Country Selection

Brazil

Regulatory Authority

Regulatory Authority

Regulatory authority(ies), relevant office/departments, oversight roles, contact information

Scope of Assessment

Regulatory review and approval processes, renewal, monitoring, appeals, termination

Regulatory Fees

Regulatory fees (e.g., applications, amendments, notifications, import) and payment instructions

Ethics Committee

Ethics Committee

Ethics review landscape, ethics committee composition, terms of reference, review procedures, meeting schedule

Scope of Review

Ethics committee review and approval processes, renewal, monitoring, termination

Ethics Committee Fees

Ethics review fees and payment instructions

Oversight of Ethics Committees

Authorization of ethics committees, registration, auditing, accreditation

Clinical Trial Lifecycle

Submission Process

Submission procedures for regulatory and ethics reviews

Submission Content

Essential elements of regulatory and ethics submissions and protocols

Timeline of Review

Regulatory and ethics review and approval timelines

Initiation, Agreements & Registration

Pre-trial approvals, agreements, clinical trial registration

Safety Reporting

Safety reporting definitions, responsibilities, timelines, reporting format, delivery

Progress Reporting

Interim/annual and final reporting requirements

Sponsorship

Definition of Sponsor

Sponsor role and responsibilities, contract research organizations, representatives

Site/Investigator Selection

Site and investigator criteria, foreign sponsor responsibilities, data and safety monitoring boards, multicenter studies

Insurance & Compensation

Insurance requirements, compensation (injury, participation), post-trial access

Risk & Quality Management

Protocol and regulatory compliance, auditing, monitoring, inspections, study termination/suspension

Data & Records Management

Electronic data processing systems and records storage/retention

Personal Data Protection

Responsible parties, data protection, obtaining consent

Informed Consent

Documentation Requirements

Obtaining and documenting informed consent/reconsent and consent waivers

Required Elements

Essential elements for informed consent form and other related materials

Participant Rights

Rights regarding participation, information, privacy, appeal, safety, welfare

Emergencies

Obtaining or waiving consent in emergencies

Vulnerable Populations

Definition of vulnerable populations and consent/protection requirements

Children/Minors

Definition of minors, consent/assent requirements, conditions for research

Pregnant Women, Fetuses & Neonates

Consent requirements and conditions for research on pregnant women, fetuses, and neonates

Prisoners

Consent requirements and conditions for research on prisoners

Mentally Impaired

Consent requirements and conditions for research on persons who are mentally impaired

Investigational Products

Definition of Investigational Product

Description of what constitutes an investigational product and related terms

Manufacturing & Import

Investigational product manufacturing and import approvals, licenses, and certificates

Quality Requirements

Investigator's Brochure and quality documentation

Labeling

Investigational product labeling, blinding, re-labeling, and package labeling

Product Management

Investigational product supply, storage, handling, disposal, return, record keeping

Specimens

Definition of Specimen

Description of what constitutes a specimen and related terms

Specimen Import & Export

Specimen import, export, material transfer agreements

Consent for Specimen

Consent for obtaining, storing, and using specimens, including genetic testing
Hide
«
Brazil

Quick Facts

Clinical trial application language
Regulatory authority & ethics committee review may be conducted at the same time
Clinical trial registration required
In-country sponsor presence/representation required
Age of minors
Specimens export allowed

Regulatory Authority

Last content review/update: April 11, 2023

National Health Surveillance Agency (ANVISA)

As per ResNo9, ResNo61, and ResNo176, the National Health Surveillance Agency (Agência Nacional de Vigilância Sanitária (ANVISA)) is the regulatory authority responsible for clinical trial oversight, approval, and inspection of drugs to be registered in Brazil. ANVISA grants permission for clinical trials to be conducted in accordance with the provisions of ResNo9, ResNo61, and ResNo176.

LawNo9.782 states ANVISA is an independent administrative agency linked to the Ministry of Health (MOH) that is responsible for regulating, controlling, and supervising products and services involving public health risks. LawNo9.782 and ResNo61 explain that the goods and products under the agency’s purview include medicines for human use and their active ingredients, immunobiologicals and their active substances, and blood and blood derivatives.

As indicated in LawNo9.782 and ResNo61, ANVISA is headed by a Collegiate Board of Directors composed of up to five (5) members, one (1) of whom serves as the Chief Executive Officer. Among the Collegiate Board’s key responsibilities are its role in defining ANVISA’s strategic guidelines and proposing governmental policies and directives to the Minister in support of the agency’s sanitary surveillance objectives.

LawNo9.782 and ResNo61 further indicate that ANVISA has an Advisory Board. Per ResNo61 and BRA-36, the Advisory Board’s main objectives include requesting information and proposing guidelines and technical recommendations to the Collegiate Board to be addressed by ANVISA, and providing opinions on proposed governmental policies. Refer to LawNo9.782, ResNo61, and BRA-36 for detailed Collegiate Board and Advisory Board responsibilities.

As delineated in ResNo61, ANVISA oversees five (5) directorates including the Sanitary Authorization and Registration Board, the directorate responsible for granting approval to conduct clinical trials for drugs to be registered in Brazil. Per ResNo61 and ResNo176, the Sanitary Authorization and Registration Board oversees the administration of the General Management of Medicines and Biological Products (Gerência-Geral de Medicamentos e Produtos Biológicos (GGMED)). The GGMED coordinates and supervises the organizational units responsible for the regulation of active pharmaceutical ingredients, medicines, and biological products, and manages the implementation of international cooperation activities aimed at regulating active pharmaceutical ingredients, medicines, and clinical research involving human beings. The Coordination of Clinical Research on Drugs and Biologicals (Coordenação de Pesquisa Clínica em Medicamentos e Produtos Biológicos (COPEC)) is an administrative unit operating within GGMED that evaluates the processes and petitions related to clinical research on drugs and biological products, and issues technical opinions with the goal of granting approval to initiate clinical research in Brazil. See ResNo61 and ResNo176 for detailed information on ANVISA’s organizational structure and administrative units.

Please note: Brazil is party to the Nagoya Protocol on Access and Benefit-sharing (BRA-63), which may have implications for studies of investigational products developed using certain non-human genetic resources (e.g., plants, animals, and microbes). For more information, see BRA-81.

Contact Information

Per BRA-42, the following is ANVISA’s contact information:

ANVISA
Setor de Indústria e Abastecimento (SIA)
Trecho 5
Area Especial 57
CEP: 71.205-050
Brasília (DF)

Phone: 0 800 642 9782 (Public Service Center for domestic inquiries)*

*Per BRA-99, while ANVISA does not have phone service to receive international calls, general inquiries may be sent via email using ANVISA’s Electronic Contact Form (BRA-68). In-country calls can be made to specific administrative offices posted on ANVISA’s Who’s Who website (BRA-39).

Per BRA-12, the medicines and biological products contact information is as follows:

General Management of Medicines and Biological Products (GGMED)
Phone: (61) 3462-6724
Email: medication.assessoria@anvisa.gov.br

Per BRA-18, the clinical research contact information is as follows:

Coordination of Clinical Research in Medicines and Biological Products (COPEC)
Phone: (61) 3462-5599/5526
Email: pesquisaclinica@anvisa.gov.br

Articles 3-4, 8-10, and 15
Articles 1-2 and 4, and Annex III amending ResNo61
Articles 1-6, 60-61, 63, 88, 91, 97, 103, 208, and Annex III
Chapter I (Articles 1 and 2)

Scope of Assessment

Last content review/update: August 9, 2023

Overview

As delineated in ResNo9, ResNo61, and ResNo176, the National Health Surveillance Agency (Agência Nacional de Vigilância Sanitária (ANVISA)) is responsible for reviewing and approving clinical trial applications for drugs to be registered in Brazil. In addition, per ResNo9, the G-DDCMManual, and BRA-8, the clinical trial application (Clinical Drug Development Dossier (Dossier de Desenvolvimento Clínico de Medicamento (DDCM))) must contain at least one (1) Specific Clinical Trial Dossier (Dossiê Específico de Ensaio Clínico (DEEC)) in order for the DDCM to be approved. ResNo9 and the G-DDCMManual define a DEEC as a collection of documents submitted as part of the Experimental Drug Development Plan in the DDCM. Per the G-DDCMManual, the DEEC may be linked as a new process to the DDCM being submitted or as a process that modifies a previously submitted DDCM. Per ResNo9 and BRA-8, while the DDCM may be submitted at any stage of development, Phase IV post-marketing trials are only subject to Clinical Trial Notification by ANVISA after obtaining ethical approvals. See ResNo506 for information on ANVISA’s role in reviewing and approving clinical trial applications submitted for studies using advanced therapy products in Brazil (i.e., medicines for human use that are based on genes, tissues, or cells).

In addition, ResNo205 repealed the ResNo9 requirement that ethics committee (EC) (Comitê de Ética em Pesquisa (CEP)) approval must be submitted as part of the DDCM submission to ANVISA. Therefore, as explained in BRA-2 and BRA-1, regulatory and ethics reviews may be conducted in parallel. As indicated in ResNo9 and also noted in BRA-2, the National Research Ethics Commission (Comissão Nacional de Ética em Pesquisa (CONEP))’s approval is required for certain studies (e.g., foreign studies), but ANVISA’s decision to approve the DDCM is not dependent on CONEP. Similarly, when a protocol amendment is submitted to ANVISA, CONEP approval is not mandatory for all studies, but may be requested, according to BRA-1. However, per ResNo9, the EC (CEP) is required to approve substantial protocol amendments prior to implementation. Refer to the Ethics Committee topic for additional information on the CEP/CONEP System; CLNo038 for the criteria CONEP uses to process protocol amendments; and CLNo24 and CLNo24-Note for general guidelines on conducting clinical trials.

Clinical Trial Review Process

As delineated in ResNo61 and ResNo176, ANVISA’s Coordination of Clinical Research in Medicines and Biological Products (Coordenação de Pesquisa Clínica em Medicamentos e Produtos Biológicos (COPEC)) is responsible for conducting the review and approval of clinical trial applications (DDCMs). ResNo9 and the G-DDCMManual explain that following DDCM analysis and approval, ANVISA issues an authorizing document known as a Special Notice (Comunicado Especial (CE)). The CE lists all the trials included in the DDCM that are permitted to initiate the clinical study. BRA-8 further explains COPEC experts conduct a preliminary review that includes a benefit-risk assessment based on various criteria such as drug registration status and drug status in other agencies (e.g., fast-track or breakthrough therapy). After this evaluation, the reviewer may release the dossier by the expiration deadline date so that the sponsor (applicant) may proceed with conducting the trial, requesting a meeting, or conducting a more detailed and complete dossier evaluation. See the Timeline of Review section for additional ANVISA timeline information. Also, see BRA-79 for additional information on ANVISA’s clinical trial review and approval framework, and BRA-40 for information on ANVISA drug registration requirements.

ANVISA has also released ServBltnNo104 to expedite the evaluation of clinical drug research development in Brazil without compromising the quality of the technical analysis. ServBltnNo104 provides detailed procedures for a simplified technical review of the following:

  • DDCM petitions containing at least one (1) clinical trial protocol, at any stage of development, approved by at least one (1) regulatory authority of a member country of the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) or by the United Kingdom’s (UK’s) Medicines and Healthcare Products Regulatory Agency (MHRA). The protocol submitted to ANVISA need not be the same as the one (1) approved by the member country.
  • DDCMs for experimental drugs (also referred to as investigational products (IPs)) that are registered in at least one (1) ICH member country or the UK. This DDCM must be identical to the one (1) approved by the ICH member country or the UK, with the exception of the labels and secondary packaging models.
  • Substantial quality changes approved by at least one (1) ICH member country or the UK (i.e., changes potentially impacting the quality or safety of the IP, active comparator, or placebo).

According to ServBltnNo104, the IP manufacturing process must also meet the criteria and recommendations described in the ICH guidelines, as applicable, according to the phase of clinical development. In addition, the technical experts in ANVISA’s COPEC require DDCM petitions and substantial quality modifications to meet ServBltnNo104 criteria and be accompanied by the documentation required in ResNo9. COPEC will then analyze: the results of stability studies under accelerated and long-term conditions that support the proposed expiration date for the IP and, where applicable, for the modified placebo and comparator, when the storage recommendation is at room temperature (between 15 and 30 degrees Celsius); and the sample IP label for DDCM petitions.

In the event of non-compliance, COPEC will conduct a non-simplified analysis per ResNo9. ServBltnNo104 further explains that ANVISA may also at any time analyze all the documents required by ResNo9 relating to the IP risk analysis. Refer to the Submission Content section for DDCM petitions and substantial quality modifications documentation requirements.

See BRA-98 for a list of COPEC documents, regulations, and clinical research guidelines available on the ANVISA portal and their corresponding locations, and BRA-60 for COPEC’s 2020-2021 annual report. See also BRA-19 and BRA-90 for guidance on scheduling pre-submission meetings with COPEC to discuss the clinical development of a drug (e.g., DDCM, an amended DDCM (secondary petition), or DEEC), or a meeting to discuss a clinical trial application previously submitted to ANVISA. BRA-90 also provides the items required for scheduling each type of meeting and the corresponding request form to be submitted.

Priority Submissions

In addition to the previously stated DDCM requirements, ResNo204 establishes a priority category to register, amend previously registered, or request prior approval for drug submissions. ResNo204 states that the priority submission may be submitted as a DDCM or DEEC. A priority DDCM submission is required to meet one (1) or more of the following criteria: new drug trial in any phase to be carried out in Brazil, the drug is part of the Ministry of Health (MOH)’s National Immunization Program, or the product is determined to be of strategic public health interest and included under the MOH’s Unified Health System (SUS) (BRA-53). A priority DEEC submission is required to comply with the following: the drug is to be used for neglected, emerging or reemerging diseases, health emergencies, or serious debilitating conditions for which there is no alternative; the trial is to be conducted exclusively with the pediatric population; or the drug will be used in a Phase I trial only to be manufactured in Brazil. The sponsor should specify at the time of submission that the new or amended protocol is a priority category request. If not confirmed prior to the technical review phase, the request for approval may be denied. ANVISA is required to issue a first written opinion letter within 45 calendar days from the first working day following protocol submission, a final opinion in 120 days for new drug registration requests, and a final opinion 60 days for post-registration petitions. See the Timeline of Review section detailed timeline information. Refer to ResNo204 and BRA-14 for detailed information on priority submissions. See also BRA-2, BRA-1, and BRA-42 for additional information on priority submission.

New Drugs for Rare Diseases

ResNo205 sets forth specific approval procedures for clinical trials to be conducted to register new drugs to treat, diagnose, or prevent rare diseases. The applications may be submitted as an initial DDCM, a secondary petition linked to the original DDCM, or a DEEC either linked to the original DDCM or for a new process. The sponsor must delineate at the time of submitting a new drug submission (DDCM), an amended DDCM (secondary petition), or DEEC, whether the DDCM is pertaining to a rare disease drug. If not confirmed prior to the technical review phase, the request for approval may be denied.

In addition, per ResNo763, which modifies ResNo205, and BRA-3, ANVISA has suspended the requirement for the sponsor to hold a pre-submission meeting to present a rare disease DDCM or amended DDCM. The pre-submission meeting is optional, if the sponsor deems necessary, and ANVISA should hold the meeting within 60 days following this request. Refer to ResNo205 for additional submission documentation requirements. BRA-2 also provides a helpful summary of ResNo204 and ResNo205.

Special Reviews During COVID-19 Public Health Emergency

During the COVID-19 public health emergency as described in OrdNo188, ANVISA issued ResNo573 to implement an urgent and temporary amendment to ResNo9. Although OrdNo913 declared an end to the public health emergency as of May 22, 2022, ResNo790 has extended the validity of ResNo573 to May 23, 2024. In addition, ResNo791 has extended the validity of ResNo601 to May 23, 2024.

The ResNo573 amendment specifically affects ANVISA’s technical reviews of DDCMs that fall into at least one (1) of the following categories: national development, biological product clinical development including vaccines, and Phase I or II clinical development studies as delineated in ResNo9 (see Art. 36). Per ResNo573, ANVISA is required to evaluate this category of applications within 120 calendar days, counting from the date of linking the first DEEC to the DDCM. The 120-day review deadline only amends the original 180-day deadline specified in ResNo9 for these types of studies.

Pursuant to ResNo573 and BRA-3, in the event that ANVISA fails to respond within the 120-day deadline, the agency will issue a Document for Importation of Product(s) under Investigation for a DDCM (also known as the Import Document (DI)) that has one (1) or more studies approved by at least one (1) regulatory authority of an ICH founding or standing member country or by the UK’s MHRA. BRA-3 explains that the DI is the list of clinical supplies necessary to carry out the clinical trial, including the experimental drug, as described in the clinical trial submission form (BRA-22). BRA-3 further states that ANVISA will send the initial DDCMs/DEECs and the DI to the sponsor. To prove compliance with the ResNo573 criteria, the sponsor must then submit the subject codes: “12102 – ENSAIOS CLÍNICOS – Análise Simplificada de Anuência em Processo de Pesquisa Clínica Previsto no Plano de Desenvolvimento” (12102 – CLINICAL TRIALS – Simplified Analysis of Consent in the Clinical Research Process Provided for in the Development Plan) for each initial DEEC linked to the DDCM, and “11634 – ENSAIOS CLÍNICOS – Análise Simplificada de Dossiê de Qualidade” (11634 – CLINICAL TRIALS – Simplified Analysis of the Quality Dossier). Once submitted, simplified analysis will be performed only for the corresponding document (i.e., the initial DEEC or the Quality Dossier) for each of the subject codes.

Per ResNo573, the DDCM must also be identical to the one (1) approved by the ICH member country or the UK. An official document issued by the regulatory authority or a declaration of compliance with the criteria described in this document must be presented to prove the authorization or non-objection to carry out the clinical trial by the ICH member country or the UK. In the case of a DDCM that falls within the previously stated provisions, clinical development may begin after the relevant ethical approvals. However, this rule does not apply to DDCMs of vaccines, whose clinical development can only be started after analysis and consent by ANVISA and the relevant ethical approvals. ResNo573 delineates that the provisions of this regulation apply to DDCMs received by ANVISA and whose analysis was not initiated by the technical area. See Submission Process section for details on complying with ResNo573.

ResNo601, in turn, provides for the simplified analysis, on an exceptional and temporary basis of DDCMs, amended DDCMs, and substantial amendments to clinical protocols that are of national importance due to the COVID-19 public health emergency. These submissions may be analyzed in a simplified manner provided that they are identical to the one (1) approved by the ICH member country or the UK. Refer to ResNo601 and BRA-3 for further information on simplified analysis submission requirements.

5.1, 7, and 9
Articles 1-2 and Annex III amending ResNo61
Articles 1, 3-6, and 10-13
Articles 5-11 and 22-23
Chapters I (Articles 1, 2, and 4), II (Article 7), and III-IV
Articles 1 and 2
Articles 91, 103, and Annex III
Chapters I (Articles 1-3 and 6), III (Articles 33-38), IV (Article 43), and X (Article 78)
Conducting a Clinical Trial in Brasil
Priority Review, Rare Diseases, and ANVISA Review in Parallel with Ethics Process
2 and 3
4.2
Introduction and Regulatory Framework
3.1, 3.5, and 3.10
1, 2, and Annexes 1-2

Regulatory Fees

Last content review/update: April 11, 2023

National Health Surveillance Agency (ANVISA)

As set forth in ResNo9, ResNo222, and ResNo76, the sponsor is responsible for paying a Sanitary Surveillance Inspection Fee (Taxa de Fiscalização de Vigilância Sanitária (TFVS)) to submit a clinical trial application (Clinical Drug Development Dossier (Dossier de Desenvolvimento Clínico de Medicamento (DDCM))) to the National Health Surveillance Agency (Agência Nacional de Vigilância Sanitária (ANVISA)). As per ResNo222 and ResNo76, once the sponsor has completed the process of submitting a DDCM request (“petition” in Portuguese), ANVISA’s Electronic Petition Request System (BRA-38) generates a Union Collection Guide (Guia de Recolhimento da União (GRU)). According to BRA-43, ANVISA uses the GRU as its primary method to generate TFVS fees. Refer to BRA-51 for detailed information on the GRU and BRA-69 for information on the TFVS fee. See also BRA-10 for additional information on TFVS requirements.

Per BRA-69, ANVISA determines the TFVS fee based on the company’s size and the subject code assigned to the application request. Per the TFVS fee table provided in BRA-11 that was implemented by OrdNo45 and ResNo198, the fees range from 983.85 Brazilian Reals to 19,677 Brazilian Reals to obtain clinical research approval. BRA-8 further notes that ANVISA charges a fee for substantial amendments to the clinical protocol.

Payment Instructions

As described in ResNo222, the GRU contains a bar code that may be scanned for payment purposes at the Bank of Brazil or any participating financial institution participating in the bank clearing system. BRA-43 states that bank payments may be completed in person, or by using the bank’s website or self-service (ATM) terminals. Payment must be made within 30 days after the GRU has been issued. See BRA-67 for further guidance on how to complete the electronic petition request process for fee payments.

Annex I (4.7)
3.2
2
1-4
Articles 6 and 7
Articles 2, 14, and 16
Chapter III (Article 38)
Articles 2 and 14-16

Ethics Committee

Last content review/update: April 11, 2023

Overview

As per ResNo466, ResNo446, and OSNo001, Brazil has a centralized registration process for ethics committees (ECs) and requires institutional level EC approval for each trial site. The National Research Ethics Commission (Comissão Nacional de Ética em Pesquisa (CONEP)) is the central body responsible for coordinating the network of institutional ECs (Committees of Ethics in Research (Comitês de Ética em Pesquisas (CEPs)), and for registering and accrediting the ECs (CEPs). ResNo466, ResNo446, and OSNo001 state that CONEP is a collegiate advisory body directly linked to the National Health Council (Conselho Nacional de Saúde (CNS)), a permanent body within the Ministry of Health (MOH)’s Unified Health System (SUS) (BRA-53).

