The recent reductions in the US Food and Drug Administration’s workforce are poised to have a substantial impact on drug and biologic development programs. This LawFlash discusses strategies to optimize interactions with the Agency and keep development programs on track.
Strategies that sponsors can use to optimize US Food and Drug Administration (FDA) interactions and keep development programs on track include the following:
- Confirming current development pathways, while also considering opportunities for new or different approaches
- Employing specialized pathways and programs to increase FDA interactions, while also ensuring that interactions meaningfully contribute to the progress of the development program
- Monitoring potentially precedential FDA decisions for similar products
- Creating internal and external teams and structures to make strategic decisions when FDA guidance is not available
There have been substantial recent shifts within the ranks of FDA. FDA staffing cuts began in February 2025 and, on April 1, 2025, a predicted 3,500 full-time FDA employees—about 19% of the agency’s workforce—were subject to a US Department of Health and Human Services (HHS)-wide consolidation and reduction in force. While this reduction does not appear to have been focused on review staff, the trade press reports that employees supporting application reviews were affected, including policy, dispute resolution, advisory committee, and inter-center (i.e., combination product) staff. Also impacted were legislative staff charged with user fee negotiations, a process that will begin this year and affect FDA’s future funding and resources.
Further adding to these shifts, voluntary departures from the agency have broadly taken place among FDA’s leadership, including Dr. Peter Marks, the Director of the Center for Biologics Evaluation and Research (CBER); Dr. Patrizia Cavazzoni, the Director of the Center for Drug Evaluation and Research (CDER); and several Deputy Center Directors of CBER, CDER, and the Oncology Center of Excellence. Dr. Peter Stein, the Director of the Office of New Drugs (OND), and Dr. Hilary Marston, the FDA chief medical officer, have also been reported to have left. While some employees may be reinstated, additional voluntary departures are expected in the coming months.
This creates a tumultuous environment for biotechnology and pharmaceutical new product development. Especially for rare disease products, biotechnology, cell and gene therapies, complex generics, combination products and products incorporating artificial intelligence or other novel developments, close communication and collaboration with FDA are essential. Many may now be wondering, “What are the next steps?” Below are strategies to consider for keeping development programs on track.
REMEMBER: THINGS ARE NOT AS THEY WERE
With the rapid changes occurring within FDA, coupled with the departure of many of the agency’s key leaders, this is a time of transformation that could present both hurdles and opportunities. When approaching regulatory questions or challenges, application sponsors should be prepared to present well-reasoned and clearly supported positions to FDA. It will be important to recognize that previous support resources may no longer be available to remaining staff, who are experiencing greater workloads, increased demands on their time, and new areas of responsibility. On the other hand, with new people and leadership, over time, the Agency may be open to new ideas and approaches. Even for previously “settled” approaches, sponsors should check in with FDA as the opportunity presents to ensure that their strategies still align with the Agency’s expectations, as some decision-makers who drove prior approaches and were comfortable exercising regulatory flexibility have since left.
CONTINUE TO FIND OPPORTUNITIES FOR FDA INTERACTION AND FEEDBACK
Moving forward, informal feedback from review divisions, as well as formal meetings not mandated by statute or regulation, will likely be more challenging to obtain on a timely basis or at all. Accordingly, participating in FDA programs under which meetings and feedback would be required, including the fast track and breakthrough designation programs, Special Protocol Assessments (SPAs), the Model-Informed Drug Development (MIDD) Paired Meeting Program, the Complex Innovative Trial Design (CID) Paired Meeting Program, and the Initial Targeted Engagement for Regulatory Advice on CDER and CBER Products (INTERACT) meetings, may become more valuable. However, applying for these designations or programs involves regulatory, legal, and strategic decisions that must be evaluated.
Further, FDA’s policies will likely be implemented through individual adjudications and actions on specific products, which may or may not be publicly available. It will be increasingly important for sponsors to pay attention to decisions regarding third-party products and assess their scientific, legal, and regulatory applicability to the sponsor’s own development programs.
ENSURE INTERACTIONS ARE MEANINGFUL
When sponsors are able to interact with FDA, it will be important to ensure that such interactions provide the best opportunity for FDA constructive guidance. In this regard, sponsors will need to be deliberate and strategic in the meetings sought, the information presented, the questions asked, and how the questions are asked. This is critical in the current environment, where meeting responses may frequently be written response only (WRO), meaning that real-time back-and-forth interaction may not be possible.
Sponsors should ensure that they are asking questions in the right way and presenting meaningful information. In written materials, sponsors should clearly set forth their positions, justifying any preferred approaches, and provide sufficient regulatory and scientific information and precedent to aid FDA in assessing the questions. This gives the Agency a clear approach to which it can react and provide tailored guidance, potentially avoiding a response from FDA that its position will be a “review issue” (a response that is occurring with increasing frequency).
This will also outline the issues and pertinent information for FDA decision-makers who, due to increased demands, cannot attend in person. It can also be useful to convey the future value of a product candidate to FDA, whether that be in terms of meeting an unmet medical need, providing improved or important alternative treatment options, or—while not directly within FDA’s jurisdiction—decreasing the cost of medical care.
These strategies require a concerted and focused approach to FDA interactions. Sponsors should rely on their internal and external subject-matter experts for advice around key FDA communications. Frequently, having an experienced second set of eyes can help sponsors anticipate and address any areas where there may be gaps that could hinder productive FDA interactions.
CREATE A TEAM FOR STRATEGIC AND INFORMED DECISION-MAKING
With more limited FDA resources, there may be questions for which sponsors are not able to obtain FDA answers, either on an individual or industry-wide basis. For instance, a January 31, 2025 executive order (EO) requires that “whenever an agency promulgates a new rule, regulation, or guidance, it must identify at least 10 existing rules, regulations, or guidance documents to be repealed.” This EO, coupled with drastic reductions in policy staff, makes it more difficult for FDA to issue industry-wide guidance interpreting the Agency’s regulations, which is particularly important in this time of rapid technological innovation.
The inability to speak directly to regulators will further require significant adjustments for companies’ Regulatory Affairs personnel and will impact communications with the C-suite and boards of directors when there are drug development questions or issues. Thus, it is important for companies to have both internal and external teams with experience navigating FDA trends and changes, who can contribute to informed and risk-based decisions. This requires scientific, clinical, commercial, regulatory, and legal expertise, as decisions may impact many regulated areas, including FDA regulation, pricing and reimbursement, commercial messaging, supply chain and manufacturing, finance and investor relations, and intellectual property.
Companies should establish a broad knowledge base, as well as structures for collaborative discussions and problem-solving. Companies should also ensure that they properly document and justify any such decisions to preserve institutional knowledge and facilitate future discussions with regulators. Finally, sponsors may also need to consider the use of legal levers when disagreements arise with the Agency.
CONCLUSION
FDA is in a time of flux, which inevitably will increase regulatory uncertainty for regulated industry. However, with changes also come opportunities. The key will be for companies to use legal and regulatory professionals effectively, to position themselves to successfully take on this new environment so that they can continue to move therapeutic products and healthcare progress forward.
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