Medicinal products, medical devices, food, and food supplements are subject to regulation by Federal Laws enacted by the Government, as well as by Rulings (known as “Resoluções” or “RDCs”) issued by the National Public Health Agency (ANVISA).

The Rulings of the Collegiate Board of Directors (RDCs) are regulatory guidelines put forth by ANVISA to ensure adherence to good practices and uphold quality standards for products and services. In each distinct field, these RDCs outline standards and responsibilities applicable to both companies and professionals.

ANVISA is the primary regulatory authority, and it operates independently despite its affiliation with the Ministry of Health. ANVISA oversees and controls the production, marketing, and utilization of products and services falling under health regulations. This encompasses a range of elements such as environments, processes, ingredients, technologies, as well as the supervision of ports, airports, and borders.

Key legislation for pharmaceuticals, medical devices, food, and dietary supplements are:

Medicinal Products

• The Law No. 5,991/73, known as the Law of Sanitary Control of the Distribution and Sale of Medicines, is a legal landmark for public health in Brazil. It establishes the basis for the regulation, inspection and control of medicines, sanitizers, and other products of interest to health. Over the years, amendments have aligned such law with the realities of Brazil’s pharmaceutical market.
• The Law No. 6,360/76 is the main statute for pharmaceutical products. It regulates the production, commercialization, advertising, labelling, inspection, quality control, penalties, importation, and marketing approval of medicines, drugs, active ingredients, and medical devices. It is regulated by Decree No. 8,077/13.
• The Law 6,437/77 sets out the penalties for infringing sanitary federal statutes and corresponding regulations, including criminal sanctions.
• The Law 9,294/96 imposes restrictions on the use and advertising of smoking products, alcoholic beverages, medicines, therapies, and agricultural pesticides. It is regulated by Decree No. 2018/96.

Biologicals

• The RDC No. 55/2010, as amended by RDC No. 406/2020, sets out specific and technical requirements applicable to biological products.
• The RDC No. 413/2020, as amended by RDC No. 710/2022 provides for post-registration changes and inclusions, suspensions, and reactivations of the manufacture and cancellation of registration of biological products.
• IN 65/2020 – Regulates the classification of post-registration changes and the conditions and technical documents necessary to instruct the petitions for post-registration changes and for canceling the registration of biological products.
• The RDC No. 412/2020 and RDC No. 317/2019 provides for procedures and conditions for conducting stability studies, registration, or post-registration changes of biological products.

Medical Devices

• The RDC No. 751/2022 sets rules for assessment of risk, procedures for notification, registration, amendment, cancellation, labelling, and use of medical devices, among others.
• The RDC No. 830/2023 sets the validity term for medical devices marketing approvals.
• The RDC No. 36/2015 as amended by RDC No. 549/2021 establishes rules for in vitro diagnostic devices.
• The RDC No. 657/2022 sets the regulation of software as a medical device (SaMD).

Food:

• The Decree-Law 986/1969 establishes basic food standards.
• The Resolution RES No 16/1999 determines the procedures for registering foods and novel ingredients. This resolution was amended by RDC No 243/2018.
• The Resolution RES No 19/1999 sets the procedures for the registration of foods with claims of functional and/or health properties on their labeling.
• The RDC No. 22/2000 sets the basic procedures for registration and exemption from mandatory registration of imported food products.
• The RDC No. 23/2000 sets the Manual of Basic Procedures for Registration and Exemption from the Obligation to Register Food Products. This resolution has been amended in accordance with RDC No. 27/2010.

Food Supplements

• The RDC No. 243/2018 regulates the health requirements for food supplements. This resolution has been amended in accordance with RDC No. 429/2020.
• The Normative Instruction 28/2018 establishes the lists of constituents, limits of use, claims and supplementary labeling for food supplements. This NI has been amended in accordance with NI No. 76/2020 and NI No. 102/2021.
• The RDC No. 27/2010 sets the categories of food and packaging that are exempt from and require health registration.

With the aim of prioritizing the most relevant resolutions within the aforementioned markets, it is crucial to acknowledge the existence of numerous supplementary resolutions offering additional guidance.

Bringing new medicines and medical devices to the Brazilian market demands navigating ANVISA’s rigorous, multi-stage process. This ensures safety and efficacy through strict adherence to GLP and GCP guidelines in R&D, clinical trial approvals, and comprehensive dossier submissions. Ongoing vigilance requires continuous reporting of adverse events, safety updates, and inspections.

The process complexity depends on product classification and risk, but leveraging foreign agency assessments can streamline efforts. While fees and timelines may vary, ANVISA’s comprehensive approach ultimately prioritizes public health protection.

The primary regulations concerning the authorization for the marketing of pharmaceuticals and medical devices are as follows:

• Federal Law No. 5,991/1973 and Decree No. 74,170/74, which regulates the commerce of pharmaceutical and other health-related products; and
• Federal Law No. 6,360/1976 and Decree No. 8,077/2013, which regulate sanitary surveillance activities in connection with the production, manufacturing, packaging, import and export of products subject to health surveillance.
• Resolution of the Collegiate Board (RDC) No. 185/2001, which is the central regulation applicable to the registration of medical devices and provides information related to registration, alteration, revalidation, and cancellations of the registration, with the exception of in vitro diagnostic devices (which are covered by ANVISA’s RDC No. 36/2015) – RDC No. 185/2001 also lists the documents required to legally register a medical device in Brazil;
• RDC No. 305/2019 as amended by RDC No. 562/2021, which provides requirements for manufacturing, marketing, import and exposure to use of personalized medical devices; and
• RDC No. 579/2021 provides for the import, marketing, and donation of used medical devices.

