacéutico o en aduana de acuerdo con lo establecido en la Ley General de Salud y la Ley de Promoción de la Competencia y Defensa Efectiva del Consumidor. El primer control de calidad que se realice a los medicamentos biológicos se efectuará al primer lote de comercialización, sin desmerecer los controles postcomercialización de verificación e inspección que eventualmente ordene la Dirección de Regulación de la Salud. 10.2. Para efectos de control el fabricante del medicamento biológico o el titular del mismo deberá presentar ante el Ministerio de Salud las actualizaciones de los reportes generados a razón de los Planes de Manejo de Riesgo y de Farmacovigilancia, los cuales formarán parte del expediente del producto ante el Ministerio de Salud. 10.3. En el caso de demostrarse el incumplimiento o la falsedad de lo declarado en el registro ante el Ministerio de Salud, la autoridad sanitaria detendrá, decomisará o retirará de circulación el producto respectivo o se cancelará su registro según corresponda previa notificación al representante legal, quien deberá asumir los costos de la medida sanitaria aplicada. Lo anterior sin perjuicio de otras sanciones que establezca la Ley de Promoción de la Competencia y Defensa Efectiva del Consumidor. El Ministerio de Salud procederá a la aplicación de estas medidas especiales con fundamento en lo establecido en el artículo 386 de la Ley General de Salud, sin menoscabo de la responsabilidad civil o penal que hayan incurrido las personas físicas o jurídicas responsables del tal incumplimiento y sin perjuicio de cualquier otra sanción que proceda de conformidad con la legislación vigente.". Por su parte, el Reglamento de Inscripción, Control, Importación y Publicidad de Medicamentos, número 28466 del 08 de febrero del año 2000, estableció las regulaciones pertinentes para la inscripción, control, importación y publicidad de medicamentos, rigiendo para todas las personas que fabrican, importan y comercializan medicamentos en el territorio nacional (ordinal 2 ibid). Además, en tal norma, se define la Biodisponibilidad como la velocidad y la medida en que se absorbe el ingrediente activo o la fracción activa de una forma farmacéutica y se hace disponible en el sitio de acción, la Bioequivalencia: como la relación entre dos productos farmacéuticos que son equivalentes farmacéuticamente y cuya biodisponibilidad en términos de tasa y grado, después de ser administrados a la misma dosis molar, bajo las mismas condiciones, son similares a tal grado, que sus efectos serían esencialmente los mismos, Buenas prácticas de manufactura: como el conjunto de normas y procedimientos destinados a garantizar la producción uniforme de los lotes de productos farmacéuticos que cumplan con los requerimientos de calidad que demanda la necesidad de los usuarios, certificado de análisis: como el certificado en el cual se indican las especificaciones y los resultados de los análisis físicos, químicos, biológicos, microbiológicos y biofarmacéuticos de un producto farmacéutico, emitido por un laboratorio nacional o extranjero que a juicio del Ministerio garantice su identidad y calidad, certificado de Buenas Prácticas de Manufactura: como el documento expedido por la autoridad sanitaria del país de origen, en el que se certifica que el laboratorio al que se refiere, cumple satisfactoriamente con los requerimientos de las Buenas Prácticas de Manufactura vigentes en ese país para la forma farmacéutica a la que pertenece el producto. Dichos requerimientos deben cumplir como mínimo con los estándares de la OMS equivalentes a los de la normativa vigente en Costa Rica. En el caso de betalactámicos, citotóxicos, hormonales y biológicos, el certificado debe declarar específicamente que el laboratorio fabricante está autorizado para la fabricación de esos productos farmacéuticos, Certificado de Libre Venta: como el documento expedido por la autoridad reguladora o responsable del registro de productos farmacéuticos del país de origen o de procedencia debidamente legalizado, en el que se certifica que el producto farmacéutico a que se refiere el certificado tiene su registro vigente y está autorizado para la venta o distribución en ese país. En caso de fabricación por terceros puede ser del país donde se localiza el titular o responsable de la comercialización del producto, Certificado de Producto Farmacéutico: la certificación propuesta por la Organización Mundial de la Salud (OMS) y emitida por la Autoridad Reguladora del país o región de origen o procedencia como parte del sistema de certificación de la calidad de los productos farmacéuticos objeto de comercio internacional. En caso de fabricación por terceros, el certificado de producto farmacéutico debe ser emitido por la Autoridad Reguladora del país titular del producto. Para filiales el certificado de producto farmacéutico puede emitirlo la Autoridad Reguladora del país del fabricante o del titular y como contrato de Fabricación: el Documento legal celebrado entre el titular del medicamento y el fabricante en el cual se establecen las condiciones, compromisos y demás circunstancias para la fabricación de uno o más productos; y que debe indicar como mínimo: 1) El vínculo contractual existente entre las partes involucradas. 2) Que el contratista cumple con Buenas Prácticas de Manufactura. 3) Que el contratista tiene del contratante toda la información necesaria para realizar las acciones contratadas, así como los procesos que debe implementar para el medicamento sujeto del contrato. 4) Que el contratante realizará auditorías periódicas al contratista. Se define además, el Equivalente farmacéutico: Producto farmacéutico que contiene idénticas cantidades de los mismos principios activos del producto al que es equivalente, por ejemplo, la misma sal o éster del principio activo, en idénticas formas farmacéuticas, que cumplan las especificaciones establecidas, pero que no necesariamente contienen los mismos excipientes. En consecuencia, dos equivalentes farmacéuticos pueden mostrar diferentes biodisponibilidades y actividades farmacológicas y la Equivalencia terapéutica: referida a dos productos farmacéuticos que son terapéuticamente equivalentes si son farmacéuticamente equivalentes y después de su administración en la misma dosis molar, sus efectos con respecto a eficacia y seguridad serán los mismos, determinados por estudios apropiados in vivo de bioequivalencia, farmacodinamia y estudios clínicos y/o estudios in vitro de disolución. Se conceptualiza además el término de Producto farmacéutico biológico: como un producto farmacéutico obtenido a partir de organismos vivos o de sus tejidos y el Registro sanitario como un acto administrativo mediante el cual se establece que el producto farmacéutico a registrar cumple los requisitos sanitarios de la normativa vigente relativos a la calidad, eficacia y seguridad y que, por lo tanto puede ser comercializado en el país. Por su parte el ordinal cuarto dispone que serán funciones del organismo técnico, establecido en el artículo 113 de la Ley General de Salud, centralizado en lo sucesivo en la Dirección de Atención al Cliente, la aprobación o denegación de la inscripción de todo producto a que se refiere este Reglamento y a la Dirección de Regulación de la Salud le corresponderá establecer o aprobar las normas técnicas farmacológicas