Quality & Compliance
Safety & Vigilance
19 july 2022
Brazil has a longstanding tradition and experience of performing clinical trials, with a good infrastructure of investigational sites, laboratories, and medical professionals. With its large and diverse population – over 200 million inhabitants – from different origins and ethnicities, and a high incidence of diseases prevalent in developed regions, the country offers favorable conditions to conduct trials across diverse medical fields.
However, before starting a clinical study, the Clinical Trial Application (CTA) must be evaluated by the National Health Surveillance Agency (ANVISA) and Ethical System. The historically long timelines required for these assessments represent one of the main reasons Brazil does not participate as actively as other nations in international multicenter studies.
ANVISA through its Coordination of Clinical Research on Drugs and Biologicals (COPEC) is responsible for granting regulatory approval for clinical trial applications supporting development of new medicines. ANVISA’s evaluation focuses on the quality and safety of the investigational product. An approval document issued by ANVISA is needed for the release of imported investigational drugs at customs. The estimated time for ANVISA’s evaluation is around 90 days, not considering any time that may be needed for answering contingency letters.
As for ethical approval for clinical trials, it is the responsibility of two regulatory bodies, comprised of the Local Ethics Committee (CEP) and the National Research Ethics Commission (CONEP). CONEP is the central body responsible for coordinating the network of institutional ethics committees and for registering, training, and accrediting the local ethics committees (ECs). The ECs are usually linked to or present at each investigational site. If there is no local EC available at the site, the principal investigator must make a request to CONEP for the appointment of a qualified local EC from another site to be responsible for the ethical approval of that particular study.
CONEP is also responsible for the assessment of clinical trials in some specific thematic areas, including human genetics, human reproduction, studies with indigenous populations and other vulnerable populations. CONEP involvement also occurs for clinical trials with coordination or sponsorship originating outside Brazil, no matter the thematic area involved.
Until March 2022, the clinical trial applications were assessed by the institutional/local committee from the one selected site known as “Main/Coordinator”. The coordinator site is responsible for leading the submission throughout “Plataforma Brasil” using an electronic system where all submissions, approvals and contingencies are published/issued. After this initial step, and after an Opinion Letter has been issued by the local EC from the “Main/Coordinator” site, it is forwarded to CONEP for an additional assessment (of the same ethical aspects founded in Resolution CNS 466/2012). Timelines for ethical approval in these cases (CEP + CONEP), often reached 8 to 12 months before 2017; in the period 2017 to 2022 this reduced to approximately 5-6 months.
This duplicated analysis system was the trigger for many different claims from the regulated sector. The overlapping did not add value and the prolonged timelines seriously impacted competitiveness by reducing the time available to enroll subjects into CT. The pre-2022 CTA system made Brazil less attractive to companies seeking to conduct clinical trials despite the potentially good source of country wide participants, sites and investigators. However, CONEP was proactive and in response to public complaints from medical associations, laboratories and clinical research organizations (CROs) it implemented several changes to streamline the process. Based on this context, a project for accreditation of institutional ethics committees (“CONEP Acredita”) was created by the National Health Council in 2016 (Resolution CNS 506/2016) and effectively implemented in March 2022 when the first projects could be submitted under this new system. The expectation of the revised system is to deliver a significant reduction in timelines for CTA approval.
The project plans to decentralize ethics assessment, through accreditation of institutional ethics committees. These accredited committees would be entitled to perform complete ethical assessment with no need of a second assessment by CONEP, whilst still maintaining the uniformity of analysis criteria established by the Central/National body.
To select the CEPs, CONEP carried out a survey on the CTAs received in recent years, to identify the Brazilian state making the largest number of applications. Based on this survey, it was decided that the project would begin in the metropolitan region of São Paulo and then later extended to other regions covering the entire country.
From a first public call in 2020, 5 institutional committees were selected, based on the historical quality of their assessment reports. These committees passed through a 6-month pre-accreditation period, where their activities were monitored and evaluated by CONEP with the aim of assessing quality and consistency of opinion letters issued and adherence to the CONEP Resolutions and General Ethical principles. This accreditation required in loco audits by CONEP to the selected institutional ECs. Due to the COVID-19 pandemic, there was a delay in the audit programs and accreditation only occurred in February 2022.
After the process, 5 institutions in the city of Sao Paulo were accredited in this first phase in the following “ranking”: Faculdade de Medicina do ABC – FMABC; Fundação Antônio Prudente – A.C. Camargo Câncer Center; Instituto Dante Pazzanese de Cardiologia; Hospital Israelita Albert Einstein and Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo – HCFMUSP. Accreditation for these institutions will be re-evaluated in 2025. These committees are now entitled to perform ethics assessments for the thematic areas previously attributed to CONEP, either submitted directly by the sponsors or forwarded by CONEP itself.
A significant reduction in the time required for approval is anticipated and currently estimated as 2 – 3 months. These current timelines are more in line with international scenarios: in the USA, the approval timeline is 45 days, in Europe 60 days and in Argentina and Mexico 30 to 90 days.
The sponsors/CROs who are interested in initiating a new protocol in Brazil and conducting their Sites Selection process can now choose one of the sites supported by Accredited CEPs to be their Main/Coordinator site and enjoy the benefits and advantages of the reduced timelines for CTA.
The project is to be implemented at National level and will take into consideration the volume of projects submitted to CEPs in each region. The project’s second phase has already started, with four additional institutional committees located in Sao Paulo state selected and undergoing the pre-accreditation process. These sites include: Faculdade de Medicina de Botucatu – Unesp; Faculdade de Medicina de São José do Rio Preto – FAMERP; and Universidade de Franca – UNIFRAN and Faculdade Ceres – FACERES.
One concern is that the few accredited CEPs operating in Brazil may face excessive workloads. However, bottlenecks are not evident to date. Based on feedback from the CROs and Pharma companies who have already tried the new system, timelines of less than 2 months are being frequently reported.
Thus, with the continuation of the decentralization of the CEP/CONEP System, accreditation of CEPs in an expedited manner as well as the geographic expansion it is expected that CONEP will strengthen itself as the coordinator of the System. CONEP will prioritize its CEP qualification activities, including monitoring and regulation, whilst also continuing to maintain itself as the highest source of research ethics regulation in the country.
The new approval system represents an improvement in the process of clinical trials assessment and brings Brazil into alignment with international standards.
Support to make an application in Brazil can be provided by our experienced team at PLG so that your multicentre clinical trials can get underway without delay. If you want to know more about CTA in Brazil, contact us here.
Resolution CNS 466 of 12-12-2012
Resolution CNS 506 of 03-02-2016
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