Pharmaceuticals are categorized into various groups, such as small molecules (whether new, generic, or branded generics), biological, radiopharmaceuticals, and phytotherapeutic. These categories are defined by distinct regulations that account for their specific characteristics and requirements for authorization. Pharmaceuticals can further be classified based on their prescription status, including non-prescription, prescription-only, hospital use, or subject to special control for commercial purposes.

Medical devices can be categorized as invasive, non-invasive, or active, and the regulatory framework depends on factors like patients’ exposure time and the invasiveness of the product, leading to device classifications as Class I, II, III, or IV. Regarding commercial purposes, medical devices may be intended for general or professional use.

To secure approval for marketing all medicinal products, the applicant must be a duly authorized manufacturer or importer. ANVISA’s marketing authorization is necessary for (i) the production and sale of pharmaceutical products and/or (ii) the importation of pharmaceutical products. This authorization must be acquired before the product is introduced to the market.

Regarding the application for the authorization process for marketing medicinal products:

The application must be submitted to ANVISA. The application form and instructions for the application process can be found on Anvisa’s website under: Request Operating Authorization or Special Authorization – Medicines and Supplies (AFE, AE)

Regarding the authorization conditions:

Approval for marketing is provided upon the presentation of scientific and analytical evidence demonstrating the safety and efficacy of the medicinal product for its intended purpose, along with adequate quality standards, activity, and purity for human use (Article 16, Law No. 6360/76).

The authorization for marketing grants the entity the right to manufacture, distribute, sell, trade, and import a specific medical product. The holder of the marketing authorization can be an individual, a limited company, or any other entity, such as a partnership or charitable organization. This authorization is product specific. Marketing authorization holders are required to adhere to the good manufacturing practices (GMP) and other good practices (GxP) standards outlined in Anvisa’s guidelines. A marketing authorization can be renewed for up to a ten-year term, depending on the nature of the product and the health risk involved.

Regarding medical devices, the notification or registration with ANVISA is contingent on the risk classification of the device. Companies involved in the medical equipment sector, including those engaged in the production, distribution, and import of medical equipment, will be issued a company operating authorization by ANVISA. Additionally, state, or municipal health surveillance institutions will mandate an operating license or permit for these companies.

Certain products need a certificate from INMETRO to verify that the device adheres to relevant standards and requirements before Anvisa can grant authorization.

In Brazil, the regulatory process for food supplements is simplified compared to that of medicines and devices. Companies initiate the journey with a notification, providing Anvisa with product details and technical data for compliance, along with assessment of authorized ingredients/limits. Depending on complexity and risk, the product might be exempt from registration or undergo a comprehensive dossier review. After entering the market, manufacturers are required to report serious adverse events, maintain traceability, and may undergo inspections. Furthermore, periodic updates on ingredients, labeling, or claims may trigger re-evaluation. It’s important to note that complexity can vary, but the overall focus of the process is to ensure product safety and compliance with specific labeling and ingredient regulations. It is also worth mentioning that even food supplements exempt from registration in ANVISA must still comply with a set of rules and regulations; while a simplified notification replaces the full dossier, compliance remains crucial. Ingredients must stay within authorized lists and limits, claims must be truthful and non-disease related, and labeling adheres to specific formats. Post-market, manufacturers report serious adverse events, maintain traceability, and follow Good Manufacturing Practices.

After the publication of RDC No. 240/2018, which amended RDC No. 27/2010, only food supplements containing enzymes or probiotics fall within the categories requiring registration with Anvisa. Other food supplements, including those designed for children, are exempt from the registration mandate and must adhere to the regulations specified in Resolution RES No. 23/2000 for regularization with the Health Surveillance agency in the location of the manufacturing company. While RDC No. 27/2010 underwent subsequent modifications, the requirements related to food supplements remained unchanged. Products now categorized as food supplements must fully comply with the stipulations outlined in RDC No. 243/2018 and IN No. 28/2018, along with any subsequent updates.

The following legislations are also relevant:

• RDC 243/2018: created the category of food supplements and laid down health requirements.
• RDC 242/2018: amended the legislation on specific medicines to make it consistent with the new regulatory framework for food supplements.
• RDC 241/2018: established the requirements for proving the safety and health benefits of probiotics for use in food.
• RDC 240/2018: amended RDC 27/2010. Provides for the categories of food and packaging exempt from and requiring health registration.
• RDC 239/2018: establishes the food additives and processing aids authorized for use in food supplements.
• Normative Instruction 76/2020: amended Normative Instruction 28/2018 which establishes the lists of constituents, limits of use, claims and complementary labeling of food supplements.

As mentioned in the questions above, the specific ongoing obligations after obtaining marketing authorization for pharmaceuticals or conformity assessment for medical devices in Brazil vary significantly. This variation depends on two key factors: product category and the applicable legislation.

With this in mind, here are the general obligations for medical devices and pharmaceuticals:

Regulations on pharmacovigilanceRDC No. 625/2022:

Such regulations require the submission of post-marketing safety reports to the National Health Surveillance System (SNVS) for serious and unanticipated adverse reactions from any source, domestic or foreign. In addition, reports are required for spontaneously reported adverse reactions that occur domestically, including those that are serious and expected, non-serious and unexpected, and non-serious and expected.

