Pharmacovigilance Requirements in Brazil

Introduction 

Brazil has established a comprehensive pharmacovigilance framework designed to ensure the continuous monitoring of the safety and benefit–risk profile of medicinal products throughout their lifecycle. The Agência Nacional de Vigilância Sanitária (ANVISA) is the national health regulatory authority responsible for overseeing pharmacovigilance activities in Brazil. 

The current framework is primarily based on RDC No. 406/2020, which establishes Good Pharmacovigilance Practices for holders of registrations of human medicines, and IN No. 63/2020, which addresses the Periodic Benefit-Risk Evaluation Report (RPBR). These regulations introduced a more structured and internationally aligned approach to post-marketing safety surveillance. 

For companies marketing medicinal products in Brazil, understanding these requirements is essential. Pharmacovigilance is not limited to adverse event reporting; it encompasses the establishment of an effective PV system, signal detection and management, risk management, periodic benefit–risk evaluation, regulatory communication, quality management, and appropriate oversight of outsourced activities. 

1. Regulatory Framework for Pharmacovigilance in Brazil

The cornerstone of the Brazilian pharmacovigilance framework is RDC No. 406/2020, which defines Good Pharmacovigilance Practices and establishes responsibilities and working standards for holders of registrations of human medicines distributed or marketed in Brazil. 

Another important regulation is IN No. 63/2020, which establishes requirements for the Relatório Periódico de Avaliação Benefício-Risco (RPBR), Brazil’s periodic benefit–risk evaluation report. 

The Brazilian framework also incorporates internationally recognized pharmacovigilance concepts, including principles derived from relevant ICH guidelines. RDC 406/2020 specifically incorporates the updated approach to post-marketing safety surveillance and benefit–risk assessment. 

Companies should therefore ensure that their Brazilian PV systems are aligned not only with local legislation but also with applicable international pharmacovigilance standards where relevant. 

2. Responsibilities of the Marketing Authorization Holder

Under RDC 406/2020, the Detentor de Registro de Medicamento (DRM), or Marketing Authorization/Registration Holder, has primary responsibility for pharmacovigilance activities related to its products. 

This responsibility includes ensuring that an effective pharmacovigilance system is established and maintained and that safety information is appropriately collected, assessed, documented, and communicated to ANVISA. 

The DRM is also responsible for providing information requested by the health authority within the specified timeframe. RDC 406/2020 states that information requested for pharmacovigilance purposes should be provided within the timeframe established by the authority. 

Importantly, outsourcing PV activities does not eliminate the DRM’s responsibility for ensuring that its pharmacovigilance obligations are fulfilled.

3. Establishment of a Pharmacovigilance System

A robust pharmacovigilance system is a fundamental requirement for companies operating in Brazil. 

The system should be capable of: 

• Collecting and processing safety information. 

• Evaluating individual case safety reports. 

• Conducting signal detection and assessment. 

• Performing continuous benefit–risk evaluation. 

• Managing safety signals and emerging risks. 

• Implementing risk management activities. 

• Preparing periodic safety evaluations. 

• Maintaining appropriate documentation and records. 

• Supporting regulatory inspections and requests from ANVISA. 

The system should also be supported by appropriate written procedures, trained personnel, quality controls, documentation, and appropriate oversight. 

The company’s PV system should reflect actual operations rather than existing only as a collection of documents. This principle is particularly important during inspections, where ANVISA may assess whether documented procedures correspond to the activities actually performed. 

4. Responsible Pharmacovigilance Professional

Brazilian requirements include the designation of a Responsável pela Farmacovigilância (RFV), or person responsible for pharmacovigilance. 

The RFV plays an important role in the implementation and oversight of the company’s pharmacovigilance activities and serves as an important point of contact for pharmacovigilance matters. 

The responsibilities associated with the RFV may include oversight of: 

• Safety information management. 

• Adverse event reporting. 

• Signal detection and evaluation. 

• Benefit–risk assessment. 

• Risk management activities. 

• Regulatory communication. 

• Compliance with applicable PV procedures. 

• Inspection readiness. 

Companies should ensure that the RFV has sufficient authority, resources, competence, and access to relevant safety information to perform the role effectively. 

ANVISA’s guidance on RDC 406/2020 specifically addresses the role of the RFV as part of its pharmacovigilance requirements. 

5. Adverse Event Collection and Reporting

An essential component of Brazilian pharmacovigilance is the collection and management of adverse event information. 

Companies should establish mechanisms to identify safety information from relevant sources, including: 

• Healthcare professionals. 

• Patients and consumers. 

• Medical information departments. 

• Clinical and post-marketing studies. 

• Scientific literature. 

• Regulatory authorities. 

• Partners, distributors, and other third parties. 

• Digital and other relevant sources where applicable. 

