Clinical Trial with humans: all you need to know about the legal framework recently approved in Brazil

24/09/2024
Clinical Trial with humans: all you need to know about the legal framework recently approved in Brazil

Brazil Approves New Legal Framework For Clinical Trial With Humans. Federal Law Establishes Rights And Duties For Researchers, Sponsors, And Participants In Clinical Trials With Humans

On May 29, 2024, the President of the Republic sanctioned Federal Law 14,874/2024, which established the principles, guidelines, and rules for conducting clinical trials with humans by public or private institutions in Brazil.

Federal Law 14,874/2024 established rules that seek to (i) harmonize the Brazilian regulatory environment with international standards and best practices in clinical trials; and (ii) supervise public and private institutions that conduct research with human beings in Brazil. As well as covering clinical trials into medicines, the law also applies to medical devices and advanced therapy products.

The sanction is a historic milestone and expands Brazil’s potential to stand out on the international clinical trial scene, removing gaps and legal uncertainties by regulating the issue at the federal level.

Until this time, the issue was regulated through resolutions issued by the National Health Surveillance Agency (“Anvisa”) and the National Health Council (“CNS”).

When does the law come into force?

On August 27, 2024 (90 days after the publication in the Federal Register).

Vetoes issued by the President of the Republic:

The President of the Republic vetoed two articles. The first veto was over the legal provision that allowed the commercialization of experimental drugs to participants after 5 (five) years from the commercial availability of the experimental drug in Brazil.

The reasons for the veto indicate that setting a maximum time limit for the supply of the post-study drug would be contrary to the public interest, as well as hurting the rights of clinical trial participants and jeopardizing the possible development of ethical research based on the principles of dignity, beneficence, and justice. In addition, the veto points out that there was no maximum time limit for the continuation of the free supply of the experimental drug post-study to trial participants, and that the supply should be continued regardless of its commercial availability by the private sector.

Moreover, President Lula vetoed the provision that required the Public Prosecutor’s Office to be notified of the participation of indigenous people in clinical trials, as it violated the principle of isonomy.

Despite the publication of the law, vetoes will be analyzed by the National Congress and must be rejected or confirmed. Congress would have 30 days to deliberate on presidential vetoes in a joint session of senators and the house of Representatives, and an absolute majority of Congress is required to reject vetoes (arts. 57, §3, IV and 66, Federal Constitution). Nevertheless, this deadline has already passed, and National Congress is still not considering the President’s vetoes.

If the Congress rejects the vetoes, the corresponding parts of the law will be sent for promulgation by the President of the Republic within 48 hours (art. 66, §7, of the Federal Constitution).

Note published by the Ministry of Health:

In a note published on August 27, 2024, the Ministry of Health reported that:

  • The publication of Federal Law 14,874/2024 contemplates legal certainty, the predictability of deadlines in the ethical analysis of research projects and promotes transparency in the processes. The law will be regulated by an act of the Executive Branch, establishing transition rules that will guide the work of the system, which includes approximately 1.2 million users, 35,000 institutions and 900 Research CEPs across the country, and which should not suffer any interruptions.

  • The decree, as well as subsequent documents, will deal with the organization, coordination and functioning of the National System of Ethics in Research with Human Beings, as well as addressing the peculiarity of the specific issues provided for in the law. Until specific rules are published, the existing rules will remain in force, respecting the provisions of Federal Law 14,874/2024, ensuring that research with human beings does not suffer discontinuity or unnecessary delays in ethical analysis.

  • The transition process does not change the procedures for submitting research protocols to “Plataforma Brasil”, which remains the national and unified basis for registering research involving human beings.