According to ANVISA RDC No. 406/2020, an adverse reaction is defined as any unfavorable medical event in a patient who has received a medicinal product. It does not necessarily have to be causally related to the treatment and may include any unintended and undesirable sign, symptom, or temporary association with the use of the medicinal product.

Ordinance No. 618/2019 of the Ministry of Justice may also be applicable, requiring notification to the consumer protection authorities.

ANVISA’s RDC No. 406/2020 entered into force on October 28, 2020, replacing ANVISA’s RDC No. 4/2009 and Normative Ruling No. 14/2009. The new regulation consolidates and aligns with the guidelines of the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use.

Regarding medical devices, technovigilance (devices vigilance) and field actions are governed by ANVISA’s RDC No. 67/2009 and RDC No. 702/2022.

The legislation stipulates that marketing authorization holders, whether manufacturers or importers, are obliged to inform the SNVS of specific adverse events and problems related to their devices. In cases where they become aware that their devices may have caused or contributed to a significant threat to public health, death, a serious adverse event not resulting in death, a technical complaint with the potential to cause death or a serious adverse event, a non-serious adverse event, or counterfeiting, marketing authorization holders must report to the SNVS.

Quality and Good Manufacturing Practices (GMP) – RDC No. 15/2012; RDC 653/2022; RDC 658/2022:

The Brazilian regulatory system is complex and has different requirements depending on the category of medicine. In this sense, when we talk about the continuity of maintaining good manufacturing practices, despite the specific regulation for each king of medicine, we can consider two basic guidelines, which are (i) maintaining a quality system that meets ANVISA standards and (ii) carrying out quality tests in accredited laboratories.

Labeling and Advertising – RDC No. 47/2009 – Rules for drug package leaflets – Amended by RDC No.831/2023:

Package Leaflets must be clear, concise, objective, and easily understandable by the patient, and attend to formal requirements as specific font size, type, and layout requirements.

This must include sections on:

• Name of the medication and active ingredient(s).
• Therapeutic indications.
• Contraindications and precautions.
• Dosage and administration instructions.
• Adverse reactions and side effects.
• Storage and handling instructions.
• Registration number and manufacturer information.
• Specific requirements for different types of medications and presentations.

Advertisements are also ruled, and there are specific guidelines, which are:

• Must be true, accurate, and not misleading.
• Cannot exaggerate the benefits or minimize the risks of the medication.
• Must be directed to healthcare professionals in most cases.
• Limited direct-to-consumer advertising allowed under specific conditions.
• Specific restrictions on visuals, claims, and comparisons to other medications.
• Prior authorization by ANVISA required for most types of advertising.

Consequences of the non-compliance to the after-approval obligations – Law No.6.437/77:

Holders of market authorizations, encompassing manufacturers or importers in each product category, bear responsibility for any regulatory, civil, and criminal matters associated with their products.

The consequences of non-compliance with post-approval obligations for drugs in Brazil, governed by RDC 47/2009 as amended by RDC 831/2023, can be significant and vary depending on the nature and severity of the infraction:

Administrative sanctions:

• Fines: Ranging from R$2,000.00 to R$1,500,000.00, with doubling for repeat offenses.
• Product seizure: Removal of non-compliant medications from the market.
• Partial or complete suspension of company activities: Temporary or permanent closure of operations until compliance is achieved.
• Cancellation of drug registration: Permanent removal of the product from the market.
• Import/export ban: Prohibiting the import or export of drugs by the company.
• Publication of the infraction: Public disclosure of the violation, damaging the company’s reputation.

Civil and criminal liability:

• The company may be held responsible for harm caused to consumers due to non-compliance.
• In severe cases, individuals within the company may face criminal charges.

The primary regulatory authority is the National Public Health Agency (ANVISA), which oversees and control the production, marketing, and utilization of products and services falling under health regulations such as medicinal products, medical devices, food, and food supplements. This encompasses a range of elements such as environments, processes, ingredients, technologies, as well as the supervision of ports, airports, and borders.

The management of ANVISA falls under the oversight of the Collegiate Board of Directors (Diretoria Colegiada or Dicol). Dicol is tasked with assessing, guiding, and overseeing the activities of ANVISA. It formulates regulations related to ANVISA’s jurisdiction, providing technical justifications and, whenever feasible, reporting on the economic and technical implications for the regulated sector and public health. In cases of severe public health risks, the obligation to report the impact on public health is exempted.

The National Health Council (Conselho Nacional de Saúde or CNS) is a collaborative committee established by Law No. 8142/90, with a wide-ranging mandate that includes the regulation of clinical trials within Brazil.

The Pharmaceutical Market Regulation Chamber (Câmara de Regulação do Mercado de Medicamentos or CMED) is an inter-ministerial entity responsible for the economic oversight of the Brazilian pharmaceutical market. ANVISA serves as the Executive Secretary of CMED, and its functions include establishing price limits for drugs post their marketing authorization, incorporating a mandatory minimum discount for public purchases, implementing regulations that encourage competition in the sector and monitors commercialization activities, applying penalties for non-compliance with its regulations.

Brazil’s sanitary control may involve various players. For instance, the Ministry of agriculture and livestock (MAPA) oversees animal-origin foods, beverages, and fresh vegetables, while National Institute of Metrology, Quality and Technology (INMETRO) ensures standardization and conformity of medical devices and other products, including labeling issues. Each agency contributes its expertise, collaborating to ensure public health and product safety across diverse sectors. Specific regulations and entities vary by product.

