A Step-by-Step Guide to Regulatory and Ethical Considerations
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Learn about the stages of a pre-commercialization clinical study conducted in Brazil
The National Health Surveillance Agency (ANVISA) is responsible for analyzing and approving requests for clinical trials of drugs and medical devices to be registered in Brazil. Therefore, the sponsor, the designated Contract Research Organization (CRO), or the investigator-sponsor must request ANVISA's approval for a clinical trial application for a drug or medical device to be registered in Brazil, which will have all or part of its development conducted in Brazil.
The regulatory and ethical process before the start of a pre-commercialization study in Brazil is described below:
Preparation of Basic Study Documentation: Study Protocol, Investigator?s Brochure, Informed Consent Form, researcher and institutional statements.
Electronic Submission to the Ethics Committee (CEP): The Ethics Committee (CEP) is required to issue an initial report within 30 days from the date the principal investigator (PI) submits the analysis request. The review of the protocol documentation by the CEP regarding its integrity must be completed within 10 days after submission. The analysis period will be counted from the date the project enters "Ethical Evaluation" (i.e., after passing the document validation which takes about 10 days and when the Certificate of Presentation for Ethical Appreciation (CAAE) is issued). Additionally, if the project needs to be reviewed by the National Research Ethics Commission (CONEP), the deadline is 15 days for document validation and 45 days for ethical evaluation.
Preparation of Regulatory Documentation: Clinical Drug Development Dossier (DDCM) and Specific Clinical Trial Dossier (DEEC) for studies with drugs, or Clinical Investigation Dossier for Devices (DICD) for studies involving medical devices.
Payment of the Sanitary Surveillance Inspection Fee (TFVS): ANVISA will only analyze the submission after the sponsor pays the TFVS fee and the original proof of electronic bank payment is sent along with the original printed Guide for Union Collection (GRU), the petition, and all necessary documentation for protocol analysis.
Electronic Submission to ANVISA of All Requested Documents: Submissions to ANVISA and the Ethics Committee can be made in parallel. ANVISA has 90 calendar days to evaluate the request. If the agency does not issue a response within 90 days after receipt, clinical development may begin, provided that all ethical approvals have been obtained. Companies have up to 120 days to respond to any type of process issued by the agency and/or petition requirements.
ANVISA Approval: ANVISA issues an authorization document known as a Special Communication (CE). The CE lists all the trials included in the submission that are allowed to start the clinical study. ANVISA is also responsible for authorizing the importation of Investigational Products (IPs). The sponsor may request approval for the import/export of IPs for study purposes at the same time the petition is submitted to ANVISA.
Furthermore, BEFORE the clinical study can begin, several steps are necessary:
Preparation of Essential Documents: Documents that ensure the trial is conducted rigorously and ethically, meets regulatory requirements, and provides evidence of the safety and efficacy of the investigational product. Additionally, an electronic database is created.
Feasibility and Site Selection: Assessment of internal and environmental capacity, alignment of the clinical trial in terms of study design, dose of the experimental product, comparator, patient profile, with the local environment and evaluation of the potential for conducting a clinical trial in a specific country. A robust feasibility assessment also ensures a realistic evaluation and capacity to conduct the clinical trial. Based on the information provided by the centers regarding their availability to conduct the study, the study site is selected.
Site Initiation Visit: A meeting organized to discuss the new protocol before the research project is ready to track and enroll potential patients. It also serves as training for the protocol of interest and the use of the database.
With all regulatory and ethical approvals, along with the initial steps mentioned, the clinical study can finally begin.
DURING the study, the sponsor or designated CRO is responsible for:
Study Monitoring and Quality Assurance: To ensure that the rights and welfare of human subjects are protected, the reported trial data is accurate, complete, and verifiable from the original documents, and the trial is conducted in accordance with the protocol/amendment(s), GCP, and applicable regulatory requirements.
Data Management: Managing discrepancies, data coding, data review, and data transfer.
Site Management: Ongoing communication and support to study sites and investigators to ensure that the study is conducted according to all regulatory requirements and study protocol, ensuring high-quality results in a timely manner.
Preparation of Interim Reports: Progress reports, including safety summaries and protocol deviations.
When the last patient completes the final study visit, the following procedures are carried out AFTER data collection:
Study Close-out Visit: An organized visit and process to ensure that all necessary aspects of study closure have been addressed, including the organization and completion of documentation and reports.
Statistical Analysis: Analysis of study results.
Study Report: Providing an overview of the study, describing the methods employed, presenting the results in an understandable format, and discussing the interpretation and implications of the results.
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