The 2025 U.S. executive administration has ushered in significant changes at the Food and Drug Administration (FDA), including a reduction in personnel and the departure of key leadership figures across drug, biologics, and device centers. These changes have created uncertainty regarding the FDA's efficiency, prompting sponsors to question the impact on FDA operations and its ability to uphold user-fee commitments. Additionally, new policy directions are anticipated under the new executive branch and Health and Human Services (HHS) leadership. With key FDA positions yet to be filled and new leadership in place, it is expected that top-down policy shifts and organizational changes will significantly influence future FDA policy and decision making.

Anticipating the short- and long-term impacts of these changes is challenging: how will they affect sponsors' regulatory timelines and their ability to bring products to patients? Medical product manufacturers, particularly those developing innovative products and life-saving therapies in the pre-market or early stages of the product lifecycle, cannot afford to adopt a "wait and see" approach; changes to FDA may impact overall commercial regulatory timelines due to potential longer pre-market review times and delayed inspections.

However, even with changes yet to be seen, sponsors can take steps to help strengthen their regulatory planning and interactions as the Agency undergoes a state of change. Well-prepared regulatory submissions, a careful focus on regulatory precedent in anticipation of institutional knowledge loss, and regulatory strategies that highlight product long-term benefits to American public health could be beneficial. These three recommendations may prove essential to navigating the new FDA, in addition to consultation with regulatory science experts.

1. Structure and streamline FDA interactions.

   The FDA has experienced significant organizational changes over the past six months, marked by the departure of half of its senior leadership and substantial employee reductions across various offices and divisions that review biomedical products. This includes the loss of approximately 3,500 employees, including those from the Center for Drug Evaluation and Research (CDER) and Center for Devices and Radiological Health (CDRH). The organizational turbulence and shifts in leadership may hinder review teams’ ability to provide comprehensive expert feedback for complex regulatory issues that require scientific leadership’s guidance and support. The reduction in personnel also places additional stress on lead reviewers, who now face increased workloads due to smaller teams and fewer subject matter experts, such as medical officers and expert reviewers for real-world evidence. Consequently, this could lead to longer review times, slower responses to informal interactions (e.g., low-priority administrative questions via email), and a diminished capacity to provide detailed and clear responses during communications.

   Recognizing that review teams face external pressures which may hinder their review capacity and detailed communication, sponsors should ensure their communication packages—including meeting requests, designation requests, and pre-market applications—are optimized for readability and clarity with a clear regulatory rationale. Extra care should be put towards creating a well-organized submission that is easy for review teams to navigate and that highlights must-see information critical to the product. Sponsors should organize their formal interaction documents in a structure that closely follows FDA decision making frameworks and guidance documents.

2. Strengthen regulatory arguments with established regulatory precedents.

   In the past six months, numerous FDA senior leaders and internal regulatory champions who provided critical guidance on clinical, scientific, and regulatory matters to the pharmaceutical industry have departed the FDA. This includes the departures of now former CBER director Peter Marks, a strong advocate for gene therapies that impact rare disease treatments during his tenure as CBER director, and former associate director of RWE Analytics John Concato who transitioned from his role this past December after a career of developing CDER’s Real-World Evidence (RWE) program. Additionally, January’s “10-for-1” presidential executive order Unleashing Prosperity Through Deregulation was signed, mandating the elimination of 10 regulations for each new regulation issued. Consequently, the finalization of FDA guidance documents may be delayed in an effort to preserve current policies, further slowing the development of new and finalization of draft guidance documents. The loss of internal championing resulting from the departure of Agency-wide leadership, combined with deregulation efforts initiated by January’s presidential executive order, may hinder the development of policies related to the application of novel regulatory methodologies and the review of innovative products.

   Without the development of new guidance documents for innovative products and the long-term leadership needed to ensure continuity of regulatory frameworks, review teams may increasingly depend on prior FDA decision making to inform their evaluations. Less-experienced review teams may refer to the body of past decisions, guidance documents, and established practices that the FDA has used to make regulatory determinations for similar products or situations. In turn, sponsors should consider strengthening regulatory arguments by firmly grounding them in established regulatory precedents. In addition to following decision making frameworks set by existing guidance documents, highlighting prior Agency determinations could provide support for regulatory arguments in the absence of senior scientific direction.

3. Refine unmet need with a heavier focus on public health.

   New HHS Commissioner Robert F. Kennedy, Jr. and the establishment of the Make America Healthy Again Commission may cause broader policy shifts across the FDA, influencing the directions of regulatory decision making. Chaired by Kennedy, the commission aims to address the root causes of chronic illnesses and disease prevention in the United States, creating a focus on the American public and preventative medicine for chronic illness. “We are realigning the organization with its core mission and our new priorities in reversing the chronic disease epidemic,” Kennedy stated in a March HHS announcement. His leadership appears to be a departure from the more siloed approach of previous U.S. administrations where various health initiatives and regulatory efforts were often handled separately, without much integration or coordination between different areas such as public health, agriculture, and biomedical research. Kennedy's leadership is expected to bring broader policy shifts, including a focus on improving public health.

   Sponsors should consider refining their definition of unmet need to include a broader focus on American public health. Typically, the severity of an unmet need for regulatory purposes is contextualized by the absence of satisfactory methods for diagnosing, preventing, or treating a disease or condition. This criterion is crucial for qualifying medical products for expedited programs such as Fast Track, Breakthrough Therapy, Accelerated Approval, and Priority Review. Sponsors should also consider providing additional context on diseases from a broader American public health perspective, especially when seeking entry into these expedited programs.

Navigating an uncertain landscape with the right regulatory partner

The evolving landscape of the FDA under the new administration presents new uncertainties for sponsors. As the agency undergoes significant organizational changes and policy shifts, it is imperative for sponsors to proactively adapt their regulatory strategies. By optimizing communication packages, leveraging established regulatory precedents, and redefining unmet needs with a focus on public health, sponsors can navigate this period of uncertainty effectively. Our team of regulatory experts – including former FDA regulators, lead reviewers, and policymakers, and science communicators – help innovative, healthcare product makers navigate the regulatory landscape effectively in times of uncertainty.

References:

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2. Al-Faruque, F. (2025, March 27). HHS to cut 10,000 more jobs across HHS, including 3,500 from FDA. RAPS Regulatory Focus.
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7. McKenzie, H. (2024, January 18). FDA’s Marks advocates for flexibility in rare disease gene therapy trials. Biospace. Accessed 2025, April 9.
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