por las cuales se rige la evaluación de los medicamentos y el listado de los productos farmacéuticos multiorigen de riesgo sanitario. Para tales efectos se dispone en el numeral 24 del decreto 28466, que el Ministerio de Salud deberá publicar en su sitio web una lista de las solicitudes de inscripción de registro sanitario en proceso dentro de un plazo máximo de 15 días hábiles desde la recepción de la solicitud y deberá publicar una lista de los productos farmacéuticos a los cuales se haya otorgado un registro sanitario dentro de un plazo máximo de 15 días hábiles contados a partir de la emisión del registro sanitario. En lo referente a las solicitudes de registro sanitario de productos farmacéuticos multiorigen, se debe aportar a) Una solicitud para la cual no se presente información sobre seguridad y eficacia deberá ser considerada por el Ministerio como una solicitud para el registro de un producto farmacéutico multiorigen. El Ministerio sólo podrá otorgar el registro sanitario a un producto farmacéutico multiorigen que sea un equivalente farmacéutico) De un producto farmacéutico para el cual se hayan presentado previamente datos sobre seguridad y eficacia ante el Ministerio por parte de su solicitante y para el cual se haya otorgado un registro sanitario previamente en Costa Rica. ii) De un producto farmacéutico que cumpla todas las siguientes condiciones: a) Que no se encuentre protegido por patentes, b) Que no contenga datos de prueba protegidos, c) Que contenga una entidad química presente en la formulación de un producto que haya obtenido un registro sanitario previamente en Costa Rica, d) Que el solicitante demuestre, mediante un documento emitido por una autoridad reguladora, que el principio activo tenga más de 5 años de estar autorizado para su comercialización en cualquier país; y e) Que exista información internacional que garantice la seguridad y eficacia del producto farmacéutico ante el Ministerio de Salud. Lo anterior para garantizar el acceso a medicamentos de interés sanitario. b) Los solicitantes que pidan un registro sanitario para un producto farmacéutico multiorigen deberán indicar en la solicitud el nombre del producto farmacéutico previamente registrado en el país con el que el producto del solicitante es equivalente farmacéutico o terapéutico, así como la fecha de expiración de cualquier dato de prueba protegido y cualquier patente cubierta por el producto farmacéutico previamente registrado en el país, de conformidad con la información contenida en las bases de datos del Ministerio de Salud. c) El Ministerio no deberá, sin el consentimiento del titular legítimo de los datos de prueba presentados ante el Ministerio como apoyo para una solicitud de registro sanitario de un producto farmacéutico nuevo, otorgar el registro sanitario al solicitante de un producto farmacéutico multiorigen, sobre la base de: i) Esos datos de prueba; o ii) El registro sanitario otorgado a ese producto farmacéutico nuevo, antes de la expiración del plazo de protección de dichos datos de prueba. d) El solicitante de un registro sanitario de un producto farmacéutico multiorigen o su representante legal podrá solicitar que el Ministerio revise los datos de prueba presentados como apoyo de una solicitud de registro sanitario para un producto farmacéutico nuevo como evidencia y apoyo a su solicitud de registro sanitario, en los supuestos establecidos en el Capítulo XI del presente Reglamento. A su vez, en torno a las solicitudes de un registro sanitario de un producto farmacéutico nuevo, se deberá presentar una declaración jurada emitida ante notario público indicando cualquier patente de producto o procedimiento otorgada y vigente en Costa Rica que cubra el producto farmacéutico, indicando el número de patente y su fecha de expiración. Los solicitantes o su representante legal podrán actualizar esta lista para incluir patentes que se otorguen con posterioridad a la solicitud para el registro sanitario. No obstante, estas actualizaciones no suspenderán el trámite ni el otorgamiento del registro sanitario de las solicitudes que ya se encuentren presentadas, ni afectará los registros sanitarios ya otorgados. El Ministerio deberá publicar en su sitio web, para cada producto farmacéutico al cual se haya otorgado un registro sanitario, la lista de patentes de producto o procedimiento vigentes en el país que cubren dichos productos farmacéuticos, según la información suministrada por el solicitante o su representante legal. El Ministerio deberá incluir esta información es su sitio web en un plazo máximo de 15 días hábiles contados a partir de la recepción de dicha información. El Ministerio publicará en dicha lista, el número y fecha de expiración de cada patente que sea presentada por un solicitante o su representante legal. En el caso de solicitudes de registro sanitario por primera vez de productos farmacéuticos multiorigen, cuando el solicitante no pueda cumplir con ninguno de los requisitos establecidos en los subpárrafos i) ó ii), el solicitante o su representante legal deberá presentar una declaración jurada emitida ante notario público indicando que no existe ninguna patente otorgada y vigente en Costa Rica que reivindique el producto farmacéutico objeto del registro sanitario o, cuando existan tales patentes, la fecha de expiración o vencimiento de la o las patentes que lo reivindiquen e indicando que el producto farmacéutico multiorigen no será comercializado hasta después de la fecha de expiración de dichas patentes. El solicitante o su representante legal, deberá indicar en su declaración jurada emitida ante notario público que ha revisado el sitio web del Ministerio con el propósito de verificar esta información. En tal caso, el Ministerio no emitirá el registro sanitario al solicitante hasta después del vencimiento del plazo de protección de todas las patentes que reivindiquen el producto farmacéutico multiorigen para el cual se solicita registro sanitario, según la información proporcionada por el solicitante o su representante legal, o del plazo de protección de los datos de prueba, cualquiera que sea posterior, salvo lo establecido en el Capítulo XI del presente Reglamento. Por su parte el ordinal 27 estipula los requisitos para obtener un registro sanitario por primera vez, para lo cual se abrirá un expediente de solicitud de registro sanitario. En lo atinente al control de los medicamentos, expone el artículo 50 ibid, que la verificación post registro la realizará la Dirección de Regulación de la Salud, a través de los inspectores designados al efecto, mediante inspección y toma de muestras en el mercado, en el laboratorio farmacéutico o en la aduana, de acuerdo con lo establecido en la Ley General de Salud, Ley N° 5395 del 30 de octubre de 1973; y la Ley de Promoción de la Competencia y Defensa Efectiva del Consumidor, Ley Nº 7472 del 20 de diciembre de1994; y demás normativa aplicable y el primer control de calidad que se realice a los productos farmacéuticos se efectuará durante el primer año de comercialización, sin desmerecer los controles que eventualmente ordene la Dirección de Regulación de la Salud.

VIII- SOBRE EL VICIO PROCEDIMENTAL ALEGADO DE LOS ACTOS ADMINISTRATIVOS REGLAMENTARIOS, POR AUSENCIA DE LA AUDIENCIA PREVISTA EN EL NUMERAL 361 DE LA LEY GENERAL DE LA ADMINISTRACION PÚBLICA.

