Anvisa updates clinical trial regulations

On December 2, 2024, the Brazilian Health Regulatory Agency (Anvisa) published Resolution No. 945/2024, which regulates the conduct of clinical trials in Brazil aimed at granting drug marketing authorization, and Instruction No. 338/2024, which details the criteria for adopting an optimized analysis procedure for clinical trials by reliance (use of equivalent foreign regulatory authorities’ assessments) and based on risk and complexity assessment of petitions.

The regulations were approved in a meeting of Anvisa’s Collegiate Board of Directors (Dicol) and aim to establish optimized analysis and approval procedures for clinical trials, in addition to simplifying and accelerating the trial approval process and aligning the new regulations with the ICH’s Guideline for Good Clinical Practice E6(R2) and with the new clinical trial law (Law No. 14,874/2024), enacted in May this year.

New guidelines and scope

Resolution No. 945/2024 defines the guidelines and procedures for conducting clinical trials with synthetic and semi-synthetic drugs, herbal medicines, radiopharmaceuticals, biologicals, and biosimilars, which have all or part of their clinical development in Brazil for marketing authorization purposes in the country. The new standard included relevant definitions in its body, such as the risk categories of clinical trials, classifying them as low, moderate, and high risk — in line with the classification provided for in Law No. 14,874/2024, and the definitions of complex clinical trials and investigational products.

The Resolution exempts post-marketing clinical trials (phase IV) and non-interventional clinical trials from sanitary analysis, which now only require ethical approval by the competent Research Ethics Committee (CEP), and presents the possibility of continuous submission of partial data before the definitive submission of the Clinical Drug Development Dossier (DDCM).

Additionally, in order to standardize with Law No. 14,874/2024, Resolution No. 945/2024 expressly provides that clinical trial dossiers can be submitted in parallel to ethical and regulatory bodies, as these bodies hold independent decisions.

Sponsor-investigator

Although not provided for in Law No. 14,874/2024, the approved draft maintains the definition of sponsor-investigator, providing for the figures of the primary sponsor (institution) and secondary sponsor (sponsor-investigator) in the event that the primary sponsor delegates responsibilities to the investigator.

Furthermore, the new resolution maintains the wording of Resolution No. 9/2015 regarding the donation of drugs with marketing authorization in Brazil for use in clinical trials. In this case, the donor assumes the role of sponsor only if there is an agreement to transfer the clinical trial data to the donor or if the latter holds ownership of the data. On the other hand, If the donated drug is not yet marketed in Brazil, the donor shares responsibilities with the sponsor.

Requirements for DDCM submission and clinical trials tacit approval

Requests for the approval of the DDCM can be submitted to Anvisa at any stage of the drug clinical development for one or more phases of the clinical trial and should only be submitted in cases where the sponsor intends to conduct clinical trials with the drug in national territory.

The new resolution details that the DDCM analysis occurs only after the submission of at least one Specific Clinical Trial Dossier (DEEC), which should be carried out within 15 business days from the issuance of the DDCM file by Anvisa. Despite this, new DEECs can be linked to the DDCM at any time.

If no DEEC is submitted within the aforementioned deadline, the DDCM is rejected without technical analysis — except in the case of clinical trials involving more than one investigational drug whose DEEC has already been linked to one of the DDCMs of those drugs.

Once the DDCM is submitted and the DEEC is attached, Anvisa will evaluate the documents within 90 business days from the date of issuance of the DEEC file. If there is no response from Anvisa within this period, the DDCM and respective DEEC are tacitly approved through the publication of a Resolution-RE in the Federal Official Gazette (DOU), and the clinical development can begin after ethical approvals.

The new framework extends the application of tacit approval, already provided for in Law No. 14,874/2024, to other petitions beyond the primary ones. According to the approved draft, tacit approval also applies to secondary petitions for substantial modifications to the investigational product and significant amendments to the clinical protocol.

Investigational products importation

Aiming to expedite the clinical trial sanitary approval and all procedures arising from it, Resolution No. 945/2024 determines that Anvisa will issue the Import Document (DI), which authorizes the importation of investigational products for use in the clinical trial, within 30 business days from the issuance of the DEEC file by Anvisa, before the clinical trial approval or rejection.

Once the DI is issued, the sponsor is authorized to import the products at any time. However, if the products are effectively imported before the clinical trial approval, the sponsor must store them in a protected area until the approval of the DDCM and DEEC — through publication in the DOU — when it will be authorized to distribute and use them in the clinical trial.

If the clinical trial is not approved and the products have already been imported, it is the sponsor’s responsibility to dispose of or destroy the imported products and provide proof to Anvisa.

Optimized analysis and safety monitoring procedures

Resolution No. 945/2024 and Instruction No. 338/2024 also establish and detail the admissibility requirements, necessary documents, and deadlines for submitting clinical trials through optimized analysis procedures by reliance and based on the risk and complexity assessment of DDCM, DEEC, substantial modifications to the investigational product, and substantial amendments to the clinical protocol.

Despite this, the new resolution clarifies that the optimized analysis procedure’s admissibility does not imply petition analysis prioritization. Still, it provides that Anvisa may create specific queues for allocating and analyzing these petitions.

Additionally, relevant issues regarding the monitoring and notification of safety reports on clinical trials were included, such as the sponsor’s responsibility to systematically collect, monitor, and evaluate all adverse effects, including non-serious ones occurring throughout the clinical development, the deadlines for notifying SUSARs (Suspected Unexpected Serious Adverse Reactions) to Anvisa, and the way they should be carried out.

Transition Flow

The approval of DDCM, DEEC, and secondary petitions submitted to Anvisa before the resolution publication and still awaiting technical analysis will be carried out according to the rules and requirements in force at the time of submission.

Resolution No. 945/2024 revokes Resolutions No. 9/2015 and No. 449/2020 and takes effect 30 days after publication.

For more information on the new regulation of clinical trials conducted with human beings in Brazil, click here.

Learn more about Mattos Filho’s Life Sciences and Healthcare practice.

*With the collaboration of Marina Castro de Amorim