Clinical trial: established legal concept

The Federal Law established the concept of clinical trial as the set of scientific procedures developed in a systematic way with humans aiming to:

I. evaluate the action, safety, and efficacy of drugs, products, techniques, procedures, medical devices, or health care, for therapeutic, preventive or diagnostic purposes;

II. verify the distribution of risk factors, diseases or conditions in the population;

III. evaluate the effects of factors or states on health.

The goals:

The Federal Law aims to:

  • Provide legal certainty to all agents involved in conducting clinical research;

  • Rush the approval of clinical trial in Brazil;

  • Expand Brazil’s potential to stand out in the international clinical trial scenario, placing it among the top 10 countries in the global clinical trial ranking;

  • Benefit people suffering from serious illnesses such as cancer and rare diseases.

It is worth noting that the study conducted by the Pharmaceutical Research Industry Association (“Interfarma”), IQVIA, and Aliança Pesquisa Clínica Brasil, estimates that by rising to 10th position in the overall clinical trial ranking, Brazil could attract direct investment estimated at R$ 3 billion per year, with more expressive economic impacts in the order of R$ 5 billion per year¹.

Institution of the National System of Ethics in Research with Human Beings:

To be regulated by the Executive Branch, the National System of Ethics in Research with Human Beings is divided into:

I. The National Research Ethics Body, which is responsible, among other things, for issuing regulations on research ethics and supervising the Research Ethics Committees (CEPs);

II. The Research Ethics Review Body, represented by the CEPs, which is responsible for, among others, (a) ensuring the rights, safety, and well-being of research participants, especially those in vulnerable situations; (b) considering the qualifications of the researcher for the proposed research following their academic and professional curriculum; (c) conducting the analysis of the research submitted to it and monitoring its execution; and (d) ensuring that adequate means are provided for obtaining the consent of the research participant or their legal representative.

All trials with humans will be subject to prior ethical analysis, to be carried out by the CEPs, which cannot exceed 30 working days from the date of acceptance of the full research documents, and this acceptance, or its denial, must be made by the CEP within ten working days from the date of submission.

Trial of strategic interest to the Unified Health System (SUS) and which is relevant to dealing with public health emergencies will have priority and special analysis procedures so that the deadline for analysis cannot exceed 15 working days from the date of receipt of the research documents.

Ethical and scientific requirements:

The Federal Law established the following technical and scientific requirements to bring legal certainty to clinical trial participants:

  • Respect for the rights, dignity, safety, and well-being of the participant, which must prevail over the interests of science and society;

  • Scientific basis in a favorable assessment of the risk-benefit ratio for the research participant and society;

  • Conduct in compliance with the protocol approved by the CEPs;

  • Ensuring the competence and technical and academic qualifications of the professionals involved in carrying out the research;

  • Guarantee of voluntary participation, through the free and informed consent of the research participant;

  • Respect for the privacy of the participant and the rules of confidentiality of their data, guaranteeing the preservation of secrecy about their identity;

  • Providing the necessary care in cases involving intervention;

  • Adoption of procedures that ensure the quality of the technical aspects involved and the scientific validity of the research; and

  • Conducting the research in compliance with good clinical practice.

Legal protection for trial participants:

The law guarantees trial participants protection, whose participation is conditional on the express authorization of the participant or their legal representative, by signing an Informed Consent Form.

Participants may not be paid. However, Federal Law 14,874/2024 allows payment for the participation of healthy individuals in phase I clinical trials or bioequivalence trials, provided that the participant: (i) joins the national register of volunteers in bioequivalence and phase I studies (to be regulated); (ii) does not simultaneously take part in more than one study. 

Furthermore, the following do not constitute remuneration or advantages for the research participant: (i) reimbursement of expenses with transportation, food, or prior material provision; (ii) other types of reimbursement necessary, according to the research project.

Besides, the sponsor must guarantee the participant compensation for any damages suffered as a result of their collaboration in the research, with the receipt of necessary health care related to these damages.

Last but not least, the trial will be conducted in such a way as to guarantee the anonymity and privacy of the participant, as well as the confidentiality of the information.

Overview of Sponsor’s responsibilities:

The Federal Law defines a sponsor as a natural or legal person, under public or private law, who supports research by providing funding, infrastructure, human resources, or institutional support.