Both the ECs (CEPs) and CONEP are responsible for evaluating the ethical aspects of all research involving human beings and for approving the research protocols when applicable, as explained in ResNo466, ResNo446, and OSNo001. ResNo466 further notes that institutions conducting research involving human participants may establish one (1) or more ECs (CEPs) according to their particular requirements. For those institutions lacking an EC (CEP), or in the case of an investigator without an institutional affiliation, CONEP is required to suggest an EC (CEP) to conduct the protocol review. Together, the ECs (CEPs) and CONEP represent the ethical review system in Brazil, known as the CEP/CONEP System, as described in ResNo466, OSNo001, and G-ClinProtocols-FAQs. See also BRA-50, BRA-16, and BRA-49 for useful information on CONEP and the CNS.

Ethics Committee Composition

National Research Ethics Commission (CONEP)

As per OSNo001 and ResNo446, CONEP is an independent and multidisciplinary organization consisting of 30 appointed members and five (5) alternate members. The members represent a balanced gender composition; eight (8) members must equally represent various segments of the CNS. In addition, according to BRA-16, five (5) members must have a background in ethical research and health, and eight (8) members must represent the theological, legal, health management, and other related professions. Per ResNo446, CONEP also has an Executive Secretary appointed by the MOH’s Secretariat for Science, Technology and Strategic Inputs and an Assistant Secretary appointed by the CNS to coordinate CONEP’s work and to manage the technical and operational work to be carried out by the Executive Secretary. See ResNo466, OSNo001, ResNo446, and BRA-16 for detailed information on CONEP composition and responsibilities. See also BRA-50 for useful information on CONEP.

Ethics Committees (Committees of Ethics in Research (CEPs))

As per the PANDRH-GCPs, an institutional EC (CEP) must have at least five (5) members who collectively encompass the qualifications and experience required to review and evaluate the scientific, medical, and ethical aspects of a proposed clinical trial. By comparison, the OMREC requires the EC (CEP) to be composed of a minimum of seven (7) members having proven expertise in research. The PANDRH-GCPs, the OSNo001, and OMREC also indicate that the EC (CEP) should be multidisciplinary, represent a balanced gender and age composition, and consist of members embodying community interests and concerns. The OMREC further states that not more than half of its members should belong to the same professional category. In addition, as per the PANDRH-GCPs, in communities where minority ethnic populations predominantly reside, the EC (CEP) should include a member, alternate, or consultant from that group. The EC (CEP) may also designate alternate members whose functions are delineated in the EC’s (CEP’s) standard operating procedures (SOPs). ResNo647 further establishes standards and mandatory requirements for all ECs (CEPs) in Brazil to include Research Participant Representatives (RPPs) who represent the interests of research participants. RPPs must be at least 18 years old; have a history of participation in a social and/or community movement in which the participation is not limited to health areas and can cover all segments of social movement activity; and must be able to express the viewpoints and interests of individuals and/or groups of research participants in order to represent the collective interests of different audiences in the CEP/CONEP System. See ResNo647 for detailed information on RPPs.

Additional criteria for EC (CEP) membership is available in Section 3.2 of the PANDRH-GCPs and Section 2 of OMREC.

Terms of Reference, Review Procedures, and Meeting Schedule

As set forth in the PANDRH-GCPs and OMREC, each EC (CEP) must have written SOPs, including a process for conducting reviews. The SOPs should include information on EC (CEP) composition, meeting schedules, frequency of reviews, requirements for initial and ongoing evaluation of the research study, and requirements for notifying the investigator and the institution of results related to the study’s initial and ongoing evaluation.

Per the PANDRH-GCPs and OMREC, the majority of committee members must be involved in the review and approval process, and the necessary quorum must be obtained to approve or deny permission to conduct a study as specified in each EC’s (CEP’s) SOPs. As per ResNo370, the registration and appointment terms of EC (CEP) members are valid for three (3) years and may be renewed at the end of that period.

The PANDRH-GCPs also state that the EC (CEP) must retain all relevant records (e.g., SOPs, member lists, member affiliations and occupations, documents presented, meeting minutes, and correspondence) for three (3) years after the study’s conclusion, and make them available to the regulatory authorities upon request.

For detailed EC (CEP) procedures and information on other administrative processes, see Sections 3.3 and 3.4 of the PANDRH-GCPs and the OMREC. Also, see CLNo1-2022 for instructions on submitting administrative documents via email to CONEP to speed up EC (CEP) accreditation and renewal processes and maintain regular functioning of ECs (CEPs), and CLNo25 for guidance on conducting virtual CEP/CONEP system meetings.

Chapter I
3.2-3.5
Introduction, 6, and Summary Chart
Sections 2, 3, and 18
1, 2.1, 2.3, and 3
Chapter I.4
Preamble, Articles 1 and 16
Sections VI-X
Preamble, Chapters I-III, and Chapter VII

Scope of Review

Last content review/update: April 11, 2023

Overview

As set forth in ResNo466, the PANDRH-GCPs, ResNo251, and the G-ClinProtocols-FAQs, the primary scope of information assessed by ethics committees (ECs) (Committees of Ethics in Research (Comitês de Ética em Pesquisas (CEPs)) and the National Research Ethics Commission (Comissão Nacional de Ética em Pesquisa (CONEP)), jointly known as the CEP/CONEP System, relates to maintaining and protecting the dignity and rights of research participants and ensuring their safety throughout their participation in a clinical trial.

Per ResNo466, the PANDRH-GCPs, ResNo251, and OSNo001, the CEP/CONEP System members must pay special attention to reviewing informed consent and to protecting the welfare of certain classes of participants deemed to be vulnerable (See the Vulnerable Populations; Children/Minors; Pregnant Women, Fetuses & Neonates; Prisoners; and Mentally Impaired sections for additional information about these populations). ResNo304 further establishes specific ethical requirements for research studies involving indigenous populations. Detailed information on documentation and consent requirements for studies involving indigenous populations is available in the Documentation Requirements, Vulnerable Populations, and Consent for Specimen sections.

The CEP/CONEP System members are also responsible for ensuring an independent, timely, and competent review of all ethical aspects of the clinical trial protocol as stated in ResNo466, the PANDRH-GCPs, and OSNo001. It must act in the interests of the potential research participants and the communities involved, evaluating the possible risks and expected benefits to participants, confirming the suitability of the investigator(s), facilities, and methods, and verifying the adequacy of confidentiality and privacy safeguards. Refer to ResNo466, the PANDRH-GCPs, and OSNo001 for detailed ethical review guidelines that govern the CEP/CONEP System.

National Research Ethics Commission (CONEP)-Designated Protocol Reviews

Per ResNo580, the Ministry of Health (MOH)’s Secretary of Science, Technology and Strategic Inputs refers protocols to CONEP that are determined to be of strategic public health interest for the Unified Health System (SUS) (BRA-53). ResNo580 recognizes strategic research protocols as those studies that may contribute to public health, justice, reduction of social inequalities and technological dependencies, and those that address public health emergencies. Refer to the Oversight of Ethics Committees section for additional information on CONEP’s review requirements for this type of protocol. A working group was also created to support the MOH’s assessment of research involving human beings when carried out in the SUS sphere, per OrdNo552. The interagency working group includes National Health Surveillance Agency (Agência Nacional de Vigilância Sanitária (ANVISA)), CONEP, and the National Health Council (Conselho Nacional de Saúde (CNS)), and is coordinated by an MOH representative.

In addition to conducting public health and international project reviews, per ResNo466, ResNo446, and ResNo340, CONEP is required to review certain studies involving human genetics, human reproduction, invasive therapeutic procedures, indigenous populations, genetically modified organisms, embryonic stem cells, and the establishment and operation of biobanks for research. Refer to ResNo466, ResNo446, and ResNo340 for specific details on CONEP protocol review requirements. See also CLNo172 for additional guidance on classifying protocol thematic areas that require CONEP review (e.g., protocols on the constitution and operation of biobanks for research purposes); CLNo34 for guidance on processing biobank development protocols electronically, and; CLNo041 for CONEP specimens consent instructions. See also ResNo506 for information on the role of CEP/CONEP System members in reviewing protocols submitted for clinical trials with advanced therapy products in Brazil (i.e., medicines for human use based on genes, tissues, or cells).

Review Pathways

ResNo674 provides review criteria and corresponding timelines to classify research and the processing of research protocols involving human beings in the CEP/CONEP System based upon study type and level of intervention in the human body. The regulation divides research into two (2) groups: 1) studies seeking to describe or understand phenomena that has happened or happen in the research participant’s daily life; and 2) studies that aim to verify the effect of an investigational product (IP) or technique used in research, deliberately applied to the participant, prospectively monitored, and which may or may not involve a control group. The studies are further characterized according to procedure and whether it involves intervention in the human body and if it is invasive.

Classification by study design and procedure is as follows: Type A – observational research; Type B – observational research with human body intervention; and Type C – investigational research designed to verify the effect of an IP (including a medicine, drug, biological product, or health device) or an investigational technique used in research, deliberately applied to the participant, prospectively monitored, with or without a control. Type C studies are further divided into two (2) subtypes: C1 studies, in which the object of investigation is not an IP in the health area, and C2 studies, in which the object of investigation is an IP in the health area.

EC analysis varies according to the type of research and modulation factors (i.e., consent process, confidentiality, and/or research methods), and requires the reviewer to verify the documentation the investigator submits in Plataforma Brasil (BRA-34). Per BRA-93, Plataforma Brasil is a national and unified database of human subjects research records that represents the entire CEP/CONEP System. The platform is also used to track research applications from submission to final approval by the EC (CEP), and when necessary, by CONEP. See BRA-33 for the most current Plataforma Brazil CEP and investigator manuals.

There are four (4) ways of processing protocols in the CEP/CONEP System: express, simplified, collegiate, and special collegiate; the modulation factors per Annex II of ResNo674 provides additional characteristics to further modify the protocol processing method to be used. See ResNo674, BRA-4, and BRA-5 for additional information on the CEP/CONEP System’s protocol research classification and processing procedures. (Please note: Per BRA-9, the protocol classification and processing system has not yet been implemented in BRA-34. The ClinRegs team will continue to monitor the Plataforma Brasil webpage for any developments.)

Role in Clinical Trial Approval Process

As delineated in ResNo9, ResNo466, the PANDRH-GCPs, and OSNo001, ANVISA and the EC (CEP) (and CONEP, if applicable) must approve a clinical trial application before a trial is permitted to commence. However, ResNo205 repealed the ResNo9 requirement that EC (CEP) approval must be submitted as part of the Clinical Drug Development Dossier (Dossier de Desenvolvimento Clínico de Medicamento (DDCM)) submission to ANVISA. Therefore, as explained in BRA-2 and BRA-1, regulatory and ethics reviews may be conducted in parallel.

In addition, as indicated in ResNo9, and also noted in BRA-2, CONEP’s approval is not a requirement for ANVISA to approve the DDCM. However, the PANDRH-GCPs, ResNo9, and OSNo001 states that the EC (CEP) must review and approve any protocol amendments prior to those changes being implemented. According to BRA-1, when a protocol amendment is submitted to ANVISA, CONEP approval is not mandatory, but may be requested. In these cases, only the EC (CEP) is required to approve the amended protocol prior to implementation and ANVISA should be notified. Per ResNo9, the EC (CEP) is required to approve substantial protocol amendments prior to implementation. See ResNo9 and the G-DDCMManual for additional information on preparing DDCMs, and CLNo038 for the criteria CONEP uses to process protocol amendments.

ResNo466 and OSNo001 specify that the development and submission of research, as well as the implementation and disclosure of EC (CEP) and CONEP opinions, must occur via BRA-34. Also see the Timeline of Review section for additional EC timeline information. There is no stated expiration date for an EC (CEP) approval in ResNo466, the PANDRH-GCPs, ResNo9, or OSNo001. However, in the event that an EC (CEP) revokes its approval of a clinical protocol, it must record its reasons for doing so and immediately communicate this decision to the investigator and ANVISA.

Following the review process, the PANDRH-GCPs also states that the sponsor must receive the following information prior to the trial’s commencement:

  • EC (CEP) member profiles (names and addresses)
  • Documented approval of EC (CEP)’s favorable opinion
  • Copy of EC (CEP) recommendations in case it has based its approval on change(s) in any aspect of the study (e.g., protocol modifications, written informed consent form, (ICF) or any other written information or other procedures)

The sponsor should also obtain documentation and dates relating to any EC (CEP) re-evaluations, re-approvals, withdrawals, or suspensions of approval from the investigator. (See the Submission Content section for additional details on the EC review process).

Additionally, CONEP has published a number of circular letters to clarify protocol review and processing procedures, submission instructions, and investigator responsibilities related to the following:

  • Classifying protocol thematic areas requiring CONEP review (CLNo172)
  • Processing protocol amendments (CLNo038)
  • Providing general clinical trial guidelines (CLNo24 and CLNo24-Note)
  • Presenting documentation required for CONEP analysis (CLNo062)
  • Conducting virtual CEP/CONEP System meetings (CLNo25)
  • Updating the informed consent form (ICF) (CLNo17)
  • Additional clarifications on ICF text (CLNo51)
  • Obtaining consent for human specimens (CLNo041)
  • Using medical records data for research purposes (CLNo039)
  • Submitting requests for research center inclusion/exclusion (CLNo046)
  • Citing clinical trial registries in protocols (CLNo060)
  • Processing biobank development protocols electronically (CLNo34)
  • Linking investigator/institutions to the responsible EC in submissions (CLNo183)
  • Standardizing consent and electronic assent for research participants and biobanks (CLNo23)
  • Submitting research protocols with human bodies and/or anatomical parts (CLNo26)
  • Processing adverse events for Brazil and abroad (CLNo13)
  • Submitting the Serious Adverse Event (SAE) form and instructions (CLNo008)

The above circulars are described in more detail where appropriate across the Brazil profile.

Foreign Research

As delineated in ResNo292, ResNo446, and ResNo466, applications with coordination and/or sponsorship originating outside of Brazil require additional EC review by CONEP. Per ResNo446, an exception to the required CONEP review applies to studies that have been fully carried out abroad and have been approved by an EC or equivalent body in the country of origin. ResNo580 also amends the ResNo466 requirements related to co-sponsored research projects and those involved with shipping human biological materials. This regulation states that when the MOH’s Secretariat of Science, Technology and Strategic Health Inputs issues an official agreement for a specific research project, the EC (CEP) for the proposing institution may conduct its review without the need for additional review by CONEP.

ResNo292 also explains that the scope of research from abroad or with foreign participation includes: collaboration between public or private foreign individuals or legal entities; sending and/or receiving biological materials from humans; sending and/or receiving data and information collected to aggregate research results; and international multicenter studies. For protocols within this thematic area, per ResNo292, special attention should be given to insuring the EC or equivalent institution within the originating country has issued an approval. If not, the Brazilian EC (CEP) and CONEP must approve the protocol. Refer to ResNo292 and the G-ClinProtocols-FAQs for additional guidance on research studies submitted from abroad.

Multicenter Research

ResNo346 establishes the submission process for multicenter research protocols and indicates that the coordinating center’s EC (CEP) should initially review the protocol and forward it to CONEP for review. Per OSNo001, the principal investigator is also required to submit a list of the participating institutions and associated protocols, the coordinating center, and the EC (CEP) designated to monitor the study’s progress as part of the research protocol package sent to the EC (CEP) for review. ResNo346 further notes that CONEP will only evaluate the first protocol submitted and then send its final opinion to the original EC (CEP) and the other participating institutions. ResNo674 similarly explains that the initial analysis of the research protocol using the research classification procedure will occur at the EC (CEP) of the coordinating center or the accredited EC (CEP), when applicable, and will be subsequently forwarded for analysis by the EC (CEP) of the other co-participating centers and/or institutions, after approval.

See ResNo346 for additional multicenter protocol processing information and OSNo01 for detailed information on the coordinating center’s role in this process.

Regulatory Submission Process and Conducting a Clinical Trial in Brasil
Priority Review, Rare Diseases, and ANVISA Review in Parallel with Ethics Process
Chapters 2 (2.3), 3 (3.1 and 3.3-3.4), 4 (4.3), 5 (5.5-5.6), 6 (6.10-6.11 and 6.23), and 9
Introduction, 6, and Summary Chart
5
1, 2.1, and 3
Chapters I-VII, Chapter X (Article 28), and Annexes I and II
Preamble, I, and VII-VIII
III-VI
IV and VI
II
Preamble and Articles 1 and 16
III and VII-X
Articles 1 and 11-12
I and III-V
Articles 1-2
Article 9
Chapter I (Articles 1, 2, and 4), II (Articles 7 and 15), III (Article 26)
Chapter III (Articles 35-36 and 38) and Chapter V (Articles 46-47)

Ethics Committee Fees

Last content review/update: April 11, 2023

National Research Ethics Commission (CONEP)

According to ResNo466 and OMREC, the National Research Ethics Commission (Comissão Nacional de Ética em Pesquisa (CONEP)) does not permit ethics committees (ECs) (Committees of Ethics in Research (Comitês de Ética em Pesquisas (CEPs)), to charge a fee to review clinical trial protocols. CONEP states that financing to support ethical reviews should come from a specific scientific committee budget designated within each institution.

2.5
Section VII

Oversight of Ethics Committees

Last content review/update: April 11, 2023

Overview

The National Research Ethics Commission (Comissão Nacional de Ética em Pesquisa (CONEP)) is the central statutory body responsible for the registration, audit, and accreditation of ethics committees (ECs) (Committees of Ethics in Research (Comitês de Ética em Pesquisas (CEPs)). As per ResNo466, OSNo001, and ResNo446, CONEP was created by the Ministry of Health (MOH) to provide ethical oversight of clinical research and to safeguard the rights and welfare of human participants involved in clinical studies. CONEP reports to the National Health Council (Conselho Nacional de Saúde (CNS)), the advisory body to the MOH.

As delineated in ResNo466, OSNo001, and ResNo446, CONEP’s core responsibilities center on:

  • Examining the ethical aspects of research involving human participants
  • Analyzing and monitoring research protocols and issuing opinions on applications with coordination or sponsorship originating outside Brazil, unless the co-sponsor is the Brazilian Government and applications are related to specialized thematic areas (i.e., human genetics, human reproduction, vaccines, and human biological materials)
  • Preparing and updating relevant ethical standards
  • Registering, auditing, accrediting, and training ECs (CEPs)
  • Monitoring EC (CEP) processes
  • Promoting and participating in educational EC (CEP) activities

See also the Scope of Review section for detailed EC (CEP) and CONEP review requirements associated with protocols originating outside of Brazil.

Registration, Auditing, and Accreditation

As per ResNo466, ResNo370, SP006REC, OSNo001, and ResNo446, all ECs (CEPs) must be registered and accredited by CONEP. CONEP’s Executive Secretariat who performs a documentation review to ensure compliance with the requirements delineated in ResNo446 carries out accreditation. ResNo370 and CNSResNo506 state that accreditation is valid for three (3) years. To apply for renewal, an EC (CEP) must follow the same procedures as in its initial application. The renewal application must be submitted within the window of 60 days before to 60 days after the accreditation’s expiration date, as noted in ResNo370, SP006REC, and CNSResNo506. See ResNo370, SP006REC, and CNSResNo506 for additional details on CONEP’s accreditation process. See CLNo1-2022 for instructions on submitting administrative documents via email to CONEP to speed up EC (CEP) accreditation and renewal processes and maintain regular functioning of ECs (CEPs).

High-Risk Research Protocols

In addition to being accredited by CONEP per the earlier stated requirements, CNSResNo506 explains that ECs (CEPs) may also be certified for their role in the ethical analysis of high-risk research protocols. As per ResNo674, the CNS has published protocol risk classification and processing guidelines to be used in the CEP/CONEP System to provide criteria to assess the risk level of research protocols.

Per CNSResNo506, until ResNo674 becomes operational, CONEP has determined that protocols falling within the special thematic areas of human genetics, human reproduction, indigenous populations, genetically modified organisms, and the establishment and operation of biobanks must be considered high risk. Refer to ResNo466, ResNo446, and ResNo340 for a complete listing of the special thematic areas. See also CLNo172 for additional guidance on classifying protocol thematic areas that require CONEP review (e.g., including protocols on the constitution and operation of biobanks for research purposes); CLNo34 for guidance on processing biobank development protocols electronically; and CLNo26 for information on submitting research protocols with human bodies and/or anatomical parts.

CNSResNo506 further states that at the time of obtaining accreditation, the EC (CEP) should submit a statement signed by the EC coordinator that commits the EC (CEP) to evaluating high-risk protocols at least equal to the protocol submitted to CONEP. This process also supports CONEP’s plan to decentralize the CEP/CONEP System and delegate more high-risk protocol reviews to certified ECs (CEPs). If the number of high-risk protocols exceeds the EC’s (CEP’s) operational capacity to review, then CONEP will evaluate the outstanding protocols. BRA-2 also provides helpful information on this process.

Additionally, ResNo674 notes CONEP will be solely responsible for the registration of biobank development protocols, and the research classification and modulation factors used to further characterize the protocols in BRA-34 will not be applicable. (Please note: Per BRA-9, the protocol classification and processing system has not yet been implemented in BRA-34. The ClinRegs team will continue to monitor the Plataforma Brasil webpage for any developments.)

Local Accreditation
2.3
2
Chapter X (Articles 29-30, and 32)
IV and VI
I and II
Preamble and Sections I, V, and VII
Sections VII, IX, and XIII
Chapters I, II, IV, and VI-VIII

Submission Process

Last content review/update: April 11, 2023

Overview

As stated in ResNo9, the G-DDCMManual, and BRA-8, the sponsor, the designated contract research organization (CRO), or the sponsor-investigator must apply to the National Health Surveillance Agency (Agência Nacional de Vigilância Sanitária (ANVISA)) to obtain approval for a clinical trial application (Clinical Drug Development Dossier (Dossier de Desenvolvimento Clínico de Medicamento (DDCM))) for a drug to be registered in Brazil that will have all or part of its development in Brazil. Per ResNo9, ResNo466, the PANDRH-GCPs, and OSNo001, the principal investigator (PI) must also obtain approval from the ethics committee (EC) (Comitê de Ética em Pesquisa (CEP)). Applications with coordination or sponsorship originating outside of Brazil require additional EC review by the National Research Ethics Commission (Comissão Nacional de Ética em Pesquisa (CONEP)), unless the co-sponsor is the Brazilian Government. ResNo205 repealed the ResNo9 requirement that EC (CEP) approval must be submitted as part of the DDCM submission to ANVISA. Therefore, as explained in BRA-2 and BRA-1, regulatory and ethics reviews may be conducted in parallel.