Regulatory decisions can be challenged through either an Administrative Appeal, directly to the competent regulatory authority, or by lawsuits before the federal courts. The process for filing administrative appeals against ANVISA’s decisions is outlined in Law No. 9,784/99, that regulates the administrative procedure within the Federal Public Administration and RDC No. 266/2019, with decisions made through a maximum of three instances within ANVISA:

• 1^st instance – Organizational units
• 2^nd instance – Appeals Division (known as “Gerência-Geral de Recursos – GGREC”)
• Last instance – Collegiate Board of Directors (known as “Diretoria Colegiada – Dicol”)

First instance appeals are petitions filed against decisions issued by the Organizational Units of the ANVISA. First instance appeals must be addressed to the authority that made the decision. The appellant shall identify the specific subject code adopted by the Agency in order to file the brief. If not withdrawn in the initial stage, these appeals are reviewed by the General Appeals Management at the second stage. When not resolved at first instance, administrative appeals are judged by the Appeals Division (CGREC), at second instance, and, ultimately, by the Board of Directors (DICOL).

Appeals must be submitted in writing and adhere to formal requirements (see RDC No. 266/2019, Article 4 onwards). The deadline to appeal a decision issued by the ANVISA is 30 days, starting from the notification date.

Clinical Trials for medicinal products:

The primary regulations include:

• RDC No. 09/2015 (as amended by RDC 205/2017) (a special procedure for rare diseases in Portuguese), outlining the procedures and technical requirements for conducting clinical trials with medicinal products. RDC No. 09/2015 aims to harmonize Brazilian standards with international guidelines, promoting an increased number of clinical trials in Brazil and encouraging Brazilian participation in global trials.
• CNS Resolution No. 251/1997, which delineates regulatory standards, procedures, and bioethical guidelines for human clinical trials.
• CNS Resolution No. 466/2012, providing general rules for all types of clinical trials.
• RDC No. 506/2021, Anvisa’s specific resolution on conducting clinical trials for the investigation of all medicinal products for advanced therapies.

The trial sponsor is required to submit a Drug Clinical Development Dossier (DDCM) to Anvisa for approval, as outlined in RDC No. 09/2015. This requirement is applicable to all clinical trials involving medicinal and health products, irrespective of their nature, such as new medicines or therapeutic indications. Anvisa’s Co-ordination of Research and Clinical Trials department (COPEC) evaluates the DDCM for potential sanitary risks before deciding on approval.

RDC No. 9/2015 stipulates specific timeframes for Anvisa’s analysis of the DDCM:

• 180 days for Phase I or II clinical development studies involving biologicals or those conducted solely in Brazil.
• 90 days for Phase III studies involving synthetic drugs, conducted in other countries as part of the dossier.

To obtain Anvisa’s approval, the sponsor must also provide evidence of filing a detailed protocol with the Research Ethics Committee (CEP) of the institution where the trial is to be conducted. This protocol should encompass the freely given and informed consent of trial subjects (or their legal representatives), as discussed further below (see Consent). Trials cannot commence until Anvisa grants approval.

Imported products intended for research involving humans must also receive approval from Anvisa, according to RDC No. 172/2017. The sponsor, whether an individual or a legal entity initiating, managing, or financing the trial, can be foreign. However, the institute conducting the research must be Brazilian. While a sponsor can delegate its functions to a Clinical Research Organization (CRO) per RDC No. 9/2015, any transfer does not exempt the sponsor from responsibility for the quality and integrity of trial data.

Clinical Trials for Medical Devices:

The primary regulations include:

• RDC No. 837/2023 – Regulates clinical trials with medical devices in Brazil.
• RDC No. 751/2022 – Regulates the risk classification, notification and registration regimes, labeling requirements, and instructions for use of medical devices.
• Normative Instruction No. 21/2017 – Regulates the inspection procedures for Good Clinical Practice for Clinical Trials with Medical Devices in Research. This NI has been amended in accordance with RDC No. 557/2021 and RDC No. 702/2022.

RDC 837/2023 aligns the Brazilian regulatory scenario with international practices, as well as establishing, in a clearer way, the clinical investigations that can be submitted to the Agency. The RDC removes the need to submit the Clinical Research Process Consent, which was mandatory for each clinical investigation under the Medical Device Clinical Investigation Dossier (DICD) regime. All the documentation relating to the medical device and the clinical investigation plan will be submitted under a single DICD process, making analysis faster (After receiving the DICD, Anvisa will evaluate it and issue a manifestation within 90 (ninety) calendar days).

Therefore, the need to submit notifications for post-marketing studies and class I and II medical devices for prior approval by Anvisa is eliminated. In addition, there is no requirement for the Research Ethics Committee (“CEP”) to provide a substantiated opinion in the list of documents for the submission of clinical research with medical devices. The reason for this is that it is an ethical requirement. This means that clinical investigations involving risk class III or IV medical devices that have not yet been registered in Brazil are subject to the submission of a DICD.

Yes. ReBEC (Registro Brasileiro de Ensaios Clinicos) is the official Brazilian Registry of Clinical Trials, a public platform operated by ANVISA (the National Health Surveillance Agency). Anyone can access and search the ReBEC database for information on clinical trials conducted in Brazil, including details like study design, participant criteria, and contact information.

