The regulatory regime
Medicines in Brazil are subject to stricter regulation than medical devices. For example, medicines are subject to price controls, while medical devices are not.
Medical devices are regulated by ANVISA under Resolution RDC 185/2001, Resolution RDC 36/2015 and Resolution RDC 40/2015. Restrictions on the advertising of medical devices are not as strict as those applicable to medicines (Resolution RDC 96/2008).
Activities related to the manufacture, import, export and distribution of products that are subject to sanitary control (encompassing both medicines and medical devices) require authorisation by ANVISA and licensing by local sanitary authorities.i Classification
According to Law 9,782/1999, the goods and products submitted to the control and surveillance of ANVISA are:
- medicines for human use, their active substances and other inputs, processes and technologies;
- foods, including beverages;
- cosmetics, personal care products and fragrances;
- disinfectants meant for cleaning, disinfection or disinfestation of homes, hospitals and public places;
- kits, reagents and inputs used for diagnosis;
- medical and hospital, dental and haemotherapy equipment and materials, as well as equipment and materials for laboratory and image diagnosis;
- immunobiologicals and their active substances;
- blood and blood products;
- human and animal organs and tissues to be used in transplants or reconstructions;
- radioisotopes for use in in vivo diagnosis and radiopharmaceuticals, and radioactive products used in diagnosis and treatment;
- cigarettes, cigarillos, cigars and any other smoking products, whether derived from tobacco or not; and
- any products that may result in the possibility of risk to health, obtained by genetic engineering, by other procedures or submitted to radiation sources.
There are legal definitions of medicines and medical products. Article 4 of Law 5,991/1973 defines a medicine as a pharmaceutical product, technically obtained or prepared, for prophylactic, curative, palliative or diagnostic purposes. In turn, Article 25 of Law 6,360/1976 defines medical devices as appliances, instruments and accessories used in medicine, dentistry and related activities, as well as in physical education, beautification or aesthetic correction.
Based on these definitions, to correctly classify a product under these categories, it is important to study its characteristics and uses.ii Non-clinical studies
Law 11,794/2008 establishes procedures for the scientific use of animals. It also created the National Council for the Control of Animal Experimentation (CONCEA), a body linked to the Ministry of Science and Technology (currently Ministry of Science, Technology, Innovations and Communications), responsible for coordination of the procedures for scientific use of animals.
Articles 11 to 16 of that law contain specific rules regarding protection of animal welfare: any entity involved in the breeding of animals for educational or scientific purposes must be licensed by the Ministry of Science and Technology, and for that purpose it must establish an internal ethics committee with the participation of veterinary surgeons, biologists, professors and researchers in the specific area of interest and one representative from an animal protection society legally established in Brazil.iii Clinical trials
The rules that govern clinical trials in Brazil, issued by ANVISA and by the National Health Council (CNS), are Resolution CNS 466/2012, Resolution RDC 9/2015 and Resolution RDC 10/2015. No federal law has been enacted yet regarding this matter, but there is currently a bill of law pending in the Senate (PLS 200/2015), under scrutiny of the House of Representatives.
The National Research Ethics Committee (CONEP/MS), a body linked to the Ministry of Health, is responsible for deliberation, surveillance, follow-up and monitoring of public policies for health. It evaluates the ethical aspects of the studies; the research protocol is scrutinised to ensure its correctness, clearness and compliance with ethical standards). This is followed by an analysis by ANVISA, which focuses on the technical and health aspects.iv Named-patient and compassionate use procedures
According to Resolution RDC 81/2008, pharmaceutical products for which marketing authorisations have not been granted can be imported by individuals for personal use only. A request should be presented to ANVISA with documents that allow for an assessment of (1) whether the product has had marketing authorisation issued in its country of origin, and (2) the efficacy and safety of the drug.
Resolution 203/2017 was released by ANVISA on 26 December 2017. It establishes criteria and procedures for the importation, on an exceptional basis, of products subject to sanitary surveillance without registration in Brazil, intended exclusively for use in public health programmes by the Ministry of Health and its related entities.
In addition, Article 24 of Law 6,360/1976 establishes that new medicines, exclusively for experimental use but under medical control, are exempt from registration, and may also be imported with the express authorisation of the Ministry of Health. This exception is valid for up to three years.
