The U.S. Food and Drug Administration (FDA) is undergoing substantial workforce reductions and leadership changes that are creating significant challenges for pharmaceutical and biotechnology companies navigating the drug approval process.
Beginning in February 2025, FDA staffing cuts have affected approximately 3,500 full-time employees—representing about 19% of the agency's workforce—as part of a broader Department of Health and Human Services (HHS) consolidation. While review staff were largely spared, key support personnel in policy, dispute resolution, advisory committees, and combination product coordination have been impacted.
Leadership Exodus Compounds Regulatory Uncertainty
The workforce reduction coincides with notable voluntary departures among FDA leadership. Key officials who have left include Dr. Peter Marks, Director of the Center for Biologics Evaluation and Research (CBER); Dr. Patrizia Cavazzoni, Director of the Center for Drug Evaluation and Research (CDER); Dr. Peter Stein, Director of the Office of New Drugs; and Dr. Hilary Marston, FDA Chief Medical Officer. Several Deputy Center Directors across CBER, CDER, and the Oncology Center of Excellence have also departed.
Industry experts note that these changes create particular challenges for developers of specialized therapeutics that typically require close FDA collaboration, including rare disease treatments, cell and gene therapies, complex generics, and products incorporating artificial intelligence.
Strategic Approaches for Drug Developers
In response to these changes, regulatory experts recommend several strategies for pharmaceutical companies to keep development programs on track:
Leveraging Specialized Regulatory Pathways
With informal feedback and non-mandatory meetings becoming more difficult to secure, companies are advised to pursue programs that mandate FDA engagement. These include:
- Fast track and breakthrough therapy designations
- Special Protocol Assessments (SPAs)
- Model-Informed Drug Development (MIDD) Paired Meeting Program
- Complex Innovative Trial Design (CID) Paired Meeting Program
- INTERACT meetings (Initial Targeted Engagement for Regulatory Advice on CDER and CBER Products)
"Participating in FDA programs under which meetings and feedback would be required may become more valuable," notes one regulatory expert familiar with the situation. However, companies must carefully evaluate the regulatory, legal, and strategic implications before pursuing these designations.
Maximizing Value of FDA Interactions
When interactions with the FDA do occur, companies must ensure these engagements provide meaningful guidance. This is particularly important as meeting responses increasingly come as written response only (WRO), limiting real-time discussion.
Regulatory professionals recommend that sponsors:
- Present well-reasoned, clearly supported positions
- Clearly articulate preferred approaches with scientific and regulatory justification
- Provide sufficient precedent to aid FDA assessment
- Highlight a product's potential to address unmet medical needs or provide alternative treatment options
"Sponsors should rely on their internal and external subject-matter experts for advice around key FDA communications," explains a pharmaceutical regulatory consultant. "Having an experienced second set of eyes can help anticipate and address gaps that could hinder productive FDA interactions."
Building Decision-Making Capacity
With reduced FDA resources limiting guidance availability, companies must develop internal capabilities to make informed decisions without direct regulatory input. This is further complicated by a January 31, 2025 executive order requiring agencies to identify ten existing regulations or guidance documents for repeal whenever a new one is promulgated.
Experts recommend creating cross-functional teams with scientific, clinical, commercial, regulatory, and legal expertise to navigate this uncertainty. These teams should:
- Monitor precedential FDA decisions for similar products
- Establish structures for collaborative problem-solving
- Document and justify regulatory decisions to preserve institutional knowledge
- Consider legal options when disagreements with the agency arise
Impact on Specialized Therapeutic Development
The regulatory uncertainty poses particular challenges for developers of specialized therapeutics. Companies working on rare disease treatments, cell and gene therapies, and combination products typically rely on close collaboration with the FDA due to novel scientific approaches and limited precedent.
"This creates a tumultuous environment for biotechnology and pharmaceutical new product development," states an industry analyst. "Close communication and collaboration with FDA are essential for these innovative therapies."
Looking Forward: Challenges and Opportunities
While the current situation creates significant regulatory uncertainty, some experts note that leadership changes may eventually create openings for new approaches. Companies are advised to check in with the FDA when possible to ensure development strategies still align with the agency's expectations, as decision-makers who previously exercised regulatory flexibility may have departed.
The key for pharmaceutical and biotechnology companies will be effectively utilizing legal and regulatory professionals to navigate this changing landscape while continuing to advance therapeutic development. Despite the challenges, industry leaders emphasize that with strategic planning, companies can continue to move healthcare innovation forward in this new regulatory environment.