Tal y como se indicó en considerandos anteriores, la Ley Constitutiva de la Caja Costarricense del Seguro Social en su ordinal 72 impone que deberá establecer y mantener actualizado un registro de oferentes de los productos. En amparo de esa norma la Caja Costarricense del Seguro Social dictó mediante acuerdo CCF-1445-06-209, sesión 2009-21 del 10 de junio de 2009 la Normativa con Requisitos para el Registro de Oferentes para Medicamentos Biotecnológicos, publicado mediante Gaceta 127 del 02 de julio de 2009, misma que mediante acuerdo 3376-11-10, sesión 2010-44 del 17 de noviembre de 2010, el Comité Central de Farmacoterapia de la Institución se procedió a dejar sin efecto todos los acuerdos previos dictados de esa normativa, estableciendo la siguiente Normativa con Requisitos para el Registro de Oferentes para Medicamentos biotecnológicos y biológicos, el cual se indicó dirigido a los oferentes registrados y oferentes a registrarse en el Registro de oferentes de a CCSS en los medicamentos biológicos del Grupo 1 y Grupo 2 en el enunciados, imponiendo de acatamiento obligatorio también para aquellos oferentes que participen en la Caja con medicamentos que no cuenten con Registro sanitario del Medicamento. De igual forma el Comité Central de Farmacoterapia de la Caja Costarricense del Seguro Social mediante acuerdo CCF-0275-02-09, sesión 2009-21 publicado en el mes de marzo de 2009, se dictó las Condiciones específicas para la adquisición de medicamentos denominados antineoplásicos y otros medicamentos de uso específico en patologías oncológicas y hemato-oncológicas, mismo que mediante sesión 2011-08 del 23 de febrero de 2011 del Comité Central de Farmacoterapia procedió a modificar el punto 6. La parte accionante presentó en primer término alegatos de fondo y finalizó tanto su libelo de acción como sus conclusiones con argumentos tendentes a destacar la existencia de un vicio formal del reglamento en su condición de acto administrativo de carácter general. En razón de lo anterior, este Colegio de Jueces aclara que resulta entonces pertinente en primer término, iniciar el estudio de los alegatos de forma, posteriormente, de ser necesario, a fin de conocer íntegramente el resto de pretensiones de la accionante, se ingresará en consideraciones de fondo. Así las cosas se tiene que la parte actora alega la inexistencia de la audiencia que impone el numeral 361 de la Ley General de la Administración Pública para la adopción de disposiciones de carácter general, lo cual en su criterio resulta un elemento de validez y su omisión implica su nulidad absoluta. La representación de la accionada, sostiene que tal requisito no es aplicable a las disposiciones y/o lineamientos científico-técnicos que emita el Comité Central de Farmacoterapia, ya que lo previsto por el numeral 361 de la Ley General de la Administración Pública, lo es para la elaboración de disposiciones de carácter general en sentido estricto del Poder Ejecutivo que en ejercicio de su potestad reglamentaria ejecutiva estime necesario adoptar, es decir, que tal requisito en criterio de su representada no es aplicable a regulaciones técnicas adoptadas por Órganos técnicos asesores como en este caso. A fin de atender los argumentos de ambas partes, resulta de importancia aclarar algunos conceptos. La participación ciudadana y la doctrina de la casa de cristal en el ejercicio de la función pública establece como máxima que salvo situaciones muy excepcionales debe permitirse la participación de los habitantes tanto por la exhibición de las decisiones, como por la posibilidad de combatirlas. Si la actuación pública presenta su debida fundamentación, la Administración no tiene que tener el menor temor es poder expresar las debidas justificaciones a partir de sus diferentes actos. Ahora, por Reglamento debemos entender toda disposición jurídica de carácter general dictada por la Administración pública y con valor subordinada a la ley, resulta ser una de las manifestaciones del ejercicio de la función administrativa, mediante la creación de un cuerpo normativo de grado inferior y sujeto a la ley, pero con la autoridad de crear efectos jurídicos. El reglamento desarrolla una ley de la cual pende su vigencia. El reglamento es norma, de ahí su doble condición. La potestad reglamentaria tiene como fundamento en la necesidad de generar normas cuyo procedimiento de aprobación, derogación o modificación sean lo suficientemente expeditos como para asegurar mecanismos de resolución ágiles a la actividad ordinaria propia de la Administración, en tanto que la ley en su trámite de aprobación resulta más lenta, por la dinámica propia parlamentaria y además no puede prever todos los supuestos que puede afrontarse en cada caso en particular a la hora del ejercicio de las competencias públicas. Tal potestad tiene como consecuencia el dictado de un acto administrativo de carácter general llamado reglamento, sujeto a determinados límites formales y sustanciales. Sobre su clasificación se ha pronunciado la Sala Constitucional en los siguientes términos: “ IV.- DE LOS REGLAMENTOS AUTÓNOMOS DE SERVICIO Y DE ORGANIZACIÓN. Se acusa que mediante normativa, que no reúne las características de un reglamento ejecutivo, ni de un reglamento autónomo de servicio o de organización, se regula materia que es propia de la ley formal, al establecerse limitaciones a derechos fundamentales, en lo que corresponde a la creación de órganos administrativos sancionatorios y al establecimiento de sanciones; además de que no fue dictado por el respectivo órgano jerárquico, sino por el proveedor del Banco Nacional de Costa Rica. A efecto de analizar la normativa consultada, se hace necesario recordar lo que con anterioridad este Tribunal Constitucional ha señalado respecto de las distintas categorías o tipos de reglamentos que constitucionalmente son posibles: "Las categorías en las cuales se distinguen los reglamentos son: a.) reglamentos de ejecución: que tienden a realizar la ejecución concreta de las leyes, especialmente cuando sean de alcance más bien genérico; b.) reglamentos independientes o autónomos de cualquier disposición legislativa, y relativos a materias de competencia del Poder Ejecutivo no reguladas por ley, o reguladas parcialmente. Entre estos pueden figurar los llamados reglamentos de organización, que se refieren a la institución y estructura de los diversos oficios públicos. Derivado de lo anterior puede definirse la materia propia de los reglamentos: la materia administrativa , que comprende los aspectos organizativos de la Administración Pública -entiéndase Poder Ejecutivo en el desempeño de las funciones que le son propias-. Por ello existe impedimento de normar la materia referente a los derechos y obligaciones de los ciudadanos como tales, la limitación de su libertad o de sus derechos -incluyendo el régimen de tributos, de penas, y de los derechos fundamentales- vía reglamentaria. Estos conceptos ya han sido indicados por esta Sala en reiteradas ocasiones, mediante resolución número 1876-90, de las dieciséis horas del diecinueve de diciembre y número 1635-93, de las diecisiete horas del catorce de noviembre, entre otras." (Sentencia número 5227-94, de las quince horas seis minutos del trece de setiembre de mil novecientos noventa y cuatro.) En virtud de lo anterior, claramente se puede diferenciar el contenido de los reglamentos independientes o reglamentos autónomos de los ejecutivos, ya que se caracterizan por regular la competencia propia de su autor –Administración- y de las autoridades inferiores, en tanto tienen por organizar y regular la actividad de su autor e inferior, para lograr un mejor cumplimiento del fin público asignado. Son de dos tipos: los reglamentos autónomos de organización y los reglamentos autónomos de servicio. Los primeros encuentran su fundamento en la potestad de auto-organización de la propia administración, y los segundos tienen su sustento en la competencia del jerarca administrativo