A brief overview of the situation regarding regulation, pricing and reimbursement of drugs in Argentina. Prepared in association with Marval, O’Farrell & Mairal, a leading global law firm, this is an extract from The Pharma Legal Handbook: Argentina, available to purchase here for USD 99.

1. What are the regulatory authorities with jurisdiction over drugs, biologicals, and medical devices in your country?

The National Ministry of Health (MoH) is the main health authority in Argentina. Nonetheless, in the year 1992, the National Agency of Medicines, Food and Medical Technology (ANMAT) was created by Decree No. 1,490/1992 (amended and complemented by Decree No. 1,271/2013). The ANMAT is an independent government agency and is granted jurisdiction to control the safety, efficacy, and quality of medicines and to control the activities, process, and technologies performed for the supply, production, manufacturing, fractioning, import and/or export, warehousing, and commercialization of products and materials used for human medicine.

In addition, ANMAT is the national health authority in charge of registering and/or granting authorization to the persons and companies which are involved in the supply, production, manufacturing, fractioning, importation and/or exportation, warehousing, and commercialization of pharmaceutical products and medical devices and controlling the execution of such activities. Each province has its own health authority that works jointly with ANMAT and may issue regulations.

Under the scope of the MoH, the Superintendence of Health Services (SSS) has monitoring, control, and enforcement capacities over insurers of the National Health Insurance System and has authority over the national insurers’ providers and the National Institute of Social Security for Retired Persons and Pensioners. At a provincial level, the SSS does not have regulatory authority over the provincial health insurers.

The Secretariat for Programming Drug Abuse Prevention and Fight against Drug Trafficking (SEDRONAR) is the national agency acting on behalf of the Executive Branch that controls all operations with certain chemical substances capable of being used in the illicit manufacture of narcotic drugs and psychotropic substances. Decree No. 1,095/96, as amended and complemented by Decree No. 1,161/2000 and others, governs the activities of production, manufacturing, preparing, repackaging, distribution, commercialization as wholesale or retail, storage, import, export, transport, transship and/or perform any other type of transaction both nationally and internationally of the substances included in lists I and II of Annex I of Decree Number 1,095/96. These activities can only be performed upon the prior authorization and control of the National Registry of Chemical Precursors dependent on SEDRONAR.

2. What is the regulatory framework for the authorization, pricing, and reimbursement of drugs, biologicals, and medical devices?

Pursuant to Law No. 16,463 (Law on Medicines), the import and commercialization of medicines and medical devices can only be carried out upon the prior authorization and under the control of the national health authority.

The main national regulations concerning registration of pharmaceutical products (pharmaceutical products and biological drugs) and medical devices include the following:

PHARMACEUTICAL PRODUCTS

• The Law on Medicines (as amended and complemented) governs the activities of production, manufacturing, import, export, fractioning, commercialization, storage of medicines, chemical products, reactives, pharmaceutical forms, medicines, medical devices, diagnostic devices, and any other product for use or application of medicine on human beings and who ever participates – individuals or corporations – in such activities and can only be performed upon the prior authorization and control of the health authority, in premises duly licensed and managed by a technical director duly appointed with the health authority.
• Executive Decree No. 150/92 (as amended) applies to the registration, elaboration, fractionation, prescription, sale, marketing, export and import of medicines. It also provides that as long as the product whose marketing approval is sought has been approved in any of the countries included in Annex I of the Decree, any person may apply for marketing approval with out time limitations, submitting minimum information (bioavailability data and a project of label, leaflet and prospect). The list of countries includes, inter alia, Denmark, Japan, the U.S.A., Germany, the U.K., Spain, Italy, and France.
• ANMAT Regulation No. 5,755/1996 (as amended) complements Executive Decree No. 150/92 and regulates the proceedings to register medicines before the health authority providing different pathways for filing the application form.
• Decree No. 1,299/97 also regulates the Law on Medicines. This Decree set up the rules for the supply chain of medicines, requiring being prior and duly authorized by the health authority to engage in such activities. Pharmaceutical laboratories must only commercialize their manufactured or imported products (medicines), by themselves or through their distributors, exclusively with pharmacies, drugstores and/or public or private sanitary or healthcare establishments, duly authorized by the corresponding health authority. All medicine products should comply with the legal requirements regarding labeling, packaging, safety requirements, etc. prior to being commercialized.
• The authorization for commercialization approval granted by the health authority with respect to each product should be obtained in order to be allowed to market the product in the country, by correctly passing the “first batch technical inspection” at the facilities of the pharmaceutical company (ANMAT Regulation No. 5,743/09).
• ANMAT Regulation No. 7,075/2011 establishes the requirements and demands for the registration of biological medicines, including the medical specialties of biological origin for human use; industrially manufactured or manufactured with intervention of an industrial proceeding, such as hemoderivatives; products obtained by means of recombinant DNA; monoclonal antibodies; drugs obtain from biological flows or animal tissues; and other biological products.
• The registration of a biological product with the ANMAT requires the submission of a dossier which must include details of the manufacturer and holder of the certificate of registration of the product, quality information, pre-clinical and clinical information, and a plan for post-marketing surveillance.
• ANMAT Regulation No. 3,397/2012 approved the specific requirements for the authorization of biological drugs and/or monoclonal antibodies obtained from recombinant DNA methods. Those requirements are considered complementary to the ones provided by ANMAT Regulation No. 7,075/2011.
• The registration proceeding for biosimilars is provided by ANMAT Regulation No. 7,729/2011. These drugs are defined as biological drugs whose qualiquantitative composition, therapeutic indication, and pro-posed administration have backgrounds in other biological drugs registered with the ANMAT or by any foreign health authority (biological reference medicine or comparator), of which there is evidence of effective commercialization and sufficient characterization of its risk- benefit profile.
• Law No. 26,689 (rare diseases) seeks to promote integral healthcare of people with rare diseases (diseases whose prevalence in population is equal to or less than one in 2,000 people in relation to a national epidemiological situation). It also establishes that the social security sector (obras sociales), prepaid medicine companies, and any other healthcare insurance provider must give healthcare coverage to patients with this condition, including at least those benefits determined by the competent authority.
• ANMAT Regulation No. 4,622/12, as amended and complemented, regulates drugs or medicinal specialties aimed at preventing, diagnosing and treating rare or serious diseases for which there is no secure or effective treatment available (orphan drugs). It sets out the conditions for registering orphan drugs that will be assigned to the category of products authorized under special conditions. The granting of the product registration and the validity term of the marketing authorization certificate will be made by the competent authority on a case-by-case basis taking into account, among other things, the specific characteristics of the involved drug, the complexity of the disease to be treated, and information related to the phases of its development. The labels, leaflets and all information made available for professionals must include the legend “authorized under special conditions” (“autorizado bajo condiciones especiales”), with the same size and highlighting as the brand name and the Argentine Common Denomination or the International Common Denomination.

MEDICAL DEVICES

• Law on Medicines;
• ANMAT Regulation No. 2,319/02 as amended and complemented: it sets forth the requirements for a company to be holder of marketing authorization certificates and to commercialize medical devices;
• ANMAT Regulation No. 2,318/02 as amended and complemented, it defines what types of medical devices can be registered depending on the intrinsic risk for human health;
• ANMAT Regulation No. 727/2013, it sets forth the requirements for the registration of medical devices at the National Registry of Manufacturers and Medical Devices as well as the necessary documentation to be submitted in case of modifications to the marketing authorization certificates already issued by the health authority.
• Medical devices are classified for registration purposes in classes (I, II, III, and IV), depending on the intrinsic risk for human health. Medical devices to be implanted in the body are included in Class III or Class IV, depending on their intrinsic characteristics. Instruments (intended to integrate and complement the medical device) are classified and registered separately from the medical device they integrate.

So far, ANMAT has not issued specific regulations for fixing prices applicable to the products under its control.

However, since 2014 in relation to medicines, the ANMAT has issued regulations aimed at compelling the holders of marketing authorization certificates to report the suggested price of sale of their products, in order to publish such reference prices on its website in the National Vademecum of Medicines.

3. What are the steps to obtaining authorization to develop, test, and market a product?

Any company that intends to directly commercialize and market medicines and/or medical devices products in Argentina must first be duly licensed as a pharmaceutical and/or medical device company by ANMAT to manufacture or import/export medicines/medical devices. Once the company is licensed as a pharmaceutical/medical devices company it will be allowed to hold the marketing authorization certificates of the products for manufacturing or importing products for sale in the Argentine market.