Regulatory Submission

Per ResNo9, the G-DDCMManual, and BRA-8, the DDCM must contain at least one (1) Specific Clinical Trial Dossier (Dossiê Específico de Ensaio Clínico (DEEC)) in order for the DDCM to be approved. ResNo9 and the G-DDCMManual define a DEEC as a collection of documents submitted as part of the Experimental Drug Development Plan in the DDCM. Per the G-DDCMManual, the DEEC may be linked as a new process to the DDCM being submitted or as a process that modifies a previously submitted DDCM. ResNo9 further notes that DDCM submissions to ANVISA can only be made by a CRO when the sponsor has no headquarters or subsidiary in Brazil. See also BRA-42 for additional information on ANVISA protocol filing requirements.

As indicated in the G-DDCMManual and BRA-8, ANVISA recommends that the DDCM and associated documents (including the protocol, investigator’s brochure, informed consent form, and sponsor and institutional declarations) be translated into Portuguese. If a translated version of the submission is not provided, ANVISA’s technical area reviewer may issue a requirement for the sponsor to provide a free translation of the submitted documentation.

For substantial protocol modifications, the sponsor must submit a secondary petition to ANVISA, as stated in ResNo9 and the G-DDCMAmdmts. These modifications may be made at any time after initial DDCM submission. If the modification has occurred following ANVISA’s issuance of the authorizing document known as a Special Notice (Comunicado Especial (CE)), per BRA-8, ANVISA will send the sponsor an updated CE to reflect the most current approved protocol version. While sponsors are required to submit all amendments to ANVISA, per ResNo9 and the G-DDCMAmdmts, they are only required to submit substantial protocol amendments via a secondary petition whereas non-substantial DDCM protocol amendments should be submitted as part of the annual clinical trial report. Non-substantial amendments that do not impact the protocol should be presented to ANVISA as part of the drug development safety update report. See BRA-13 for updated ANVISA application forms.

See ResNo742, BRA-8, BRA-6, and BRA-7 for requirements associated with submitting DEECs for comparative bioavailability studies and comparative pharmacokinetic studies for biosimilars.

As described in the G-DDCMManual and BRA-8, all DDCM petitions (both initial and secondary) should be submitted electronically to ANVISA via the Electronic Petition Request System (BRA-38). Per BRA-58, once the DDCM has been submitted, the sponsor is then required to electronically file all the documents corresponding to the initial DDCM petition’s subject code checklist. As explained in BRA-75, the sponsor must electronically attach all the documents required in the related DDCM checklist (accessed online via BRA-38) that corresponds to one (1) of the following related subject codes: 10748, 10749, 10750, 10751, 10752, 10753, 10754, and 10755. BRA-59 provides detailed instructions for submitting the DDCM checklist documents via BRA-38.

As per BRA-59, the sponsor must first submit the DDCM petition request along with payment of the Sanitary Surveillance Inspection Fee (Taxa de Fiscalização de Vigilância Sanitária (TFVS)) fee. In accordance with ResNo222 and ResNo76, ANVISA will only review the DDCM once the sponsor has paid the TFVS fee and the original electronic bank payment receipt is forwarded together with the original printed copy of the Union Collection Guide (Guia de Recolhimento da União (GRU)), the petition (request), and all of the documentation required for protocol review. (See the Regulatory Fees section for detailed information on the payment process.)

ResNo222 and ResNo76 and further state that if a petition is filed without due payment of the TFVS fee, the request and the documentation will be returned to the sponsor. BRA-43 specifies that ANVISA will accept the following documents as proof of payment from the sponsor:

  • Presentation of the original GRU receipt collected electronically, which must be accompanied by the original electronic banking network payment receipt
  • Presentation of the original GRU receipt collected from the banking network, which must contain the original receipt stamp for authentication
  • The transaction number issued by ANVISA’s Electronic Petition Request System (BRA-38)

BRA-59 explains that once the fee is paid, a reference (transaction) number is generated that will be required for the subsequent submission of the associated checklist documents. The processing of this request can take up to two (2) days, which is the time given to the banking network to clear the payment. Refer to BRA-59 for additional instructions. See also BRA-67 for step-by-step instructions on how to submit the initial DDCM petition and TFVS fee, and BRA-21 for the DDCM Petition Request Form.

Per the G-DDCMManual, all of the other documentation associated with the original DDCM including the secondary petitions and the DEEC(s) should be submitted electronically via BRA-38. ResNo204 and BRA-14 further note that DEECs may be submitted as priority requests to ANVISA to register, amend previously registered, or request prior consent for drug submissions. For detailed information on priority petition requirements, see the Scope of Assessment and Timeline of Review sections. The G-DDCMManual also specifies that for the electronic submission of secondary petitions and DEECs, the sponsor should append at least one (1) PDF file for each item contained in the petition checklist to enable text searching. It is possible to attach up to five (5) files of 750 kb each. BRA-8 also provides an example of an electronic submission in Annex 1.

In addition, BRA-92 provides detailed instructions for companies to comply with ANVISA’s requirement to submit an official document issued by an International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) member country regulatory authority or by the United Kingdom’s (UK’s) Medicines and Healthcare Products Regulatory Agency (MHRA), or a declaration of compliance with the criteria described in ResNo573. (Refer to the Scope of Assessment section for detailed information on ResNo573 requirements). Per BRA-92, if the company has already submitted a DDCM, the official document or declaration may be submitted as an attachment via email with the corresponding DDCM file number to: Pesquisaclinica@anvisa.gov.br, using the following subject line: RDC 573/2021 - Amendment - File XXXXXXX/XX-X. This will ensure that the request is reviewed in the shortest time possible. However, this additional submission is unnecessary for those cases in which the official document or declaration has already been attached to the DDCM by subject code of the subject code of “11634 - ENSAIOS CLÍNICOS - Análise Simplificada de Dossiê de Qualidade” (11634 - CLINICAL TRIALS - Simplified Analysis of the Quality Dossier) per ServBltnNo104. Refer to BRA-92 for additional information.

Refer to the Submission Content section for detailed DDCM petitions content requirements and substantial protocol modification documentation requirements.

See also BRA-19 and BRA-90 for guidance on scheduling pre-submission meetings with ANVISA’s Coordination of Clinical Research in Medicines and Biological Products (Coordenação de Pesquisa Clínica em Medicamentos e Produtos Biológicos (COPEC)) to discuss the clinical development of a drug (e.g., DDCM, secondary petition, or DEEC), or a meeting to discuss a clinical trial application previously submitted to ANVISA. BRA-90 also provides the items required for scheduling each type of meeting and the corresponding request form to be submitted. Refer to BRA-98 for a list of COPEC documents, regulations, and clinical research guidelines available on the ANVISA portal and their corresponding locations.

Ethics Review Submission

Per ResNo9, ResNo466, the PANDRH-GCPs, and OSNo001, the PI must also obtain approval from the EC (CEP). The PI is responsible for submitting the EC (CEP) application online via Plataforma Brasil (BRA-34). If applicable, the PI must also submit the application to CONEP for additional review and approval via BRA-34. Applications with coordination or sponsorship originating outside of Brazil require additional EC review by CONEP, unless the co-sponsor is the Brazilian Government. See BRA-33 for the most current Plataforma Brazil CEP and investigator manuals. Please refer to Scope of Review and Oversight of Ethics Committee sections for detailed information on CONEP responsibilities and other studies requiring CONEP approval. See also CLNo183 for instructions on linking investigator/institutions to the responsible EC in submissions; CLNo062 for guidance on submitting documentation required for CONEP analysis; and CLNo046 for instructions on submitting requests for inclusion/exclusion of research center(s).

Per OSNo001, the investigator is required to submit the research protocol in Portuguese to the CEP/CONEP System via BRA-34, and when applicable, accompanied by the originals in the foreign language.

In addition, per OSNo001, in the event of a multicenter clinical trial, the PI is required to submit a list of the participating institutions and the associated protocols as part of the research protocol package sent to the EC (CEP) for review.

Regulatory Submission Process and Conducting a Clinical Trial in Brasil
Priority Review, Rare Diseases, and ANVISA Review in Parallel with Ethics Process
3.1-3.2, 4, and 7.1 (Annex 1)
1, 2, and Annexes 1-2
Annexes I and II
10
2.3, 3.1, 3.3, 4.3, 5.5-5.6, 6.10-6.11, and 6.23
5 and 7-9
5-6, 10 (Annexes), and 11
2.1 and 3
VI, VIII, IX-XI
Articles 1, 3-6, and 10-13
Articles 5-11 and 22-23
Articles 9 and 16
Chapters I (Articles 1-3 and 6), II (Article 8), III (Articles 32-39), IV-V, and X (Article 78)
Articles 9, 14, and 16

Submission Content

Last content review/update: April 11, 2023

Regulatory Authority Requirements

As delineated in ResNo9 and the G-DDCMManual, to complete the clinical trial application (Drug Clinical Development Dossier (Dossier de Desenvolvimento Clínico de Medicamento (DDCM))), the sponsor, the designated contract research organization (CRO), or the sponsor-investigator is required to submit the National Health Surveillance Agency (Agência Nacional de Vigilância Sanitária (ANVISA))’s DDCM Petition Request Form (BRA-21) along with the following documentation (Note: The sources provide overlapping and unique elements so each of the items listed below will not necessarily be in each one.):

  • Sanitary Surveillance Inspection Fee (Taxa de Fiscalização de Vigilância Sanitária (TFVS)) as per ResNo222 and ResNo76 (tax payment imposed on individuals and companies engaged in clinical research)
  • Drug development plan (known as experimental drug dossier) (See the G-BioIProdManual for instructions on completing a biological products dossier and the G-SynthDrugProdManual for completing a synthetic/semi-synthetic products dossier)
  • Certified copy of the clinical agreement (contract or statement) that has been written, dated, and signed by the sponsor or the CRO
  • Clinical research protocol
  • Investigator’s Brochure (IB)
  • Summary of the investigational product (IP)’s safety aspects based on previous research in humans
  • Information on any discontinued development or withdrawal of IP
  • IP dossier
  • Specific dossier for each clinical trial to be conducted in Brazil
  • Proof of clinical trial registration in a registry listed on the World Health Organization (WHO)’s International Clinical Trials Registry Platform (ICTRP) (BRA-52) or any other registry recognized by the International Committee of Medical Journal Editors (ICMJE) (Note: the Brazilian Clinical Trials Registry (Registro Brasileiro de Ensaios Clínicos (ReBEC) (BRA-45) is a primary registry in the ICTRP network.) Per ResNo449, which amends ResNo9, if a registration receipt is not available to submit with the DDCM, it must be provided with the Start of Clinical Trial Notification Form in Brazil (BRA-25). Note that per ResNo205, the ResNo9 requirement to include the ethics committee (EC) (Comitê de Ética em Pesquisa (CEP)) approval in the initial DDCM or in any protocol amendment submission has been revoked.

Substantial Protocol Modifications

For substantial protocol modifications, the sponsor must submit a secondary petition to ANVISA using the DDCM Petition Request Form (BRA-21), as stated in ResNo9 and the G-DDCMAmdmts. These modifications may be made at any time after initial submission of the DDCM. Per BRA-8, if the modification has occurred following ANVISA’s issuance of the authorizing document known as the Special Notice (Comunicado Especial (CE)), ANVISA will send the sponsor an updated CE to reflect the most current approved protocol version.

While the sponsor is required to submit all amendments to ANVISA, per ResNo9 and the G-DDCMAmdmts, they are only required to submit substantial protocol amendments via a secondary petition whereas non-substantial DDCM protocol amendments should be submitted as part of the annual clinical trial report. Non-substantial amendments that do not impact the protocol should be presented to ANVISA as part of the drug development safety update report. See ResNo9 and the G-DDCMManual for detailed ANVISA application submission requirements, BRA-22 for the clinical trial submission form, and BRA-13 for updated ANVISA application forms. See also BRA-95 for instructions on providing expiration date information for imported IPs to be used during the trial and which the sponsor must include in its submission in BRA-22.

In order to fulfill the DDCM and the substantial quality modification requirements delineated in ServBltnNo104, the sponsor or the legal representative (also known as CRO in some sources) must provide all of the documentation required in ResNo9 and the following:

  • An official document issued by at least one (1) of the regulatory authorities from one (1) International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) member country to prove the clinical trial or the substantial quality modification is authorized to be carried out
  • A declaration of compliance with the ServBltnNo104 Form Attachment criteria regarding the IP to be administered in the trial to be conducted in Brazil: that it is identical to the one (1) administered in the ICH authorized country; is registered in at least one (1) ICH member country; contains the same substantial quality changes as the IP, active comparator, or placebo, if applicable, as those approved in at least one (1) ICH member country; complies with ICH manufacturing guidelines, where applicable, to the clinical development phase

Per ServBltnNo104, in the absence of the previously described official document, a justification must be presented showing that the conduct of the clinical trial or the substantial quality modification has been authorized.

In addition, ServBltnNo104 states that the previously listed documentation must be presented using the subject code of “11634 - ENSAIOS CLÍNICOS - Análise Simplificada de Dossiê de Qualidade” (11634 – CLINICAL TRIALS – Simplified Analysis of the Quality Dossier) to be linked to the DDCM petition or the substantial quality modification of interest, while the petition is in the queue waiting for ANVISA’s Coordination of Clinical Research in Medicines and Biological Products (Coordenação de Pesquisa Clínica em Medicamentos e Produtos Biológicos (COPEC))’s technical analysis to begin. The status of the petition code will remain as the subject code of simplified analysis if all of the documentation requirements are met. In the event of non-compliance with the ServBltnNo104 criteria, COPEC will proceed with the non-simplified analysis per ResNo9. These provisions may be applied to DDCM and substantial quality modification petitions submitted prior to the publication of ServBltnNo104, upon request using the subject code of “11634 - ENSAIOS CLÍNICOS - Análise Simplificada de Dossiê de Qualidade” (11634 - CLINICAL TRIALS - Simplified Analysis of the Quality Dossier), as long as the relevant petition is still in the queue waiting for the technical analysis to begin. The ServBltnNo104 provisions do not presuppose prioritizing the analysis of these petitions. Furthermore, ANVISA may at any time analyze all of the documents required in items VII, art. 38 and item III, art. 43 of ResNo9 based on the risk analysis related to the IP. See ServBltnNo104 for detailed information.

Ethics Committee Requirements

As per OMREC and OSNo001, the CONEP requires sponsors to submit the following documentation online via BRA-34 (Note: The sources provide overlapping and unique elements so each of the items listed below will not necessarily be in each one.):

  • Cover Sheet for Research Involving Human Beings (BRA-20)
  • Clinical research protocol (in Portuguese)
  • Background, justification, and registration in the country of origin for drug and device health products
  • Description of materials, methods, rationale, expected results, and bibliography
  • Critical risk and benefit analysis
  • Duration
  • Responsibilities of investigator, institution, and sponsor
  • Criteria for project suspension or termination
  • Location of implementation of various project steps
  • Necessary infrastructure and agreement of the institution
  • Statement of Commitment from the principal investigator (PI)
  • Informed consent form (ICF) (See Informed Consent topic for additional information)
  • Detailed research financial budget and investigator remuneration
  • Ownership of information
  • Characteristics of the participant population, and justification for the use of vulnerable groups
  • Number of participants locally and globally (multicenter)
  • Description of methods that affect research participants
  • Sources of material and details of the specific collection
  • Recruitment plans, inclusion and exclusion criteria
  • PI/investigator(s) Curriculum Vitaes (CVs)
  • Research project schedule
  • Foreign Research or Foreign Cooperation documentation (commitments and advantages for research participants and the country; identification of the national investigator and co-responsible institution; EC approval document in the country of origin or justification; response to the need for personnel training in Brazil; and lists of participating centers abroad and in Brazil)
  • Research with new drug, vaccine, and diagnostic test document requirements (current clinical trial phase and demonstration of compliance with previous clinical trial phases; drug substance registration in the country of origin and status of research; IB; clinical information from previous trial phases; justification for using placebo or wash out period; access to the drug, if its superiority is proven; investigator's statement to agree to comply with BRA-20; justification for inclusion of healthy participants; forms of recruitment)

See OMREC and OSNo001 for detailed CEP/National Research Ethics Commission (Comissão Nacional de Ética em Pesquisa (CONEP)) System submission requirements. See also BRA-33 for the most current Plataforma Brazil CEP and investigator manuals.

Clinical Protocol

As delineated in the PANDRH-GCPs, OMREC, and OSNo001, the clinical protocol should include the following elements:

  • Protocol summary
  • Sponsor or authorized representative name and contact information
  • PI CV and contact information
  • PI statement of responsibility
  • IP description (See Investigational Products topic for detailed coverage of this subject)
  • Form, dosage, route, method, and frequency of administration; and treatment period
  • Summary of potential risks and known benefits to research participants
  • Trial objectives and purpose
  • Trial design, random selection method, and blinding level
  • Participant selection/withdrawal
  • Participant treatment
  • Safety evaluation
  • Adverse event reporting requirements (See Safety Reporting section for additional information)
  • Statistics and methods to track trial data
  • Sponsor specifications for direct access to source data/documents
  • Quality control/quality assurance procedures and practices
  • Ethical considerations
  • Data management and record maintenance
  • Financing and insurance details
  • Publication policy

For complete protocol requirements, refer to the PANDRH-GCPs, OMREC, and OSNo001. See also CLNo060 for instructions on citing clinical trial registries in research protocols.

3.1-3.2
Annexes I and II
Chapters 2 (2.3), 3 (3.1 and 3.3), 4 (4.3), 5 (5.5-5.6), 6 (6.10-6.11 and 6.23), and 8
5-6
5-6, 10 (Annexes), and 11
9.1 and Annex C
2.1 and 3
2
2
Articles 5-11
Article 1
Articles 9, 14, and 16
Chapters I (Articles 1-2 and 6), III (Articles 33-38), and IV (Article 43)
Articles 9, 14, and 16

Timeline of Review

Last content review/update: June 2, 2023

Overview

ResNo205 repealed the ResNo9 requirement that ethics committee (EC) (Comitê de Ética em Pesquisa (CEP)) approval must be submitted as part of the clinical trial application to the National Health Surveillance Agency (Agência Nacional de Vigilância Sanitária (ANVISA)). Therefore, as explained in BRA-2 and BRA-1, the regulatory and ethics reviews may be conducted in parallel.

Regulatory Authority Approval

As specified in ResNo9, upon receipt of the clinical trial application (Drug Clinical Development Dossier (Dossier de Desenvolvimento Clínico de Medicamento (DDCM))), ANVISA has 90 calendar days to evaluate the application. If the agency fails to issue a response within 90 days of receipt, clinical development can begin as long as all of the ethical approvals have been obtained.

During the COVID-19 public health emergency as described in OrdNo188, ANVISA issued ResNo573 to implement an urgent and temporary amendment to the original ResNo9 180-day review timeline for DDCMs that fall into at least one (1) of the following categories: national development, biological product clinical development including vaccines, and Phase I or II clinical development studies as delineated in ResNo9. Although OrdNo913 declared an end to the public health emergency as of May 22, 2022, ResNo790 has extended the validity of ResNo573 to May 23, 2024.

The ResNo573 amendment requires ANVISA to evaluate these application categories within 120 calendar days, counting from the date of linking the first Specific Clinical Trial Dossier (Dossiê Específico de Ensaio Clínicos (DEEC)) to the DDCM. In the event that ANVISA fails to respond within the 120-day deadline, the agency will issue a Document for Importation of Product(s) under Investigation for a DDCM (also known as the Import Document (DI)) that has one (1) or more studies approved by at least one (1) regulatory authority of an International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) founding or standing member country or by the United Kingdom’s (UK’s) Medicines and Healthcare Products Regulatory Agency (MHRA).

The DDCM must also be identical to the one (1) approved by the ICH member country or the MHRA. An official document issued by the regulatory authority or a declaration of compliance with the criteria described in this document must be presented to prove the authorization or non-objection to carry out the clinical trial by the ICH member country or the MHRA. In the case of a DDCM that falls within the previously stated provisions, clinical development may begin after the relevant ethical approvals. However, this rule does not apply to DDCMs of vaccines, whose clinical development can only be started after analysis and consent by ANVISA and the relevant ethical approvals. ResNo573 delineates that the provisions of this regulation apply to DDCMs received by ANVISA and whose analysis was not initiated by the technical area. See Submission Process section for details on complying with ResNo573.

According to BRA-60, DDCM petitions that require a longer review period (up to 120 days per ResNo573) are described as “exceptions” requiring technical analysis whereas the 90-day review period for typical petitions are referred to as “no exceptions” and do not require technical analysis. BRA-60 notes that the deadline for analyzing initial DEEC petitions may be relatively longer when dealing with processes considered to be complex, such as with biological products, including the development of vaccines, which are also referred to as “exceptions.”

BRA-60 further states that the median deadline required by ANVISA to complete an analysis of a DDCM petition with technical requirements by the companies was 30 days, with 2 days being the shortest time observed and 197 days being the longest, in cases where there was more than one (1) technical requirement and times for meeting more than one (1) requirement added up. Refer to BRA-60 for detailed petition review timelines. Currently, companies have up to 120 days to respond to any type of agency-issued process and/or petition requirements. Typically, submissions with more complicated DDCM processes require companies to spend more time fulfilling ANVISA’s requirements.

Timeline information for ANVISA’s simplified analysis of DDCMs that meet the criteria for ServBltnNo104 is not available. (See Scope of Assessment section for details on the criteria for the DDCM to undergo a simplified analysis.)