para regular la prestación del servicio que está a su cargo, sin necesidad de la existencia de una ley previa en la materia. Se trata de reglamentos que crean regímenes de sujeción especial y que vienen a limitar los derechos de los administrativos de los ciudadanos que han entrado en relación con la Administración.” voto número 2000-2856 de 15:48 horas del 29 de marzo de 2002. En realidad, el acto reglamentario autónomo esta reservado a aspectos de organización y funcionamiento, donde incluso ni la ley puede entrar a establecer algunas limitaciones. Eso llevo a generar la doctrina del acto interna corporis, como al facultad de auto organizarse de los poderes públicos. La Constitución patria desarrolla con claridad el tema del reglamento ejecutivo y la facultad del reglamento de organización. Quedando claro la sumisión de este último al primero, toda vez que el ordenamiento nacional no establece materias reservadas a norma reglamentaria. Respecto al procedimiento para la formación de los reglamentos, la Ley General de la Administración Pública, en su numeral 361 impone que en la elaboración de las disposiciones de carácter general: "1. Se concederá audiencia a las entidades descentralizadas sobre los proyectos de disposiciones generales que puedan afectarlas. 2. Se concederá a las entidades representativas de intereses de carácter general o corporativo afectados por la disposición la oportunidad de exponer su parecer, dentro del plazo de diez días, salvo cuando se opongan a ello razones de interés público o de urgencia debidamente consignadas en el anteproyecto. 3. Cuando, a juicio del Poder Ejecutivo o del Ministerio, la naturaleza de la disposición lo aconseje, el anteproyecto será sometido a la información pública, durante el plazo que en cada caso se señale. ". De estudio del inciso segundo de dicha norma, se observan varios presupuestos legales que deben cumplirse, como lo son tratarse del proceso de creación de una norma general, el afectar intereses de carácter general o corporativo al denegar, agraviar, suprimir o limitar derechos subjetivos y/o intereses legítimos y directos y tratarse de entidades representativas de los mismos. No esta demás indicar que el Acuerdo General sobre Aranceles Aduaneros y Comercio (GATT) y la Ronda de Uruguay, ambos normas jurídicas ratificadas por Costa Rica y que tienen supremacía sobre las legales, consideran que toda norma reglamentaria que lleve implícito de manera directa o indirecta restricción a las condiciones del comercio (barreras no arancelarias) deben ser consultadas previo a su vigencia. Lo que permite hacer eco entre la norma legal y la establecida en las regulaciones internacionales. Respecto al primer requisito de tratarse una norma general, debemos indicar que el acto administrativo produce efectos individuales o concretos (resoluciones y acuerdos administrativos) y de tipo colectivo o general como los decretos y reglamentos, al dirigirse a sujetos indeterminados. En cuanto a la afectación de intereses generales o corporativos, estos se refieren a entes privados o públicos que representen con su gestión a la colectividad, a la población o tratarse de una corporación, la cual constituye "una organización colectiva debidamente constituida, personificada y organizada que represente y defienda los intereses de un grupo o sector determinable de personas (v.gr. cámaras, asociaciones, colegios profesionales) (...) ". Jinesta Lobo, Ernesto. Tratado de Derecho administrativo. Tomo tercero, San José, Costa Rica, editorial jurídica Continental, 2007, página 244. Sobre el procedimiento la Sala Primera de la Corte Suprema de Justicia, en el voto número 10 de las 14:20 horas del 22 de enero del año 2002, dispuso que " III ° La Ley General de la Administración Pública ideó un procedimiento especial para la elaboración de disposiciones de carácter general, que son actos administrativos de alcance normativo. En la especialidad que adoptó el legislador, está la respuesta a las interrogantes que plantea el subjudice, en cuanto al valor que dentro de ese proceso especial tiene el trámite de audiencia. Una simple lectura del articulado que regula ese procedimiento especial descubre que éste se ideó con el objeto, precisamente, de consagrar el trámite de audiencia, en algunos casos, a entidades del propio conglomerado estatal (Artículo 361, párrafo 1), en otros, a entidades -no hace distinción entre públicas y privadas- representativas de intereses de carácter general o corporativo, afectadas por la disposición (Artículo 361, párrafo 2). De ahí resulta indiscutible el valor y trascendencia de la audiencia en el procedimiento de elaboración de disposiciones generales, siendo esta una formalidad sustancial, insoslayable, a no ser por la concurrencia de los supuestos de excepción que la misma norma dispone. Esta obligación, en el indicado procedimiento especial, constituye el desarrollo legislativo de normas que, con carácter de principio general, informan el procedimiento administrativo. Los artículos 217, 218 y 220, en relación con el 239 y siguientes, de la Ley General de la Administración Pública disponen sobre la necesaria intervención del administrado en el procedimiento. No existiendo en la adopción de actos reglamentarios, sujetos individualizados a quienes se les pueda considerar interesados directos, el legislador dispuso que en tales casos el traslado, la audiencia, debía hacerse a entidades representativas de intereses corporativos o generales. ". En virtud de de ello, se reconoce el trámite de audiencia citado, como un requisito necesario de validez y eficacia insoslayable, de raigambre legal y supra legal, del procedimiento especial de creación de normas administrativas de carácter general. Conforme lo anterior, la audiencia que debe otorgarse resulta un requisito esencial del procedimiento, el cual tiene su fundamento en principios constituciones no solo de debido proceso sino el derecho de participación de los ciudadanos, como lo ha dispuesto reiteradamente nuestro Tribunal Constitucional en su fallos: II .-SOBRE LA PARTICIPACION CIUDADANA. La participación de los ciudadanos en la toma de decisiones públicas se encuentra prevista en el artículo 9 de la Constitución Política, por lo que adquiere el rango y la fuerza de un derecho constitucional de carácter fundamental. No se trata de una desconstitucionalización del principio de legalidad de la Administración Pública, aunque sí por supuesto, de una forma de gobierno más democrático, que amplía los foros de debate sobre diferentes temas que le afectan a la colectividad, y que por virtud de ello, quedan abiertos a la intervención y opinión ciudadana. Estamos, pues, ante una opción ya muy aceptada en la evolución del concepto de democracia y este amparo ofrece una magnífica oportunidad de darle clara y efectiva vigencia, para que no se quede en el mero discurso. El precepto comentado, entonces, recoge el principio citado a través del acceso a la información de que se dispone y a la divulgación de ella, para que la toma de decisiones no se circunscriba a un limitado grupo de intereses. De esta forma, y de conformidad a nuestro sistema democrático, el ARESEP se encuentra en la obligación de convocar a tal audiencia, particularmente para garantizar el derecho de defensa y el acceso a una información que atañe a todos y cada uno de los habitantes de nuestro país, de manera que las decisiones no se tomen sorpresivamente para los interesados "afectados". Precisamente, en la Ley de la ARESEP y su reglamento, el legislador dispuso un procedimiento administrativo especial, que es la audiencia pública cuya característica principal es la de dar transparencia en las decisiones del Ente Regulador y la posibilidad de dar participación a los consumidores y usuarios dentro del trámite. Asimismo, al dar la oportunidad de que participen en ella vecinos, organizaciones sociales, el sector estatal y el privado, instituciones de defensa al ciudadano y