The database includes details like trial title, sponsor, investigational product, phase, primary and secondary endpoints, inclusion/exclusion criteria, and participating research centers.

Under CONEP Resolution No. 466/2012 and Law No. 13,709/18, also known as the General Data Protection Law (Lei Geral de Proteção de Dados Pessoais or LGPD), health data is considered sensitive, and confidentiality of trial participants’ data is mandated for both private and public institutions.

Sponsors are obligated to ensure that adverse events, particularly those that are fatal or life-threatening, are documented and reported to Anvisa in electronic form within seven days from the sponsor’s awareness of such events (RDC No. 9/2015).

Chapters III and IV of RDC No. 09/2015 – Amended by RDC No. 790/2023 – specify that sponsors must submit to Anvisa: • Annual monitoring reports on the progress of the trial drug, providing details on all adverse events and utilizing codes to identify trial subjects. • A final report, compiled upon the completion of the trial across all participating countries, containing information on the number of subjects withdrawn from the trial and a list of verified adverse events.

These reports should exclusively pertain to Brazilian centers and must meet the minimum requirements outlined in Article 68 for annual reports and Article 69 for the final report. The annual report is required to be submitted within 60 consecutive days from the annual reference date (the trial’s commencement date in Brazil), while the final report must be submitted within 12 months from the clinical trial’s conclusion.

• CONEP Resolution No. 466/2012.
• Law No. 13709/18, also known as the General Data Protection Law (Lei Geral de Proteção de Dados Pessoais or LGPD).
• Chapters III and IV of RDC No. 09/2015 – Amended by RDC No. 790/2023.

Creation of the RBPClin: RBPClin stands for Rede Brasileira de Pesquisa Clínica, which translates to Brazilian Network for Clinical Research. It’s an initiative launched in the end of 2022 by the Brazilian Ministry of Health, in partnership with the Ministry of Science, Technology, and Innovation, and the Ministry of Education,

It was created to strengthen clinical research in Brazil by connecting researchers, institutions, and companies; promote collaboration and knowledge sharing across different sectors; stimulate participation in clinical trials, both nationally and internationally; reduce dependence on foreign clinical research and build national capacity and support the development of new drugs, medical devices, and healthcare technologies.

In addition, the Health Ministry published Brazil’s digital health strategy to the period of 2020-2028 (ESD28). In this regard, ANVISA counts as a relevant author in this project, as it is an autarchy that has institutional purpose to promote the protection of the health of the population, working in a contributor position in the engagement area.

Resolution 658/2022 of the National Health Surveillance Agency (ANVISA) seeks to adopt the general guidelines for Good Manufacturing Practices for Medicines of the Pharmaceutical Inspection Cooperation System, as minimum requirements to be followed in the manufacture of medicines.

In this sense, authorization to manufacture a drug will be required, and its inmate, according to the Resolution, must manufacture it in a way that guarantees and corresponds to the intended purpose, always looking forward to fitting the “Pharmaceutical Quality System” by presenting documentation and monitoring its effectiveness, having adequate resources and trained personnel, appropriate facilities, and equipment. Also, it should be applied to all the steps of the product fabrication process.

In this way, national requirements for authorization to manufacture medicines, etc., require manufacturers to establish and implement a system that guarantees and focuses on pharmaceutical quality.

Beyond this, regional representative on the ground works as a prerequisite for authorization in Brazil, more specifically the Brazilian Registration Holder (BRH), that’s legally responsible for the authorized device in the country. In this regard, the following steps are included: (i) communicating with ANVISA; (ii) applying for B-GMP certificate; (iii) submit authorized documents; and (iv) post market vigilance.

Also, regarding devices as electrical medical devices, breast implants, condoms, rubber gloves and sterile single use syringes, there should be an INMETRO certificate, i.e. National Institute of Metrology Standardization, that confirms the Brazilian standards to the product.

ANVISA, in the Good Practices Guide for Medical Manufacturing highlights the following requisites: pharmaceutical quality system; good practices in the fabrication of medicines; quality control; revision on the quality of the product and quality risks management.

In the food sector, RDS no. 23/2000 it’s the Manual of Basic Procedures for Registration and Exemption of Obligation for Product Registration and establishes that the basic procedures for registration and exemption from the obligation to register products pertinent to the food area.

Also, there´s RDC no. 241/2018 that focuses on the requirements for producing proof of health benefits and safety of probiotics used in food. Finally, RDC no. 275/2002, that approve the Technical Regulation of Standard Operating Procedures applied to the checklist of good manufacturing practices in food establishment.

Companies engaged in activities such as importing, exporting, manufacturing, distributing, storing, or transporting must secure a sanitary license from the local authority, which may be either the state or municipal authority based on the establishment’s location. Additionally, they need to apply for a permit from ANVISA. Generally, licenses are obtained for each facility, while permits may be applicable to the entire corporation (except for medical devices, where each facility must obtain its own permit).

License fees vary based on the location, while ANVISA permit fees depend on factors like the company’s tax regime, size, and the scope of activities. Licenses must be renewed annually, whereas ANVISA permits do not have an expiration date but rely on the continuous validity of the initial licenses supporting their issuance.

The licensing process typically involves an on-site inspection by the local authority to assess facility compliance with regulations. It also includes a review of the company’s manuals and standard operating procedures, their implementation, accuracy, and their alignment with the applicant’s product portfolio.