Priority Submissions

As delineated in ResNo204, ANVISA is required to issue a final decision on applications for registration and post-registration of drugs classified as a priority within 120 days for new drug registration requests and in 60 days for post-registration petitions. The deadlines will be counted from the date of submission, and any requests for clarification or additional technical requirements will result in suspending the counting of deadlines until the requests have been met. See also BRA-40 for additional information on ANVISA drug registration requirements.

In addition, per ResNo204, ANVISA must first issue a written opinion letter within 45 calendar days from the first working day following protocol submission for priority petitions in the following categories:

  • Prior consent petitions in the clinical development dossier process
  • Prior consent petitions in the drug research process
  • Secondary petitions referring to the prioritized primary process

Refer to ResNo204 for detailed information on DEEC submissions. See also BRA-8 and BRA-14 for additional information on priority petitions. See the Scope of Assessment section for further information on priority submissions.

Ethics Committee Approval

As delineated in OSNo001 and BRA-91, the institutional EC (CEP) is required to issue an initial report in 30 days from the date the principal investigator (PI) submits an application for review. The CEP’s review of the protocol documentation for completeness should be accomplished within 10 days following submission. Per BRA-91, the review period must be counted from the date the project entered “Ethical Assessment” (i.e., after going through the validation of documents which takes around 10 days and when the Certificate of Presentation for Ethical Assessment (CAAE) is issued). In addition, per BRA-91, if the project needs to be reviewed by CONEP, the deadline is 15 days for document validation, and 45 days for ethical assessment. If these deadlines have expired, BRA-91 further suggests that the investigator responsible for the research project, contact the CEP to request explanations and, in parallel, send a notification to CONEP (conep.cep@saude.gov.br) requesting a case investigation.

CLNo040 further explains that new investigational brochure (IB) versions to be uploaded to the CEP/CONEP System via Plataforma Brasil (BRA-34) are often limited to updates pertaining to the investigational product’s efficacy and safety data and research team instructions. Updates should not alter research that has already been approved and must be processed as notifications in BRA-34. However, CLNo040 specifies that if the IB changes result in modifications to the detailed protocol and/or the informed consent form (ICF), it is necessary to submit a protocol amendment. In this case, the EC (CEP) will analyze the IB together with the other documents pertaining to the amendment, and, if necessary, the required amendments and/or clarifications will be requested. If the project needs to go through CONEP's appraisal, the deadline for Document Validation is 15 days and for Ethical Review, 45 days.

See the Submission Process section for CEP/CONEP System submission requirements.

Regulatory Submission Process and Conducting a Clinical Trial in Brasil
Priority Review, Rare Diseases, and ANVISA Review in Parallel with Ethics Process
2.1 and 4.2
Process of Processing Projects in the CEP
3.1 and 3.5
2.1 and 3
Articles 1, 3-6, and 10-13
Article 9
Chapters I (Articles 1-3 and 6), 3 (Articles 33-36 and 38), and X (Article 78)

Initiation, Agreements & Registration

Last content review/update: April 11, 2023

Overview

In accordance with ResNo9, the PANDRH-GCPs, and the G-DDCMManual, a clinical trial can only commence after the sponsor, the designated contract research organization (CRO), or the sponsor-investigator receives clinical trial application (Drug Clinical Development Dossier (Dossier de Desenvolvimento Clínico de Medicamento (DDCM))) approval from the National Health Surveillance Agency (Agência Nacional de Vigilância Sanitária (ANVISA)). Per ResNo9, ResNo466, the PANDRH-GCPs, and OSNo001, the principal investigator (PI) must also obtain approval from the ethics committee (EC) (Comitê de Ética em Pesquisa (CEP)). Applications with coordination or sponsorship originating outside Brazil require an additional review and approval by the National Research Ethics Commission (Comissão Nacional de Ética em Pesquisa (CONEP)), unless the co-sponsor is the Brazilian Government. Please refer to Scope of Review and Oversight of Ethics Committees sections for detailed information on CONEP responsibilities and other studies requiring CONEP approval. No waiting period is required following the sponsor’s receipt of these approvals.

In addition, per ResNo9, the sponsor or the designated CRO is required to obtain an import license from ANVISA for the shipment of the investigational product (IP) to be used in the trial. (See the Manufacturing & Import section for additional information). The trials should be conducted in compliance with the PANDRH-GCPs, ResNo466, and ResNo9. Clinical trials must also be conducted in a laboratory complying with the Organisation for Economic Co-operation and Development (OECD)’s Good Laboratory Practices (GLP) (BRA-15) as mandated by Brazil’s National Institute of Metrology, Quality and Technology (INMETRO). Refer to BRA-15 and BRA-48 for additional information on GLP requirements.

ResNo9 further states that the sponsor should register the clinical trial start and end dates within 30 calendar days of each date by submitting a secondary petition to the corresponding DDCM (see BRA-21 for the DDCM Petition Request Form).

Clinical Trial Agreement

As delineated in the PANDRH-GCPs, the sponsor or the CRO must sign an agreement or contract with the participating institution(s) and the investigator. In addition, if a sponsor decides to engage a CRO to conduct the trial, a letter of agreement should also be submitted to ANVISA as specified in the PANDRH-GCPs and ResNo9.

Clinical Trial Registration

As delineated in ResNo9, the sponsor must register the clinical trial in a registry listed on the World Health Organization (WHO)’s International Clinical Trials Registry Platform (ICTRP) (BRA-52) or any other registry recognized by the International Committee of Medical Journal Editors (ICMJE). According to BRA-52, the Brazilian Clinical Trials Registry (Registro Brasileiro de Ensaios Clínicos (ReBEC)) (BRA-45) is a primary registry in the ICTRP network. See also BRA-45 and BRA-46 for further information about ReBEC. Per ResNo449 which amends ResNo9, if a registration receipt is not available to submit with the DDCM, it must be provided with the Start of Clinical Trial Notification Form in Brazil (BRA-25).

5.1
2.1 and 3
2.3, 3.1, 4.3, 5.5-5.6, 6.2, and 6.10-6.11
Article 1
VI and VIII-XI
Chapter I (Articles 1-3 and 6) and Chapter III (Articles 33, 35-36, 38, and 40)

Safety Reporting

Last content review/update: April 11, 2023

Safety Reporting Definitions

In accordance with the PANDRH-GCPs, ResNo9, the AESafetyManual, and CLNo13, the following definitions provide a basis for a common understanding of Brazil’s safety reporting requirements (Note: The sources provide overlapping and unique elements so each of the items listed below will not necessarily be in each one):

  • Adverse Event/Experience (AE) – Any adverse medical occurrence in a research participant to whom a drug product was administered, and which does not necessarily bear a causal relationship to the treatment
  • Adverse Drug Reaction or Adverse Reaction (ADR) – All harmful unintended responses to a medicinal product related to any dose
  • Serious Adverse Event (SAE) or Serious Adverse Drug Reaction (SADR) – Any unfavorable occurrence that at any dose results in death, is life-threatening, requires or extends patient hospitalization, results in persistent or significant disability or permanent damage, or is a birth defect or congenital anomaly; significant medical occurrence, which based on appropriate medical judgment, may harm the participant and/or require medical or surgical intervention to prevent any of the other occurrences mentioned
  • Unexpected Adverse Drug Reaction – One whose nature or severity is inconsistent with the applicable product information (i.e., the investigator’s brochure for an unapproved investigational product (IP), or package insert/summary of the characteristics of an approved product)

Safety Reporting Requirements

Investigator Responsibilities

As specified in ResNo9 and the AESafetyManual, the investigator must inform the sponsor within 24 hours of all SAEs/SADRs occurring during the study. The PANDRH-GCPs also states that the immediate reports should be followed promptly by detailed, written reports in which the participants are identified by unique code numbers. AEs/ADRs identified in the protocol as critical to safety evaluations should also be reported to the sponsor. Per the AESafetyManual, the investigator(s) should treat all participants who incur AEs/ADRs and assist them until the situation is resolved. In the event of a participant’s death, the investigator must provide the sponsor and the ethics committee (EC) (Comitê de Ética em Pesquisa) (CEP)) with any additional requested information (e.g., autopsy reports and terminal medical reports).

Sponsor Responsibilities

The AESafetyManual states that the sponsor should classify all AEs/ADRs and SAEs/SADRs according to the World Health Organization’s Uppsala Monitoring Centre (WHO-UMC)’s standardized causality assessment system (BRA-31). The recommended criterion to categorize each event is as follows: Certain, Probable/Likely, Possible, Unlikely, Conditional/Unclassified, and Unassessable/Unclassifiable.

As per ResNo9 and the AESafetyManual, the sponsor should ensure all relevant information pertaining to fatal or life-threatening SAEs/SADRs occurring in Brazil is documented and electronically reported to the National Health Surveillance Agency (Agência Nacional de Vigilância Sanitária (ANVISA)) no more than seven (7) days after first knowledge. ResNo9 also indicates that any additional information should be included in the assessment up to eight (8) calendar days from the notification date. Additionally, per ResNo9 and the AESafetyManual, all other unexpected SAEs/SADRs whose causality is possible, probable, or certain for the products under investigation should be reported to ANVISA within 15 calendar days from the date of first knowledge by the sponsor.

Per the AESafetyManual, AEs/ADRs and SAEs/SADRs do not need to be reported to ANVISA under the above timelines when they occur outside of Brazil or are defined in the protocol as a primary or secondary outcome. Additionally, SAEs/SADRs that are categorized as Unlikely, Conditional/Unclassified, or Unassessable/Unclassifiable do not need to be reported under the above timelines. Per ResNo9 and the AESafetyManual, for events occurring within Brazil, this information should be included in the annual drug development safety update report (DDSUR), which must be filed within a maximum of 60 calendar days of the yearly anniversary of the date that ANVISA approves the clinical trial application (Drug Clinical Development Dossier (Dossier de Desenvolvimento Clínico de Medicamento (DDCM))). Per ResNo9, in the case of international trials, within 12 months of the study in all countries, the sponsor must submit a final report, which must include information on AEs/ADRs and SAEs/SADRs occurring in other countries.

ResNo9 requires the sponsor to notify investigators of AEs/ADRs and SAEs/SADRs for which the causality has been assessed as possible, probable, or certain. The sponsor must adopt procedures for updating the Investigator’s Brochure (IB) and reassess the risk and benefits to study participants. The PANDRH-GCPs states that the sponsor is also required to notify all concerned investigator(s), institution(s), and ANVISA of findings that could adversely affect participant safety, impact the conduct of the trial, or alter the EC (CEP)’s approval of the trial.

In addition, ResNo9 and the G-DDCMAmdmts state that in cases where the sponsor temporarily suspends a clinical trial or DDCM as an immediate safety measure, they must notify ANVISA within seven (7) consecutive days from the suspension date. Per ResNo9, the reasons for suspension, the scope, the interruption of treatment, and the suspension of participant recruitment must be clearly explained in the notification of temporary suspension. See also BRA-8 for additional information on ANVISA’s AE reporting requirements.

See ResNo506 for detailed information on AE and SAE safety reporting requirements involving investigational advanced therapy products.

Ethics Committee Responsibilities

CLNo13 establishes specific CEP/National Research Ethics Commission (Comissão Nacional de Ética em Pesquisa (CONEP)) System processing requirements for SAEs occurring in Brazil and outside the country. As delineated in CLNo13, only SAEs should be reported to the CEP/CONEP System; it is optional for the investigator or sponsor to report an AE. SAE ethical analysis is the exclusive responsibility of CEPs, and CONEP prefers not to be involved in the review, except when at the CEP’s discretion, it is deemed necessary.

Per CLNo13, CEPs must present SAE notifications about a participant’s SAE index (initial SAE) and subsequent events in a single document, in tabular format, and submit it online to the CEP/CONEP System via Plataforma Brasil (BRA-34) using the “notification” function. This document must also be updated with each occurrence of a subsequent SAE. The document must contain the study identification research title and Certificate of Presentation of Ethical Appreciation (Certificado de Apresentação de Apreciação Ética) (CAAE)) number, name of the research center, name of the responsible investigator, coded identification of the participant and description of the index and subsequent events. Per BRA-70, the CAAE is the number generated by Plataforma Brasil (BRA-34) to identify the research project when it is received by CEP for ethical review.

CLNo13 explains that each SAE must be characterized according to the following:

  • Date of SAE occurrence
  • Participant number or code
  • SAE number or code
  • SAE classification (index or subsequent)
  • Breakdown of the occurrence (e.g., febrile neutropenia, pneumonia, etc.)
  • SAE type (death, life threatening, need for hospitalization, prolonged hospitalization, significant damage, permanent damage, congenital anomaly, at the investigator's discretion, others)
  • Participant status on the date of the last update (in progress, recovered without sequelae, recovered with sequelae, and death)
  • Description of research participant withdrawal(s)

Additionally, in the case of multicenter studies, the investigator at the coordinating center must prepare the consolidated report (partial and final reports) containing information on SAEs from all of the participating research centers and submit it to the CEP to which it is linked via Plataforma Brasil (BRA-34) using the “notification” functionality. CLNo13 also explains that for SAEs occurring outside the country, it is the responsibility of the coordinating research center investigator to prepare the consolidated SAEs report. If the CEP is linked to the coordinating center, CONEP will also evaluate the SAEs if the protocol is included in item IX.4 of ResNo466.

Refer to CLNo008 for detailed instructions and the CONEP form to report SAEs to the CEP/CONEP System for review, and CLNo13 for information on processing AEs for Brazil and abroad.

Other Safety Reports

For investigational advanced therapy products, SAEs must be reported through the Online Adverse Event Notification Form for Advanced Therapy Products (BRA-101).

Form Completion & Delivery Requirements

As per BRA-37, VigiMed (BRA-83) is ANVISA’s online system for citizens, health professionals, drug registration holders, and study sponsors to report unexpected SAEs related to drugs and vaccines. Upon registration with BRA-83, BRA-37 indicates that companies (sponsors) must submit SAE notifications exclusively via BRA-83. See also BRA-85 for additional information on VigiMed.

Per BRA-78 and BRA-37, sponsors must email notifications of unexpected SAEs to notivisa.pesquisa@anvisa.gov.br. BRA-78 indicates that the title of the email must state “EVENTO ADVERSO GRAVE INESPERADO [NOME DO MEDICAMENTO]” (Unexpected Serious Adverse Event [Name of the medication]). BRA-78 and BRA-37 specify that the email must include the ANVISA Serious Adverse Event Notification Spreadsheet (BRA-84) containing all of the information that was previously registered with ANVISA. BRA-37 states that ANVISA advises sponsors of clinical research with medicines and biological products that have not yet been registered in VigiMed (BRA-83) to also include the following information for the company’s registration in the system:

  • Corporate name
  • Sender identifier (the official name should be used, if possible, since it will be used to identify the company in VigiMed)
  • CNPJ (National Registry of Legal Entities (Cadastro Nacional de Pessoas Jurídicas), which serves as tax identification
  • Short name: company name abbreviation [the company name abbreviation will be used in the Notification Identification, following the structure: BR-Company Name-Notification Number (Data element C.1.1 Sender’s (case) Safety Report Unique Identifier, from the ICH E2B (R3) (Electronic Transmission of Individual Case Safety Reports) (BRA-88)
  • Data of users to be registered in VigiMed: name and e-mail of two (2) notifiers, who will be registered to enter data from notifications of SAEs occurring in clinical trials
7
Chapters 5 (5.11), 6 (6.5 and 6.16-6.17), and 9
IX.4
Chapter V
Chapters I (Article 6), VI (Article 52), and VII
3.7
Introduction, VigiMed-Clinical Research, and Registration in VigiMed-Clinical Research

Progress Reporting

Last content review/update: April 11, 2023

Interim and Annual Progress Reports

As per ResNo9 and the G-CTReptsManual, the sponsor must file a progress report, known as an annual clinical trial protocol monitoring report, to the National Health Surveillance Agency (Agência Nacional de Vigilância Sanitária (ANVISA)) in the form of a secondary petition electronically attached to the respective protocol to which it is linked. ResNo9 indicates that the annual report should contain the following information for each clinical trial protocol, in tabulated form, exclusively from Brazilian centers:

  • Trial title
  • Protocol code
  • Participant(s) status
  • Number of participants recruited by center
  • Number/description of deviations and protocol violations by center
  • Description of all adverse events/adverse drug reactions occurring by center

The report should be filed within 60 calendar days from the annual anniversary date of the trial’s commencement in Brazil. BRA-8 further explains that currently ANVISA does not require a template to be used to complete the annual clinical trial protocol monitoring report since the information should be based on the ICH Harmonised Tripartite Guideline: Structure and Content of Clinical Study Reports (E3) standardized report format (BRA-27). See BRA-23 for the annual/final report form that may be used.

The PANDRH-GCPs state that the investigator or institution must submit written summaries on the status of the trial to the ethics committee (EC) (Comitê de Ética em Pesquisa (CEP) in Brazil) annually, or more frequently, if requested by the EC (CEP).

Final Report

ResNo9 and the G-CTReptsManual state that the sponsor should submit a final report to ANVISA in the form of a secondary petition electronically attached to the respective protocol to which it is linked. The final report must be filed within 12 months of the clinical trial end date. Per ResNo9 the final report should contain at least the following:

  • Trial title
  • Protocol code
  • Breakdown of the number of participants recruited or removed from the trial
  • Description of participants included in each statistical analysis and those who were excluded from the efficacy analysis
  • Participant demographics and statistics
  • Number/description of protocol deviations and violations
  • All adverse events/laboratory abnormalities with causality assessment occurring in participants
  • Results obtained in the measurement of outcomes for each participant
  • Rationale for early termination in Brazil or elsewhere in the world, where applicable

Per G-CTReptsManual, the annual and final reports for each clinical protocol shall contain the minimum requirements set forth in Articles 68 and 69 of ResNo9, or they may be submitted using the ICH E3 format (BRA-27). See BRA-23 for the annual/final report form.

As specified in the PANDRH-GCPs, upon the trial’s completion, the investigator or the institution should also provide the sponsor with all required reports, present the EC (CEP) with a summary of the trial’s outcome, and supply any additional report(s) required by ANVISA.

Other Reporting Requirements

As stated in ResNo9 and the G-CTReptsManual, in addition to submitting a final report, the sponsor is also responsible for submitting clinical trial start and end date forms for trials conducted in Brazil. The forms with the trial start and end dates must be filed as a secondary petition to the corresponding trial dossier within 30 calendar days after each start and end date. The secondary petition should be submitted to ANVISA using the Clinical Drug Development Dossier (Dossier de Desenvolvimento Clínico de Medicamento (DDCM)) Petition Request Form (BRA-21). See BRA-38 for the petition request system website that allows users to submit these forms electronically, and BRA-25 and BRA-24 for links to the notification forms.

3 and 5-7
5.10 and 5.13
Articles 40, 68, and 69
3.6

Definition of Sponsor

Last content review/update: April 11, 2023

As per ResNo466, ResNo9, and the PANDRH-GCPs, a sponsor is defined as an individual, company, institution, or organization that supports research through the initiation, management, or financing of a clinical trial.

ResNo9 states that a sponsor can authorize a contract research organization (CRO) to carry out certain work and obligations regarding the trial. As delineated in ResNo9, any trial-related responsibilities to be transferred and assumed by a CRO should be specified in a written agreement or contract.

As delineated in ResNo9, when a clinical trial is developed by a sponsor-investigator, the institution with which the individual is linked is the primary sponsor. The primary sponsor may delegate responsibilities to the investigator, who will be responsible for conducting the clinical trial at the institution, and the sponsor-investigator will serve as the secondary sponsor. See also BRA-79 for additional information on sponsor and CRO requirements in Brazil.

Chapter 9
II (11)
Articles 6, 20, and 27
Sponsor and Contract Research Organizations

Site/Investigator Selection

Last content review/update: April 11, 2023

Overview

As set forth in the PANDRH-GCPs, the sponsor is responsible for selecting the investigator(s) and the institution(s) for the clinical trial while taking into account the appropriateness and availability of the study site and facilities. The sponsor must also ensure that the investigator(s) are qualified by education, training, and experience to assume responsibility for the proper conduct of the trial. Investigator(s) should also provide evidence of all the qualifications specified by the applicable regulatory requirements through up-to-date curriculum vitae(s) (CVs) and/or other relevant documentation requested by the sponsor, the ethics committee (EC) (Comitê de Ética em Pesquisa (CEP)), and/or the regulatory authority(ies).

Prior to entering into an agreement with the investigator(s) and the institution(s) to conduct a study, the sponsor should provide the investigator(s) with the protocol and an investigator’s brochure. Additionally, the sponsor must define and allocate all study related duties and responsibilities to the relevant parties participating in the study. See the Submission Content section for additional information on clinical trial application requirements. See also CLNo046 for the National Research Ethics Commission (Comissão Nacional de Ética em Pesquisa (CONEP)) guidance on submitting requests for inclusion/exclusion of research center(s).

Foreign Sponsor Responsibilities

As specified in the PANDRH-GCPs and ResNo9, the sponsor may transfer any or all of the sponsor’s study related duties and functions to a contract research organization (CRO). However, the sponsor is ultimately responsible for the study data’s quality and integrity. Any study related duties, functions, or responsibilities transferred to and assumed by a local representative or CRO must be specified in writing. Other duties, functions, or responsibilities not specifically transferred shall be deemed as retained by the sponsor. However, as per ResNo9, a CRO can only submit a clinical trial application on the sponsor’s behalf when the sponsor has no headquarters or subsidiary in Brazil.

Data Safety and Monitoring Board

According to ResNo9, an Independent Safety Monitoring Committee (ISMC) should be established to systematically evaluate aggregate adverse event/adverse drug reaction data.

Multicenter Studies

Per the PANDRH-GCPs, in the event of a multicenter clinical trial, the sponsor or the CRO should ensure that all investigators conduct the trial in strict compliance with the protocol as well as with the National Health Surveillance Agency (Agência Nacional de Vigilância Sanitária (ANVISA))’s and the EC(CEP)’s requirements. The sponsor must also organize a coordinating committee or select coordinating investigators.