4. What are the approximate fees for each authorization?

The costs for obtaining the license to commercialize pharmaceutical products and medical devices in Argentina would mainly consist in the fees to be paid to ANMAT for requesting the authorization to act as a pharmaceutical or medical devices company and to obtain the marketing authorization certificates of the products. These fees vary depending on the type of product to be registered (i.e. synthetic, biological, orphan medicines, etc.). The fees are updated every year by ANMAT.

5. For how long are marketing authorizations/registrations valid? How are marketing authorizations/registrations renewed?

Each pharmaceutical product (medicine) or medical device product requires being previously authorized by the health authority for manufacturing or import purposes and -as an evidence of such authorization- a marketing authorization certificate (“MA”) should be issued per product. MAs have a valid period of five (5) years, being able to be renewed for the same period. Registrations of orphan drugs have a specific validity term that is defined on a case-by-case basis by ANMAT.

6. How does the authorization process differ between brand-name products and generic products? Are there differences for local manufacturers versus foreign-owned manufacturers?

ANMAT approves drugs on a similarity basis. Biological drugs including monoclonal antibodies obtained from recombinant DNA methods and biosimilars have a specific regulatory pathway for obtaining product approval.

There are no substantive differences between local and foreign-owned manufacturers. However, it should be noted that the MoH together with the Secretary of Trade have issued a joint regulation regulating the mandatory coverage of certain high-costs medicines by healthcare insurance providers and prepaid medicine companies by giving preference to those national produced products available in the market with the same active ingredient or biosimilar from those produced abroad, provided that their final sale price is significantly lower than the average price of the similar/biosimilar foreign produced medicines.

The Executive Decree No. 150/92 sets forth the requirements applicable to several possible registration scenarios (e.g., depending on whether a similar drug to the one to be registered has already been authorized by the local authority or not, depending on the countries where the drug has been authorized, depending on whether the drug will be imported or locally manufactured, etc.).

ANMAT Regulation No. 5,755/1996 (as amended) complements the Executive Decree No. 150/92 and regulates the proceedings to register medicines before the health authority providing different pathways for filing the application form. Regarding “similarity,” ANMAT Regulation No. 5,755/96 sets forth the following definitions:

1. Similar medicinal or pharmaceutical specialty: the one that contains the same active pharmaceutical ingredients, the same concentrations, the same pharmaceutical form, same form of administration, same therapeutic indication, and same dosage being equivalent to the reference product and can differ in characteristics such as size, form, excipient components, lifetime period, and primary package.
2. Similar Pharmaceutical form: the one that is found in the same physical form (solid, liquid, gaseous), has the same form of administration and is equivalent to the pharmaceutical form of the reference product.

Therefore, as a practical matter a generic competitor may obtain marketing approval quite easily without submitting a complete registration dossier.

ANMAT’s regulation No. 3,185/99, as amended and complemented, provides a list of the medicines that require bioequivalence studies to be approved. Bioequivalence studies are thus, only compulsory for the medicines included in such list.

Regulation No. 3,185/99 also provides that bioequivalence studies are performed through a proceeding in which the generic drug is compared with a product (i.e. a reference product) that ANMAT has selected to perform the bioequivalence study so as to establish its interchangeability.

In principle, the reference products selected for performing bioequivalence studies are the leading products in the market. In general, it is very difficult to argue against the approval of a generic product at ANMAT or before the Courts. To successfully argue against a generic approval before ANMAT it would be necessary to prove that either the generic drug is not similar to the drug approved in another country or that there is a danger for the health of consumers. Unfortunately, there is no case law on these issues in Argentina so far.

7. How are combination products (drug + drug, drug + biologic, drug + device, biologic + device, drug + biologic + device) regulated?

Combination of products (medicines) must obtain the corresponding marketing authorization with ANMAT. The combination of drugs and medical devices is not expressly regulated.

The combination of a medical device product with another medical device product is regulated by ANMAT Regulation No. 2,318/02, as amended and complemented.

8. How is compliance with regulation monitored and evaluated? Is the regulatory regime comparable with the U.S. Food and Drug Administration or the European Medicines Agency expectations and requirements?