otras instituciones gubernamentales se logra obtener un mayor provecho, lo cual facilita un mejor intercambio de información de los participantes, constituyéndose la audiencia en un instrumento trascendental en la toma de decisiones y un instrumento de transparencia en un sistema democrático como el nuestro. En virtud de lo anterior, la fijación o modificación tarifaria debe ser sometida a una audiencia pública en la cual pueden participar aquellos ciudadanos que presenten una oposición fundamentada en criterios técnicos, dándole derecho al interesado de ejercer el uso de la palabra en la celebración del acto respectivo con el objeto de que defienda su interés en el asunto. De esta forma, la audiencia pública que debe realizar la Autoridad Reguladora de los Servicios Públicos en aquellos casos en los que tramita un estudio de fijación tarifaria de servicios públicos, tiene por objeto permitir el ejercicio del derecho a la participación de la comunidad en un asunto que le afecta, directamente, con anterioridad a la toma de la decisión administrativa y, en esa forma, se constituye en una manifestación del principio democrático. Con esa audiencia se pretende que las personas interesadas manifiesten lo que a bien tengan, respecto de la solicitud de fijación de tarifas que esté en estudio ante la Autoridad Reguladora, por lo que no se le aplica la rigurosidad que se exige para los procedimientos que pretendan la supresión de un derecho subjetivo (sentencia 2002-08848 de las dieciséis horas cincuenta y siete minutos del diez de septiembre de dos mil dos); sin embargo, no se trata de un simple requisito formal, de manera que se pueda fijar de tal forma que haga nugatorio el ejercicio del derecho que pretende tutelar, al otorgarse en condiciones que impidan u obstaculicen el cumplimiento de los objetivos que está llamada a obtener, en protección del derecho a la información y participación ciudadana…” III .- En conclusión, es claro que en aras de garantizar el derecho de participación ciudadana previsto en el artículo 9 de la Constitución Política, la audiencia pública que debe realizar la Autoridad Reguladora de los Servicios Públicos en aquellos casos en los que tramita un estudio de fijación tarifaria de servicios públicos, debe permitir el ejercicio del derecho a la participación de la comunidad en un asunto de su interés y debe de darse dentro de un plazo razonable que permita a la comunidad manifestarse. Así las cosas, lo procedente es acoger el reclamo planteado por violación al derecho de participación ciudadana y se anula la convocatoria realizada por la Autoridad Reguladora de los Servicios Públicos para conocer aumento tarifario planteada por COOPEMORAVIA, para aumentar la tarifa de la ruta 40MB, descrita como San José-Moravia-Ramales y corredores comunes de las rutas 40, 41, 42 y 43 tramitadas en el expediente ET-29-2010.” Sentencia: 10708 del 18 de junio de 2010.

IX- SOBRE EL CASO CONCRETO.

Resta entonces establecer el tipo de disposición de carácter general que constituyen los actos administrativos aquí impugnados y si debía otorgarse la audiencia conforme el numeral 361 de la Ley General de la Administración Pública previo a su adopción. De lo expuesto supra se concluye que efectivamente la Caja Costarricense del Seguro Social dictó dicha normativa al amparo del ordinal 72 de su ley Constitutiva, que efectivamente los reglamentos dictados son de naturaleza técnica. Por el órgano que los dictó no constituyen reglamentos ejecutivos, sino reglamentos independientes y sumamente sui generis. Respecto al acto dictado mediante acuerdo 3376-11-10, sesión 2010-44 del 17 de noviembre de 2010, el Comité Central de Farmacoterapia de la Institución procedió a dejar sin efecto todos los acuerdos previos dictados de esa normativa, estableciendo la siguiente Normativa con Requisitos para el Registro de Oferentes para Medicamentos biotecnológicos y biológicos, dictándose un nuevo reglamento. De la revisión del contenido de dicho reglamento tenemos que los requisitos, en la realidad no son para el oferente como tal, sino respecto al producto, grupo 1 medicamentos de origen biológico que en su proceso de manufactura no utilizan como materia prima proveniente de hemoderivados, y el grupo 2 de origen biológico que utilizan en su proceso de manufacturación materia prima de hemoderivados, -entendidos éstos según el punto 4.53 del decreto ejecutivo 37006, como el obtenido por procedimientos industriales, cuya materia prima sea la sangre o el plasma humano, lo que según los expertos que depusieron en el juicio oral y público (Julián Cuesta Ramírez, Renato Murillo Masis y Albín Chávez Matamoros) son de alta complejidad en su producción y utilizados para enfermedades muy específicas y graves. De la revisión de dicho reglamento se extrae tanto para los medicamentos del grupo 1 como del grupo 2, se impone requisitos técnicos, para los medicamentos innovadores, biosimilares, biológicos y biotecnológicos, entre otros; certificados en su proceso de fabricación, producción, etc. Inclusive se dispone que para la obtención de los medicamentos la Caja Costarricense del Seguro Social pueda tomar como parámetro de calificación su experiencia clínica del medicamento y eximir de otros requisitos técnicos. Con relación a la segunda normativa impugnada, dictada mediante sesión 2011-08 del 23 de febrero de 2011 por parte del Comité Central de Farmacoterapia en la cual procedió a modificar el punto 6 de las Condiciones Específicas para la adquisición de medicamentos denominados antineoplásicos y otros medicamentos de uso específico en patologías oncológicas y hema-oncológicas, dictadas en acuerdo CCF-0275-02-09, sesión 2009-21 publicado en el mes de marzo de 2009, se imponen para su oferta requisitos igualmente técnicos. De las declaraciones de todos los expertos que se recibieron en el juicio oral y público, se concluye que efectivamente los medicamentos deben contar con tres elementos básicos; calidad, seguridad y eficacia los cuales son indispensables para que el medicamento surta los efectos en los pacientes para lo cual fueron producidos. La actora tanto para la normativa relativa a los medicamentos biológicos, biotecnológicos y antineoplásicos, argumenta por el fondo, que las reformas introducidas en las normativas cuestionadas por el Comité Central de Farmacoterapia de la Caja Costarricense del Seguro Social, atentan contra la salud y vida de los costarricenses, al no existir la garantía de que dichos medicamentos cuenten los elementos esenciales de calidad, seguridad y eficacia, realiza en forma detallada una serie de cuestionamientos de orden técnico. De la revisión de forma minuciosa de dichas normativas efectivamente se establecen requisitos técnicos o bien se eximen respecto de la anterior normativa para la compra de medicamentos, mismos que finalmente son utilizados para cumplir el fin público encomendado a la institución, la salud pública. No debe perderse de vista que efectivamente dichas disposiciones sin entrar al fondo del proceso, van dirigidas a regular los requisitos que deben contener los medicamentos para su compra. Mismos de los cuales dependen gran cantidad de personas en nuestro país, para proteger no solo su salud, sino para preservar y rescatar su vida, normativa que tiene de forma evidente regulaciones que deben garantizar la salud pública, lo que torna de forma indefectible la discusión de sus normas un tema de interés público, pues los efectos de dichas disposiciones, si bien inicialmente son un parámetro para la compra de medicamentos, el objetivo implícito de los mismos, es precisamente salvaguardar la salud de todos los pacientes que acuden a los centros de salud públicos en nuestro país en búsqueda de mejorar y preservar su salud y su vida, por lo que, los efectos de dichas normativas no se supeditan a un tema de organización de la Institución, sino de forma evidente a un tema de Salud Pública. Las disposiciones generales, no solo deben