WHAT ARE THE STEPS FOR OBTAINING AUTHORIZATION FOR CLINICAL STUDIES IN BRAZIL?
Bringing a medicine to market involves a lengthy process, with clinical studies being the most extensive phase in this journey.
In Brazil, for a clinical study to be approved and initiated at a research center, it requires approvals from three specific institution:
• Research Ethics Committee (CEP);
• National Research Ethics Commission (CONEP);
• National Health Surveillance Agency (ANVISA).
Research Ethics Committee (CEP)
The Research Ethics Committee is an interdisciplinary and independent collegial body of public importance, estabiblished to protect the integrity and dignity of research participants and to promote research within ethical standards through consultation, deliberation, and education.
CEPs meet periodically to approve clinical studies, evaluating their feasibility and benefits for patients. It is up to the CEP of the institution where the study will be conducted to approve the protocol and the respective Informed Consent Form (ICF), as well as other documents that research participants will come into contact with.
Once approved by the local CEP where the research is conducted, it must be submitted through Plataforma Brasil for approval by the National Research Ethics Commission (CONEP). Plataforma Brasil is the official system for launching research for analysis and monitoring of the CEP/Conep System. Researchers are required to register on Plataforma Brasil to submit their projects to the CEP.
The Committee monitors the study as it progresses. If new information is added to the protocol, it must be submitted for new approval by the Ethics Committee.
The CEP is empowered to modify or suspend the study when it assesses that there is a risk to the research participant.
Brazil is embarking on an experiment involving Accredited CEPs, which possess greater independence and autonomy in project evaluation. However, this is a new initiative, and currently, fewer than ten CEPs fall into this category.
National Research Ethics Commission (CONEP).
The National Research Ethics Commission (CONEP) is a commission of the National Health Council (CNS), a departament of the Ministry of Health responsible for regulating research involving human subjects in Brazil. This committee is made up of members and substitutes from different training areas, who work on a voluntary basis, being responsible for approving or not the study, respecting the rules and regulations in force for their protection. After the documentation has been received by the CEP and the study has been approved by CONEP, all centers involved in the same clinical research receive this approval. CONEP approval is required when research involves international participation, a vulnerable population, or the use of medication or health devices not registered in the country.The ethical approvals in Brazil are governed by CONEP resolution RDC 466/12.
National Health Surveillance Agency (ANVISA)
ANVISA, the health surveillance regulatory authority in Brazil, is responsible for granting regulatory approval for the commencement of a study and authorizing the import of necessary inputs and medicines for the research. Since the implementation of RDC 09/15, the institution must also approve the Drug Clinical Development Dossier (DDCM), which includes comprehensive information about the active ingredients and finished product of the drug under evaluation, in addition to information on Good Manufacturing Practices (GMPs).
The DDCM also contains the product's clinical development plan, that is, the strategic plan for clinical projects scheduled for the medication to be tested. Each Specific Clinical Trial Dossier (DEEC) must also receive approval from ANVISA. The Special Communication (CE) is issued by DDCM, listing its associated studies. It is important to highlight that clinical trials of an exclusively scientific or academic nature do not require authorization from ANVISA, only the consent of the ethical body.
Regarding regulatory monitoring of the project, amendments to protocols can only be implemented after approval, except if an amendment and respective consent form provide information; and a change for greater safety of participants, administrative changes or no impact on the design of the research project. In this case, both can be implemented immediately and their approvals will follow the regular flow.
“On average, ANVISA takes 120 days to provide an opinion. In cases where a study will be conducted in Brazil by a multinational industry, having been validated by a regulatory agency such as the FDA (Food and Drug Administration) or EMA (European Medicines Agency), or another agency in a highly regulated country, ANVISA has a 90-day period to provide an opinion. "If the Agency does not meet this deadline, it may result in tacit authorization of the research project”, explains Camille Rodrigues, managing partner at Inovatie Serviços em Saúde, a consultancy responsible for projects in Clinical Research and Medical Affairs.
Difficulties in approving studies in Brazil
In Camille's opinion, double approval (two in the ethical body – CEP/CONEP – and one in the regulatory body – ANVISA) is an issue that certainly impacts the approval deadlines for studies in the country, causing them to take longer than what is practiced in other countries. In Brazil, the approval process can take 90 to 150 days or even longer for more complex projects, while in some countries it takes ten days, with an average of four to six weeks.
“There is no doubt about Brazil’s potential for conducting studies, thanks to its large population, capable research centers with high expertise, and extensive experience with research projects. Our main challenges to enhance the country´s competitiveness are the lengthy approval times for clinical research and the mandatory supply of post-study medication.”
There is a bill, authored by former senator Ana Amélia, from Rio Grande do Sul, that has been under consideration in the National Congress since 2017. This bill aims to simplify the study approval process, reducing the time and steps involved. Additionally, the bill limits the supply of post-study medication to five years or until it is incorporated into the Unified Health System (SUS). Currently, the project is being expedited and is awaiting a vote in the National Congress.