FDA in Flux – October 2025 Newsletter

Welcome to FDA in Flux – A Mintz newsletter tracking rapid changes in policy and agency actions that impact medical, life sciences, and consumer product investment decisions and development strategies.

Not in Kansas Anymore: FDA Signals New Era of Drug Safety Warnings Being Imposed on Sponsors Without Notice

What is happening: President Donald Trump, Health and Human Services (HHS) Secretary Robert F. Kennedy Jr., and FDA Commissioner Dr. Marty Makary (along with the National Institutes of Health director) spent the afternoon of September 22, 2025 at a press conference making unsupported, unbalanced, and unprecedented claims about the existence of a causal connection between acetaminophen taken during pregnancy and autism. FDA followed up the same day with an announcement that it had (1) sent a letter to all US physicians about the issue and (2) “initiated a process for a label change” for all acetaminophen products.

Although FDA’s notice to doctors was much more tempered than government officials’ comments during the press conference, and much more aligned with scientific consensus about the relative strength of the evidence supporting the safety alert, the agency did not provide any indication of what this “label change” would say or how it would be accomplished procedurally. As of mid-October, no proposal to amend the over-the-counter (OTC) monograph authorizing acetaminophen for use as an analgesic-antipyretic product has been released by FDA.

Why it matters: Typically, when either the agency or a drugmaker becomes aware of a safety signal with a marketed product, they engage in direct notifications, negotiations, and shared responsibility for ensuring that appropriate revisions are made to all drug labeling, from the Drug Facts Label on OTC cartons to product package inserts (or prescribing information in the case of a prescription drug). Language used in drug safety warnings and precautionary statements is of critical importance and is highly dependent upon the state of the scientific evidence. Unsubstantiated warnings are therefore unusual due to the lightly adversarial interactions that take place between drugmakers and FDA, which builds a level of credibility assurance into the labeling update process.

Based on public reporting, however, FDA’s recent move to impose new warnings on a prevalent OTC drug product (which is also available in combination with other active drug ingredients in prescription products) was not communicated to or negotiated in advance with the manufacturer and distributor of name-brand acetaminophen. It appears the first time that the company, not to mention its competitors selling “generic” acetaminophen, became aware of the mandated new warnings was while watching the administration’s September 22 publicity stunt. It is unclear how much leverage companies will have on the ultimate language used in FDA’s autism-related warning, or whether any entities with marketed OTC acetaminophen products will challenge the agency’s administrative action when it emerges.

Who may be affected: Manufacturers and distributors throughout the FDA-regulated ecosystem should be on heightened alert for such unilateral government actions. Companies should also be ready to explore options for pushing back on governmental conclusions that are not supported by the weight of scientific evidence and that may be arbitrary or otherwise inconsistent with applicable laws. Executive agencies, including FDA, are legally prohibited from imposing arbitrary or capricious requirements on the parties that they regulate, so there may be strong arguments for administrative procedural, due process, or other violations depending on the facts and circumstances of each FDA-imposed mandate for a new warning on OTC or prescription drug products. The impact of unsupported FDA safety alerts or unsubstantiated warning statements on manufacturers’ product liability defenses, as well as the conduct of mass tort litigation involving such drug products, is also likely to be significant.

Key Regulatory Updates: AI in Medical Products

What is happening: As the sophistication of AI-based software deployed for use in health care, as well as its adoption and integration by providers, continues to accelerate, it is becoming increasingly urgent to gather robust and reliable data about such uses and potential risks to providers and patients. To this end, FDA is actively expanding its information-gathering efforts in this space by:

1. Scheduling a virtual meeting of its Digital Health Advisory Committee for November 6, 2025 to explore possible benefits, risks, and risk mitigation measures for generative AI–enabled digital mental health devices; and
2. Publishing a Request for Public Comment to gather information and feedback on “current, practical approaches to measuring and evaluating the performance of AI-enabled medical devices in the real-world...” (current comment deadline is December 1, 2025).

Separately, AdvaMed recently published a revised version of its Code of Ethics on Interactions with Health Care Professionals (AdvaMed Code), which includes a newly added section on “Data-Driven Technologies.” Although it does not mention AI specifically, this new section of the device manufacturer association’s guidance for members is clearly intended to capture such technology within its scope because they collect and use novel, large data sets for “sophisticated data analysis” and “augmented intelligence.” The guidelines focus on ethical practices for collecting, using, and protecting patient data used in such technologies.