The sponsor’s main responsibilities are:

  • implement and maintain quality assurance and quality control systems, based on SOPs, to ensure that the research is conducted, and the data is generated, documented, and reported in compliance with the protocol, good clinical practice, and the requirements of the regulations;

  • establish the contract between the parties involved in the research;

  • control the quality of each stage of data processing, to guarantee its reliability and correct processing;

  • to maintain the quality and completeness of the research data, even if some or all of the functions have been transferred to third parties;

  • selecting the researchers and institutions carrying out the trial, taking into account the qualifications needed to conduct and supervise the research;

  • guarantee adequate resources to conduct the trial, including the cost of all expenses related to procedures, and actions to resolve adverse events;

  • verify that the trial participant has authorized direct access to their data and information for monitoring, auditing, review by the competent ethical bodies, and inspection by regulatory agencies;

  • promptly notify the researcher, the executing institution, the competent ethical review bodies, and the health authority of findings that may adversely affect the safety of the research participant, compromise the conduct of the research, or affect the approval granted by the REC;

  • promptly notify the health authority of all serious or unexpected adverse events whose causality is possible, probable, or defined in relation to the product under investigation;

  • monitor the research;

  • inform the researchers involved, the executing institution and the health authority of the reasons for the suspension or premature termination of the research, when applicable;

The sponsor, ultimately responsible for the trial, may delegate the execution of certain functions to the Clinical Research Representative Organizations (CROs), which will assume shared responsibility for the object of the delegation.

Criteria for post-study supply:

The Federal Law provides that the free supply of the experimental drug under the post-study supply program may be interrupted upon submission of a justification to the CEP, only in the following situations:

  • Decision by the trial participant or their legal representative;

  • Cure of the disease or introduction of a satisfactory therapeutic alternative;

  • Lack of benefit from the continued use of the experimental drug, considering the risk-benefit ratio outside the context of the clinical trial or the appearance of new evidence of risks related to the safety profile of the experimental drug;

  • The occurrence of an adverse reaction that makes the continuation of the investigational drug unfeasible;

  • The experimental drug cannot be obtained or manufactured for technical or safety reasons – provided that the sponsor provides an equivalent or superior therapeutic alternative on the market; or

  • Supply of the drug in the SUS.

Anvisa’s deadline for analysis of applications for clinical trials:

To rush the process of making new products available on the market, the Federal Law established a maximum time limit for approval of clinical trials with humans by Anvisa.

The health analysis related to primary petitions for clinical trials with humans intended to obtain the marketing authorization of the product under investigation cannot exceed 90 working days. If Anvisa does not issue a decision within this period after the primary clinical trial application has been received, clinical development can begin, provided it contains the relevant ethical approvals.

Main points to be regulated:

Despite the publication of the legal framework for clinical trial, some issues will be the subject of regulations, such as:

  • Rules on publicity, transparency, and the monitoring of research;

  • Rules on the manufacture, use, dispensing, import, export, storage, and disposal of products intended for clinical trial;

  • Guidelines on SOPs and good practices;

  • Rules for biobanks (organized, non-commercial collection of human biological material and associated information, collected and stored for research purposes);

  • Criteria and procedures for the operation, suspension, or termination of CEPs;

  • Rules on the process of ethical analysis of research before CEPs;

  • Rules for the clinical research protocol;

  • Mandatory clauses for clinical research contracts;

  • Creation of fast-track procedure for ethical analysis of research of strategic interest to the SUS and relevant to public health emergency care;

  • Rules for creation of National Registry of Volunteers in Bioequivalence and Phase I Studies;

  • Rules for creating a post-study supply program or continuity of experimental treatment.

Souto Correa’s Life Sciences & Healthcare practice can support your team in clinical trial projects. Please contact us by e-mail: lifesciences@soutocorrea.com.br and/or anderson.ribeiro@soutocorrea.com.br.

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[1] https://www.interfarma.org.br/wp-content/uploads/2023/08/Pesquisa-clinica-2022_atualizado.pdf

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