5.1, 5.6, 6.2, 6.5-6.6, and 6.23
Articles 6, 20, 37, and 56

Insurance & Compensation

Last content review/update: April 11, 2023

Insurance

As set forth in the PANDRH-GCPs, the sponsor is responsible for providing insurance coverage for any unforeseen injury to research participants. Before the clinical trial begins, the sponsor should also provide insurance or indemnify the investigator and the institution against claims arising from malpractice or negligence.

In addition, according to BRA-1, in the event that ANVISA asks for additional information to assess insurance and indemnity coverage for injures related to the study, the sponsor must provide a Medical Assistance Letter. See BRA-79 for additional information on sponsor/contract research organization (CRO) insurance coverage requirements in Brazil.

Compensation

Injury or Death

As specified in the PANDRH-GCPs and ResNo466, the sponsor is responsible for providing compensation to research participants and/or their legal heirs in the event of trial-related injuries or death. The sponsor must also ensure that participants who suffer any trial-related injuries are provided with free medical treatment for such injuries.

Trial Participation

As specified in ResNo466 and the G-ClinResSubjectRts, compensation to participants is only provided for transportation costs and meals for the participants and/or their legal representative(s) or guardian(s) during the trial.

Post-Trial Access

According to ResNo563, for protocols involving research participants diagnosed with ultra-rare diseases, the sponsor must ensure free access to the best prophylactic, diagnostic, and therapeutic methods that have proven to be effective at the end of the study, for a period of five (5) years after obtaining National Health Surveillance Agency (Agência Nacional de Vigilância Sanitária (ANVISA)) registration. In addition, per ResNo466, at the end of the study, the sponsor much ensure free and indefinite access to the best prophylactic, diagnostic, and therapeutic methods that have proven to be effective. Access must also be guaranteed to participants between the time they stop their participation in the trial and the end of the study.

Furthermore, ResNo311, which amends ResNo38, states that the sponsor/CRO should guarantee access to the post-study drug supply program for research participants enrolled in a clinical study in accordance with the Resolutions of the National Health Council (Conselho Nacional de Saúde (CNS)). The free supply of medicines should also be made available to participants when the study is terminated early. The sponsor is required to complete the Sponsor’s Responsibility and Commitment Statement Form for Expanded Access, Compassionate Use, or Post-Study Medicine Supply Programs (see Annex VI of ResNo38). See also BRA-79 for additional information on sponsor/CRO insurance coverage.

Documentation Required
Financing the Clinical Trial and Supply of Products to the Research Participants
6.8
4, 10, 15, 18, and Annex VI
Sections II-V
Articles 1, 3, and 4

Risk & Quality Management

Last content review/update: April 11, 2023

Quality Assurance/Quality Control

As stated in ResNo9 and the PANDRH-GCPs, the sponsor or the contract research organization (CRO) is responsible for implementing and maintaining quality assurance (QA) and quality control (QC) systems with written standard operating procedures (SOPs) to ensure that trials are conducted and data are generated, recorded, and reported in compliance with the protocol, the PANDRH-GCPs, the International Conference on Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R2) (BRA-28), and other applicable requirements.

The sponsor is responsible for obtaining agreement from all involved parties to ensure direct access to all trial related sites, source data/documents, reports for monitoring and auditing purposes, and inspection by domestic and foreign regulatory authorities. QC should be applied to each stage of data handling to ensure that all data are reliable and have been correctly processed.

The sponsor must also obtain the investigator(s) and the institution(s) agreement to:

  • Conduct the trial in compliance with the PANDRH-GCPs, applicable regulatory requirement(s), and the protocol agreed to by the sponsor and approved by the ethics committee (EC) (Comitê de Ética em Pesquisa (CEP))
  • Comply with data recording and reporting procedures
  • Permit monitoring, auditing, and inspection
  • Retain essential documents until the sponsor indicates they are no longer needed

Monitoring Requirements

As part of its QA system, ResNo9 and the PANDRH-GCPs note that the sponsor or the CRO should ensure the trial is monitored and audited. The purpose of the audit should be to evaluate trial conduct and compliance with the protocol, SOPs, and other applicable regulatory requirements. The sponsor should appoint auditors to review the clinical trial. The sponsor should ensure that the auditors are qualified by training and experience, and the auditor’s qualifications should be documented. The sponsor must also verify that the audit is conducted in accordance with their own SOPs, the auditor observations are documented, and data is available as needed for the National Health Surveillance Agency (Agência Nacional de Vigilância Sanitária (ANVISA))’s review. No specific timeframe is provided for the audit process.

In addition, per ResNo449, which amends ResNo9, ANVISA is allowed to use remote Good Clinical Practice (GCP) inspection mechanisms for temporary and emergency use in lieu of in-person inspections. Remote inspections are carried out by means of videoconferencing and data transmission technologies for GCP verification. Remote inspections replace the need for in-person inspectors in the establishment. Establishments under inspection may be inspected remotely at any time by ANVISA.

NormNo122 provides further guidance on ANVISA inspection procedures to ensure drug clinical trials are conducted in compliance with GCPs delineated in ResNo9, the PANDRH-GCPs, and the BRA-28. Per BRA-30, ANVISA’s administrative unit, the Coordination of Clinical Research on Medicines and Biological Products (Coordenação de Pesquisa Clínica em Medicamentos e Produtos Biológicos (COPEC)), requires all clinical trial inspections to be conducted in accordance with BRA-28.

In the event of a routine inspection, NormNo122 states that ANVISA will notify the institution at least 15 calendar days in advance of the visit. Both the sponsor and/or the CRO are responsible for preparing for the inspection. ANVISA shall also notify the principal investigator (PI) of the scheduled visit to the center to be inspected, when applicable, by means of a GCP Inspection Notification Letter. For more detailed information on ANVISA’s inspection process, refer to NormNo122.

ANVISA has also published GuideNo35-2020 and GuideNo36-2020 to provide guidance on the procedures for conducting GCP inspections in clinical trial centers, and provide guidance for sponsors and CROs respectively for clinical trials involving medicines and biological products. Both guides describe ANVISA’s compliance with the GCP inspection requirements set forth in NormNo122 with the goal of guiding those involved in the inspection procedures to ensure a unified standard and the safety of all involved parties.

GuideNo35-2020 and GuideNo36-2020 explain that GCP inspections of sponsors and clinical research organization representatives and in clinical trial centers may be carried out before, during, or after a clinical trial has been conducted and will be classified as either a routine inspection or complaint/suspected irregularity, per NormNo122. In addition, per GuideNo35-2020 and GuideNo36-2020, the inspections will involve at least two (2) ANVISA inspectors, one (1) of whom will be the lead inspector and the focal point for communication with either the clinical trial center or the sponsor/CRO(s). The inspections for both entities will take place over a maximum period of five (5) working days unless the period is altered with due justification. See GuideNo35-2020 and GuideNo36-2020 for additional details.

See ResNo620 for information on the Certification of Good Practices for conducting bioavailability/bioequivalence drug studies and requirements for which bioavailability/bioequivalence drug studies must be carried out in certified research centers.

Premature Study Termination/Suspension

As set forth in ResNo9, the sponsor may cancel or suspend a clinical trial application (Clinical Drug Development Dossier (Dossier de Desenvolvimento Clínico de Medicamento (DDCM))) or a clinical trial, at any time, provided that the appropriate technical-scientific justifications are submitted to ANVISA along with a plan to monitor the research participants in clinical trial(s) that have already begun. Per ResNo9 and the G-DDCMManual, DDCM or clinical trial suspensions and cancellations must be submitted to ANVISA in the form of a secondary petition attached to the previously submitted DDCM or Specific Clinical Trial Dossier (Dossiê Específico de Ensaio Clínico (DEEC)). Refer to the Submission Content section for instructions on submitting a secondary petition to suspend or cancel a DDCM or clinical trial.

ResNo9 and the G-DDCMAmdmts state that the sponsor must notify ANVISA within a maximum period of 15 consecutive days following a decision to suspend or cancel a clinical trial or DDCM. In cases of the temporary suspension of a clinical trial or DDCM as an immediate safety measure, the sponsor must notify ANVISA within seven (7) consecutive days from the suspension date. Per ResNo9, the reasons for suspension, the scope, the interruption of treatment, and the suspension of participant recruitment must be clearly explained in the notification of temporary suspension. As per the G-DDCMAmdmts, in the case of a temporary suspension of a DDCM or a clinical trial protocol, the suspension can be reversed with the submission of a secondary petition to ANVISA. ResNo9 specifies that these requests must be accompanied by due justification so that the trial(s) can be restarted. The clinical trial(s) or DDCM may be reactivated only after approval is obtained by ANVISA. The timeline for ANVISA’s review of these cases is not delineated in ResNo9 or in the G-DDCMAmdmts.

Regarding DDCM cancellations, the G-DDCMAmdmts emphasizes that cancellations, under the terms of ResNo9, are definitive, with no possibility of further reactivation, and that once a DDCM is cancelled, no clinical trial related to it can be continued in the country. In the specific case of a voluntary request to cancel a DDCM, the sponsor must follow the requirements detailed in the AESafetyManual when submitting the follow-up plan and the risk minimization/mitigation measures to protect the participants of clinical trials already underway. A DDCM cancellation can occur even if it has not yet been evaluated. Similarly, clinical trial cancellations are also definitive under ResNo9, with no possibility of further reactivation. The cancellation only applies to clinical trial protocols that have already been initiated by the sponsor. If the protocol is provided for in the DDCM, but has not yet been started, the protocol must be deleted.

In addition, ResNo9 states that ANVISA may, at any time, cancel or suspend a DDCM or any related clinical trial if it believes that the approval conditions have not been met or if there are safety or efficacy reports that significantly affect either the trial participants or scientific validity. In this case, ANVISA will inform the sponsor of the reasons for this cancellation or suspension. Per ResNo9, the sponsor must immediately inform those involved in a clinical trial when it is prematurely cancelled or suspended for any reason. The PANDRH-GCPs also explains that if the sponsor or the CRO chooses, or is required to terminate a study, the investigator(s) should promptly inform the institution. The investigator or institution should also immediately inform the EC (CEP) and provide a detailed explanation of the cancellation or suspension.

5
1, 2, 4, and 5
1, 2, 4, and 5
5.12, 6.1, and 6.19
8
7 and 11
Articles 1-2 and 12
Article 1
Chapters I (Article 6), II (Articles 9-10, 18-20, and 27), VI, and VIII (Article 71)

Data & Records Management

Last content review/update: April 11, 2023

Electronic Data Processing System

Per the PANDRH-GCPs, when using electronic trial data processing systems, the sponsor or the contract research organization (CRO) must ensure that the system conforms to the sponsor’s established requirements for completeness, accuracy, reliability, and consistency of intended performance, and that standard operating procedures (SOPs) are maintained when using these systems. Refer to the PANDRH-GCPs for detailed information on electronic trial data systems.

Records Management

As set forth in ResNo9, the sponsor or the CRO should maintain the clinical trial data on file in physical or digital format for a period of five (5) years after the last approval of a request for registration in Brazil. ResNo9 and the PANDRH-GCPs also state that the sponsor should retain clinical trial data in physical or digital format for at least two (2) years in case of the following instances: the investigational product’s clinical development is discontinued, completion of the registration application is not achieved, a marketing application receives the last approval, or there are no pending or contemplated marketing applications. Per the PANDRH-GCPs, the sponsor should inform the investigator(s) and the institution(s) in writing when trial-related records are no longer needed.

6.5-6.6
Chapters I (Article 6) and II (Article 11)

Personal Data Protection

Last content review/update: April 11, 2023

Responsible Parties

For the purposes of data protection requirements, LawNo13.709 delineates that the sponsor acts as the “controller” who is responsible for decisions regarding the processing of personal or sensitive personal research data. Within this context, the sponsor may carry out studies as a research body, guaranteeing, whenever possible, the anonymization of personal data.

Data Protection

As set forth in C-AmndtNo115, the protection of personal data is a guaranteed fundamental right in Brazil. LawNo13.709 further delineates data protection principles (e.g., purpose, adequacy, necessity, free access, data quality, transparency, security, prevention, non-discrimination, and accountability) with which the sponsor must comply.

Per LawNo13.709, the data quality principle is fulfilled when the sponsor can guarantee to the data subjects that their personal data is processed with accuracy, clarity, and relevance, and is updated as required to meet the compliance requirements for the stated purpose. The sponsor must keep a record of the personal data processing operations carried out, especially when the processing operation is for an official purpose. The sponsor must also provide instructions to the operator, the person responsible for processing the personal data on the sponsor’s behalf, to check compliance with the specified instructions and rules. Additionally, the sponsor is required to protect the confidentiality of the personal data holder and their background. The holder is defined as the person whose personal data are being processed.

LawNo13.709 also provides a definition for sensitive personal data or information that encompasses health related considerations. Sensitive personal data refers to personal data about racial or ethnic origin; religious belief; political opinion; union membership or organization of a religious, philosophical, or political nature; data relating to health or sexual life; and genetic or biometric data, when linked to a natural person.

Pursuant to LawNo13.709, the sponsor may implement a privacy governance program that, at a minimum:

  • Demonstrates the sponsor’s commitment to adopt internal processes and policies that ensure comprehensive compliance with the rules and good practices regarding the protection of personal data
  • Is applicable to the entire set of personal data that are under its control, regardless of the way it was collected
  • Be adapted to the structure, scale, and volume of its operations, as well as to the sensitivity of the processed data
  • Establish adequate policies and safeguards based on a systematic assessment of impacts and risks to privacy
  • Has the objective of establishing a relationship of trust with the holder through transparent action and that ensures participation mechanisms exist for the holder
  • Is integrated into its general governance structure and establishes and applies internal and external supervisory mechanisms
  • Counts on incident response and remediation plans
  • Is constantly updated based on information obtained from continuous monitoring and periodic evaluations

See LawNo13.709 and BRA-76 for detailed information on data protection requirements in Brazil.

Consent for Processing Personal Data

As set forth in LawNo13.709, the processing of sensitive personal data may only be carried out when the holder or the holder’s legal guardian consents, in a specific and obvious way, for the purpose of processing sensitive personal data. The consent must be provided in writing or by another means that demonstrates the holder’s intention. If the consent is provided in writing, it must be included in a separate clause of the other contractual clauses. The sponsor bears the burden of proving that the consent was obtained in accordance with the provisions of this law. The processing of personal data is prohibited by the absence of consent. The consent must refer to specific purposes; generic authorizations for the processing of personal data will be voided. The consent can be revoked at any time by express statement of the holder, by a free and facilitated procedure. If the information is changed, the sponsor must inform the holder and specifically highlight the content of the amendments. In cases where the holder’s consent is required, the holder can revoke consent if opposed to the changes.

In addition, data holders have the right to be informed about the collection and use of their personal data. The data holder is entitled to obtain from the sponsor access to their treated data at any time and upon request. Treatment is defined as any operation performed with personal data. See Chapter III of LawNo13.709 for additional information on the rights of data holders.

See CLNo1-2021 for National Research Ethics Commission (Comissão Nacional de Ética em Pesquisa (CONEP)) guidelines for investigators and ethics committees (Comitês de Ética em Pesquisas (CEPs)) related to contact with research participants (e.g., obtaining informed consent and ensuring confidentiality) and/or data collection at any phase of a research study in a virtual environment. See also CLNo039 for CONEP guidance on accessing and using a participant’s medical records for research purposes while ensuring compliance with privacy and confidentiality standards. The guideline also states that all participants should be treated with dignity, respect for their autonomy, and ensure protection for vulnerable populations.

Consent for Processing Personal Data of Children/Adolescents

Per LawNo13.709, the processing of personal data of children and adolescents must be carried out in their best interest with specific and highlighted consent given by at least one (1) of the parents or the legal guardian. However, the sponsors are permitted to collect personal data from children without the consent of a parent or legal guardian when collection is necessary to contact the parent or legal guardian, used only once and without storage, or for their protection, and in no case may be passed on to a third party without the consent of at least one (1) parent or the legal guardian.

The sponsor must make all reasonable efforts to verify that the consent was given by the individual responsible for the child, considering the available technologies. Additionally, information on the processing of the personal data of children and adolescents must be provided in a simple, clear, and accessible manner, considering the physical-motor, perceptual, sensory, intellectual, and mental characteristics of the user, using audiovisual resources when appropriate, in order to provide the necessary information to the parents or legal guardian, and that is appropriate to the child's level of understanding.

Article 1
Chapter I (Articles 1-2 and 5), Chapter II (Articles 8 and 11), Chapter III, Chapter VI (Articles 37 and 39), and Chapter VII (Article 50)

Documentation Requirements

Last content review/update: April 11, 2023

Obtaining Consent

In all Brazilian clinical trials, a freely given informed consent is required to be obtained from each participant in accordance with the requirements set forth in the PANDRH-GCPs, ResNo466, and the G-ClinResSubjectRts. Per OMREC and G-ClinResSubjectRts, the informed consent form (ICF) is also known as the Free and Informed Consent Form (Termo de Consentimento Livre e Esclarecido (TCLE)) in Brazil.

As per the PANDRH-GCPs, ResNo466, the G-ClinResSubjectRts, and OMREC, the ICF is viewed as an essential document that must be reviewed and approved by an ethics committee (EC) (Comitê de Ética em Pesquisa (CEP)) and provided to the National Health Surveillance Agency (Agência Nacional de Vigilância Sanitária (ANVISA)) with the clinical trial application (Drug Clinical Development Dossier (Dossier de Desenvolvimento Clínico de Medicamento (DDCM))). CLNo51 further clarifies that the ICF should be written as an invitation rather than as a statement as this may reduce the participant’s autonomy. Refer to CLNo51 for detailed information. See the Required Elements section for details on contents to be included in the form.

The PANDRH-GCPs, the G-ClinResSubjectRts, and OMREC state that the investigator, or their designated representative, must provide detailed research study information to the participant and/or the legal representative(s) or guardian(s). As delineated in ResNo466, the PANDRH-GCPs, the G-ClinResSubjectRts, OMREC, and the G-ClinProtocols-FAQs, the ICF content should be presented in a clearly organized format using practical and non-technical language commensurate with the participant’s level of understanding. Per the PANDRH-GCPs and the G-ClinResSubjectRts, neither the investigator nor the research staff should coerce or improperly influence a potential participant to enroll in the clinical trial. The PANDRH-GCPs further explains that none of the oral and written information concerning the research study, including the written ICF, should contain any language that causes the participant or the legal representative(s) and/or guardian(s) to waive or to appear to waive their legal rights, or that releases or appears to release the investigator(s), the institution, the sponsor, or their representatives from their liabilities for any negligence. ResNo466 and the G-ClinResSubjectRts further note that the investigator must bear in mind that the prospective participant's ability to understand the information required to give consent depends on their maturity, ethics, intelligence, education, and cultural beliefs. Per the PANDRH-GCPs, the G-ClinResSubjectRts, and the G-ClinProtocols-FAQs, the information should be in both written and oral form, and the participant and the legal representative(s) or guardian(s) should also be given adequate time to consider whether to participate.

Re-Consent

According to the PANDRH-GCPs and CLNo17, any change in the ICF due to a protocol modification or an alteration in treatment modality, procedures, or site visits, should be approved by the EC (CEP) and submitted to ANVISA before such changes are implemented. Per the PANDRH-GCPs, the G-ClinResSubjectRts, and CLNo51, the investigator must ensure that the participant and/or the legal representative(s) or guardian(s) sign the revised ICF and any other updated information. CLNo17 further notes that changes made to the ICF through separate documents are not considered acceptable. The update requires the investigator to generate a single and complete version of the new document, free of addenda and/or other documents associated with it. The investigator or their delegated representative should also emphasize the changes contained in the updated ICF. The clarifications delineated in CLNo17 also apply to assent forms.

Language Requirements

As earlier stated, the PANDRH-GCPs and the G-ClinResSubjectRts require the ICF to be presented orally and in writing at a level that the participant is able to understand. Per the PANDRH-GCPs, the investigator should provide the ICF in the participant’s own language when they do not speak the language currently spoken in the country. The G-ClinProtocols-FAQs further notes that the ICF must be adequately adapted and be fully revised in Portuguese to ensure that the document is properly translated.

Documenting Consent

The PANDRH-GCPs, the G-ClinResSubjectRts, and OMREC state that the participant and/or the legal representative(s) or guardian(s), and the investigator(s) must sign and date the ICF. In addition, the PANDRH-GCPs explains that if the participant and/or the legal representative(s) or guardian(s) is illiterate, an impartial witness should be present throughout the consent process. At this time, the participant and/or the legal representative(s) or guardian(s) will give verbal, and, if possible, written consent, and the witness should sign and date the form, certifying that the written information was explained accurately and understood.

Before participating in the study, per the PANDRH-GCPs, OMREC, and the G-ClinResSubjectRts, the participant should receive a copy of the signed and dated ICF, and any other written information provided during the informed consent process. ResNo466 and the G-ClinProtocols-FAQs specify that two (2) original copies of the ICF should be prepared with all pages initialed and signed by the participant and/or the legal representative(s) or guardian(s), and the investigator(s) or person(s) overseeing the consent process.

Waiver of Consent

No information is available on consent waivers for research participants. See the Consent for Specimen section information on waivers pertaining a participant’s stored genetic materials.

Introduction (Chart 1), 1.1, 1.19-1.20, and Summary Chart
9 and Annexes C-D
2.6, 3.1, 4.1-4.3, 5.5, and Annex 3
II-IV

Required Elements

Last content review/update: April 11, 2023

Based on the PANDRH-GCPs, ResNo466, and OMREC, the informed consent form (ICF) should include the following statements or descriptions, as applicable (Note: The sources provide overlapping and unique elements so each of the items listed below will not necessarily be in each one):

  • The study purpose, the procedures, and duration of the trial
  • The participant’s responsibilities
  • Experimental aspects of the study
  • The approximate number of participants in the study
  • Any expected risks or discomforts to the participant, and when applicable, to an embryo, fetus, or nursing infant
  • Any expected benefits to the participant; if no benefit is expected, the participant should be informed of this point
  • Treatments available to participants, how they are administered, and the probability of receiving every treatment
  • Compensation and/or treatment available for the participant in the case of trial-related injury
  • The disclosure of specific appropriate alternative procedures or therapies available to the participant
  • The probability for random assignment to each treatment
  • Any expenses the participant needs to pay to participate in the trial
  • Confidentiality of records identifying the participant will be maintained, and permission given to monitors, auditors, the ethics committee(s), and the National Health Surveillance Agency (Agência Nacional de Vigilância Sanitária (ANVISA)) to access the participant’s medical records to verify the procedures or trial data without violating the participant’s confidentiality, insofar as the applicable laws and regulations permit
  • That participation is voluntary, and that the participant can withdraw from the study at any time without penalty or loss of benefits, including medical treatment, to which the participant is otherwise entitled
  • Contact information for the sponsor and investigator in the event of participant problems or trial-related injuries
  • Foreseeable circumstances under which the investigator(s) may remove the participant without consent
  • The consequences of a participant’s decision to withdraw from the research, and procedures for orderly withdrawal by the participant
  • That the participant and/or the legal representative(s) or guardian(s) will be notified in a timely manner if significant new findings develop during the course of the study which may affect the participant's willingness to continue

See the Vulnerable Populations and Consent for Specimen sections for further information.