Why it matters: Recent steps by FDA to gather real-world risk information on AI-enabled technologies and the update to the AdvaMed Code are critically important to the development of practical regulations and best practices to mitigate actual, emergent risks associated with these tools. A recent study published in the Journal of the American Medical Association analyzed US recall data for 950 FDA-cleared, AI-enabled medical devices and concluded that such devices are associated with a high number of recalls, especially when developed and marketed by publicly traded companies. The study further found that of the recalled AI-enabled devices analyzed, many were not clinically validated prior to commercialization, including 40% of those from privately traded companies, almost 78% from large publicly traded companies, and almost 97% from smaller publicly traded companies. Such data emphasize the crucial need for information-gathering efforts by government regulators and industry associations to identify real-world risks and possible solutions.

Who may be affected: FDA’s measures to gather additional information and the updates to the AdvaMed Code will impact all stakeholders in the AI-enabled medical device industry. In particular:

• Manufacturers should demonstrate that they are taking appropriate actions to evaluate and mitigate risks throughout the life cycle of each device and respond to calls for additional regulations on AI-enabled technologies;
• Health care providers / institutions should provide information to FDA and other regulators about actual risks presented by AI-enabled devices and any steps they are taking to mitigate emerging risks to patient safety and privacy; and
• Patients will be directly affected by any efforts to mitigate risks to their safety and privacy from AI-enabled technologies, and thus will be incentivized to provide information on risks they experience to providers and government regulators.

Given the Trump administration’s ongoing advocacy against strict legislative or regulatory guardrails on AI (with the aim of encouraging US advancements in AI technologies), any efforts to propose requirements on the use of AI in health care may encounter staunch resistance at the federal level. Even if the US government quells regulatory actions relating to AI-enabled health care technologies, however, states are passing — and may continue to pass — legislation restricting their uses. Individual health care institutions also may implement strict rules limiting the purchase and integration of AI-enabled technologies to tools that meet specific quality and ethical standards. Ultimately, manufacturers will have to balance (1) shareholder interests in aggressively pushing cutting-edge AI technology into the marketplace and (2) health care provider and patient interests in safety, privacy, and ethical practices.

State Legislatures Rush to Enact Laws that Undermine FDA’s Federal Drug Approval System

What is happening: Over the past several years, and seemingly accelerating in 2025, states from Florida to Montana have enacted laws authorizing the provision of certain and potentially high-risk medical products to their citizens notwithstanding a lack of FDA approval. For example, Montana recently passed a law that would license so-called “experimental treatment centers” to provide unapproved medical products — whether stem cells, other forms of biological products, traditional small-molecule drugs, or devices — to patients. The text of the Montana law suggests that the only requirements are that the experimental treatment has gone through a Phase 1 clinical trial and that patients be informed and give their consent to treatment.

Why it matters: The new Montana law and similar state actions to advance what is broadly called “right to try” or “medical freedom” are part of a rapidly escalating trend of Americans searching for miracle treatments for both rare, fatal conditions and widespread, chronic conditions like aging. While there are situations in which a patient’s autonomy should take priority over the public health — such as when a patient living with a neurodegenerative genetic disease that has no available treatment receives access to an experimental cell therapy via an emergency research protocol — the commodification and commercialization of “experimental” treatments that have not been proven safe or effective for any use could upend FDA’s century-old national drug approval system. Among other possible adverse effects:

• If patients can travel to Montana (or another state) for access to unapproved drugs, the incentives for those patients to participate in clinical trials are diminished.
• Medical product developers have less incentive to go through the onerous (but gold-standard) FDA approval process if they can start making money with a product after completing a Phase 1 trial.
• Health care providers have less incentive to partner with those developers to test investigational products if they can set up and profit from an “experimental treatment center” instead.

Who may be affected: Consumers, patients, and their caregivers may have more freedom to choose between approved and unapproved treatments, but they will also shoulder more risk in the nation’s evolving value system that is prioritizing “medical freedom” over “public health.” Notably, the settings in which these unapproved treatments are being offered most often charge patients directly and do not accept insurance. Innovators and developers positioned to provide investigational products to willing consumers therefore stand to bring in revenue earlier due to lowered regulatory barriers in such jurisdictions. At the same time, companies with significant sunk costs in product development face the danger that their investments in legitimate clinical trials will yield losses if the expected market for a product dissipates because unapproved options become available for the same patient populations. Businesses that offer unapproved or experimental treatments also may be at greater risk of malpractice claims or claims that a patient did not receive adequate information and was not able to fully consent to such a procedure.