GMP certifications are mandatory for companies seeking marketing authorization for medicinal products or specific medical devices (Classes III and IV). These certifications have a two-year expiration and can be obtained through inspections conducted by ANVISA’s authorities, either locally or internationally. In the medical devices sector, ANVISA participates in the Medical Device Single Audit Program (MDSAP), accepting assessments by third-party auditing organizations for facilities with MDSAP certification.

Certain medical devices may require certification by the National Institute of Metrology, Quality, and Technology (INMETRO). This is often necessary for electromedical equipment compliant with IEC 60601 standards, and it may extend to other product categories such as needles, syringes, mattresses, gloves, breast implants, mechanical wheelchairs, handpieces, and infusion sets.

Therefore, a distributor is required to:

• Acquire an AFE from the Ministry of Health. However, this is not obligatory for companies exclusively engaged in the distribution of raw materials, components, and ingredients not subject to special control, intended for the production of health products, cosmetics, personal hygiene products, perfumes, and sanitizing products.
• Have the support of a Responsible Technician.

Anvisa, in RDC No. 430/2020, amended by amended by RDC No. 653/2022, outlines the principles of Good Distribution Practice (GDP). It’s important to note that this resolution does not extend to the distribution of raw materials, medicinal gases, or labels and packages. Violations of GDP can lead to sanctions by the relevant authorities.

In Brazil, much like in numerous other countries, the drug prices are subject to government regulation.

Every year, CMED (Chamber of Regulation of the Medicine Market) defines a readjustment index that serves as the basis for determining the PMC (Maximum Price to the Consumer) allowed for the industry. It’s important to note that manufacturers must provide ANVISA with sales information from the previous year for a price adjustment to be considered. However, adherence to the prescribed adjustment percentage, up to the permissible limit, remains compulsory.

CMED holds significance for various ministries within the Brazilian Government, as any decisions made by CMED directly impact the Ministries of Health and Economy. Furthermore, CMED is tasked with establishing norms for the setting and adjustment of drug prices in Brazil. These norms aim to promote the pharmaceutical sector, monitor sales, and impose penalties for non-compliance with regulations.

CMED has established a resolution categorizing drugs into groups:

• Released Medicine: Manufacturers have the flexibility to adjust the factory price at their discretion without the obligation to publish changes for the consumer.
• Medicine Released from the Factory: Changes to the factory price are permitted, but they must adhere to the specified marketing margin, which includes compliance with the consumer price cap.
• Monitored Medicine: Annual readjustments, as mandated by CMED, apply to both the factory price and the consumer price cap. The objective is to ensure that the value charged does not exceed the permitted limit.

The primary regulations governing the marketing, advertising, and promotion of medicinal products and food supplements include:

• Federal Law No. 9,294/1996, which oversees the advertising of drugs.
• RDC No. 96/2008 issued by the National Public Health Agency (ANVISA), amended by ANVISA’s RDC No. 23/2009, regulating advertising and promotional practices for prescription and over-the-counter drugs.
• ANVISA’s Normative Ruling No. 5/2009, offering additional clarification on ANVISA’s RDC No. 96/2008.
• Law No. 8,078/1990, containing general provisions related to product advertising in various sectors.
• The Advertising Self-Regulation Code, established in 1978, which outlines ethical rules for advertisements and prescribes regulations applicable to over-the-counter drugs. This code is enforced by the Advertising Self-Regulation Council.
• RDC No. 243/2018 issued by the National Public Health Agency (ANVISA), amended by ANVISA’s RDC No. 466/2021, regulating the health requirements for food supplements.
• Decree-Law No. 986/1969, which establishes basic food standards, including the labeling rules for supplements (article 23).
• RDC No. 727/2022, provides for the labeling of packaged foods.

PATENTS

• Industrial Property Law (Law No. 9,279/1996): This law establishes the general framework for intellectual property protection in Brazil, including patents. It defines patentable inventions, outlines the application and granting process, and establishes rights and obligations of patent holders.
• Paris Convention for the Protection of Industrial Property: Brazil is a signatory to the Paris Convention, which sets international standards for patent protection.

TRADEMARK

• RDC No. 59, of October 10, 2014, establishes the criteria and minimum conditions for the names of medicines, their complements, and the formation of families of medicines.
• Law No. 6,360, of September 23, 1976, regulates the labeling, packaging inserts, printed materials, labels, and leaflets for products and medications.
• ANVISA Service Guidance No. 43, of December 22, 2017, establishes the complementary criteria for the evaluation and decision of names in petitions for registration and post-registration modifications of medications, within the scope of the General Management of Medicines and Biological Products.

Initiation: Patent infringement cases can be initiated by the patent holder through a civil lawsuit filed in a state court. ANVISA may also be involved if the infringement impacts product safety or public health.

Evidence and Burden of Proof: The patent holder has the burden of proving infringement, usually through documentary evidence such as technical and legal opinions.. Such burden is reversed in the case of a process patent.

An unbiased court-appointed expert will be assigned to assess infringement from a technical standpoint. Such expert usually works in collaboration with technical assistants appointed by the parties. The Judge will apply the law to the specific case after assessing the appointed technical expert’s report.

Possible Remedies: If infringement is proven, the court may order various remedies, including:

• Injunctions to stop the infringing activity.
• Monetary damages for profits lost by the patent holder due to the infringement.
• Product seizure and destruction.
• Publication of the infringement decision.