9 and Annex C
2.6, 3.1.8, 4.3, 5.5, and Annex 3
III-IV

Participant Rights

Last content review/update: April 11, 2023

Overview

In accordance with ResNo466, the PANDRH-GCPs, and OMREC, Brazil’s ethical standards promote respect for all human beings and safeguard the rights of research participants, including rights to their autonomy, culture, beliefs, and values. A participant’s rights must also be clearly addressed in the informed consent form (ICF) and during the informed consent process. (See the Required Elements; Vulnerable Populations; Children/Minors; Pregnant Women, Fetuses & Neonates; Prisoners; and Mentally Impaired sections for additional information regarding requirements for participant rights.)

See CLNo1-2021 for National Research Ethics Commission (Comissão Nacional de Ética em Pesquisa (CONEP)) guidelines for investigators and ethics committees (ECs) (Comitês de Ética em Pesquisas (CEPs)) related to contact with research participants (e.g., obtaining informed consent and ensuring confidentiality) and/or data collection at any phase of a research study in a virtual environment. See also CLNo039 for CONEP guidance on accessing and using a participant’s medical records for research purposes while ensuring compliance with privacy and confidentiality standards. The guideline also states that all participants should be treated with dignity, respect for their autonomy, and ensure protection for vulnerable populations.

The Right to Participate, Abstain, or Withdraw

As set forth in the ResNo466, the PANDRH-GCPs, the G-ClinResSubjectRts, and OMREC, the participant or the legal representative(s) or guardian(s), should be informed that participation is voluntary, that they may withdraw from the research study at any time, and that refusal to participate will not involve any penalty or loss of benefits to which the participant is otherwise entitled.

The Right to Information

As delineated in the ResNo466, the PANDRH-GCPs, the G-ClinResSubjectRts, and OMREC, a potential research participant, and/or the legal representative(s) or guardian(s), has the right to be informed about the nature and purpose of the research study, its anticipated duration, study procedures, any potential benefits or risks, any compensation for participation or injury/treatment, and any significant new information regarding the research study.

The Right to Privacy and Confidentiality

As per the ResNo466, the PANDRH-GCPs, and OMREC, all participants must be afforded the right to privacy and confidentiality, and the ICF must provide a statement that recognizes this right. The PANDRH-GCPs also states that it is the responsibility of the investigator(s) to safeguard the confidentiality of research data to protect the identities and records of research participants.

The Right of Inquiry/Appeal

The PANDRH-GCPs, OMREC, and the G-ClinResSubjectRts explain that the research participant, and/or the legal representative(s) or guardian(s), should be provided with contact information for the sponsor and the investigator(s) to address trial-related inquiries and/or to appeal against a violation of their rights.

The Right to Safety and Welfare

ResNo466 and PANDRH-GCPs clearly state that a research participant’s right to safety and the protection of the participant’s health and welfare must take precedence over the interests of science and society.

9 and Annex C
Chapters 2 and 4
III-IV
Last content review/update: April 11, 2023

As per the PANDRH-GCPs, in an emergency, if the signed informed consent form (ICF) cannot be obtained from the research participant, the consent of the legal representative(s) or guardian(s) should be obtained. If the prior consent of the participant or the legal representative(s) or guardian(s) cannot be obtained, the ethics committee (EC) (Comitê de Ética em Pesquisa (CEP)) must provide documented approval in order to protect the participant’s rights, safety, and well-being, pursuant to the applicable regulations. The participant or the legal representative(s) or guardian(s) should provide consent as soon as possible. OMREC and ResNo251 similarly state that the EC (CEP) is responsible for approving the conditions or limits in which the informed consent should be approved in an emergency situation, and the investigator should inform the research participant in a timely manner about participation in the study.

9
4.3.19
V

Vulnerable Populations

Last content review/update: April 11, 2023

Overview

As per the PANDRH-GCPs and the G-ClinResSubjectRts, in all Brazilian clinical trials, research participants selected from vulnerable populations must be provided additional protections to safeguard their health and welfare during the informed consent process. The PANDRH-GCPs, ResNo466, and the G-ClinResSubjectRts characterize vulnerable populations as those who are relatively (or absolutely) incapable of protecting their own interests due to a lack of autonomy, intelligence, education, resources, strength, or other necessary attributes. These participants may include those with incurable diseases, people in convalescent homes, the unemployed or indigent, patients in emergency situations, ethnic minorities, homeless people, seasonal workers, refugees, minors, and those who cannot give their consent.

The G-ClinResSubjectRts further notes that in general, all individuals including healthy research participants should be seen as intrinsically vulnerable. These participants may currently be exposed to or are at risk of being exposed to an investigational product of unknown safety and efficacy, or one that is not fully understood, which could affect their overall health. In addition, other social, cultural, economic, psychological, or medical factors may adversely affect a participant’s ability to make rational and objective decisions that protect their own interests; however, this factor(s) may not be easily perceptible to the investigator.

The ResNo466 and PANDRH-GCPs specify that ethics committees (ECs) (Comitês de Ética em Pesquisas (CEPs)) must pay special attention to protecting participants who are from vulnerable populations. If the EC (CEP) regularly evaluates studies involving vulnerable populations, it should consider including members or consultants who know or have had experience working with the group in question. ResNo466 and the G-ClinResSubjectRts also state that vulnerable groups should not be included unless the research is necessary to promote the health of the population represented, and this research cannot instead be performed on legally competent participants.

See CLNo1-2021 for National Research Ethics Commission (Comissão Nacional de Ética em Pesquisa (CONEP)) guidelines for investigators and ECs (CEPs) related to contact with research participants (e.g., obtaining informed consent and ensuring confidentiality) and/or data collection at any phase of a research study in a virtual environment. See also CLNo039 for CONEP guidance on accessing and using a participant’s medical records for research purposes while ensuring compliance with privacy and confidentiality standards. The guideline also states that all participants should be treated with dignity, respect for their autonomy, and ensure protection for vulnerable populations.

Indigenous Peoples

As delineated in ResNo304, special attention should be paid when conducting a study involving indigenous peoples in Brazil. Studies involving this population should comply with ethical requirements while also considering the unique qualities of each community. The benefits and advantages resulting from conducting a study with indigenous peoples must also meet the needs of individuals or groups targeted by the study or of related societies, and/or the country as a whole. Investigators should take into account the need to promote and maintain the well-being of participants while protecting and preserving their biological, cultural, individual, and collective health while also contributing to the development of the participants’ knowledge and abilities. Refer to ResNo304 for detailed information on research and protection requirements when conducting a study with this population.

See the Children/Minors; Pregnant Women, Fetuses & Neonates; Prisoners; and Mentally Impaired sections for additional information about these vulnerable populations.

Chapter 3 (3.1-3.2) and Chapter 9
III and V
II-III (2) and IV (6(a))

Children/Minors

Last content review/update: April 11, 2023

The applicable regulatory requirements do not specify the age of minors.

As per PANDRH-GCPs, ResNo466, and OMREC, when the research participant is a child, the child’s legal representative(s) and/or guardian(s) must sign the informed consent form. However, all pediatric participants should be informed to the fullest extent possible about the study in language and terms that they are easily able to understand.

As stated in the G-ClinResSubjectRts, children should only participate in clinical studies when their participation is necessary to promote the health of the population represented.

Assent Requirements

ResNo466 also indicates that an assent form should be used to obtain informed consent from children. The form should be prepared in a language that is accessible to minors or those legally incapable of giving their own consent. After the form is explained and the research study is clarified, the child participants should provide their consent to participate in the study, without the influence of their legal representative(s) or guardian(s).

See the Personal Data Protection section for requirements on processing personal data of children and adolescents.

9
4.3
II and IV

Pregnant Women, Fetuses & Neonates

Last content review/update: April 11, 2023

As per ResNo466, the PANDRH-GCPs, and the G-ClinResSubjectRts, any Brazilian clinical studies involving women of childbearing age or who are pregnant, require additional safeguards to ensure that the participants are fully aware of the risks and that the research assesses the risks and benefits as well as any potential impact on fertility, pregnancy, the embryo or fetus, labor, lactation, and the newborn. ResNo466 further states that research on pregnant women should be preceded by research on women outside the gestational period, except when pregnancy is the fundamental purpose of the study. The investigator(s) should also ensure that female participants have the right to participate in the research without the use of compulsory contraceptives—if they have expressly indicated that they are free from the risk of pregnancy and sexual practices, or they are sexually active in a non-reproductive way.

Annex 3
III
Last content review/update: April 11, 2023

According to the PANDRH-GCPs, prisoners are considered vulnerable because incarceration could affect their ability to make a voluntary decision regarding participation in research. ResNo466 also states that freedom of consent must be guaranteed to those research participants who are fully competent but are exposed to specific constraints or have restricted autonomy. These participants must have the freedom to decide whether to participate without any fear of reprisal.

Chapter 9
IV

Mentally Impaired

Last content review/update: April 11, 2023

According to ResNo466 and the G-ClinResSubjectRts, the ethics committee (Comitê de Ética em Pesquisa (CEP)) must approve the participation of research participants who are mentally or physically incapable of giving consent, and sufficient justification must be provided for involving this population in a study. As delineated in the PANDRH-GCPs, consent should only be provided once the participant is informed about the study, to the extent that the participant is able to understand it, and if able, the participant should sign and date the written informed consent in person. The participant’s legal representative(s) or guardian(s) must also be present during the informed consent process and sign and date the informed consent form.

4.3
IV

Definition of Investigational Product

Last content review/update: April 11, 2023

As delineated in the PANDRH-GCPs, an investigational product (IP) is defined as a dosage form of an active ingredient or placebo that is being tested or used as a reference in a clinical trial. ResNo9, the G-BioIProdManual, and the G-SynthDrugProdManual add that the IP may also be referred to as an experimental drug, comparator, or any other product to be used in a trial. According to BRA-8, the definition of an IP in ResNo9 differs from that of the PANDRH-GCPs because when ResNo9 was adopted, an IP was mainly thought of in relation to the imports required to carry out each clinical trial. For this reason, the definition of “product under investigation” encompasses all products to be used in a trial, including medicine comparators, equipment, and laboratory kits. In addition, the PANDRH-GCPs definition further states that an IP may include a product with a marketing authorization when it is used or assembled (formulated or packaged) in a different way from the approved form, or when it is used to gain further information about an approved use. Note: The terms experimental drug and IP are used interchangeably throughout the profile.

9
11
Chapter 9
Article 6
3.10

Manufacturing & Import

Last content review/update: April 11, 2023

Manufacturing

As stated in ResNo9, the National Health Surveillance Agency (Agência Nacional de Vigilância Sanitária (ANVISA)) is responsible for authorizing the manufacture of investigational products (IPs) in Brazil. ANVISA approves the manufacture of an IP as part of its review and approval of the clinical trial application (Drug Clinical Development Dossier (Dossier de Desenvolvimento Clínico de Medicamento (DDCM))).

ANVISA has also released ServBltnNo104 to expedite the evaluation of clinical drug research development in Brazil without compromising the quality of the technical analysis. (See Scope of Assessment section for details on the criteria for the DDCM to undergo a simplified analysis.) According to ServBltnNo104, the IP manufacturing process must meet the criteria and recommendations described in the current International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH)’s guidelines, as applicable, according to the phase of clinical development. In addition, the technical experts in ANVISA’s Coordination of Clinical Research in Medicines and Biological Products (Coordenação de Pesquisa Clínica em Medicamentos e Produtos Biológicos (COPEC)) require DDCM petitions and substantial quality modifications to meet ServBltnNo104 criteria and be accompanied by the documentation required in ResNo9. COPEC will then analyze the following:

  • The results of stability studies under accelerated and long-term conditions that support the proposed expiration date for the IP and, where applicable, for the modified placebo and comparator, when the storage recommendation is at room temperature (between 15 and 30 degrees Celsius)
  • The sample IP label for DDCM petitions

In the event of non-compliance, COPEC will conduct a non-simplified analysis per ResNo9. ServBltnNo104 further explains that ANVISA may also at any time analyze all the documents required by ResNo9, related to the IP risk analysis. Refer to the Submission Content section for DDCM petitions and substantial quality modifications documentation requirements.

Import

Per ResNo9 and the G-DDCMManual, ANVISA is also responsible for authorizing the import of IPs. The sponsor may request approval to import/export IPs for study purposes at the same time that a DDCM is submitted to ANVISA, as indicated in ResNo9. Following DDCM analysis and approval, ANVISA issues an authorizing document known as a Special Notice (Comunicado Especial (CE)) that may also be used for IP import/export requests for the trial. ANVISA may also issue either a Specific Special Notice (Comunicado Especial Específico (CEE)) to permit the sponsor to import/export an IP while their DDCM is still awaiting review and is within ANVISA’s 90-day approval window, or a Document for Importation of Product(s) under Investigation in the case of non-manifestation of the DDCM. The sponsor is required to present one (1) of these ANVISA documents at the location where IPs for import/export are unloaded. (See Submission Process and Submission Content sections for additional application requirements). See also BRA-103 for detailed instructions on obtaining a drug import license authorization and BRA-102 to check on the status of a petition submission.

BRA-95 provides instructions to sponsors and/or their legal representatives in Brazil on completing the expiration date information for imported IPs in the clinical trial submission form (BRA-22). The expiration date is frequently updated, and is, therefore, often linked to inconsistencies and requests for clarification of requirements by those responsible for importing drugs and products for clinical trials. See BRA-95 for detailed information on stability requirements and instructions on completing the form.

ResNo208 (amending ResNo81) and ResNo613 (amending ResNo172) delineate the procedures associated with importing IPs for clinical research purposes following ANVISA’s approval of a DDCM. Pursuant to ResNo74, the process involves electronically submitting ANVISA’s Industry Petition Form (BRA-71) to the Integrated Foreign Trade System (SISCOMEX)’s Single Portal (BRA-80). ResNo81 explains that the following documentation must be included with the petition:

  • Copy of the CE (Note: per ResNo9, other ANVISA authorizations may need to be included as well—i.e., CEE and Document for Importation of Product(s) under Investigation)
  • Shipment document (Includes shipment date, proof of IP deposit to the importer, and carrier/transportation type: Airborne Cargo - Air Waybill (AWB), Aquatic Cargo - Bill Landing (BL), and Land Cargo – Knowledge of International Transport by Highway (CTR))
  • Access inspection authorization
  • Commercial invoice
  • Finished product analysis certificate or copy of IP purchase invoice, specifying all lots; and statement signed by technical manager containing number of lots, IP active ingredient name and trade name if IP is produced by a manufacturer other than the importer/clinical study sponsor

See ResNo81 for detailed import documentation requirements. See also BRA-8 for frequently asked questions on importation requirements and BRA-87 for additional information on BRA-80.

Per ResNo172, investigators accredited by the National Council for Scientific and Technological Development ((Conselho Nacional de Desenvolvimento Científico e Tecnológico) (CNPq)) and whose tax regime is exempt, will be automatically granted an import license via BRA-80.

However, ResNo172 specifies that imports intended for clinical trials whose objective is registration or alteration of product registration will be analyzed within five (5) days after protocol approval and compliance with legal requirements.

Other requirements delineated in ResNo81 and ResNo172 include, but are not limited to, a prohibition on imports with accompanied and unaccompanied baggage; compliance with packaging, transportation, and storage standards provided by manufacturer or supplier; and a mandate that once research is completed, the investigator or institution authorize final destination of the materials in accordance with the legal provisions of environmental control.

LawNo10.742 (amending LawNo6.360) also notes that new drugs, intended exclusively for experimental use and under medical supervision, may be imported with the express authorization of the Ministry of Health (MOH) and are exempted from registration. This exemption will only be valid for up to three (3) years. Following this period, the product must be registered or be subject to a penalty of seizure to be determined by the MOH.

In addition, per ResNo102, in the case of a company requesting a global transfer of ownership for product registration or the updating of company operation and certification data as a result of corporate transactions or business operations, the CE, CEE, or Document for Importation of Product(s) under Investigation will be issued in the name of the new company. Company registration updates should include any changes to the company operating authorization, Good Manufacturing Practices Certificate (CBPF), or Good Distribution and Storage Practices Certificate (CBPDA). Please refer to ResNo102 for detailed instructions on submitting appropriate documentation for these updates. See also the Submission Process section for detailed information on documentation to be submitted.

Per BRA-96, ANVISA has also modified the global transfer of responsibility request process for a clinical trial or assistance program for medicines and biological products. The requests must be carried out electronically by the company that has requested the transfer via BRA-38 using the DDCM petition’s subject code 12130 for medicines and 11795 for advanced therapy products. See BRA-96 for additional information.

In addition, per BRA-55, ANVISA, is a member of the Pharmaceutical Inspection Co-operation Scheme (PIC/S). Per BRA-100, as a PIC/S member, ANVISA meets internationally harmonized good manufacturing practices (GMP) inspection standards and quality systems of inspectorates in the field of medicinal products for human or veterinary use. Refer to BRA-55 for additional information.

Advanced Therapy Products

Per BRA-86 and BRA-94, ANVISA has also initiated a project for applicants to request an import license for advanced therapy products to be used for clinical research or commercial/industrial purposes. The process involves registering an import license through the Licenses, Permissions, Certificates and Other Documents (LPCO) module of BRA-80, and attaching the ANVISA import license petition to this application—which is obtained using ANVISA’s Electronic Petition Request System (BRA-38). See G-LPCOImprtPetition for additional information on filing an import license petition for an advanced therapy product with ANVISA. Per ResNo506, advanced therapy products refer to medicines for human use that are based on genes, tissues, or cells. Refer to ResNo506 for information on ANVISA’s role in reviewing and approving clinical trial applications submitted for studies using advanced therapy products. See also BRA-104 for detailed instructions on submitting an import license petition to ANVISA through LPCO.

Per ResNo172, ANVISA will analyze and release imported goods and products intended for use in human subjects research within 48 hours after arrival in Brazil, provided that the legal requirements are met and that the purpose of the research is not to register or change the registration of a product. Also specified in ResNo208 (amending ResNo81) and ResNo613 (amending ResNo172), is the requirement that the investigator and institution submit the imported products through one (1) of the following methods: BRA-80 or Express Shipping. While each import option has different documentation requirements, they all require the submission of an Industry Petition Form (BRA-71), a commercial invoice, a signed statement of responsibility (see ResNo81 (Chapter XXVII) and ResNo172 (Annex I)), ethics committee (EC) (Comitê de Ética em Pesquisa (CEP)) approval, and where applicable, National Research Ethics Commission (Comissão Nacional de Ética em Pesquisa (CONEP)) approval. Refer to ResNo81 for additional required items based on the import method used.

Please note: Brazil is party to the Nagoya Protocol on Access and Benefit-sharing (BRA-63), which may have implications for studies of IPs developed using certain non-human genetic resources (e.g., plants, animals, and microbes). For more information, see BRA-81.

What is PIC/S?
3.4
7
Article 24
Article 24
Chapters I (Article 1), II, III (Section III), and V, and Annex I
Articles 3-4 and 16
Chapter I (Articles 1, 2, and 4), II (Articles 7 and 15), and III-IV
Chapters I (1.9), II (1.2), III (Sections I-IV), XXII, XXVI (Sections I and V), XXVII, and XXXI
Chapters I (Article 6), III (Articles 34-36 and 38), IV (Article 43), and IX
Chapters I, II (Sections II and III), and IV, and Annex I

Quality Requirements

Last content review/update: April 11, 2023

Investigator's Brochure

In accordance with ResNo9, the PANDRH-GCPs, and the G-DDCMManual, the sponsor is responsible for providing investigators with an Investigator’s Brochure (IB). ResNo9 and the G-DDCMManual state that the IB must provide coverage for the following areas:

  • Experimental drug
  • Formulation
  • Pharmacological and toxicological effects of the experimental drug in animals and in humans, where applicable
  • Information on safety and efficacy in humans obtained from clinical trials that have already been carried out
  • Possible risks and adverse events related to experimental medications, based on past experience, as well as precautions or special procedures to be followed during development

The sponsor should also update the IB as significant new information becomes available.

Quality Management

The G-DDCMManual, the G-BiolProdManual, and BRA-8 further explain that the sponsor must include manufacturing process information in the Experimental Drug Dossier as part of the clinical trial application (Drug Clinical Development Dossier (Dossier de Desenvolvimento Clínico de Medicamento (DDCM))) submission as described in ResNo9. Please refer to ResNo9, the G-DDCMManual, and the G-BiolProdManual for additional experimental drug dossier requirements.

As specified in ResNo9 and the PANDRH-GCPs, the sponsor must also ensure that the products are manufactured in accordance with the Good Manufacturing Practices (GMPs) as laid down in ResNo301. In addition, per ResNo205, the DDCM submitted to National Health Surveillance Agency (Agência Nacional de Vigilância Sanitária (ANVISA)) to conduct a clinical trial using investigational products for rare diseases should also be accompanied by a request for GMPs certification. See ResNo205 for detailed submission information.