Brazilian legislation also allows patients, under compassionate use programmes, to have access to medicines that are still in the clinical development phase. Finally, under the expanded access programmes, patients may have access to medicines during and after Phase III clinical trials.v Pre-market clearance
The first step to obtaining marketing authorisation for a pharmaceutical product is to obtain the proper licence from ANVISA. The bureaucratic process and technical requirements for these licences vary depending on the applicant's activity (i.e., whether manufacturer, distributor, importer or exporter).
The applicant must be Brazilian; foreign companies are not authorised to apply directly, but can do so through local distributors.
The applicant must then file the request for marketing authorisation. Along with the necessary forms, documents regarding the product, its composition, trade name (brand), pharmaceutical form, presentation, sanitary restrictions, validity term and instructions for conservation must be presented. The same goes for reports on production and quality control and reports on experiments (including clinical trials) conducted by the company. A draft of the proposed instruction sheet to be included in the product package, a sample of the label's layout, proof of payment of the sanitary fee and the intended price of the product must also must be submitted.
Issuance of marketing authorisation still takes a year or more. Law 13,411/2016 was enacted in order to rationalise the analysis and establish strict time limits based on transparent criteria of technical complexity and urgency in providing the drug to patients has been enacted.
For medicines, this law establishes an examination procedure that takes into consideration the technical complexity of the matter and the clinical, economic and social benefits derived from use of the product, subject to the request. Processes are classified as prioritised (120 days for a decision, starting from the request for priority examination) or ordinary (365 days for a decision, starting from the date of the market authorisation request). These deadlines can be extended by one-third, once only, by ANVISA.
Law 13,411/2016 was followed by Resolution RDC 204/2017, which sets forth the products to which prioritised analysis applies.
According to ANVISA's regulations, the fees for obtaining marketing approval vary according to the size of the company and are measured by annual gross revenue – the amount may be as much as 157,4416 reais for a new product that is part of a large group. For generic and branded generic medications, the costs are lower.
Medical devices are subject to either simply being listed by ANVISA or a registration process, depending on the level of risk attributed to the product. The listing process is simpler, since no registration examination is required. For some technical and more specific products, further certification by a technical agency (National Institute of Metrology, Quality and Technology (INMETRO), linked to the Ministry of Development, Industry and Foreign Trade) may be necessary.vi Regulatory incentives
Intellectual property rights, including patents, trademarks and industrial designs, are considered fundamental rights, as per Article 5, Paragraph XXIX, of the Brazilian Constitution.
Brazil is also a Contracting State of the Paris Convention for the Protection of Industrial Property, the Stockholm Act, the Patent Cooperation Treaty and the TRIPS Agreement.
Law 9,279/96 regulates the rights and obligations related to industrial property, establishing the procedure for granting patents, the requirements placed on patent holders, and the extent of the exclusive rights granted by a patent. It also encompasses the procedures for granting trademarks and industrial designs. Copyrights and software are subject to separate laws.
Patents are valid for a period of 20 years starting on the filing date. It usually takes more than 10 years after an application is filed for a pharmaceutical patent to be granted, mainly because of the backlog faced by the National Industrial Property Institute (INPI). According to the Sole Paragraph of Article 40 of Law 9,279/1996, a patent of invention is valid for a minimum period of 10 years from the date it is granted (or seven years for utility model patents), thus ensuring that the patent owner has a minimum protection period. The Sole Paragraph of Article 40 of Law 9,279/1996 is the subject of two direct actions for alleged unconstitutionality, which are awaiting judgment by the Supreme Court.
There is no specific link between marketing authorisations and patent protection. According to Article 43, Paragraph VII, a patent violation is not deemed to have occurred in connection with 'acts practised by unauthorised third parties, related to the invention protected by a patent, for the sole purpose of producing information, data and test results, aiming at obtaining marketing authorisation in Brazil or abroad for the exploitation and commercialisation of the patented product, after expiration of the time limits set out in Article 40'.
Article 195 of Law 9,279/1996 defines the types of criminal unfair competition, among which is to 'divulge, exploit or use without authorisation the results of tests or other undisclosed data whose preparation involves considerable effort and that have been submitted to government entities as a condition for approving the marketing of products'. However, there is no specific legal provision for the protection of dossiers (which are necessary for marketing authorisation requests, or contain data about clinical trials of reference drugs). These documents are considered confidential by ANVISA.vii Post-approval controls
Post-registration alterations are regulated by Resolution RDC 73/2016.