The MoH and ANMAT are mainly responsible for supervising pharmaceutical activities. Other authorities can also intervene depending on the jurisdiction where the activities are carried out: for example, the relevant municipality or provincial MoH where the pharmaceutical activities are being developed.

Compliance with the regulations is monitored by means of inspections, sample testing, traceability systems for pharmaceutical products and prohibitions by the health authorities.

In the framework of a Pan American Health Organization (PAHO) initiative to promote the recognition of Drug Regulatory Authorities, ANMAT’s evaluation process finished on December 11, 2009. PAHO fosters this WHO initiative in the Americas by carrying out evaluation processes led by experts.

Countries submit themselves to the evaluation processes voluntarily. After exhaustive consultation and approval procedures, all the Americas countries agreed upon the election of an evaluation tool comprising all the regulatory functions an Authority should perform and the indicators proving its compliance. The first Drug Regulatory Authorities (DRA) that applied for an evaluation were: Chile’s ISP, Colombia’s INVIMA, Cuba ́s CECMED and Argentina’s ANMAT. The evaluation performed on ANMAT was rated with a level IV certification, which is the maximum rating granted and which makes it the first National Reference Authority in Drugs Regulation in the region.

The regulatory regime can be comparable with the U.S. Food and Drug Administration or the European Medicines Agency in regards to expectations and requirements, because all of them aim at similar objectives, that is to say, the health and safety of the population. Nevertheless, they do not have the same exact norms for regulating the pharmaceutical products, medicines and medical devices.

9. What is the potential range of penalties for noncompliance?

Penalties for non-compliance with local regulatory framework will vary depending on the type and degree of infringement (e.g.: potential risk for the health of patients; degree of intentionality, recidivism, unfair competition, etc.). There could be administrative, civil or criminal sanctions.

Except otherwise defined, infringements to pharmaceutical local regulations usually follow the penalties and/or preventive measures provided in the Law on Medicines No. 16,463, and Decree No. 341/92 (or complementary regulations).

Violations to the Law on Medicines and/or its regulations are punishable with:

1. Warning;
2. Fines from AR$1,000 to AR$1,000,000 (Decree No. 341/92 and ANMAT Regulation No. 1,710/08);
3. Total or partial, provisional or permanent closure of the premises where the infringement was committed, depending on the seriousness of the violation involved;
4. Suspension or forfeiture of the business or professional license during a maximum term of three years or, in case of extremely serious offenses, permanent forfeiture of the license;
5. Seizure of the infringing products; and/or
6. Forfeiture of the license for selling and manufacturing the products.

The statute of limitations for the actions arising from the Law on Medicines is five (5) years. Such term will be interrupted in the event of committing any other violation to the Law or its complementary regulations (Section No. 24).

10. Is there a national healthcare system? If so, how is it administered and funded?

Yes. The Argentine healthcare system is divided into three sectors: public, social security, and private. These sectors overlap in membership, with some affiliates of the public sector or social security insuring themselves with private insurers as well, due to a shortage of certain services or the deficient quality of others. A health emergency plan is currently in effect due to social and economic factors. The response to this emergency includes an adaptation of the Mandatory Medical Program (PMO, after its acronym in Spanish) to the available financial resources of the public healthcare providers and private health- care insurance providers’ plans.

There is a variety of (federal, provincial, and municipal) laws and regulations in diverse fields such as social security, hospitals and procurement, the medical profession, as well as medicines and medical devices. Health is considered to be a social right with constitutional recognition; thus, Argentine legislation which regulates medicines and medical devices primarily serves to protect public health.

PUBLIC SECTOR

The public sector includes the national and provincial ministries, public hospitals (which also may provide services to people who are covered by social or private healthcare insurance providers), and primary healthcare entities, which provide assistance to the uninsured population. This sector is mainly financed through taxes. The public sector has been decentralized in recent decades, and the administration of national public hospitals has mostly been transferred to provincial and municipal governments.

SOCIAL SECURITY SECTOR

The Social Security Sector is operated by trade unions and covers all workers from the formal economy and their families. It is financed through mandatory payroll contributions from employee and employers (insurance schemes) and provides significant coverage within the Argentine health system.