Defense Strategies:

• Non-infringement: Arguing that the accused product does not fall within the scope of the patent claims, often through technical analysis and expert testimony.
• Invalidity: Challenging the validity of the patent due to various reasons like lack of novelty, inventiveness, or non-patentable subject matter.
• License Agreements: Negotiating a licensing agreement with the patent holder to continue using the patented technology legally.

Additional Considerations:

• Preliminary Injunctions: In urgent cases, courts may grant preliminary injunctions to stop the infringing activity even before a full trial takes place.
• Criminal Sanctions: Infringing certain types of patents, such as those related to essential medicines, may also lead to criminal penalties.
• Alternative Dispute Resolution (ADR): Mediation or arbitration may be used to resolve patent infringement disputes outside the court system.

• RDC No. 59, of October 10, 2014, establishes the criteria and minimum conditions for the names of medicines, their complements, and the formation of families of medicines.
• Law No. 6,360, of September 23, 1976, regulates the labeling, packaging inserts, printed materials, labels, and leaflets for products and medications.
• ANVISA Service Guidance No. 43, of December 22, 2017, establishes the complementary criteria for the evaluation and decision of names in petitions for registration and post-registration modifications of medications, within the scope of the General Management of Medicines and Biological Products.

As mentioned in the questions above, Brazil has a complex regulatory framework, which includes various standards regulating the market and different criteria for liability. It is relevant to highlight the Law No. 6.360/1976 – Provides for the Health Surveillance of Medicines, Drugs, Pharmaceutical and Related Inputs, Cosmetics, Sanitizers and Other Products, and other Provisions.

It is important to understand that it is possible for all parts of the chain to be held responsible, which will vary according to the product.

Medicinal Products:

• Stricter liability: Additional liability for manufacturers and distributors due to the inherent risks associated with these products.

Medical Devices:

• Liability varies based on risk classification (Class I, II, III, IV).
• Higher liability for higher-risk devices.

Food Supplements:

• Less strict liability compared to medicinal products and medical devices.
• Manufacturers still responsible for ensuring safety and quality.

Criminal liability:

• Intentionally endangering public health (Art. 268 Brazilian Penal Code): Applies to acts like knowingly selling adulterated or hazardous products, with potential imprisonment penalties.
• Consumer fraud (Art. 175 Penal Code): Misleading information or concealment of risks can lead to imprisonment and fines.

Administrative Liability

• Fines and license suspensions by ANVISA (National Health Surveillance Agency) for violations of regulations related to quality, safety, and marketing.
• Sanctions by Ministry of Agriculture for food and supplement infractions.

Civil Liability

• Product liability lawsuits for harm caused by defective products, placing the burden of proof on the manufacturer.
• Consumer protection claims for unfair practices or misleading information.

Enforcement Practice:

ANVISA (drugs) and Ministry of Agriculture (food and supplement production)

• Routine inspections and audits of manufacturers and distributors.
• Post-market surveillance of products to detect issues and risks.
• Investigation of complaints and reports of adverse events.
• Imposition of fines, product recalls, and even market bans.

Public Prosecutor’s Office:

• Can initiate criminal investigations based on evidence of public health endangerment or consumer fraud.

Consumer Protection Agencies:

• Advocate for consumers in civil lawsuits and advocate for improved regulations.

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Federal Law No. 6,437/1977 Empowers ANVISA and local authorities to enforce food and drug regulations. Potential sanctions for violation include:

• Warnings, product seizures, and bans.
• Suspension of sales/manufacturing, registration cancellation, and site closures.

Suspension/cancellation of product advertising.Anvisa, in collaboration with state and municipal authorities, conducts thorough inspections throughout the production and consumption chain to ensure adherence to food and drug laws. Inspectors are authorized to scrutinize facilities and records within the bounds of their duties and competence. For instance, a sanitary inspector is not entitled to request access to tax records.

In addition to issuing infringement notices, enforceable undertakings, and injunctions, Anvisa, state, and municipal entities are empowered to apply civil and criminal penalties. Administrative penalties, such as fines for statutory sanitary infringements, are only imposed following administrative prosecution, with the option to appeal at both first and second instances. In cases of breaching manufacturing or distribution authorizations, a judge may impose civil and criminal penalties on entities through court proceedings.

Yes.

Law No. 14,510/2022: This law permanently legalized telemedicine after its temporary authorization during the pandemic. It sets out rules for consultations, prescriptions, and data privacy, offering a foundational framework for digital health applications used in remote consultations.

General Data Protection Law (LGPD): This law protects personal data and applies to any app collecting or processing health data in Brazil. It requires robust data security measures, transparency, and user consent for data usage.

Artificial Intelligence (AI) Legal Framework Bill: Proposed legislation like PL 2338/2023 addresses AI development and deployment, impacting AI-powered medical apps. Transparency, bias mitigation, and ethical considerations are expected to be key aspects.

The Brazilian Constitution guarantees universal and equal access to actions and services that guarantee access to health. It is the responsibility of the State to promote and protect the health system. To this end, the Unified Health System (SUS) was created in 1990, which provides a set of health actions and services provided and maintained by the Public Power. SUS is the largest government-run public healthcare system in the world by number of beneficiaries.