ser clasificadas conforme el órgano que los dicta, sino a sus efectos y hacia quienes están dirigidos éstos, en el caso concreto de las normativas impugnadas, el objetivo final es la garantía de los medicamentos que se suministran a los pacientes. Por lo que resulta en criterio de este Órgano Colegiado las normas cuestionadas Reglamentos técnicos independientes, si bien no ejecutivo, por los efectos de su aplicación y cumplimiento, por lo que su interés no solo puede ser supeditado a organizaciones o agrupaciones, personas físicas o jurídicas que se dediquen a la producción, distribución y comercialización de los medicamentos, sino de toda persona en garantía de un derecho fundamental a la salud y a la vida como así como tutela nuestra Constitución Política, por lo que no es posible aceptar la posición de sostiene la representación de la demandada, que al ser un reglamento técnico no requiere el procedimiento establecido en la Ley General de la Administración Pública. Por el contrario por la materia técnica que regula, debió para su formación otorgar la audiencia que dispone el numeral 361 de la ley de cita, no puede obviarse que dicha audiencia tiene como fin la participación de los ciudadanos en los asuntos públicos, siempre que el tema que regule en dichas normativas como en las aquí cuestionadas, sean de interés público, como en el presente caso el derecho a la vida y a la salud. Continuando con el análisis del procedimiento especial de elaboración de disposiciones de carácter general, pueden citarse otras normas y principios generales que regulan el procedimiento administrativo, interpretación que es posible de conformidad con el artículo 229, párrafo 1, de la Ley General de la Administración Pública, que reza así: "El presente Libro regirá los procedimientos de toda Administración, salvo disposición que se le oponga." Por su parte el ordinal 223 impone que causará nulidad de lo actuado por la omisión de formalidades sustanciales del procedimiento. 2. Se entenderá como sustancial la formalidad cuya realización correcta hubiera impedido o cambiado la decisión final en aspectos importantes, o cuya omisión causare indefensión." Debe tenerse claridad tal y como se indicó supra, la finalidad que tiene la audiencia dispuesta en el numeral 361 de la Ley General de la Administración Púbica, pues para los efectos que conllevan las normativas cuestionadas, la audiencia resulta esencial, no solo para las organizaciones como la accionante, sino colegios profesionales, profesionales en medicina y farmacia que puedan aportar información esencial sobre la calidad, seguridad y eficacia de los medicamentos, así como de los requisitos técnicos que se les requiera para su obtención, y mayor aún, órganos administrativos, tales como el Ministerio de Salud. Al respecto la Ley General de Salud, en su numeral 102 expresa que la importación de medicamentos y su distribución sólo serán permitidas a las personas jurídicas o físicas inscritas en el Ministerio, previa autorización y registro en el Colegio de Farmacéuticos, lo que refuerza la posición de este Tribunal, sobre la obligatoriedad de dicha audiencia, el numeral 106 de la Ley General de Salud, impone que legalmente un medicamento puede ser destinado al comercio, al uso y consumos públicos, cuando satisfaga las exigencias reglamentarias o de la farmacopea declarada oficial por el Poder Ejecutivo en cuanto a su identidad, calidad, seguridad y eficacia para los fines que se le use, consuma o prescriba, y un elemento adicional, el conocimiento pleno y aceptación de la Caja Costarricense del Seguro Social, que realiza su representante en la contestación de la demanda (folio 239, párrafo in fine del expediente principal) donde manifiesta “ que para efectos de registro de medicamentos biotecnológicos, a pesar de que no existe una reglamentación a partir del Ministerio de Salud de Costa Rica, el Comité Central de Farmacoterapia hasta tanto no exista la reglamentación emitida por el ente rector, ha sido visionario y con el fin de mantener los principios de Seguridad y Eficacia en los medicamentos que se reconozcan en el Registro de Oferentes de mi representada” lo que confirma de forma absoluta el criterio de éste Órgano Colegiado sobre la obligatoriedad de otorgar la audiencia previa al dictado de las reglamentaciones impugnadas, pues al conocerse que el órgano rector en la materia no había dictado la normativa específica respecto al registro sanitario de dichos medicamentos, resultaba necesaria, oportuna y conveniente la audiencia de ley, para que el Órgano público rector de la materia se pronunciará, nótese que las reformas realizadas en el año 2010 de la Normativa con Requisitos para el Registro de Oferentes para Medicamentos Biotecnológicos y Biológicos y a inicios del año 2011l las Condiciones Específicas para la adquisición de medicamentos denominados antineoplásicos y otros medicamentos de uso específico en patologías oncológicas y hema-oncológicas, son muy cercanas al año 2011 que se dicta el Decreto Ejecutivo 37006-S en el que se Reglamenta la Inscripción y Control de Medicamentos Biológicos, lo que significa que para aquellas fechas se estaba gestando la normativa técnica que la accionada echa de menos del Órgano rector en la materia, para cuando se dictaron las normativas impugnadas, no cabe duda entonces que otorgar la audiencia es una formalidad sustancial, porque de tal actuación puede surgir una modificación del acto final. Precisamente, la audiencia tiene por objeto brindar la oportunidad a la entidad o afectado de influir en la voluntad de la Administración, antes que ésta actúe conforme con sus potestades reglamentarias. No cumplir con el trámite de audiencia que no es discrecional, sino obligatoria, está unida necesariamente a la validez de la disposición general que se emita (como culminación del procedimiento) y, en consecuencia, su omisión puede causa invalidez, por ende, determinante de la nulidad de todo lo actuado por la Administración en relación con el dictado de las disposiciones reglamentarias cuestionadas. En consecuencia, la omisión de la audiencia por parte de la accionada en la adopción de las reglamentaciones impugnadas constituye un vicio sustancial del procedimiento para el dictado de las mismas, no siendo viable en el presente caso, efectuar distinción alguna respecto de la validez de extremos de los actos impugnados, en tanto el vicio al ser de índole procedimental afecta la integralidad de los actos, en consecuencia se declara la nulidad absoluta de los siguientes actos de carácter general; 1- Acuerdo CCF- 3376-11-10, sesión 2010-44 dictado el 17 de noviembre de 2010 dictado por el Comité Central de Farmacoterapia de la Caja Costarricense del Seguro Social, publicado en el Diario Oficial la Gaceta número 10 del 14 de enero de 2011 y 2- Acuerdo tomado mediante sesión 20011-08, celebrada el 23 de febrero de 2011 por el Comité central de Farmacoterapia, mediante el cual reforma el punto 6 de las Condiciones específicas para la adquisición de medicamentos denominados antineoplásicos y otros medicamentos de uso específico en patologías oncológicas y hema-oncológicas, por carecer de un presupuesto formal de validez. Cabe señalar que si bien la parte actora realiza una prolifera argumentación de nulidad de estas normas en diferentes vertientes, al haberse acogido una de forma resulta carente de todo interés entrar a pronunciarse de las restantes de manera expresa; más si conviene advertir al ente público que debe tener claro cuales son las competencias que le resultan propias con respecto aquellas que están reservadas para el Ministerio de Salud como órgano rector en la materia. De suerte que ambas dependencias debe coordinar el cumplimiento de sus fines públicos, pero sin la invasión de uno en el otro. En ese aspecto llamamos la atención como los temas referentes al registro sanitario la excepción de este son resorte del Ministerio, tópico que no debe perderse de vista.