Among the obligations of a marketing authorisation holder is the need to report to ANVISA any incidents, adverse effects or technical complaints related to the product. Periodic safety reports are mandatory, and proof of their submission is one of the conditions to be met when renewing a marketing authorisation.
After marketing authorisation is granted, the holder can make requests for alterations, from simple to complex ones. For requests of a simple nature, with no repercussions on safety, quality of efficacy of the product, the procedure is equally uncomplicated, with little or no analysis of documents. For complex topics (such as changes in formula or the ingredients of a product), technical evidence must be submitted to facilitate a thorough examination.viii Manufacturing controls
Companies involved in the activity of extracting, producing, manufacturing, processing, packing or repacking pharmaceutical products or ingredients must have an operating permit (AFE) from ANVISA. For certain controlled drugs, applying for special authorisation (AE) is necessary. Additionally, authorisations from municipal and state health surveillance bodies may be necessary, depending on the where the facilities are located.
In addition to general information regarding the legal entity itself, the request must consider appropriate technical information. Demonstration of the adequacy of facilities and equipment, an established quality system, clear validation policies and qualified human resources, among other things, is a condition for obtaining an AFE. If an AE is necessary, submission of additional information, such as a copy of the guidelines on good manufacturing practices (GMPs) and a list of all controlled pharmaceutical substances that will be produced at the facility, is mandatory.
Inspections for issuance of AFEs and AEs for manufacturing are conducted by municipal, state and national bodies.
ANVISA is responsible for the issuance of GMP certificates. These apply to production facilities, covering production lines, pharmaceutical forms, therapeutic or product risk classes for which companies have been inspected. GMP certificates are valid for two years, starting from the date of publication in the official federal gazette.
According to Resolution RDC 102/2016, provided that the technical characteristics inspected at the time of issuance remain the same, GMP certificates only need to be updated in the case of a commercial or corporate transaction, to reflect the new situation of the certificate holder. According to the same regulation, management of AFEs and AEs depends on the nature of the operation.ix Advertising and promotion
There are several instruments concerning the promotion and marketing of pharmaceutical products in the Brazilian legal framework, such as Law 6,360/1973, Law 9,294/1996 and Decree 2,018/1996.
The Brazilian Association of the Research-Based Pharmaceutical Industry (Interfarma) has a code of conduct for pharmaceutical product advertisements. The Brazilian Self-Regulatory Advertising Code, issued by the National Self-Regulatory Advertising Council (CONAR), also applies to drug advertising. However, the major guidelines for promotion of pharmaceutical products to both healthcare professionals and the general public are Resolution RDC 96 of 17 December 2008 and Normative Ruling 05 of 5 May 2009, both issued by ANVISA.
Promotion of prescription medicines is limited to media directed exclusively at healthcare professionals who are qualified to prescribe or dispense them. Advertisements must contain certain technical information, such as the number of the marketing authorisation, indications and counter-indications, possible adverse reactions and interactions with other medicines, food and alcohol. For specially controlled products, promotion is limited to publications of exclusively technical content, referring to diseases and medications, destined exclusively to healthcare professionals qualified to prescribe or dispense specially controlled medication. Advertisements citing scientific information must refer to data extracted from academic journals, with bibliographical data and an indication of the origin of the study.
Additionally, advertisements for specially controlled medicines can cite technical-scientific articles related to the active principle of the medication. Full bibliographical references must be disclosed.
Over-the-counter drugs (OTCs) can be advertised to the general public, through different media, but promotions must observe some limitations. Advertisements for OTC medicines must not:
- contain expressions mentioning 'scientifically proven' or 'demonstrated through clinical trials';
- suggest that a product is the only means of treatment, or that healthy habits or visits to a doctor are superfluous;
- employ celebrities or people known to the public stating that they use the product or recommending its use;
- employ direct or indirect language relating the use of the product to alcoholic or gastronomic excesses;
- relate the product to physical, emotional or sexual attributes or beauty of a person, except when these are properties approved by ANVISA;
- present abusive, deceitful or frightful images of diseases; or
- include messages, symbols or images directed at children or teenagers.
