4. Regulatory Authority (RA)/Competent Authority (CA)

4.1 Provide a list of documents needed to be submitted for RA/CA review and approval including the number of copies and/or translations as relevant. 

The following documents must be submitted to ANVISA:

1. Application form for clinical drug development dossier (DDCM) approval process.
2. Proof of payment (or exemption) from the Health Surveillance Fee (TFVS).
3. Protocol for Clinical Trial.
4. Proof that the clinical research is registered in the International Clinical Trials Registration Platform / World Health Organization (ICTRP/WHO) or other databases recognized by the International Committee of Medical Journals Editors (ICMJE).
5. Drug development plan.
6. Investigator Brochure.
7. Summary of safety information, if available.
8. Description of the investigational drug and placebo.
9. Labeling of the investigational drug.
10. Summary of non-clinical studies.
11. Summary of previous clinical studies, if available.
12. Certified copy of the clinical agreement between the sponsor and CRO.
13. Ethics in Research Committee (ERC) (also known as a CEP) opinion issued for the first clinical trial center.

4.2 Time required for RA/CA review and approval process and turnaround time if any query is raised during the review process. 

Upon receipt of the DDCM, ANVISA has 90 calendar days to evaluate the application. If ANVISA fails to issue a response within 90 days after receipt, clinical development can begin as long as all of the ethical approvals have been obtained.

More information about review timelines for various applications can be found at https://clinregs.niaid.nih.gov/country/brazil#timeline_of_review.

4.3 Does the regulation support electronic submission?

Yes.

4.4 Does the regulation require the applicant to be a Principal Investigator (PI)/Chief Investigator (CI)?

No, the submission is typically made by the sponsor. In the event that the sponsor has no presence in Brazil, then this role may be delegated to a CRO.

4.5 Please describe the process of RA/CA submission for clinical trial approval. 

• The Clinical Trial Application and associated documents (including the protocol, investigator brochure, informed consent form, and sponsor and institutional declarations), as well as all documentation provided to the CONEP/CEP System, must be translated into Portuguese.
• The Principal Investigator (PI) is responsible for submitting an application via the online Plataforma Brasil to the respective Institutional EC (CEP), and, if applicable, to the National Commission for Ethics in Research (CONEP).
• For the multicenter clinical trial, the PI shall submit a list of the participating institutions and the associated protocols as part of the research protocol package sent to the CEP for review.
• The CEP will review the protocol documentation for completeness which should be accomplished within 10 days following submission and shall issue an initial report 30 days from the date the protocol documents are fully accepted for review.
• CONEP (for which sponsorship or coordination originates outside of Brazil) must also review applications and shall issue its initial report for this additional review within 60 days from the date the documentation was accepted.
• Clinical Research Coordination on Drugs and Biologicals (Coordenação de Pesquisa Clínica em Medicamentos e Produtos Biológicos (COPEC) at ANVISA’s office is responsible for conducting the review of clinical trial applications.
• All communication between the research center, the principal investigator, and the ethical committee system should be done through the online platform.
• Once approved by the Ethics Committee, the application can be forwarded to ANVISA. ANVISA’s approval of a clinical trial application is dependent upon obtaining proof of the EC’s (CEP’s) approval.
• The application includes 
  • A hard copy of the clinical trial application (1) and
  • Electronic copy on CD-ROM in Adobe Acrobat PDF, Microsoft Word, or Open Document file format. (1) (The electronic documents should also have text searching capability). 
• The evaluation process by ANVISA is usually divided into two phases: 
  • Ensuring that all the required documentation for the clinical trial application is included.
  • Technical review of the application. 
• Upon receipt of the DDCM, ANVISA has 90 calendar days to evaluate the application. If ANVISA fails to issue a response within 90 days after receipt, clinical development can begin as long as all of the ethical approvals have been obtained.
• Once approved by ANVISA, the sponsor or CRO is required to obtain an import license from ANVISA for the shipment of the investigational product (IP) to be used in the trial.

4.6 Does the RA/CA provide written acknowledgment of the submitted application? If not, describe how the application is tracked.

The application can be tracked from submission to final approval by the CEP through Plataforma Brasil.

Clinical Research Regulation For Brazil | ClinRegs (nih.gov)

4.7 What is the relevant RA/CA fee in local currency/USD? Please provide as much information as possible (e.g. if the fee is different for notification/approval, initial submission, amendment, study with IMPD and study without IMPD, etc.)

The submission fee ranges from 1421.70 Brazilian Reals to 28,433.93 Brazilian Reals depending on the complexity of the submission (equivalent to USD270 – USD5400).

4.8 Does RA/CA accept checks or can payment be made electronically? Please provide details on (1) A/C number; (2) A/C Name; (3) Sort Code; (4) Swift Code; (5) Bank address, etc. Where can remittance advice notices be sent?

ANVISA will only review the DDCM once the sponsor (also referred to as the regulatory agent) has paid the TFVS fee, and the original electronic bank payment receipt is forwarded together with the original printed copy of the GRU, the petition (request), and all of the documentation required for protocol review. 

If a petition is filed without due payment of the TFVS fee, the request and the documentation will be returned to the sponsor. ANVISA will accept the following documents as proof of payment from the sponsor:

1. Presentation of the original GRU receipt collected electronically, which must be accompanied by the original electronic banking network payment receipt.
2. Presentation of the original GRU receipt collected from the banking network, which must contain the original receipt stamp for authentication.
3. The transaction number issued by ANVISA’s Electronic Petition Request System.

The GRU contains a barcode that may be scanned for payment purposes at the Bank of Brazil or any participating financial institution participating in the bank clearing system. Bank payments may be completed in person, or by using the bank’s website or self-service (ATM) terminals. In addition, payment must be made within 30 days after the GRU has been issued. ANVISA charges a fee for substantial amendments to the clinical protocol.

4.9 Is there any guidance tool available for making an electronic application? If yes, provide the link and/or step-by-step instructions.

No.

4.10 Does RA/CA require any screenshots/mock screens for participant-facing materials?

Yes, where patient-facing materials are presented electronically, screenshots should be provided.