X. RESPECTO A LAS RESTANTES PRETENSIONES

La accionante solicita que “ Al ser nulos los acuerdos impugnados requerimos restaurar la vigencia de los anteriores acuerdos; Normativa con Requisitos de Oferentes para Medicamentos Biotecnológicos y Biológicos del 2009 y en su lugar se aplique la Normativa con Requisitos para el Registro de Oferentes para Medicamentos Biotecnológicos y Biológicos del 2009 y que corresponde a la versión anterior de la reforma publicada en el Diario Oficial La Gaceta N° 10 del 14 de enero de 2011 relativa al acuerdo de la gerencia de Logística de la Caja Costarricense del Seguro Social (CCSS) tomando en sesión N° 2010-44 del Comité Central de Farmacoterapia (acuerdo número CCF 3376-11-10) y Acuerdo Denominado "Requisitos de los medicamentos antineoplásicos y otros de uso específico en patologías oncológicas y hematológicas publicada en la Gaceta N° 47 del 9 de marzo de 2010, que corresponde a la versión anterior de la reforma introductoria sesión del 2011-08 celebrada el 23 de febrero de 2011 por parte del Comité Central de Farmacoterapia de la CCSS, publicada en Gaceta N° 58 del 23 de marzo de 2011, y "que la Caja Costarricense del Seguro Social aplique el contenido del Decreto 37006-S publicado en Diario oficial La Gaceta Número 59 del 22 de marzo del 2012, denominado Reglamento de Inscripción y Control de Medicamentos Biológicos, el cual es conforme a la normativa anterior de la Caja Costarricense del Seguro Social, que en el punto 3 de las pretensiones de la demanda solicitamos se restaure su vigencia." Al respecto es importante resaltar, que si bien las primeras dos pretensiones, sobre restaurar la vigencia de las anteriores normativas, la Normativa con Requisitos para el Registro de Oferentes para Medicamentos Biotecnológicos y Biológicos del 2009 y Acuerdo Denominado "Requisitos de los medicamentos antineoplásicos y otros de uso específico en patologías oncológicas y hematológicas” publicada en la Gaceta N° 47 del 9 de marzo de 2010, que corresponde a la versión anterior de la reforma introductoria, fueron esbozadas por la actora desde el inicio de su demanda, y posteriormente al sobrevenir el dictado del decreto ejecutivo 37006-S (alegado como hecho nuevo), solicita la aplicación de éste último, de forma evidente para la Caja Costarricense del Seguro Social varían las circunstancias, concretamente sobre la materia que reguló debido a la ausencia de la reglamentación técnica por parte del ente rector el Ministerio de Salud, en razón de lo anterior es la Caja Costarricense del Seguro Social la que deberá determinar cual normativa le corresponde aplicar siempre en cumplimiento de sus fines y el ejercicio de su competencia, tomando en consideración la existencia y vigencia del decreto ejecutivo 37006-S. Lo pretendido por la actora, no puede ser declarado, se rechaza, en razón de la variación de las circunstancias que ella misma gestionó como hecho nuevo. Supeditar a la Caja Costarricense del Seguro Social a la aplicación de una normativa dictada por el Comité Central de Farmacología en otras circunstancias y no las que imperan en la actualidad, por lo que como se indicó supra, serìa invadir la Potestad reglamentaria de la Institución autónoma, por lo que será la institución la que defina cual normativa se ajusta mejor al cumplimiento de sus fines, dentro de sus competencia y en respeto de las competencias del órgano rector en materia de salud, el Ministerio de Salud. En aplicación del artículo 131 del Código Procesal Contencioso Administrativo, se aclara que los efectos retroactivos de la presente declaratoria de nulidad absoluta no afectarán a terceros que tengan a la fecha de la firmeza de la presente sentencia derechos subjetivos adquiridos de buena fe o situaciones jurídicas consolidadas derivadas de la norma antes indicada. Adicionalmente se debe ordenar, en aplicación del precepto 130 inc. 3) del CPCA, la publicación íntegra de la presente sentencia en el diario oficial La Gaceta a cargo de la Caja Costarricense del Seguro Social.

XI- SOBRE LAS EXCEPCIONES ALEGADAS.

Se alega por parte de la demandada una Falta de Legitimación de la actora, exponiendo que Fedefarma no pretende hacer valer los derechos de la colectividad, en cuanto al uso de los medicamentos, sino que su estrategia de fondo va dirigida a un interés de índole comercial, razón por la cual no se encuentra legitimada para demandar a la Caja Costarricense del Seguro Social. Por su parte la actora afirma que su interés es el de los pacientes, lo que justifica la defensa de los derechos colectivos, y la acción se trata de hacer respetar disposiciones de calidad y seguridad introducidas al ordenamiento jurídico por parte del Ministerio de Salud y que son recomendadas por la Organización Mundial de la Salud. Que no se trata como lo afirma la demandada de un asunto comercial, sino asegurar que la población cuente con medicamentos seguros y eficaces, razón por la cual defienden los derechos de la colectividad. Por lo que su representada se encuentra legitimada para interponer la acción. Respecto a la Legitimación es la necesaria correspondencia entre el demandado y el titular del derecho o interés legítimo pretendido. Es un presupuesto esencial de la relación jurídica procesal, imprescindible para una sentencia estimatoria. El numeral al 10 inciso b del Código Procesal Contencioso, establece que se encuentran legitimados para accionar “b) Las entidades, las corporaciones y las instituciones de Derecho Público y cuantas ostentes la representación y defensa de intereses o derechos de carácter general, gremial o corporativo, en cuanto afecten tales intereses o derechos, y los grupos regidos por algún estatuto en tanto defiendan intereses colectivos.” el inciso segundo de citado ordinal impone que podrán impugnar directamente disposiciones reglamentarias, quienes ostenten, respecto de éstas, algún interés legítimo, individual o colectivo, o algún derecho subjetivo, sin que se requiera acto de aplicación individual. Resulta necesario mencionar que la norma establece dos presupuestos diferentes, el inciso 1.B para los actos o actuaciones concretas, el inciso 2 para la impugnación de disposiciones reglamentos, como en el caso concreto y en este presupuesto otorga la legitimación para acudir en defensa de los derechos colectivos. Por lo que esencial resulta determinar, si la actora, aún cuando así lo menciona realmente se presenta en representación de intereses colectivos. El jurista nacional Manrique Jiménez Meza la definido los intereses colectivos como " típicos intereses de grupo o colectivos menores, imputables a la colectividad organizada, sea a través de personas jurídicas o a través de grupos no incorporados a tales personas, para la protección de los intereses insertos en cada categoría de pertenencia (...) los intereses colectivos son intereses de categoría y como tales, constituyen un tratamiento parcial en el contexto del amplio colectivo impersonal, anónimo e indeterminado, pero no por ello dejan de ser de vital importancia en el contexto social. Por consiguiente, los intereses colectivos son imputables a los sujetos representantes de tales intereses, sea mediante asociaciones, organizaciones, entidades varias o aún