ANVISA uses VigiMed as its electronic system for reporting adverse events associated with medicines. VigiMed Empresas enables pharmaceutical companies to submit information through a web interface and supports XML import based on ICH E2B standards. 

This means companies should ensure that their safety database and reporting processes can support the applicable Brazilian submission requirements and technical specifications. 

6. Signal Detection and Safety Signal Management

Pharmacovigilance in Brazil extends beyond the submission of individual adverse event reports. 

Companies are expected to continuously monitor accumulated safety data to identify potential new risks or changes in known risks. 

Signal management generally includes: 

1. Signal detection 
2. Signal validation 
3. Signal prioritization 
4. Signal assessment 
5. Regulatory and medical evaluation 
6. Implementation of appropriate actions 
7. Ongoing monitoring 

Potential signals may originate from spontaneous reports, literature, clinical studies, epidemiological data, regulatory communications, or other safety sources. 

If a new signal or change in the benefit–risk profile is identified, the company should assess its potential significance and determine whether regulatory action or additional risk management measures are required. 

ANVISA specifically emphasizes that changes in the benefit–risk balance and relevant new safety information should be communicated to the Agency. 

7. Risk Management Plans and Risk Minimization

Risk management is another important element of the Brazilian pharmacovigilance framework. 

RDC 406/2020 established an approach in which the Risk Management Plan (RMP/PGR) encompasses routine pharmacovigilance activities and, where applicable, additional risk minimization measures. 

Depending on the medicinal product and its safety profile, risk management activities may include: 

• Identification and characterization of important risks. 

• Identification of missing information. 

• Routine pharmacovigilance activities. 

• Additional pharmacovigilance activities. 

• Routine risk minimization measures. 

• Additional risk minimization measures where necessary. 

Risk management should be dynamic. New safety information should trigger an assessment of whether the existing risk management strategy remains appropriate. 

8. Periodic Benefit–Risk Evaluation Reports (RPBR)

One of the significant requirements under the Brazilian framework is the preparation and submission of the Relatório Periódico de Avaliação Benefício-Risco (RPBR). 

The RPBR provides a structured and cumulative assessment of the safety and benefit–risk profile of medicinal products. 

According to ANVISA, RPBRs are prepared by registration holders to review and evaluate the safety profile of their products at defined intervals. The reports should provide a comprehensive and critical analysis of new or emerging safety information and the overall benefit–risk profile. 

The Brazilian approach follows the principles of ICH E2C(R2) and uses the International Birth Date (IBD) and Data Lock Point (DLP) concepts for the preparation of reports. 

Companies should maintain an effective regulatory tracking system to monitor: 

• Applicable active substances. 

• IBD. 

• DLP. 

• Submission deadlines. 

• Applicable ANVISA requirements. 

• Regulatory commitments. 

ANVISA maintains a published list concerning RPBR submission requirements and dates, and companies are responsible for monitoring the applicable information. 

9. Literature Monitoring and Other Safety Data Sources

An effective Brazilian PV system should have mechanisms for identifying relevant safety information from scientific and medical literature. 

Literature surveillance can identify: 

• New adverse reactions. 

• Changes in the frequency or severity of known reactions. 

• Potential safety signals. 

• New information concerning special populations. 

• Drug interactions. 

• Medication errors. 

• Off-label use and misuse. 

• Information relevant to the benefit–risk profile. 

Literature findings should be assessed and incorporated into the company’s overall safety evaluation where relevant. 

Companies should also define responsibilities for reviewing other relevant sources, including regulatory authority communications, clinical studies, patient programs, partners, and other sources applicable to their products.

10. Pharmacovigilance Quality Management System

A strong Quality Management System (QMS) is essential for maintaining compliance with Brazilian pharmacovigilance requirements. 

The PV QMS should address areas such as: 

• Standard Operating Procedures (SOPs). 

• Training. 

• Deviation management. 

• Corrective and Preventive Actions (CAPA). 

• Quality controls. 

• Audits. 

• Vendor oversight. 

• Record management. 

• Business continuity. 

• Change control. 

• Compliance monitoring. 

The system should be proportionate to the company’s activities and product portfolio. 

Training is particularly important because pharmacovigilance responsibilities may extend beyond the dedicated PV department. Employees in departments such as medical information, regulatory affairs, quality, sales, and customer service may encounter safety information and therefore require appropriate training.

11. Outsourcing and Vendor Oversight

Many companies operating in Brazil outsource some or all of their pharmacovigilance activities to specialized service providers. 

Outsourcing, however, does not transfer the ultimate responsibility of the registration holder for its pharmacovigilance system. 

The company should establish appropriate written agreements defining: 

• Responsibilities of each party. 

• Safety information exchange procedures. 

• Reporting timelines. 

• Escalation mechanisms. 

• Signal management responsibilities. 