Medical devices are not subject to any specific guidelines but, according to Law 6,360/1973, health surveillance authorities may intervene if an advertisement for a specific product is considered harmful to public health.
ANVISA's website has a comprehensive Q&A about drug advertisement, which can be found at: http://portal.anvisa.gov.br/documents/33864/284972/RDC96_COMENTADA.pdf/7092f0ca-f08a-43c4-ac7a-5d8ba208f2dd).x Distributors and wholesalers
Distributors, importers and exporters (as well as companies performing the activity of storage and transport) of medicines, health products, cosmetics, personal hygiene products, perfumes and sanitisers must obtain a licence from ANVISA to operate, under Resolution RDC 16/2014. Depending on the activities to be performed, further state and municipal authorisations may be necessary.
The request must be submitted to ANVISA, comprising both general aspects (acts of incorporation, taxpayer identification number, activities performed by the company, local authorisations, service agreements or similar documents signed with companies licensed by competent authorities, proof that the technical manager is a qualified professional, GDP manual if applicable) and technical aspects (proof of technical capacity, demonstration of qualified personnel, hygiene conditions, statements of purpose for reception, identification, stock control and storage of finished, returned or withdrawn products, proven quality system, among others). Official fees for licensing are variable, linked to the company's size and revenue.xi Classification of products
There are five categories in Brazilian law regarding medicines, determined according to dispensation and restriction of access:
- drugs sold with medical prescription (without retention of the prescription);
- drugs sold with medical prescription, in which the prescription must be retained by the pharmacist or drugstore (no refill without another prescription);
- drugs subject to special control; and
- drugs exclusively used in hospitals.
OTCs can be advertised to the public, under limitations specified by Resolution RDC 96/2008. Advertising of prescription medicines (including those subject to special control and exclusively used in hospitals) is limited, and should be aimed at medical professionals only.xii Imports and exports
The importation of medicines and medical devices is regulated by Resolution 81/2008, issued by ANVISA. The holders of the marketing authorisation for a product, and third parties authorised by the marketing authorisation holder, can import and export it. In 2018, Resolution 228 brought a few changes to rules regarding the importation. The new rules require differentiated treatment for products subjected to ANVISA's inspection by creating four types of channels that consider the type of product and its risk. In addition, Resolution 228/2018 created nine criteria for managing the sanitary risk of imports, which include the history of the company, the existence of problems regarding the use of the product and the result of laboratory analyses.
Prior authorisation must be granted by ANVISA for the importation of medicines and medical devices, which can be granted either when the relevant shipment leaves its port of origin abroad, or when it arrives in Brazil.
Importers in general must be enrolled with the Integrated Foreign Trade System (SISCOMEX) and obtain authorisation for their activities from the Federal Revenue Service (i.e., an 'Ambient for Registration and Tracking of Activities of Customs Agents' licence).xiii Controlled substances
If a company intends to manufacture, manipulate, distribute, import or export certain controlled pharmaceutical products, it must apply for special authorisation from ANVISA.
When applying for it, further information and structures are required by ANVISA, such as a list of all controlled pharmaceutical substances to be distributed or transported and the existence of a separate, restricted area for these products.
Pharmaceutical products that contain controlled substances can be sold, but ANVISA's regulations require a pharmacist to retain the medical prescription and record every sale.xiv Enforcement
Law 6,437/1977 defines the infractions of sanitary regulations in the activities of manufacture, distribution, import and export, marketing and advertising of products subject to sanitary surveillance, as well as the relevant penalties.
Infractions are classified according to their importance, and penalties are applied accordingly, ranging from 2,000 to 1.5 million reais (which may be doubled in the event of recidivism).
As well as fines, sanitary authorities may impose one or more additional measures on the offender: warning, product apprehension, product destruction, product interdiction, suspension of sales or manufacture of the product, cancellation of marketing authorisation, total or partial interdiction of the company, prohibition to advertise, cancellation of sanitary authorisations, intervention in cases where the company receives public funds of any nature, and corrective advertisement.
The Brazilian Penal Code also contains a specific provision involving violation of sanitary rules: falsification and adulteration of therapeutic or medicinal products is considered a crime against public health, as is the sale of such products without marketing authorisation or with incorrect information.