Dear Commissioner Makary:

No Patient Left Behind (NPLB) is a coalition of biotech investors, innovators, researchers, physicians, and patient advocates from across the country. In the spirit of providing ongoing and open communication, we write to provide insight into how our constituents view the current regulatory environment.  

Many of us wrote in April to share our concerns about the large reduction-in-force at the US Food and Drug Administration (FDA) and its impact on FDA’s performance as the world’s pre-eminent biomedical regulatory authority. We also proposed steps to stabilize and strengthen the Agency. We are writing to you now, as US biomedical innovators and the investors that support them, to offer additional perspectives on ways to sustain and accelerate US biomedical innovation. 

We are grateful for your efforts over the past six months to help FDA maintain its institutional knowledge and capabilities. We agree that the previous status quo should be improved upon and appreciate your enthusiasm to engage in dialogue around strengthening and modernizing the FDA in order to benefit American patients, American industry, and America’s global biomedical leadership.

In that spirit, we strongly support your appointment of Dr. Richard Pazdur as the new Director of the Center for Drug Evaluation and Research (CDER). His long track record of regulatory innovation, scientific excellence, and practical problem-solving comes at an especially important time for CDER and for the Agency. His leadership will create meaningful opportunities to stabilize new drug reviews, harmonize intra-agency regulatory practices, and deepen scientific engagement with American sponsors, patients, and scientists. CDER’s leadership in adopting modern surrogate endpoints while maintaining evidentiary rigor demonstrates how thoughtful flexibility can responsibly accelerate patient access. Under Dr. Pazdur’s leadership, CDER has an opportunity to apply similar approaches where scientifically appropriate on an enterprise-wide basis for all serious and life-threatening diseases.

In parallel with this critical leadership appointment, we wish to offer additional feedback regarding FDA’s engagement with the innovation community and our ongoing concerns that may require your attention.

This month, we once again surveyed biopharmaceutical CEOs and regulatory affairs professionals – prior to the news of Dr. Pazdur’s appointment – about their recent experiences with the Agency. It is reassuring that some responded that their interactions with FDA were satisfactory or “business as usual.” Unfortunately, our survey also found that over the past several months, confidence in the FDA has been undermined by decisional volatility and unpredictability: 82% of respondents said they were worried about the FDA’s ability to function. For example: 

• CEOs cited continued gaps in institutional memory and accountability, where alignment no longer guarantees a stable regulatory framework for drug development. 

• “In one instance the Agency had not done a substantive review of our package and put forth their policy perspective and a sort of a take-it or leave-it approach,” said one.

• Some pointed out that missed deadlines and canceled meetings, including advisory committee meetings, have become common. Productive in-person or video FDA meetings are now often replaced by “written response only” feedback, delaying alignment with the FDA and hindering resolution of key development issues.

• CEOs worry about a continued exodus of FDA’s expert career staff, adversely affecting the Agency’s engagement with sponsors due to remaining staffers’ heavy workload and knowledge or experiential gaps. 

• “Not one reviewer has any clinical experience in our therapeutic category (a large category),” noted one. 

• Respondents pointed to a failure to stand up for established vaccine science and important mRNA research, and an unwillingness to address misinformation. 

• Concerns about decisional volatility were widespread. 

• “When previously agreed regulatory paths are suddenly reversed, potentially due to turnover, shifting internal interpretations, or new leadership, it undermines confidence in the entire system,” said one CEO.

CEOs further noted that the above challenges have resulted in: 

• Several surveyed companies cited difficulty in planning and initiating clinical trials, allocating resources, and maintaining investor support.

• Extended timelines and increased development costs increasingly encourage sponsor companies to explore ex-US development and regulatory options. 

• “For our ongoing operations, we have largely gone ex-US where we have better scientific engagement and greater speed,” says one CEO. 

• Another wrote: “We have gotten incredibly strange feedback from FDA on [two different] programs that we have in clinical development – that feedback has required us to increase the size of the study for for the first program given FDA’s request to adopt more conservative stats methodologies … [and for the second program] we are doing the study ex-US given some odd/strange requests and concerns raised.”

• Expected challenges for recruiting future FDA staff and leadership amid an overall FDA “brain drain.” 

In summary, CEOs fear that increased volatility in an inherently high-risk business will reduce overall investment in biomedical innovation, or divert it to other nations. 

Based on this survey, it is clear that US biotech innovators and investors value FDA prioritizing the recruitment and retention of clinical, scientific and regulatory specialists who offer innovators the benefit of experienced, case-specific guidance and problem-solving. This institutional expertise is especially important to small, early-stage, and pre-commercial US biopharma entrepreneurs, who account for the majority of new drug and biologic applications submitted to the FDA. 

We also encourage FDA leadership to embrace Dr. Pazdur’s longstanding position that the FDA takes an institutional and not an overly personal approach to its decision-making and guidance. 

Biology and chemistry are advancing rapidly. We must avoid erecting needless, new barriers to groundbreaking drug development at a time when visionary leadership, experience, flexibility, and creativity are needed most at FDA, and when global competition is at its fiercest. 

There is enough uncertainty in biology itself without the regulatory process becoming riskier. FDA must be an effective institution that can be counted on to say what it means and mean what it says, even when personnel change at the top, in the middle, or on the front lines.

Your diligent leadership can help restore order and improve the clarity and consistency of the Agency. A strong, US-focused investment environment requires a clear and consistent regulator with adequate bandwidth and expertise for reviewing applications, providing timely guidance, advancing regulatory science, and problem solving. Innovators need to have confidence that FDA will continue to be an evidence-based, science-first institution that evaluates new technologies and novel potential medicines objectively based on the risk/benefit.

Of course, the American public must trust and have confidence that new medicines are being developed under rigorous FDA oversight. As a nation, we must not erode our regulatory infrastructure, but leverage new thinking and technologies to modernize it. We should not accept increased development costs that do not serve the patient, lapsed commitments, and unfounded disdain for scientific experts. We should not accept second-best, shifting regulatory standards that undermine American biomedical superiority. And we should not tolerate FDA volatility driving companies to take their investment resources and clinical trials overseas. 

As FDA and industry embark on PDUFA VIII reauthorization negotiations and your team continues to update the Agency’s regulatory agenda, we believe the challenges and concerns cited in this letter are surmountable. This is a unique moment to ensure that modernization efforts, scientific harmonization across Centers and review divisions, and adoption of new technologies are fully aligned with the long-term needs of American patients and the US biopharmaceutical ecosystem.

Finally, we wish to reiterate our gratitude to the thousands of FDA staff who continue to serve with dedication and professionalism. Their expertise and commitment remain foundational to fulfillment of the Agency’s mission, protection of public health, and preservation of America’s life science leadership.

Thank you again for your leadership and for ensuring FDA remains a modern, science-first, globally preeminent regulatory institution. We stand ready to support your efforts and to collaborate constructively toward shared goals that benefit American patients and American innovation.