FDA Alerts Stakeholders to Enforcement Push for Clinical Trial Transparency

What is happening: On September 27, 2025, the director of FDA’s Center for Drug Evaluation and Research (CDER), Dr. George Tidmarsh, published an FDA Voices blog post entitled “FDA Focuses on Closing the Clinical Trial Reporting Gap for Research Integrity.” The post highlights public transparency as a globally recognized ethical obligation for medical research involving human subjects. Dr. Tidmarsh pointed out that although statutory amendments from 2007 (followed by a final rule in 2017) require both clinical trial registration and the reporting of summary results on the national Clinicaltrials.gov registry, some clinical study sponsors are not meeting those expectations and many informational gaps remain.

Why it matters: Clinical trial transparency has been a long-standing bipartisan policy goal, with most stakeholders in the medical research enterprise agreeing that it is important for patients and researchers alike to have access to such information. Indeed, back in 2023, then-FDA Commissioner Dr. Robert Califf published a similar blog post to Dr. Tidmarsh’s, emphasizing the need for sponsors to comply with their results-reporting obligations. Modern-day national registries, including the US-based Clinicaltrials.gov, were created in response to patient pressure that began during the height of the HIV/AIDS crisis in the 1980s, but that pressure has not dissipated much in the intervening decades. The continued noncompliance of trial sponsors is severely undermining the important transparency benefits promised by laws mandating submission of clinical trial summaries and results.

Who may be affected: All sponsors of covered clinical trials are required to register their protocols and submit summary results for completed protocols within specific time frames. Accordingly, the potential for a noncompliance finding is not limited to particular stakeholders, and past notices from FDA have been sent to sponsors of different types. Sponsors should take Dr. Tidmarsh’s recent statements seriously and conduct internal audits of their trials to determine if any reporting gaps exist and, if so, remedy those gaps quickly. As we discussed previously here, FDA and its partner the National Institutes of Health have other tools at their disposal when a sponsor has not met mandatory Clinicaltrials.gov submission requirements, in addition to public shaming through the release of a noncompliance letter.

Proposed Rule to “Close GRAS Loophole” on Near-Term FDA Regulatory Agenda

What is happening: Since taking office earlier this year, HHS Secretary Kennedy has emphasized that major changes to the federal food regulatory system are a priority for his term and for the Trump administration. The MAHA Commission’s strategy report released on September 9, 2025 includes as an action item that “FDA will update regulations to reform the GRAS designation, within the scope of statutory authority, by closing the ‘GRAS loophole’ [and] implementing a mandatory GRAS notification program.” That stated goal was preceded by a March 2025 HHS announcement in which Secretary Kennedy directed the agency to “explore potential rulemaking ... to eliminate the self-affirmed GRAS pathway.” Now that the administration’s first regulatory agenda has been posted by the White House Office of Management and Budget, it appears that a notice of proposed rulemaking (NPRM) to begin this process was planned for publication in October 2025 (see here).

Why it matters: GRAS refers to substances that are “Generally Recognized As Safe” for use in human and animal food, including dietary supplements. Under current law, ingredient developers are strongly encouraged to submit GRAS notices to FDA for review, whereupon the agency will issue a letter stating either that the notice does not provide sufficient basis to conclude that a substance is GRAS or that FDA does not have questions about the developer’s GRAS conclusions (with all such letters then posted to a public GRAS Inventory). Due to the voluntary nature of such notices, however, current leadership at HHS and FDA argue that many food companies routinely avoid such submissions and that unsafe ingredients have flooded our foods as a direct result. The upcoming GRAS NPRM is expected to mandate submission of such notices and make other related changes to the existing system.

Who may be affected: During government shutdowns, the Federal Register generally focuses its efforts on publishing documents “necessary for the protection of life and property,” making it unlikely that this particular NPRM will be issued by FDA in October as planned. Nonetheless, it is clear from the emphasis that HHS, FDA, and the White House are putting on this regulatory action that the public will have a chance to review this highly significant proposal sooner rather than later.

All food manufacturers, food packaging innovators, public interest groups, and other interested stakeholders should be ready to quickly analyze and prepare fulsome written comments on what FDA lays out in the forthcoming NPRM to reform the existing GRAS notification system, including whether the agency’s cited authorities for the changes are legally sound and whether it may have exceeded what Congress delegated to it. Once the specifics are unveiled, stakeholders will be able to evaluate to what extent FDA’s actions may be vulnerable to challenge under the Administrative Procedure Act and recent judicial review standards articulated in Loper Bright. At the same time, however, legislation to accomplish this goal has been introduced in Congress, such that a shift from voluntary to mandatory GRAS notifications appears inevitable even if FDA’s upcoming rulemaking is legally flawed.

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