incluso mediante grupos organizados en virtud de intereses compartidos frente a amenazas o perjuicios comunes." (Jiménez Meza Manrique, El Nuevo Proceso Contencioso Administrativo, San José. Poder Judicial. Departamento de Artes Gráficas, 2006, página 89.) El maestro Jinesta Lobo los define como " los propios de un grupo o una categoría, los cuales se subdividen, a su vez en corporativos y difusos. Consecuentemente, los intereses colectivos son una especie del género, cuyo titular es un grupo organizado o no, personificado o no, diferente a la colectividad nacional, dentro de otro de mayor envergadura que puede estimarse como total o general. Tal categoría o grupo, se puede identificar por una característica o rasgo común de relevancia social (afición, ocupación, giro, consumidores o usuarios de determinados bienes o servicios públicos etc.) JINESTA LOBO, Ernesto. Tratado de Derecho Administrativo Tomo III. 1 ° Edición. Editorial Jurídica Continental. San José, 2007, pág. 243. La actora desde su demanda (folio 2) informa que "FEDEFARMA es una organización civil constituida conforme a las leyes de la República de Guatemala, que representa a las empresas farmacéuticas de investigación y desarrollo que operan en el Istmo Centroamericano y en el área del Caribe (…) agrupa a catorce empresas farmacéuticas multinacionales de investigación ", de la revisión de la prueba aportada por la accionante en atención a la prevención realizada por este Tribunal sobre su personería, se tuvo a las vista a la vista el acta constitutiva de dicha Federación y en concreto a folio 483, estable la citada acta " ARTICULO 3o. La Federación es una entidad ajena a todo lucro y fines religiosos. Completamente apolítica, creada para promover el desarrollo y mejoramiento de la actividad farmacéutica, defender y coordinar los intereses de sus asociados y representarlo en sus relaciones con otras entidades públicas o privadas y con personas particulares". En análisis de la demanda, se extrae que la actora dentro de sus alegatos, ha mencionado que su interés en defensa de la calidad de los medicamentos que se suministran a los pacientes, alegando reiteradamente que exige la protección del derecho a la salud de los pacientes que son finalmente los usuarios de los medicamentos que adquiera la Caja Costarricense del Seguro Social para atender las necesidades de salud. No obstante lo anterior, de la misma demanda también se evidencia que la actora siempre informó que representa a un grupo de empresas farmacéuticas multinacionales de investigación, y del articulado de su constitución, efectivamente su objetivo es promover el desarrollo y mejoramiento de la actividad farmacéutica, por lo que en aplicación al inciso segundo del numeral 10 del Código Procesal Contencioso, la accionante si encuentra legitimada para apersonarse en defensa de los intereses colectivos que representa Fedefarma, aunado que de sus mismos alegatos se obtiene el cuestionamiento a la calidad de los medicamentos que puedan ser distribuidos y consumidos en nuestro país. De manera que el núcleo que une a las farmaceuticas a conformar la Federación esta como sustento en el proceso que nos ocupa; de suerte que el presupuesto normativo se encuentra satisfecho. Si bien esa argumentación no es desarrollada de la mejor manera en el escrito de la demanda, como ya se indicó se infiere esto sin mayores cuestionamientos. Nótese que si bien el citado inciso segundo limita para efectos de la impugnación de las disposiciones reglamentarias, intereses legítimos, individual y colectivos, más no difusos, si cumple la actora con el presupuesto legal para accionar en nombre de quien representan, una Federación compuesta por casas farmacéuticas, con la finalidad de fomentar y proteger las actividades de los laboratorios farmacéuticos. Aunado a lo anterior, conforme lo expresado por ésta Cámara los efectos de los reglamentos impugnados van dirigidos finalmente a un tema de Salud Pública, y por ser un derecho fundamental la protección de la vida y la salud de las personas, la legitimación en esta materia no puede ser restrictiva. En consecuencia, la defensa de falta de legitimación activa alegada por la representación de la demandada debe ser rechazada. A mayor abundamiento es de señalar que se han señalado por la doctrina una serie de tópicos donde la legitimación es abierta hacia cualquier habitante (casi como acción popular) por el nivel de relevancia social, entre las cuales se ubican los temas impositivos, y la materia ambiental; más alguna doctrina acepta los tópicos de salud dentro de este listado. La lógica que imperaría según este razonamiento es que en aquellas materias donde la afectación a la salud sea el fondo de la discusión; cualquier persona física o jurídica estaría legitimada. Postura que si bien no es abrazada por el Tribunal en este momento, no por ello deja de tener su debido sustento y lógica jurídica. Respecto a la Falta de Derecho, la misma se rechaza en cuanto a que efectivamente el fallo dispuso la nulidad de las disposiciones reglamentarias cuestionadas, llevando razón la actora en sus alegatos, entendiéndose acogida en las restantes pretensiones. De manera que el derecho invocado por la accionada no presenta su correspondiente sustento, sino que la balanza de la justicia se orienta en otro sentido, implicando el rechazo de la defensa previa.

XII.- SOBRE LAS COSTAS. En lo que refiere a las costas, conforme el numeral 193 del Código Procesal Contencioso Administrativo, son las costas del proceso a cargo de la accionada. Lo anterior en tanto la actora ha tenido que concurrir a esta vía a fin de hacer valer su derecho, lo que determina que en caso de no cargarse al ente público se estaría produciendo un enriquecimiento injusto para la actora.

POR TANTO:

Se admiten los hechos nuevos formulados por la parte actora. Se declaran sin lugar las defensas de Falta de Legitimación activa y la Falta de Derecho incoada por la demandada, esta última en lo concedido, entendiéndose admitida en lo restante. Se acoge con lugar parcialmente la demanda, entendiéndose denegada en lo no expresamente concedido, en consecuencia se declara la nulidad absoluta de los siguientes actos administrativos: 1- Acuerdo CCF- 3376-11-10, sesión 2010-44 dictado el 17 de noviembre de 2010 dictado por el Comité Central de Farmacoterapia de la Caja Costarricense del Seguro Social, publicado en el Diario Oficial la Gaceta número 10 del 14 de enero de 2011, en el cual se modifica la Normativa con Requisitos de Oferentes para Medicamentos Biotecnológicos y Biológicos del 2009. 2- Acuerdo tomado mediante sesión 20011-08, celebrada el 23 de febrero de 2011 por el Comité central de Farmacoterapia, mediante el cual reforma el punto 6 de las Condiciones específicas para la adquisición de medicamentos denominados antineoplásicos y otros medicamentos de uso específico en patologías oncológicas y hema-oncológicas, publicado en la Gaceta 58. Toma nota la Caja Costarricense del Seguro Social de lo expuesto en la parte considerativa de este fallo. Son ambas costas del proceso a cargo de la parte vencida. Notifìquese.

Grace Emilia Loaiza Sánchez Ricardo Ant. Madrigal Jiménez Carlos Enrique Espinoza Salas Jueces de juicio

Sección Cuarta