Regulatory, Pricing and Reimbursement
A brief legal overview of the situation regarding the regulation, pricing and reimbursement of pharmaceuticals in Brazil. Prepared in association with Trench, Rossi e Watanabe one of Brazil’s most prestigious law firms, this is an extract from The Pharma Legal Handbook: Brazil, which can be purchased for GBP 99, here.
1. What are the regulatory authorities with jurisdiction over drugs, biologicals, and medical devices in your country?
In Brazil, the authorities are the National Health Surveillance Agency (“ANVISA”), which is a federal entity linked to the Ministry of Health, and local health authorities in states and municipalities.
2. What is the regulatory framework for the authorization, pricing, and reimbursement of drugs, biologicals, and medical devices?
The main Statutes are the Federal Law 6,360/1976 and the Federal Decree No. 8,077/2013, which provide for the surveillance of drugs, medical devices and related products, and others are subject.
Federal Law No. 6,437/1977 is an important law; it sets forth the violations to federal health legislation, establishes their respective penalties, and makes other provisions.
Also, Federal Law No. 10,742/2003 created the Drugs Market Regulation Chamber (CMED) in order to regulate the prices of the drugs commercialized in the country.
Also, there are many regulations issued by ANVISA related to the products it inspects. See the list with the most important regulations below.
- Operating Authorization:
- Resolution RDC No. 16/2014: Operating Authorisation (“AFE”) authorizes a company to store, distribute, pack, export, import, manufacture, repack and transport.
- Operating License:
- Depends on the State/Municipality in which the operating facilities are established. In São Paulo, for example, the Ordinance CVS No. 1/2020, provides for the registration/licensing of facilities that develop activities subject to health legislation.
- Product registration:
- Resolution RDC No. 200/2017: provides for synthetic drugs, including generics and biosimilars.
- Resolution RDC No. 205/2017 provides for orphan drugs.
- Resolution RDC No. 55/2010 provides for biological drugs and biosimilars.
- Resolution RDC No. 238/2018 provides for dynamized drugs.
- Resolution RDC No. 26/2014 provides for phytotherapy drugs.
- Resolution RDC No. 73/2016: provides for post-registration changes and cancellation of drug registration (this resolution is applicable for synthetic and semisynthetic drugs, including generics and biosimilars).
- Resolution RDC No. 505/2021: defines the criteria necessary to develop and to request the marketing authorisation of high technology products based on human cells and genes, called “advanced therapy medicinal products”.
- Resolution RDC 465/2021: provides a registration and authorisation waiver authorisationfor emergency use of COVID-19 vaccines purchased by the Ministry of Health.
- Resolution RDC 595/2022: provides for self-tests for detecting the COVID-19 antigen.
- Best Practices Certificate:
- Resolution RDC No. 301/2019: provides for the requirements for the issuance of the Certificate of Best Manufacturing Practices for drugs. Note that drug manufacturing is subject to compliance to best practices. Import companies must request certification from the manufacturing plants located abroad.
- Resolution RDC No. 497/2021: provides for the procedure to obtain the Certificate of Best Manufacturing Practices and the Certificate of Best Practices for Distribution and Storage of drugs.
- Resolution RDC No. 16/2013: provides for the requirements for best manufacturing practices of medical devices and in-vitro diagnostic devices.
- Resolution RDC 508/2021: provides for the best practices for human cells for therapeutic use and clinical research, and makes other provisions.
- Resolution RDC 606/2022: provides exceptional temporary procedures to obtain the Certificate of Best Manufacturing Practices for active pharmaceutical ingredients and drugs and health products linked to Coronavirus;
- Technical Responsibility Certificate
- Federal Law No. 6.360/1976: provides that health companies must maintain duly qualified technical personnel, in quality and in quantity, to adequately cover the company’s needs.
- Resolution RDC No. 406/2020: provides for pharmacovigilance norms for the holders of registrations for drugs for human use.
- Resolution RDC No. 67/2009: requires the implementation of a technovigilance system.
- Promotion and Marketing
- Resolution RDC No. 96/2008: establishes the general rule regarding advertising drugs. Note that there are several restrictions for advertising drugs (i.e. prescription drugs may only be advertised in scientific publications, intended for healthcare professionals).
- Resolution RDC No. 60/2009: provides for the distribution of product samples.
- Resolution RDC No. 71/2009: rules the labeling of drugs. However, rules applicable to each type of drug will provide for specific labeling requirements.
Note that this is not an exhaustive list of the regulations related to drugs and medical devices, but only a list of the main applicable rules.
3. What are the steps to obtain authorization to develop, test, and market a product?
Clinical trials are subject to approval from the Committee for Ethics in Research (CEP) and, in certain cases, from the National Committee for Ethics in Research (CONEP) and ANVISA.
The research protocol document must be submitted to CONEP, or CEP, and must describe the trial’s purpose and other details. It must also include information about the research participants and the researchers’ qualifications and all responsible parties. One of the documents to be filed with the research protocol is the Informed Consent Form.
After the protocol is submitted to the CEP/CONEP,the relevant authority will analyze the request and if the clinical trial complies with the applicable legislation, the authority will authorize the commencement of the research.
In order to market a product (drugs, biologicals, and medical devices), it will be necessary to (i) obtain a company license from ANVISA (Operating Authorisation – AFE) and from the local health authorities (Operating License – LF); (ii) maintain a Responsible Technical Party for the company; (iii) apply for Best Manufacturing Practices certification, depending on the product, and (iv) obtain the product’s registration/enrolment before the ANVISA.
4. What are the approximate fees for each authorization?
The fees vary depending on the type of authorisation, on the product and on the company’s corporate size.