Health-related social security includes national healthcare insurance providers (OSN, after its acronym in Spanish) and the National Institute of Social Security for Retired Persons and Pensioners under the jurisdiction of the national government. At a provincial level, social security consists of individual provincial healthcare insurance providers.

Each OSN must comply with the PMO. The PMO guarantees basic health coverage in the areas of preventive care, diagnosis, medical treatment, dental care and medicines. In 2002, due to the economic crisis and the financial problems of many funds, an Emergency Mandatory Medical Plan (PMOE, after its acronym in Spanish) was implemented and still is in force. The PMOE is mostly based on practices that are cost-effective and evidence-based.

PRIVATE SECTOR

The private sector mainly includes all private healthcare insurance providers that offer health services (including private insurance agencies – prepaid medicine companies). This sector is financed through voluntary contributions to private service providers, who generally search for larger and more efficient coverage. The private sector encompasses private health facilities. These providers must comply with the PMO which, as previously mentioned, guarantees coverage in the areas of preventive care, diagnosis, medical treatment, dental care, and access to medicines.

11. How does the government (or public) healthcare system function with private sector healthcare?

The public sector coexists with the social security and the private sector, since due to a shortage of certain services or the deficient quality of others.

12. Are prices of drugs and devices regulated and, if so, how?

So far, ANMAT has not issued specific regulations for fixing prices applicable to the products under its control.

However, ANMAT Regulation No. 5,039/2014, as amended and complemented, approved the online publication of the National Vademecum of Medicines (VNM—after its acronym in Spanish), which contains the price of medicine products. It should be noted that the price listed is based on information provided by the owner of the marketing authorization.

In principle, the price of sale for each product indicated and published at the VNM would not formally imply a fixed price, and the holder would be able to negotiate the selling price of the product under its own criterion for each commercialization channel (institutional and/or through pharmacy channel).

13. How are drugs and devices used by patients paid for? What roles do public and private payers play?

In most cases, drugs and devices are paid on an out-of-pocket basis and health coverage will depend on the PMO in force and the patient’s (private and/or public) healthcare insurance.

14. Who dispenses drugs and devices to patients and how are those dispensers compensated?

The preparation of prescriptions and dispensation of medicines, including over-the-counter (OTC) and pharmaceutical specialties, whatever their condition of sale, can only be made in licensed pharmacies in the Argentine territory (Law No. 17,565 and Law No. 26,567). The sale and delivery of such products in other places is deemed an illegal practice of the pharmacy. OTC medicines must be personally dispensed at the counter by pharmacists or persons authorized to sell them. Any sale and dispatch outside these establishments is considered an illegal practice of pharmacy and, without prejudice to the sanctions established by law, offenders can be liable for violation of the Criminal Code.

The commercialization chain of medical devices does not have a specific regulation, as it does with medicines (mainly, in accordance with Decree 1,299/97). Please see Marketing, Manufacturing, Packaging & Labeling, Advertising, Question 18 for further references.

The compensation is given as in any other commercial business, through the purchase and sale of the products and agreements within the commercialization chain (e.g. rebates, discounts, etc.).

15. What are the professional and legal responsibilities of those who dispense drugs and devices? What role do they play in providing patient care, information, and safety?

Duly licensed professional pharmacists are the only responsible and trained for the duly dispense of medicines to the general public (Law No. 25,649 -Law on Generic Drugs-). Pharmacy practice is only authorized to pharmacists with a valid degree (issued by a National/Private university entitled by the National Government), and duly licensed by the sanitary authority (Section 17, Law No. 17,565). It is mandatory for pharmacists to substitute the medicine prescribed by the physician for another medicine with a lower price (but same active ingredients, concentration, etc.) if the consumer/patient requests it. Pharmacists have similar obligations and prohibitions to those of the physicians, including jointly liability in the event of failing to supervise their auxiliary personnel activities.

It is mandatory for pharmacists to prepare or dispense prescriptions and supervise the fulfillments of the instructions delivered to their auxiliary personnel in order to observe the compliance of their acts are under the limits of his/ her instructions. Pharmacists are jointly liable with their auxiliary personnel in the event of damage to third people due to insufficient and/or inadequate supervision to the activities performed by the auxiliary personnel.