3.1 and 3.3
Chapter 6 (6.6.3, 6.12.2, 6.13-6.14) and Annex 5 (1)
6.2-6.3
2 and 5.3
Articles 1 and 12-13
Chapter II
Articles 14, 38, 43, and 72
Last content review/update: April 11, 2023

Investigational product (IP) labeling in Brazil must comply with the requirements set forth in ResNo9, the PANDRH-GCPs, and the G-BiolProdManual. As described in the G-BiolProdManual, the following labeling information must be included on the primary package label (or any intermediate packaging), and the outer packaging:

  • Sponsor name
  • Pharmaceutical form, route of administration, quantity of dosage units, and the drug name and concentration in the case of open studies
  • Batch or product identification code
  • Clinical trial reference code
  • Clinical trial participant identification code
  • Instructions for use (reference may be made to an explanatory pamphlet or other document that guides the trial participants or person administering the IP
  • Storage conditions
  • Expiration date
  • Warning phrases in capital letters such as: “EXCLUSIVE USE IN CLINICAL TRIALS” and “KEEP OUT OF REACH OF CHILDREN”

In addition, per the G-BiolProdManual, all of the text labeling must be written in Portuguese. Symbols, pictograms, and warnings may also be included on both the primary and outer packaging. The G-BiolProdManual further notes it is not necessary to include the primary contact’s address and telephone number on the label to obtain IP or clinical trial information, or to break the blinding code. The trial participant receives a leaflet or card containing contact information in the case of trial-related concerns or adverse events. If the expiration date changes, additional labeling may be superimposed on the previous label to update the shelf life so that the new information does not conflict with the original batch number. The G-BiolProdManual mentions that the labeling of the other study IPs should also follow the same model as the experimental product, and when any field(s) is not applicable, justification should be provided.

The PANDRH-GCPs further indicates that the IP should be coded and labeled in a manner that protects the blinding, if applicable, and be suitably packaged to prevent contamination and unacceptable deterioration during transport and storage. BRA-8 adds that while a label template is requested for each clinical trial application (Clinical Drug Development Dossier (Dossier de Desenvolvimento Clínico de Medicamento (DDCM))) submission, if the label template differs between studies in a multicenter clinical trial, a note should be included in the DDCM to explain that separate templates will be provided for the specific dossiers.

As described in ResNo9, the following external packaging information must also be provided with the IP to be imported into Brazil:

  • Special Notice (CE), Specific Special Notice (CEE), or Document for Importation of Product(s) under Investigation
  • IP quantity
  • Special storage precautions (e.g., temperature, humidity, and brightness)
  • IP physical/pharmaceutical form
  • Period of validity of the IP
  • Batch number or serial number

The following IP packaging requirements are also delineated in the G-BiolProdManual:

  • Provide technical specifications for primary, and where applicable, outer packaging
  • Include an assessment of possible interaction between the active substance and primary packaging, if applicable
  • Describe how the tamper resistance of the packaging will be guaranteed until the time of IP use
6.3 and 10
Chapter 6 (6.13) and Annex 5 (1)
Articles 6, 14, 38, and 75
3.3.2

Product Management

Last content review/update: April 11, 2023

Supply, Storage, and Handling Requirements

As delineated in ResNo9 and the PANDRH-GCPs, the sponsor must also supply the investigator(s)/institution(s) with the investigational product(s) (IP), including the comparator(s) and placebo, if applicable. The sponsor is responsible for importing the necessary IP amount to conduct the study, but should only distribute the IP to institutions that are listed in the approved clinical trial application (known as the Drug Clinical Development Dossier (Dossier de Desenvolvimento Clínico de Medicamento (DDCM))) as authorized by the ethics committee (EC) (Comitê de Ética em Pesquisa (CEP)) and the National Health Surveillance Agency (Agência Nacional de Vigilância Sanitária (ANVISA)). Following DDCM analysis and approval, ANVISA issues an authorizing document known as a Special Notice (Comunicado Especial (CE)) that may also be used for IP import/export requests for the trial. ANVISA may also issue either a Specific Special Notice (Comunicado Especial Específico (CEE)) to permit the sponsor to import/export an IP while their DDCM is still awaiting review and is within ANVISA’s 90-day approval window, or a Document for Importation of Product(s) under Investigation in the case of non-manifestation of the DDCM. The sponsor is required to present one (1) of these ANVISA documents at the location where IPs for import or export are unloaded. (See the Submission Process and Submission Content sections for detailed application requirements).

Per ResNo9 and the PANDRH-GCPs, the sponsor must ensure that the qualitative information and specifications include the following:

  • IP product quality and stability over the period of use
  • IP manufactured according to good manufacturing practices (GMPs) as per ResNo9 and ResNo301
  • Proper coding, packaging, and labeling of the IP(s)
  • IP use record including information on the quantity, loading, shipment, receipt, dispensing, handling, reclamation, and destruction of the unused IP
  • Acceptable storage temperatures, conditions, and times for the IP
  • Written procedures including instructions for handling and storage of the IP, adequate and safe receipt, dispensing, retrieval of unused IP(s), and return of unused IP(s) to the sponsor
  • Timely delivery of the IP(s)
  • Establishment of management and filing systems for the IPs

See ResNo9 and PANDRH-GCPs for detailed sponsor-related IP requirements.

In addition, per BRA-55, ANVISA, is a member of the Pharmaceutical Inspection Co-operation Scheme (PIC/S). Per BRA-100, as a PIC/S member, ANVISA meets internationally harmonized GMP inspection standards and quality systems of inspectorates in the field of medicinal products for human or veterinary use. Refer to BRA-55 for additional information.

Record Requirements

Per the PANDRH-GCPs, the sponsor is required to maintain records that document shipment, receipt, disposition, return, and destruction of the IPs. The sponsor must also maintain a system for retrieving IPs and documenting this retrieval and maintain a system for the disposition of unused IPs. Additionally, the sponsor should maintain sufficient samples from each batch and keep a record of their analyses and characteristics for reference so that, if necessary, an independent laboratory could reconfirm the same data.

The sponsor should inform the investigator(s) and institution(s) in writing of the need for record retention and should notify the investigator(s) and institution(s) in writing when the trial-related records are no longer needed. Sponsor-specific essential documents should also be retained until at least two (2) years after the last approval of a marketing application, until there are no pending or contemplated marketing applications, or at least two (2) years have elapsed since the formal discontinuation of the IP’s clinical development.

Chapter 6 (6.12.2 and 6.13-6.14) and Annex 5 (1)
Chapter II
Articles 14-17 and 38
What is PIC/S?

Definition of Specimen

Last content review/update: April 11, 2023

As per OrdNo2201, ResNo504, ResNo441, and the G-BiolMatTransprt, a specimen is defined as any human biological material such as organs, tissues, cells, body fluids, excreta, and other fluids of human origin obtained from a single participant at a particular time. ResNo508 adds that these biological samples are intended to be used for laboratory or quality control tests.

In addition, the G-BiolMatTransprt states that these materials are not considered hazardous if they are unlikely to cause disease in humans or animals. However, they are considered infectious substances, therefore dangerous materials, if through exposure to them, these substances can spread diseases.

2
Article 3
Article 1 (1)
Chapter I (Article 3)
Chapter I (Article 7)

Specimen Import & Export

Last content review/update: April 11, 2023

ResNo208 (amending ResNo81) and ResNo613 (amending ResNo172) delineate the procedures associated with importing human biological materials for clinical research purposes. Pursuant to ResNo74, the process involves electronically submitting National Health Surveillance Agency (Agência Nacional de Vigilância Sanitária (ANVISA))’s Industry Petition Form (BRA-71) to the Integrated Foreign Trade System (SISCOMEX)’s Single Portal (BRA-80). To obtain an import license through BRA-80, ResNo208 (amending ResNo81), and ResNo613 (amending ResNo172) specify that the investigator and institution should submit the imported human biological materials through one (1) of the following methods: BRA-80 or Express Shipping. ResNo81 and ResNo172 explain that the following documentation must be included with the petition form:

  • Shipment document (Includes shipment date, proof of investigational product (IP) deposit to the importer, and carrier/transportation type: Airborne Cargo - Air Waybill (AWB), Aquatic Cargo - Bill Landing (BL), or Land Cargo - Knowledge of International Transport by Highway (CTR))
  • Inspection authorization
  • Commercial invoice
  • Bill of lading
  • Signed statement of responsibility (see ResNo81 (Chapter XXVII) and ResNo172 (Annex I))
  • Ethics committee (EC) (Comitê de Ética em Pesquisa (CEP)) approval, and where applicable, National Research Ethics Commission (Comissão Nacional de Ética em Pesquisa (CONEP)) approval

See ResNo81 for detailed import documentation requirements. See also BRA-8 for frequently asked questions on importation requirements and BRA-87 for additional information on BRA-80.

ResNo172 further notes that an import license may be automatically granted via BRA-80 to investigators accredited by the National Council for Scientific and Technological Development ((Conselho Nacional de Desenvolvimento Científico e Tecnológico) (CNPq)) and whose tax regime is exempt.

ResNo172 also states that ANVISA will analyze and release human biological samples intended for use in clinical research within 48 hours after arrival in Brazil, provided that the legal requirements are met. Refer to ResNo81 and ResNo172 for additional required items depending on the import method used.

Other requirements described in ResNo81 and ResNo172 include, but are not limited to, compliance with packaging, transportation, and storage standards provided by manufacturer or supplier; a mandate that the investigator or institution provide a final destination for the materials in accordance with the legal provisions of environmental control; and in ResNo172, a prohibition on imports with accompanied and unaccompanied baggage.

As explained in ResNo504 and the G-BiolMatTransprt, the procedures for the import and export of human biological material should be determined by the biological material type and the mode of transport. Regardless of the mode of transport or material type, transport operations are required to be recorded and standardized through regularly updated written instructions. All documents and records of activities relating to human biological material transport equipment should be readily available to the health authorities, upon request. The biological material must be packed in a form that will preserve its integrity and stability and must be validated and approved by the supervisory technician.

According to ResNo504, human biological material is classified as Category A or B infectious biological material, or Category Risk Minimum. Category A includes materials where exposure can cause permanent disability or fatal disease to humans and animals. Category B includes those materials not listed in Category A such as samples suspected or known to contain infectious agents causing diseases in humans. Category Risk Minimum or “exempt human specimens” include biological materials from healthy individuals. Human biological materials must also be classified according to the World Health Organization (WHO)’s risk classification diagram available in the WHO’s Guidance on Regulations for the Transport of Infectious Substances (BRA-54). Labeling should conform to the material type, risk classification, and specific requirements of the biological materials to be transported. The label for imported materials must be legible, understandable, and in English and Portuguese.

In addition to complying with ResNo504 and the G-BiolMatTransprt, human biological material transport should be conducted in accordance with legislation from applicable regulatory bodies including the Ministry of Infrastructure, the National Land Transportation Agency, the National Civil Aviation Agency, and the National Agency for Waterway Transport. Refer to the G-BiolMatTransprt for detailed import and export transport requirements.

Refer to ResNo504 and the G-BiolMatTransprt for detailed instructions on shipping biological materials within these categories. See also ResNo508 for detailed transport requirements relating to human cells and advanced therapy products, and BRA-97 for preparing reports on biobanking for research purposes.

4-8
Chapters I (Article 1), II (Sections III and VI), and IV (Articles 20-21 and 23), and Annex I
7.3
Chapter I (Sections I and II) and II-VI
Chapter I (Articles 3 and 6-7) and Chapter III (Section VIII)
Articles 1 and 2
Chapters I (1.9), II (1.2), III (Sections I-III), XXIII-XXVI (Sections IV and V), and XXVII

Requirements

(Bulletin) Service Bulletin No. 104 - Document Analysis Procedures Required for DDCM Petitions and Modifications that Potentially Impact Experimental Drug, Active Comparator or Placebo Quality/Safety (ServBltnNo104 - Portuguese) (Effective June 21, 2021)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Circular) Circular Letter 060/2012 - CONEP Notice on Citation of Clinical Trial Registries in Research Protocols (CLNo060 - Portuguese) (May 5, 2012)
National Research Ethics Commission (CONEP), National Health Council (CNS)
(Circular) Circular Letter No. 038/2014 - Processing of Amendments in the CEP/CONEP System (CLNo038 - Portuguese) (March 12, 2014)
National Research Ethics Commission (CONEP), National Health Council (CNS)
(Circular) Circular Letter No. 040/2015 - Investigator Brochure Processing via Plataforma Brasil (PB) (CLNo040 - Portuguese) (March 27, 2015)
National Research Ethics Commission (CONEP), National Health Council (CNS)
(Circular) Circular Letter No. 041/2015 - Guidance on CNS Resolution 340 of 2004 (Item V.1.a) (CLNo041 - Portuguese) (March 27, 2015)
National Research Ethics Commission (CONEP), National Health Council (CNS)
(Circular) Circular Letter No. 046/2015 - Research Center Inclusion/Exclusion Requirements When Submitting Responses to Pending CONEP Issues (CLNo046 - Portuguese) (April 15, 2015)
National Research Ethics Commission (CONEP), National Health Council (CNS)
(Circular) Circular Letter No. 1/2021 - Guidelines for Research Procedures with Any Step in a Virtual Environment (CLNo1-2021 - Portuguese) (March 3, 2021)
National Research Ethics Commission (CONEP), Executive Secretariat of the National Health Council (CNS)
(Circular) Circular Letter No. 1/2022 - Use of an Electronic Mail System (E-mail) to Send Administrative Documents from Research Ethics Committees (CEP) (CLNo1-2022 - Portuguese) (February 7, 2022)
National Research Ethics Commission (CONEP), Executive Secretariat of the National Health Council (CNS)
(Circular) Circular Letter No. 13/2020 - CONEP Requirements for the Processing of Adverse Events in the CEP/CONEP System (CLNo13 - Portuguese) (June 2, 2020)
National Research Ethics Commission (CONEP), Executive Secretariat of the National Health Council (CNS)
(Circular) Circular Letter No. 17/2017 - Informed Consent Form Update Requirements (CLNo17 - Portuguese) (July 26, 2017)
National Research Ethics Commission (CONEP), National Health Council (CNS)
(Circular) Circular Letter No. 172/2017 - Clarifications Regarding the Selection of Thematic Area (CLNo172 - Portuguese) (April 20, 2017)
National Research Ethics Commission (CONEP), National Health Council (CNS)
(Circular) Circular Letter No. 51/2017 - Additional Clarifications on ICF Text (CLNo51 - Portuguese) (September 28, 2017)
National Research Ethics Commission (CONEP), National Health Council (CNS)
(Guidance) Good Clinical Practices - Document of the Americas (PANDRH-GCPs - Portuguese) (March 2005)
Pan American Health Organization
(Guidance) Guidance Manual: Frequent Pending Issues in Clinical Research Protocols (Version 1.0) (G-ClinProtocols-FAQs - Portuguese) (2015)
National Research Ethics Commission (CONEP), National Health Council (CNS)
(Guidance) Guidance on the Rights of Research Subjects (G-ClinResSubjectRts - Portuguese) (Version 1.2) (March 24, 2016)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Guidance) Health Surveillance Manual on the Transport of Human Biological Material for Clinical Diagnostic Purposes (G-BiolMatTransprt - Portuguese) (2015)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Guidance) Good Clinical Practice (GCP) Inspection Guide for Clinical Trials with Drugs and Biological Products - Inspection in Clinical Trial Centers (GuideNo35-2020 - Portuguese) (Version 2) (Effective January 27, 2022)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Guidance) Good Clinical Practice (GCP) Inspection Guide for Clinical Trials with Drugs and Biological Products - Inspection of Sponsors and Clinical Research Organization Representatives (ORPC) (GuideNo36-2020 - Portuguese) (Version 2) (Effective January 27, 2022)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Guidance) Manual for Notification of Adverse Events and Safety Monitoring in Clinical Trials (AESafetyManual - Portuguese) (1st Edition) (2016)
General Management of Medicines (GGMED), Coordination of Clinical Research in Medications and Biological Products (COPEC), National Health Surveillance Agency (ANVISA)
(Guidance) Manual for Submission of Drug Clinical Development Dossier (DDCM) and Specific Dossier for Clinical Trial (G-DDCMManual - Portuguese) (English-G-DDCMManual - Google Translation) (3rd Edition) (2017)
General Management of Medicines (GGMED), Coordination of Clinical Research in Medicines and Biological Products (COPEC), National Health Surveillance Agency (ANVISA)
(Guidance) Manual for Submission of Modifications, Amendments, Suspensions and Cancellations (G-DDCMAmdmts - Portuguese) (5th Edition) (April 26, 2021)
General Management of Medicines (GGMED), Coordination of Clinical Research in Medicines and Biological Products (COPEC), National Health Surveillance Agency (ANVISA)
(Guidance) Manual for Submission of Monitoring Reports and Clinical Trial Start and End Forms (G-CTReptsManual - English, unofficial translation) (Portuguese) (1st Edition) (2016)
General Management of Medicines (GGMED), Coordination of Clinical Research in Medicines and Biological Products (COPEC), National Health Surveillance Agency (ANVISA)
(Guidance) Operating Manual for Research Ethics Committees (OMREC - Portuguese) (4th Edition revised and updated) (2008)
National Research Ethics Commission (CONEP), National Health Council (CNS)
(Guidance) Operational Standard No. 001/2013 - CEP/CONEP System Organization, Functions and Procedures (OSNo001) (Portuguese) (September 30, 2013)
National Health Council (CNS), Ministry of Health
(Guidance) Operational Standard No. 01/2012 - Process Flow of National Multicenter Projects: Coordinating Center (OSNo01 - Portuguese) (March 7, 2012)
National Health Council (CNS), Ministry of Health
(Guidance) Primer: Import License Petition through LPCO (G-LPCOImprtPetition - Portuguese) (Version 4.8) (March 22, 2023)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Guidance) Quality Data Submission Manual for Research Products Used in Clinical Trials - Synthetic and Semisynthetic Medicines (G-SynthDrugProdManual - Portuguese) (3rd Edition) (2019)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Guidance) Quality Data Submission Manual for Research Products Used in Clinical Trials – Biological Products (G-BiolProdManual - Portuguese) (3rd Edition) (2019)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Guidance) Standard Procedures No. 006 - Evaluation of Research Ethics Committees (SP006REC - Portuguese) (October 1, 2009)
National Health Council (CNS), Ministry of Health
(Legislation) Constitutional Amendment No. 115 of February 10, 2022 (C-AmndtNo115 - Portuguese) (February 10, 2022)
National Congress
(Legislation) Law No. 10.742 of October 6, 2003 (LawNo10.742 - Portuguese) (Effective October 6, 2003)
Federative Republic of Brazil
(Legislation) General Law for the Protection of Personal Data (Law No. 13.709) (LawNo13.709 - Portuguese) (Effective August 14, 2020)
Federative Republic of Brazil
(Legislation) Law No. 6.360 of September 23, 1976 (LawNo6.360 - Portuguese) (Effective December 27, 1976)
Federative Republic of Brazil
(Legislation) Law No. 9.782 of January 26, 1999 (LawNo9.782 - Portuguese) (Effective January 26, 1999)
Federative Republic of Brazil
(Regulation) CNS Resolution No. 292 of July 8, 1999 (ResNo292 - Portuguese) (July 8, 1999)
National Health Council (CNS), Ministry of Health
(Regulation) CNS Resolution No. 304 of August 9, 2000 (ResNo304) (Portuguese) (August 9, 2000)
National Health Council (CNS), Minister of Health
(Regulation) CNS Resolution No. 340 of July 8, 2004 (ResNo340) (Portuguese) (July 8, 2004)
National Health Council (CNS), Ministry of Health
(Regulation) CNS Resolution No. 346 of January 13, 2005 (ResNo346 - Portuguese) (January 13, 2005)
National Health Council (CNS), Minister of Health
(Regulation) CNS Resolution No. 370 of March 8, 2007 (ResNo370 - Portuguese) (March 8, 2007)
National Health Council (CNS), Ministry of Health
(Regulation) CNS Resolution No. 441 of May 12, 2011 (ResNo441 - Portuguese) (May 12, 2011)
National Health Council (CNS), Ministry of Health
(Regulation) CNS Resolution No. 446 of August 11, 2011 (ResNo446 - Portuguese) (Effective August 29, 2011)
National Health Council (CNS), Ministry of Health
(Regulation) CNS Resolution No. 466 of December 12, 2012 (ResNo466 - Portuguese) (Effective June 13, 2013)
National Health Council (CNS), Ministry of Health
(Regulation) CNS Resolution No. 506 of February 3, 2016 (CNSResNo506 - Portuguese) (Effective March 23, 2016)
National Health Council (CNS), Ministry of Health
(Regulation) CNS Resolution No. 563 of November 10, 2017 (ResNo563 - English, unofficial translation) (Portuguese) (November 10, 2017)
National Health Council (CNS), Ministry of Health
(Regulation) CNS Resolution No. 580 of March 22, 2018 (ResNo580 - Portuguese) (March 22, 2018)
National Health Council (CNS), Ministry of Health
(Regulation) CNS Resolution No. 251 of August 7, 1997 (ResNo251 - Portuguese) (August 7, 1997)
National Health Council (CNS), Ministry of Health
(Regulation) CNS Resolution No. 647 of October 12, 2020 (ResNo647 - Portuguese) (October 12, 2020)
National Health Council (CNS), Ministry of Health
(Regulation) Interministerial Ordinance No. 45, of January 27, 2017 (OrdNo45 - Portuguese) (Effective February 9, 2017)
Ministry of Finance
(Regulation) Normative Instruction No. 122 of March 9, 2022 (NormNo122 - Portuguese) (Effective April 1, 2022)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Regulation) Ordinance GM/MS No. 913 of April 22, 2022 (OrdNo913 - Portuguese) (Effective May 22, 2022)
Ministry of Health
(Regulation) Ordinance No. 188 of February 3, 2020 (OrdNo188 - Portuguese) (February 3, 2020)
Ministry of Health
(Regulation) Ordinance No. 2201 of September 14, 2011 (OrdNo2201 - Portuguese) (September 14, 2011)
Ministry of Health
(Regulation) Ordinance No. 552 of March 9, 2007 (OrdNo552 - Portuguese) (March 9, 2007)
Ministry of Health
(Regulation) Resolution of the Collegiate Board - RDC No. 504 of May 27, 2021 (ResNo504 - Portuguese) (Effective July 1, 2021)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Regulation) Resolution of the Collegiate Board - RDC No. 506 of May 27, 2021 (ResNo506 - Portuguese) (Effective July 1, 2021)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Regulation) Resolution of the Collegiate Board - RDC No. 508 of May 27, 2021 (ResNo508 - Portuguese) (Effective July 1, 2021)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Regulation) Resolution of the Collegiate Board - RDC No. 573 of October 29, 2021 (ResNo573 - Portuguese) (Effective October 29, 2021)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Regulation) Resolution of the Collegiate Board of Directors - RDC No. 620 of March 9, 2022 (ResNo620 - Portuguese) (Effective April 1, 2022)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Regulation) Resolution of the Collegiate Board – RDC No. 613 of March 9, 2022 (ResNo613 - Portuguese) (Effective April 1, 2022)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Regulation) Resolution of the Collegiate Board - RDC No. 102 of August 24, 2016 (ResNo102 - Portuguese) (GoogleTranslate-ResNo102) (Effective December 22, 2016)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Regulation) Resolution of the Collegiate Board - RDC No. 176 of September 15, 2017 (ResNo176 - Portuguese) (Effective September 19, 2017)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Regulation) Resolution of the Collegiate Board - RDC No. 198 of December 26, 2017 (ResNo198 - Portuguese) (Effective December 28, 2017)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Regulation) Resolution of the Collegiate Board - RDC No. 204 of December 27, 2017 (ResNo204 - Portuguese) (English-ResNo204 - Google Translation) (Effective February 25, 2018)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Regulation) Resolution of the Collegiate Board - RDC No. 205 of December 28, 2017 (ResNo205 - Portuguese) (GoogleTranslate-ResNo205) (Effective February 27, 2018)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Regulation) Resolution of the Collegiate Board - RDC No. 208 of January 5, 2018 (ResNo208 - Portuguese) (Effective January 8, 2018)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Regulation) Resolution of the Collegiate Board - RDC No. 301 of August 21, 2019 (ResNo301 - Portuguese) (Effective June 8, 2020)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Regulation) Resolution of the Collegiate Board - RDC No. 38 of August 12, 2013 (ResNo38 - Portuguese) (Effective August 13, 2013)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Regulation) Resolution of the Collegiate Board - RDC No. 449 of December 15, 2020 (ResNo449 - Portuguese) (Effective December 17, 2020)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Regulation) Resolution of the Collegiate Board - RDC No. 74 of May 2, 2016 (ResNo74 - Portuguese) (Effective May 3, 2016)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Regulation) Resolution of the Collegiate Board - RDC No. 76 of October 23, 2008 (ResNo76 - Portuguese) (Effective October 27, 2008)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Regulation) Resolution of the Collegiate Board - RDC No. 81 of November 5, 2008 (ResNo81 - Portuguese) (Effective November 5, 2008)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Regulation) Resolution of the Collegiate Board - RDC No. 9 of February 20, 2015 (ResNo9 - Portuguese) (Effective March 3, 2015)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Regulation) Resolution of the Collegiate Board – RDC No. 172 of September 8, 2017 (ResNo172 - Portuguese) (Effective October 12, 2017)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Regulation) Resolution of the Collegiate Board – RDC No. 222 of December 28, 2006 (ResNo222 - Portuguese) (Last Amended December 26, 2017)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Regulation) Resolution of the Collegiate Board – RDC No. 61 of February 3, 2016 (ResNo61 - Portuguese) (Effective February 5, 2016)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Regulation) Resolution of the Collegiate Board - RDC No. 311 of October 10, 2019 (ResNo311 - Portuguese) (Effective October 16, 2019)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Regulation) Resolution of the Collegiate Board - RDC No. 763 of November 25, 2022 (ResNo763 - Portuguese) (GoogleTranslate-ResNo763) (Effective December 1, 2022)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Circular) Circular Letter No. 34/2021 – New Guidelines for Processing Biobank Development Research Protocols through the Current Version of Plataforma Brasil (CLNo34 – Portuguese) (December 9, 2021)
National Research Ethics Commission (CONEP), Executive Secretariat of the National Health Council (CNS)
(Circular) Circular Letter No. 26/2022 – Guidelines for Studies with Human Bodies or Anatomical Parts (CLNo26 – Portuguese) (December 1, 2022)
National Research Ethics Commission (CONEP), Executive Secretariat of the National Health Council (CNS)
(Circular) Circular Letter No. 23/2022 - Standardization of the Use of Consent and Electronic Assent for Research Participants and Biobanks (CLNo23 – Portuguese) (October 17, 2022)
National Research Ethics Commission (CONEP), Executive Secretariat of the National Health Council (CNS)
(Circular) Circular Letter No. 24/2022 – General Guidelines for Conducting Clinical Trials (CLNo24 – Portuguese) (October 17, 2022)
National Research Ethics Commission (CONEP), Executive Secretariat of the National Health Council (CNS)
(Circular) Clarification Note on Circular Letter No. 24/2022 – General Guidelines for Conducting Clinical Trials (CLNo24-Note – Portuguese) (October 26, 2022)
National Research Ethics Commission (CONEP), Executive Secretariat of the National Health Council (CNS)
(Circular) Circular Letter No. 25/2022 – Conducting CEP/CONEP System Meetings in a Virtual Environment (CLNo25 – Portuguese) (October 17, 2022)
National Research Ethics Commission (CONEP), Executive Secretariat of the National Health Council (CNS)
(Circular) Circular Letter No. 183/2017 – Linking the Investigator and Institutions to the CEP (CLNo183 – Portuguese) (May 8, 2017)
National Research Ethics Commission (CONEP), National Health Council (CNS)
(Circular) Circular Letter No. 39/2011 - Use of Medical Records Data for Research Purposes (CLNo039 - Portuguese) (September 30, 2011)
National Research Ethics Commission (CONEP), National Health Council (CNS)
(Circular) Circular Letter No. 062/2011 - Documents Required for Center Inclusion; Center Exclusion; Change of Coordinating Center and Investigator; Transfer of Study Site; Change of Investigator; Cancellation; Suspension and Closure of the Study (CLNo062 - Portuguese) (July 19, 2011)
National Health Council (CNS), Ministry of Health
(Circular) Circular Letter No.008/2011 - Form to Submit Serious Adverse Events (SAEs) to CONEP (CLNo008 - Portuguese) (June 22, 2011)
National Research Ethics Commission (CONEP), National Health Council (CNS)
(Regulation) Resolution of the Collegiate Board - RDC No. 601 of February 9, 2022 (ResNo601 - Portuguese) (Effective February 16, 2022)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Regulation) CNS Resolution No. 674, of May 6, 2022 (ResNo674 - Portuguese) (May 6, 2022)
National Health Council (CNS), Ministry of Health
(Regulation) Resolution of the Collegiate Board - RDC No. 742 of August 10, 2022 (ResNo742 - Portuguese) (Effective July 3, 2023)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Regulation) Resolution of the Collegiate Board of Directors – RDC No. 790 of May 15, 2023 (ResNo790 – Portuguese) (Effective May 22, 2023)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Regulation) Resolution of the Collegiate Board of Directors – RDC No. 791 of May 15, 2023 (ResNo791 – Portuguese) (Effective May 22, 2023)
National Health Surveillance Agency (ANVISA), Ministry of Health