5. For how long are marketing authorizations/registrations valid? How are marketing authorizations/registrations renewed?
In general, marketing authorisation for drugs and medical devices authorisationis valid for ten years. In certain cases applicable to drugs, the period can be of three or five years, pursuant Resolution RDC 317/2019.
The renewal of both types of marketing authorisations must be requested from six to twelve months before the marketing authorisation expiration date, as set forth in Resolution RDC 250/2004.
6.A. How does the authorization process differ between brand-name products and generic products?
As a rule, the authorisation process does not change, but the documents and studies to be presented to ANVISA differ. The registration of generics will require studies in order to prove that the product is stable and therapeutically equivalent to the reference drug, with pharmaceutical equivalence and bioequivalence studies, while the registration of a new drug should also be attached to its clinical trial studies (with the studies necessary to prove the quality, safety and efficacy of the product).
Note that there is also the simplified procedure for the registration of generic drugs. This procedure only applies to drugs that have the same production line, manufacturer, technical and clinical reports, and composition of the drug used as reference, which is already registered with the normal procedure before ANVISA. The differences between the reference drug and the generic one are their name, labeling and packaging. Through this procedure the analysis/review by ANVISA of the documents is faster (when compared with the normal procedure), since the documents were already analyzed by ANVISA during the previous (normal) procedure.
6.B. Are there differences for local manufacturers versus foreign-owned manufacturers?
No, the authorisation process is the same. However, certain timings may differ (i.e, timings for foreign and local inspection for -Best Manufacturing Practices certification are different) and some additional documents will be required for imported products.
Note, however, that only duly licensed Brazilian legal entities may be the marketing authorisation holder.
7. How are combination products (drug + drug, drug + biologic, drug + device, biologic + device, drug + biologic + device) regulated?
Our understanding is that ANVISA will analyse a product’s purpose. For example with a drug + device, a product’s final registration will be for a drug and, therefore, the final product must be considered as a drug for all other regulatory purposes. However, there is no specific rule regarding this matter.
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?
ANVISA and the local health authorities may perform routine inspections on the premises of the companies that store, distribute, pack, export, import, manufacture, repack and transport drugs and/or medical devices. ANVISA is currently trying to focus its actions on actual monitoring and on-site inspections rather than the limited documentation analysis it used to perform.
We consider that the regime is comparable, mainly to the European agency standards, and, in that sense, ANVISA and the FDA are involved in arrangements to strengthen existing structures and develop new opportunities for cooperative engagement in regulatory and scientific matters and public health protection that are related to the products ANVISA and the FDA regulate.
9. What is the potential range of penalties for noncompliance?
A warning, a fine (varying from BRL 2,000.00 up to 1,500,000.00), the appropriation and disposal of the product, shut down of facilities, cancellation of health licenses, prohibition of advertising, suspension of sale, imposition of a rectifying message and/or suspension of advertising.
10. Is there a national healthcare system? If so, how is it administered and funded?
Yes. As provided in the Brazilian Federal Constitution of 1988, health is a right for all and a duty of the state. The public healthcare system was introduced by the Brazilian Federal Constitution of 1988 and is called the Unified Health System (SUS). The SUS provides for free and universal coverage and is funded through the social welfare budget of the federal government, the states, the Federal District and the municipalities, as well as from other sources such as fines, fees and donations.
The Federal Constitution of 1988 also allows for the complementary existence of the private sector in health assistance.
11. How does the government (or public) healthcare system function with private sector healthcare?
In the public sector, healthcare is delivered through programs and plans that are implemented at federal, state and municipal levels. Actions and services must be organized and executed on a regional basis. The SUS is a complex program and is organized according to the different federative levels; the federal government is primarily involved in the general planning of the system, organisation of health assistance centres in remote regions, and to providing financial grants to state, municipal and private health entities that operate in coordination with the SUS. The states are responsible for high and medium complexity health assistance centres, and the coordination of the efforts of the municipalities. The municipalities are responsible for primary care and low complexity health assistance institutions.
The private health system operates in parallel with the public healthcare system, with full capacity to provide health assistance to the population, whether through out-of-pocket payments or through health insurance companies.
12. Are prices of drugs and devices regulated and, if so, how?
The prices of drugs are regulated. The Drug Market Regulation Chamber (CMED) establishes the maximum price applied to a drug, depending on the party in the marketing chain. The Chamber also determines the discount that the public entity should apply in order to purchase a drug.
Prices of other categories of products, such as medical devices, diagnosis equipment are not regulated.
13. How are drugs and devices used by patients paid for? What roles do public and private payers play?
The SUS provides financial support to private health institutions by financial grants and reimbursement of medical procedures, devices and drugs upon the signature of an agreement between the private entity and the Ministry of Health. The reimbursement values are listed, along with the types of procedure and therapy covered. The private system is funded by out-of-pocket payments made by individuals (users) or by private health insurance. The coverage of health insurances is also defined according to a list of covered therapies and medical procedures issued by the Supplementary Health Agency.
14. Who dispenses drugs and devices to patients and how are those dispensers compensated?
Pharmacies, drug stores and hospitals. The compensation can be through reimbursement values or by out-of-pocket payments made by individuals.
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?
The entities that dispense drugs and devices must be assisted by a technical responsible party, who undertakes responsibility for the compliance with all sanitary legislation. Violations of duties may lead to the imposition of administrative penalties (i.e, for the legal entity), criminal sanctions (i.e, to the individual involved in the violation), civil measures (i.e, indemnification claims) and professional sanctions (i.e, applied by the professional council to the technical responsible party).