Dear Senator Cassidy:

We are US biomedical innovators, the investors that support them, and patient advocates who depend on continued medical progress, as all Americans do. We rely on the US Food and Drug Administration’s guidance and rigor to navigate policy and medical standards and to approve new medicines. Our ability to develop medicines, medical devices, vaccines, and diagnostics to better the health of all Americans is predicated on a science-focused agency that can do its job effectively and efficiently. 

While we share a desire to strengthen and modernize the FDA, we are writing to share that we are deeply concerned about the current state of the agency and its future. Specifically, we worry that the institutional knowledge that makes the FDA the world’s leading regulatory body will be irretrievably lost due to the agency’s recent reduction in force and wave of retirements. The agency’s ability to function is compounded by a hiring freeze. As a result, American patients, American industry, and American biomedical leadership will bear the consequences.

We wish to emphasize that we are grateful for the thousands of dedicated FDA staff who remain at their posts and committed to their work. Their efforts, particularly under the stress of this transition, is vital to allowing us to keep doing our own work. 

Ensuring that the FDA is adequately staffed during Commissioner Makary's reorganization process is particularly essential for small, clinical-stage biotechs that are typically resource constrained and rely on investor capital to meet the FDA's requirements and standards. Any delays in FDA reviews will substantially impact these companies’ ability to secure the funding they need to continue to advance to the next stage of development; the extreme turmoil in the biotech financial markets reflects that investors are worried about our ability to execute.

Most small companies don’t engage the agency frequently enough to know yet how their drug candidates or their research timelines will be affected by recent changes at the FDA; while some problems crop up quickly, others will take months or even years to emerge. The companies that happen to be engaging with the FDA right now are our leading indicators – and some of us have already encountered regulatory difficulties that we believe are the consequences of the FDA’s loss of experienced staff.

We are asking you to identify where FDA’s capabilities have been impacted in order to quickly preserve and restore its core functions. We encourage agency leadership to possibly re-hire key people who carry substantial institutional knowledge and lift the FDA’s hiring freeze to ensure all key roles are adequately staffed in order to: 

1. Maintain established regulatory timelines

The operating plans and development milestones of biotech companies leave little room for missing critical regulatory timelines due to unforeseen FDA delays. Our companies have already faced delays in scheduling routine meetings and receiving routine agency feedback that guides drug development. Many have concerns that approval decision deadlines will be missed.

Example: A California-based biotech now engaging the European Medicines Agency earlier in development than previously anticipated to mitigate concerns about FDA’s ability to meet development timelines. “We are now filing an investigational medical product dossier with the EMA in order to enroll patients in geographies outside the US to keep timelines, engaging foreign CRO’s, effectively ‘offshoring’ capital and investment dollars away from the US.”

Example: A Massachusetts-based biotech working through FDA’s dispute resolution process had that process suspended because their FDA counterpart wasn’t confident there would be any senior staff to review it.

Example: A Boston-based biotech working through a clinical hold with the FDA on one program and seeking advice on outcome measures on a second program is currently not sure if their FDA project managers are still with the FDA. “We do know that our toxicology reviewer who is familiar with the program is no longer with the FDA,” which will result in delays.

2. Preserve the ability to make “judgement calls” 

Applying the law and regulations in a consistent and thoughtful manner, particularly in dealing with “edge cases,” accelerated approval pathways, product development incentives, and new therapeutic modalities is essential to moving regulatory science forward for the benefit of patients. Given the cutting-edge nature of our work, “edge cases” are common. 

Example: Key policy individuals across CDER and CBER are no longer with the agency, including legal staff who work with reviewers. With new technology platforms, the interactive dialog between policy individuals and scientific reviewers is important to enable a thoughtful approach to these new modalities.

Example: Critical gaps in leadership and management at the review division level have typically been filled by senior FDA leadership. But with these individuals now gone, companies fear we are entering a period of years to build back up an experienced workforce. One biotech recently experienced conflicting feedback from the review team – a situation where someone senior should step in to make a determination of agency position, which did not happen. 

3. Ensure clarity and consistency 

Inconsistent feedback during development leads to delays, waste, and an immeasurable human cost. A culture of rigorously following the science and clearly communicating important information about product safety, regulatory guidance, policy, and FDA-decision making is crucial. The FDA should continue to participate in ongoing dialogues with patient groups, academics, other global regulators, and industry to pursue needed regulatory reforms that align with US goals. Communication is therefore a core function. 

Example: A US-based biotech reporting feedback on a submission seemed to be from particularly inexperienced reviewers, contained suggestions that seemed inconsistent with medical practice or standard approaches to trials, contained several comments that were very poorly worded, and requested multiple things that were already clearly present in the submission. 

Example: Division leadership and medical reviewers failed to attend recent meetings related to an ongoing, two-year process involving industry, patient groups, academics, and global regulators to redefine guidance for surrogate endpoints in a specific disease area. As a result, the drug development community is uncertain if the needed reforms will be aligned with FDA.  

4. Avoiding delays to PDUFA 

Negotiating PDUFA reauthorization and determining staffing requirements to meet the agency’s stated goals is crucial to ensuring timely reviews for medicines. It is the industry’s goal to continue to help fund the FDA and yet we worry that lapses at the FDA might result in the FDA not being allowed to collect fees or even renegotiate a way for industry to keep paying fees. Please protect the FDA’s ability to continue to collect user fees.

Example: The team coordinating PDUFA implementation and goals with industry in both CDER and CBER was affected by the recent RIF. 

Looking Ahead

Some of us have distilled a concrete set of solutions for your consideration that could help restore order and confidence in the FDA (these are not meant to be comprehensive nor do all signers claim to know enough to endorse these steps):

1. Rehire certain employees key to keeping the user fee program on track: Chris Joneckis and Betsy Valenti.

2. Rehire certain employees key to capacity planning and workload analysis: Yaeming Chae and Isaac Dorfman.

3. Rehire certain employees key to CDER/Office of Program and Strategic Analysis: Andy Kish, Patrick Zhou, Emily Ewing, Josh Barton.

4. Unfreeze the hiring freeze for roles that are critical, such as Head of Human Tissue, Head of Clinical Evaluations, and Head of Cell and Gene Therapy.

5. Use the RARE disease hub model for other therapeutic area pilots in which CDER and CBER can collaborate with a view to determining whether merging the two makes sense.

Our current concerns and recommendations do not mean we are advocating for business-as-usual. We recognize and support that America must strive for government efficiency, and we believe we share with the Administration a vision of a gold-standard regulatory agency that efficiently shepherds safe and effective products to the market. Some of us have served in the FDA and understand its strengths and weaknesses. Conflicting guidance and changing perspectives can be frustrating. The other side of that coin is that the FDA has never been monolithic; we’ve always had something to complain about but also something to admire. Some departments are more creative and encouraging of innovation. That means that the agency could evolve by adopting best practices from within. The current uncertainty surrounding the FDA's ability to function creates downstream uncertainty from investors who will question whether the FDA can do its job as it is being reinvented.

We urge caution in trying to centralize all functions and over-systematize a regulatory process that has to be flexible in the face of new scientific discoveries. In fact, it's often the creativity and good judgment of senior people that has allowed reviewers to set aside formal guidance that, if imposed strictly, would stymie progress. By maintaining deep agency expertise today, future reductions in force can be guided by those with the experience and vision necessary to build an efficient FDA that we and all Americans can count on. 

Thank you for your leadership and oversight and for driving accountability for decisions impacting the FDA that can have consequences that affect each and every American.