Part I of this article explored whether Law 14,874/2024 has, at least from a legal standpoint, addressed one of the primary obstacles hindering Brazil's development as a clinical research hub: the bureaucratic barriers and time-consuming approval processes associated with research protocol applications. In Part II, we now turn our attention to another significant hurdle: the requirement for sponsors to provide indefinite access to the experimental product to participants after the study concludes (post-study supply).

Prior to Law 14,874/2024, the obligation for post-study supply was solely governed by regulations issued by the Brazilian National Health Council (CNS) , particularly Resolution 466/2012, which established the supply for an “indefinite period”. This resolution required the product to be provided between the end of the study and its regulatory approval and market release, which is understandable to avoid treatment interruption. However, it also allowed the obligation to remain without any provision for ending. The exception were cases of ultra-rare diseases, in which supply could be limited to “five years post-approval”.

Brazil’s unique requirement for indefinite post-study supply has long been a concern for sponsors. The prevailing international practice is different: only a few countries require post-study supply, and when they do, it is for a defined period or with clear conditions for ending the obligation. According to December 2022 update of Interfarma's comprehensive study on clinical research in Brazil, co-authored with IQVIA, sponsors’ negative perception stems not only from the cost but also from the operational and regulatory challenges associated with supplying an unapproved product.

Law 14,874/2024 introduced a more balanced approach. Before the study begins, the sponsor and researcher must submit a “post-study access plan” to the Research Ethics Committee (CEPs), justifying “whether or not there is a need for free provision of the experimental drug” (Article 30). An example of a situation in which the supply would not be necessary is a clinical study with single-dose drugs or with treatment cycles that align with study's duration.

At the conclusion of the study, and after considering input from both the sponsor and the participant, the researcher must assess the need to continue the experimental treatment for each participant (Article 31, Paragraph 1). The specifics of this assessment will be detailed in forthcoming regulations. However, Law 14,874/2024 already stipulates that post-study supply must be provided when deemed the best option for the participant’s condition and offers a more favorable risk-benefit ratio compared to other available treatments (Article 31, Paragraph 2).

When it is concluded that the experimental treatment should continue, the sponsor is required to develop a so-called “post-study supply program,” which must include a “detailed strategy for ongoing supply” (Article 2, XLIV, and Article 30, Paragraph 1). Future regulations will provide further clarity on this program either. Importantly, the law mandates that post-study supply be provided “for a fixed period”, a seemingly small detail that marks a significant shift from previous practices (Article 30, Paragraph 2).

To fully comprehend what "post-study supply for a fixed period” entails, it is essential to consider other provisions of Law 14,874/2024. Article 33 outlines circumstances that terminate the obligation regardless of the previously established duration. These include unforeseen events such as the participant's decision, the cure of their illness, or the incorporation of the experimental drug into the Brazilian Public Healthcare System (SUS). Consequently, it is reasonable to conclude that the fixed period for post-study supply may also be influenced by factors beyond the ones provided for in Article 33, such as economic reasons (as is currently the case for ultra-rare diseases).

Among the scenarios for interrupting post-study supply outlined in Article 33, two are particularly noteworthy. The first, provided for in Subitem VII, states that post-study supply may be discontinued once the experimental drug becomes available in SUS. "Availability" in this context refers to Article 25 of the Decree 7,646/2011, which mandates that a drug or treatment incorporated into SUS must be made accessible for population within 180 days. Following this period, Law 14,874/2024 transfers the responsibility for providing the drug from the sponsor to SUS (upon approval by Anvisa).

It may seem obvious, but the sponsor’s obligation ends at this point, and there is no ongoing secondary liability for SUS's duty. Additionally, joint and several liability, which has been erroneously suggested in past rulings, is inapplicable. Article 265 of the Brazilian Civil Code expressly states that joint and several liability is not presumed and arises only from statutory provisions or contractual agreements. Law 14,874/2024 does not impose such liability, nor is there any other relevant legal connection.

This clarification is particularly significant in cases where, before the approved experimental drug is incorporated into SUS, a participant seeks court-ordered provision from one of the federative entities. As per a ruling by the Brazilian Superior Court of Justice (Theme 106), drugs must be provided even if not yet incorporated into SUS, provided that existing options are ineffective. In such situations, a government entity might contend that, under Article 31, Paragraph 4 of Law 14,874/2024, the sponsor bears the obligation for post-study supply prior to SUS incorporation, potentially resulting in a claim for reimbursement.

However, such a claim, which has been previously attempted, is legally untenable. While both the sponsor and the Government are obligated to provide the experimental drug, their respective obligations arise from distinct legal sources. The sponsor's obligation stems from Law 14,874/2024, whereas the Government's obligation is rooted in Articles 6 and 196 of the Brazilian Constitution and Article 6, I, d of Law 8,080/1990. In this context, reimbursement by the sponsor is not legally required, unlike the mandate imposed on health insurance companies by Article 32 of Law 9,656/1998 to reimburse costs when their beneficiaries receive treatment through SUS.

The second potential scenario for interruption of post-study supply relates to Subitem VI, which allows for discontinuation after “a period of five (5) years from the commercial availability of the experimental drug in the country”. The use of the word “could” here is due to a presidential veto, which has sparked significant debate since the law's enactment.

The justification for the veto explains that, despite the lawmakers' well-intentioned efforts, the proposal conflicts with public interest by restricting the continued free provision of the experimental drug to a five-year period following the study's conclusion, while such provision is currently mandated indefinitely. The veto further asserts that terminating the drug supply in the post-study period violates the rights of research participants and compromises the ethical advancement of research, which should be grounded in the principles of dignity, beneficence, and justice.

Some argue that the presidential veto could have broader implications beyond Subitem VI of Article 33, effectively eliminating not only the specific grounds for interrupting post-study supply but also the general rule that this obligation should now have a fixed term (as outlined in Article 30, Paragraph 2). In essence, the previous rule of indefinite supply could be reinstated. Such an interpretation is risky, particularly as it could be adopted by CEPs under the guise of maximizing participant protection.

However, there is no legal basis for this interpretation. A review of the legislative process clearly shows that one of the primary goals of lawmakers was to eliminate the indefinite period previously mandated by CNS regulations. By requiring the researcher and sponsor to submit a post-study supply plan and program, it was intended that the supply should be provided “for the period approved in a specific plan”. Representative Hiran Gonçalves even remarked that setting a time limit on this obligation “is crucial to prevent the Government from further discouraging research and the development of innovative drugs, particularly those targeting serious and rare diseases.”

Furthermore, the presidential veto only applied to one of the originally anticipated scenarios for interrupting post-study supply - specifically, the five-year period following the drug's commercial availability, as outlined in Subitem VI. This does not impact the other grounds for interruption stipulated in Article 33, nor does it affect the provision that the sponsor's obligation must now be for a specific duration, as specified in the post-study supply program, which remains in Article 30, Paragraph 2 of Law 14,874/2024.

It is clear that overturning the veto would be a key step in helping Brazil attract more clinical studies from now on, as it would set a reasonable maximum time limit for the supply of experimental drugs across all types of studies. Without such a limit, the likely inclination of ethical authorities would be to extend this protective period as much as possible. However, maintaining the veto does not necessarily imply that sponsors will once again be obligated to provide post-study supply indefinitely, nor does it signify a complete reversal of the progress achieved through Law 14,874/2024.

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