• Regulatory communication. 

• Quality requirements. 

• Audit rights. 

• Business continuity arrangements. 

Vendor performance should also be monitored through appropriate oversight mechanisms, such as KPIs, quality reviews, audits, and periodic performance assessments. 

ANVISA’s Q&A document specifically includes outsourcing of pharmacovigilance activities among the areas addressed under RDC 406/2020.

12. Regulatory Inspections and Inspection Readiness

ANVISA may inspect companies to assess compliance with applicable pharmacovigilance requirements. 

Inspection readiness should therefore be maintained continuously rather than initiated only after receiving an inspection notification. 

Companies should be able to demonstrate: 

• An effective pharmacovigilance system. 

• Clearly defined responsibilities. 

• Appropriate safety reporting processes. 

• Evidence of signal detection and management. 

• Compliance with regulatory reporting timelines. 

• Appropriate RPBR and risk management activities. 

• Adequate training records. 

• Vendor oversight. 

• Deviation and CAPA management. 

• Appropriate documentation and record retention. 

A key inspection principle is consistency: the actual PV system should correspond to what is described in procedures, agreements, organizational documents, and other controlled records. 

13. Regulatory Communication with ANVISA

Effective communication with ANVISA is an important part of maintaining compliance. 

Companies should establish clear internal processes for: 

• Receiving regulatory requests. 

• Assessing requests and assigning responsibilities. 

• Preparing responses. 

• Obtaining appropriate review and approval. 

• Meeting regulatory deadlines. 

• Maintaining evidence of submission. 

• Tracking commitments and follow-up actions. 

RDC 406/2020 requires registration holders to provide information requested for pharmacovigilance purposes within the timeframe established by the health authority. Where the requested information cannot be provided within the required timeframe, the regulation provides for requesting an extension with justification. 

14. Practical Compliance Approach for Companies Entering Brazil

Companies preparing to market a medicinal product in Brazil should establish a structured PV implementation plan before commercial activities begin. 

A practical approach may include: 

Step 1: Regulatory Gap Assessment 

Assess the company’s existing global PV system against Brazilian requirements. 

Step 2: Define Local Responsibilities 

Clearly identify the DRM and RFV responsibilities and establish appropriate lines of communication. 

Step 3: Establish Safety Reporting Processes 

Define how safety information will be received, processed, assessed, and submitted to ANVISA. 

Step 4: Establish the PV Quality System 

Implement appropriate SOPs, training, quality controls, agreements, and compliance monitoring. 

Step 5: Implement Signal Management 

Ensure that Brazilian safety data can feed into the company’s global signal management process. 

Step 6: Establish Risk Management Processes 

Determine whether a PGR and/or risk minimization measures are applicable and establish processes for maintaining them. 

Step 7: Establish RPBR Tracking 

Monitor applicable RPBR requirements, IBD, DLP, and submission deadlines. 

Step 8: Maintain Inspection Readiness 

Conduct periodic internal assessments to ensure that the PV system remains compliant and operational. 

Key Takeaways 

• RDC No. 406/2020 is the cornerstone of Brazil’s current Good Pharmacovigilance Practice framework for holders of registrations of human medicines. 

• The Registration Holder (DRM) has primary responsibility for pharmacovigilance activities related to its products. 

• Companies must establish an effective pharmacovigilance system supported by appropriate procedures, personnel, training, quality controls, and documentation. 

• A designated Responsável pela Farmacovigilância (RFV) plays an important role in the company’s Brazilian PV system. 

• Adverse events should be appropriately collected, assessed, documented, and reported through the applicable ANVISA processes, including VigiMed Empresas. 

• Companies must continuously monitor safety information and manage potential signals and changes to the benefit–risk profile. 

• Risk management and risk minimization should be maintained as dynamic processes based on emerging safety information. 

• RPBRs provide an important mechanism for periodic evaluation of the benefit–risk profile and should be managed according to applicable ANVISA requirements and timelines. 

• Outsourcing PV activities does not eliminate the registration holder’s overall responsibility for maintaining an effective PV system. 

• Continuous inspection readiness and accurate regulatory documentation are essential for demonstrating compliance to ANVISA. 

Brazil’s pharmacovigilance framework reflects an increasingly structured and internationally harmonized approach to post-marketing safety surveillance. For companies operating in or entering the Brazilian market, successful compliance requires more than fulfilling individual reporting obligations—it requires an integrated PV system capable of identifying, evaluating, communicating, and managing safety risks throughout the product lifecycle. 

Baupharma supports pharmaceutical companies through its Pharmacovigilance and Regulatory Affairs services, helping them manage safety and regulatory activities, maintain appropriate processes and documentation, and respond to requirements across the product lifecycle. This integrated support helps companies maintain a strong focus on compliance and patient safety as they navigate different market requirements.