SUS must act to guarantee comprehensive therapeutic assistance, including pharmaceutical assistance. To this end, several laws and regulations have been enacted, including:

• Stockpiling Requirements: ANVISA regulates the minimum stock levels manufacturers and distributors must maintain for essential medicinal products and medical devices.
• Public Procurement Programs: The Brazilian government operates various public procurement programs to acquire and distribute essential medicines and medical devices to public healthcare facilities.
• Price Regulation: ANVISA has the authority to regulate the prices of essential medicines, particularly those included in the SUS (Unified Health System).
• Law No. 5,991, of December 17, 1973: Regulates the sanitary control of the trade in drugs, medicines, pharmaceutical inputs, and related products, throughout the Brazilian territory.
• Law No. 13,021, of August 8, 2014: Dispositions on the exercise and supervision of pharmaceutical activities.
• RDC No. 44, of August 17, 2009: Establishes criteria and minimum conditions for compliance with Good Pharmaceutical Practices for the sanitary control of the operation, dispensing and commercialization of products and the provision of pharmaceutical services in pharmacies and drugstores and provides for other measures.
• CFF Resolution No. 308, of May 2, 1997: Regulates Pharmaceutical Care in Pharmacies and Drugstores.

Resolution RDC 02/2010: The primary regulatory body for medicinal products and medical devices in Brazil is ANVISA’s establishes general guidelines for advertising and marketing of both categories.

Brazilian Code of Consumer Protection: Applies to all marketing activities, including those for medicinal products and medical devices.

Code of Conduct of the Pharmaceutical Industry (CIMB): Developed by the Brazilian Pharmaceutical Industry Union (SINDIFARMA), this code provides additional ethical guidelines for marketing practices.

Code of Conduct for the Advertising Industry (Conar): Established by the National Council of Self-Regulation of Advertising (Conar), this code applies to all advertising activities, including those for healthcare products.

Code of Ethics for Physicians (CEM): Published by the Federal Council of Medicine (CFM), this code guides physicians’ conduct in various scenarios, including advertising their services.

Patent Term Adjustment (PTA) Lawsuits: Since 2021, when the Brazilian Supreme Court declared unconstitutional the provision allowing patents to remain in force for at least 10 years from their granting, patent terms have been limited to 20 years from the application or priority date. Pharmaceutical patent holders were particularly affected, as it was decided that even previously granted patents related to the pharmaceutical sector should have their term reduced to 20 years from filing. Thousands of pharmaceutical patents were impacted and several killed. Various companies sued for case-by-case adjustments due to unreasonable patent prosecution delays. Although some patents are still alive due to preliminary injunctions in PTA lawsuits, none of the plaintiffs were able to secure a favorable decision on the merits by an Appeal Court yet.

ANVISA’s Regulation of Genetically Modified Organisms (GMOs): In December 2023, ANVISA published Resolution No. 686/2023, establishing new rules for the safety evaluation and authorization of genetically modified food and animal feed. This update streamlines and simplifies the approval process for low-risk GMOs while maintaining stringent standards for risk assessment. This decision has significant implications for the agritech sector and food security in Brazil.

Federal Court Ruling on Off-Label Use of Medicines: In November 2023, the Federal Court of Rio de Janeiro issued a landmark decision recognizing the legality of off-label use of medicines by doctors under certain conditions. This means that doctors can prescribe medicines for uses beyond those approved by ANVISA, provided they have scientific evidence supporting the efficacy and safety for the specific patient and inform the patient of the off-label nature of the treatment. This decision has sparked debate on patient autonomy and the role of regulatory agencies in healthcare.

Telemedicine Regulation: Law No. 14,510/2022 permanently legalized telemedicine after the pandemic’s temporary authorization. This establishes rules for consultations, prescriptions, and data privacy, encouraging broader adoption.

AI-as-a-Medical-Device Framework: Artificial Intelligence Legal Framework Bill (PL 2338/2023 aims to provide comprehensive guidelines for responsible AI development and deployment across various sectors, including healthcare and life sciences. ANVISA is developing a regulatory framework for AI-powered medical devices, addressing issues like algorithm validation, bias mitigation, and data privacy.

Integration of Health Records: Initiatives like “e-SUS” aim to create a national electronic health record system, promoting data sharing and improving care coordination. This requires addressing data privacy concerns and ensuring interoperability across different healthcare systems.

Cannabis Regulation: On December 26th, 2023, was published by the Sao Paulo state decree 68.233/2023, that regulates the free supply of medicines based on cannabidiol and it related, by São Paulo Unified Health System. The supply must be ordered by a request made by the patient or legal representant, then it will be evaluated by Health Secretary. Last the medicine based on cannabidiol only will be provided with previous registration on ANVISA.

Skinny Labeling: Recently, ANVISA approved Skinny Labeling practice in Brazil, which means that from February 6th, 2024, generic and similar drugs that the previous patented will be allowed to have different labels than the standard label, respecting the indications protected by patents or claimed in published patent applications.

Biosimilars: Anvisa held extensive consultations with stakeholders to prepare a Public Consultation aimed at easing biosimilar development and approval. Several meetings were held with ANVISA representatives, individuals in the field and pharmaceutical companies to discuss the proposal for a Public Consultation to gather information concerning the obstacles to the development and approval of biosimilars in Brazil.

The purpose of the Public Consultation #1206/2023 (“Consulta Pública nº 1.206, de 2 de outubro de 2023”) is to simplify the process of development and registration, recognizing the possibility of exempting specific stages or studies when technically plausible. The idea is to decomplexify the regulatory procedure for registering biosimilars, starting with the repeal of Chapter V of RDC 55/2010.