Additional Resources

(Article) Advanced Research Therapy Product Imports: Pilot Project Migrates to Single Foreign Trade Portal (BRA-86 - Portuguese) (September 20, 2021)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Article) ANVISA is Approved for Pharmaceutical Inspection Cooperation Scheme - PIC/S (BRA-55 - Portuguese) (Last Updated November 3, 2022)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Article) ANVISA: An Introduction to a New Regulatory Agency with Many Challenges (BRA-1) (2018)
Huynh-Ba, Kim and Beumer Sassi, Alexandra; AAPS Open
(Article) Brazil’s Regulatory Environment Offers Positive Changes for Clinical Trials (BRA-2) (June 2018)
Fagundes, P., Dresel, P., and Miller, E.; Regulatory Focus
(Article) Clinical trials: New Flow for Requesting a Global Transfer of Responsibility (BRA-96 - Portuguese) (Last Updated November 1, 2022)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Article) DDCM Petition Procedure Changed (BRA-58 - Portuguese) (Last Updated November 1, 2022)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Article) Evolution of DDCM Electronic Petition – Check It Out (BRA-75 - Portuguese) (Last Updated November 1, 2022)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Article) Import No. 046/2021 – Inclusion of Products in ANVISA’s Administrative Treatment (BRA-94 - Portuguese) (Last Updated March 31, 2022)
Siscomex, Government of Brazil
(Article) Measure Expands the Authorization of Clinical Trials with Drugs in Brazil (BRA-92 - Portuguese) (Last Updated November 1, 2022)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Article) The New Brazilian General Data Protection Law - A Detailed Analysis (BRA-76) (August 15, 2018)
Monteiro, Renato Leite; IAPP
(Article) Validity of the ICH E6(R2) Guide (BRA-30 - Portuguese) (Version 1.0) (Last Updated December 4, 2020)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Document) 2020/2021 Activities Report - Coordination of Clinical Research on Medicines and Biological Products - COPEC (BRA-60 - Portuguese) (4th Edition) (March 28, 2022)
General Management of Medicines and Biological Products (GGMED), Coordination of Clinical Research in Medicines and Biological Products (COPEC), National Health Surveillance Agency (ANVISA)
(Document) CONEP/CNS Internal Regulations (BRA-16 - Portuguese) (June 6, 2001)
National Health Council (CNS), Ministry of Health
(Document) Clinical Trials Handbook Americas - Brazil (BRA-79) (2019)
Frizzo, Henrique Krüger, de Moraes, Carla Bacchin F., Marconi, Beatriz; Baker McKenzie
(Article) Improved Electronic Petition System (BRA-14 - Portuguese) (Last Updated November 3, 2022)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Document) Guidance on Scheduling Meetings with COPEC (BRA-19 - Portuguese) (Last Updated December 10, 2020)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Document) Location of Available Documents on the ANVISA Portal (COPEC) (BRA-98 - Portuguese) (21th Edition) (March 10, 2022)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Document) Nagoya Protocol on Access and Benefit-sharing (BRA-63) (2011)
Convention on Biological Diversity, United Nations
(Document) New Procedure for Petitioning DDCM Documents (BRA-59 - Portuguese) (Version 07) (March 2020)
General Management of Medicines and Biological Products (GGMED), Coordination of Clinical Research in Medicines and Biological Products (COPEC), National Health Surveillance Agency (ANVISA)
(Document) OECD Principles of Good Laboratory Practice (GLPs) (as revised in 1997) (BRA-15) (1998)
Environment Directorate, Organisation for Economic Co-operation and Development
(Document) Ordinance No. 45 - Annex I - Table of Discounts of the Health Surveillance Inspection Rate Values Currently Updated by the Interministerial Ordinance MF-MS-45/2017 (BRA-11 - Portuguese) (Effective February 9, 2017)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Document) Step by Step Application (BRA-67 - Portuguese) (Date Unavailable)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Document) Plataforma Brasil - Investigator User Manual (BRA-91 - Portuguese) (Version 3.2) (Last Updated August 5, 2021)
National Health Council (CNS), Ministry of Health
(Document) Questions & Answers: Top Questions about RDC 09/2015 (Conduct of Clinical Trials) (BRA-8 - Portuguese) (English-BRA-8 - Google Translation) (2nd Edition) (January 31, 2018)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Document) Roadmap for Preparing Reports on Biobanks for Research Purposes (BRA-97 - Portuguese) (Version 02) (February 2, 2022)
National Research Ethics Commission (CONEP), National Health Council (CNS)
(Document) Technical Note 008/2017 - Information on Updating the Health Surveillance Inspection Fee (TFVS) (BRA-10 - Portuguese) (January 30, 2017)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Document) Technical Note 09/2015 - Clarifications on Relative Bioavailability Studies to Show Pharmacokinetic Interaction for Purposes of Registration of Fixed-Dose Combinations or Consent to Drug Clinical Development Dossier-DDCM (BRA-6 - Portuguese) (GoogleTranslate-BRA-6) (September 3, 2015)
Coordination of Therapeutic Equivalence (CETER), Coordination of Clinical Research in Drugs and Biological Products (COPEC), General Management of Drugs (GGMED), Superintendence of Drugs and Biological Products (SUMED), National Health Surveillance Agency (ANVISA)
(Document) Technical Note 118/2016 - Clarifications on Comparative Pharmacokinetic Studies of Biological Products (BRA-7 - Portuguese) (April 15, 2016)
Coordination of Therapeutic Equivalence (CETER), Coordination of Clinical Research in Drugs and Biological Products (COPEC), General Management of Drugs (GGMED), National Health Surveillance Agency (ANVISA)
(Document) Technical Note 12/2021 - Guidance for Scheduling Hearings with the Coordination of Clinical Research in Medicines and Biological Products (COPEC) (BRA-90 - Portuguese) (May 21, 2021)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Document) Technical Note No. 01/2022: Guidelines on Completing the Clinical Trial Submission Form (FAEC) Regarding the Expiration Date of Medicines and Products to be Imported for Conducting Clinical Trials in Brazil, Pursuant to RDC No. 9/2015 (BRA-95 - Portuguese) (January 28, 2022)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Document) The Use of the WHO-UMC System for Standardised Case Causality Assessment (BRA-31) (June 5, 2013)
The Uppsala Monitoring Centre (UMC), World Health Organization (WHO)
(Document) VigiMed: Adverse Drug Event Reporting System - Questions and Answers (BRA-85 - Portuguese) (Version 1.0) (July 2019)
National Health Surveillance Agency (ANVISA), Ministry of Health
(International Guidance) Guidance on Regulations for the Transport of Infectious Substances 2019-2020 (WHO/WHE/CPI/2019.20) (BRA-54) (Effective January 1, 2019)
World Health Organization
(International Guidance) ICH Guideline E2B (R3) on Electronic Transmission of Individual Case Safety Reports (ICSRs) - Data Elements and Message Specification - Implementation Guide (BRA-88) (Step 5 Version) (July 2013)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
(International Guidance) ICH Harmonised Tripartite Guideline: Structure and Content of Clinical Study Reports (E3) (BRA-27) (Step 4 Version) (November 30, 1995)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
(International Guidance) Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2) (BRA-28) (Portuguese) (Step 5) (Implemented November 1, 2019)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
(Webpage) Advisory Board (BRA-36 - Portuguese) (Last Updated September 29, 2020)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Webpage) Document Status Query Tool (BRA-102 - Portuguese) (Current as of April 11, 2023)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Webpage) Electronic Contact Form (BRA-68 - Portuguese) (Last Updated July 1, 2022)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Webpage) Electronic Petition - Request System (BRA-38 - Portuguese) (Last Updated January 12, 2023)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Webpage) Fees - General Information (BRA-69 - Portuguese) (October 7, 2020)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Webpage) New Drug Registration (BRA-40 - Portuguese) (November 17, 2020)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Webpage) Payment Terms (BRA-43 - Portuguese) (Last Updated January 19, 2021)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Webpage) Protocol Filing FAQs (BRA-42 - Portuguese) (Last Updated December 21, 2020)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Webpage) Public Service Center (BRA-99 - Portuguese) (Current as of April 11, 2023)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Webpage) Reporting of Serious Adverse Events in Clinical Trials (BRA-37 - Portuguese) (Last Updated May 28, 2021)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Webpage) ANVISA - Who's Who (BRA-39 - Portuguese) (Last Updated September 29, 2020)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Webpage) Obtain Authorization to Import Drug Substance (BRA-103 - Portuguese) (Last Updated January 5, 2023)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Webpage) Request Product Import Licensing Subject to Sanitary Surveillance through LPCO (BRA-104 - Portuguese) (Last Updated October 23, 2023)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Webpage) Brazil Platform (BRA-93 - Portuguese) (Last Updated November 23, 2020)
Ministry of Health
(Webpage) Brazilian Clinical Trials Registry (ReBEC) - FAQs (BRA-46) (Current as of April 11, 2023)
Department of Science and Technology, Ministry of Health (DECIT/MS); Institute of Communication and Information Science and Technology in Health (Icict/Fiocruz); Pan American Health Organization (PAHO); Latin American and Caribbean Center on Health Sciences (Bireme)
(Webpage) Brazilian Clinical Trials Registry (ReBEC) (BRA-45) (Current as of April 11, 2023)
Department of Science and Technology, Ministry of Health (DECIT/MS); Institute of Communication and Information Science and Technology in Health (Icict/Fiocruz); Pan American Health Organization (PAHO); Latin American and Caribbean Center on Health Sciences (Bireme)
(Webpage) CEP - Frequently Asked Questions (BRA-70 - Portuguese) (Current as of April 11, 2023)
Institutional Ethics Committee, Pontifical Catholic University of Goiás
(Webpage) Country Profile: Brazil (BRA-81) (Current as of April 11, 2023)
Access and Benefit-sharing Clearing-house, Convention on Biological Diversity, United Nations
(Webpage) Integrated Foreign Trade System (SISCOMEX) - Single Portal (BRA-80 - Portuguese) (Current as of April 11, 2023)
Siscomex, Government of Brazil
(Webpage) International Clinical Trials Registry Platform (ICTRP) (BRA-52) (Current as of April 11, 2023)
World Health Organization
(Webpage) Siscomex Single Portal - Learning to Export (BRA-87 - Portuguese) (Last Updated June 10, 2022)
Siscomex, Government of Brazil
(Webpage) National Health Council - About Us (BRA-49 - Portuguese) (September 24, 2018)
National Health Council (CNS), Ministry of Health
(Webpage) National Health Council - Plataforma Brazil (BRA-33 - Portuguese) (Current as of April 11, 2023)
National Health Council (CNS), Ministry of Health
(Webpage) National Research Ethics Commission (CONEP) (BRA-50 - Portuguese) (Current as of April 11, 2023)
National Health Council (CNS), Ministry of Health
(Webpage) Plataforma Brazil Login (BRA-34 - Portuguese) (Current as of April 11, 2023)
Ministry of Health
(Webpage) Recognition of GLP Compliance (BRA-48 - Portuguese) (Last Updated April 6, 2022)
Ministry of Health
(Webpage) Unified Health System (SUS) (BRA-53 - Portuguese) (Current as of April 11, 2023)
Ministry of Health
(Webpage) Union Collection Guide (BRA-51 - Portuguese) (Current as of April 11, 2023)
Ministry of Economy
(Webpage) VigiMed (BRA-83 - Portuguese) (Current as of April 11, 2023)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Article) ANVISA Advises on Notification of Serious Adverse Events (BRA-78 - Portuguese) (Last Updated November 1, 2022)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Article) Draft Bill on Human Clinical Trials in Brazil (BRA-5) (June 7, 2022)
Maier, Camilla Mikaelian and Jambor, Daniela Guarita; SP Law
(Document) Technical Note No. 13/2022: Guidance on the Application of the Criteria Established by Resolution No. 763, Resolution No. 601, and Resolution No. 573 (BRA-3 - Portuguese) (December 12, 2022)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Document) Research Ethics: Note on CNS Resolution No. 674/2022 - CEP/CONEP System (BRA-4 - Portuguese) (May 21, 2022)
National Association of Graduate Studies and Research in Education (Anped)
(Not Available Online) NIAID Communication with Fiocruz (February 2023) (BRA-9)
(Webpage) General Management of Medicines (GGMED) (BRA-12 - Portuguese) (Last Updated July 29, 2022)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Webpage) Coordination of Clinical Research in Medicines and Biological Products (COPEC) (BRA-18 - Portuguese) (Last Updated November 21, 2022)
National Health Surveillance Agency (ANVISA), Ministry of Health

Form

(Form) Annexes to the Manual for Submission of Modifications, Amendments, Suspensions and Cancellations - 5th Edition (BRA-13 - Portuguese) (Date Unavailable)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Form) ANVISA Serious Adverse Event Notification Spreadsheet (BRA-84 - Portuguese) (Date Unavailable)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Form) Clinical Trial Report – Annual or Final (BRA-23 - Portuguese) (Last Updated December 3, 2020)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Form) Clinical Trial Submission Form (FAEC) (BRA-22 - Portuguese) (Version 4.0) (Last Updated August 16, 2018)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Form) Cover Sheet for Research Involving Human Beings (BRA-20 - Portuguese) (January 2013)
National Research Ethics Commission (CONEP), National Health Council (CNS)
(Form) End of Clinical Trial Notification Form in Brazil (BRA-24 - Portuguese) (Version 2.0) (Last Reviewed on October 22, 2020)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Form) Industry Petition Form (BRA-71 - Portuguese) (Date Unavailable)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Form) Online Adverse Event Notification Form for Advanced Therapy Products (BRA-101 - Portuguese) (Current as of April 11, 2023)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Form) Petition Form for Consent in the Clinical Drug Development (DDCM) Dossier Process (BRA-21 - Portuguese) (Version 1.2) (Last Updated June 21, 2021)
National Health Surveillance Agency (ANVISA), Ministry of Health
(Form) Clinical Trial Start Date Form in Brazil (BRA-25 - Portuguese) (Version 2.0) (Last Reviewed October 22, 2020)
National Health Surveillance Agency (ANVISA), Ministry of Health
Sign up to get Brazil updates Sign up to get Brazil updates
Menu
|
Announcement

Country Announcement

See the Brazil updates page for details on recent revisions to the profile.

COUNTRY NEWS (Information Not Yet Incorporated Into Country Profile):

ANVISA - Updated Import Procedures for Controlled Medicines and Substances

On November 6, 2023, the National Health Surveillance Agency (ANVISA) began implementing new import procedures for medicines and substances subject to special control, which may include certain investigational products. The import of these products requires approval in two phases: Pre-Shipment Authorization and Post-Shipment Consent. For more details, see Anvisa updates import consent request procedure with mandatory pre-boarding.

National Health Council (CNS) Update

National Research Ethics Commission (CONEP) Updates

National Data Protection Authority (ANPD) Updates

This message was reviewed on March 20, 2024