The decision to block Moderna's application was made personally by CBER Director Dr. Vinay Prasad, against the recommendation of the FDA's vaccine office staff. This unusual top-down intervention bypasses standard scientific review processes, raising concerns about politicization and the integrity of the regulatory process.
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Newly appointed FDA leaders exhibit an ideological "dualism" by promoting unproven therapies like bone marrow stem cells while showing deep skepticism towards vaccines with robust safety data. This signals a concerning shift where regulatory decisions may be driven more by ideology than by rigorous biomedical science, creating uncertainty across the industry.
Reporting reveals that FDA staff are fearful of Director Prasad due to his tendency to overturn scientific decisions and push out senior leaders. This environment stifles the voices of career scientists and has led to a "deleterious effect" on the center, potentially compromising the integrity of the review process.
Internal power shifts at the FDA, such as Vinay Prasad's rising influence, create a chilling effect on review teams. Even without direct orders, reviewers feel less emboldened to be flexible when leadership's public stance favors greater rigor. This 'tone from leadership' can shift regulatory outcomes more than explicit policy changes.
The FDA's "refuse to file" decision is highly unusual, occurring in only 4% of cases and typically for incomplete or flawed applications. Using it to block Moderna's submission over a previously-agreed-upon trial comparator suggests a strategic shift in regulatory posture, not a simple procedural issue.
The FDA's justification for rejection hinges on the vaccine's trial design for the 65+ population. Traditionally, the FDA grants broad approval, and the CDC's ACIP makes specific usage recommendations. The FDA is now blurring these lines, pre-judging post-market public health guidance.
The FDA is shifting policy to no longer allow reliance on immunogenicity data (immunobridging) for approving new or updated vaccines. This move toward requiring full clinical efficacy trials will make it harder to combat evolving pathogens and would have prevented past approvals of key vaccines like those for HPV and Ebola.
The HHS Secretary's unprecedented interview of a candidate for FDA's CEDAR Director marks a significant politicization of a traditionally scientific, civil service position. This shift suggests future directors may need political alignment with the administration, leading to greater risk aversion, erratic decision-making, and less predictability for the biopharma industry.
Moderna's trial used a standard-dose comparator, the same design basis on which the FDA previously approved two other enhanced flu vaccines for seniors. The agency's refusal to review Moderna's data ignores its own scientific and regulatory precedent, suggesting the application of a new, unstated standard.
Following its decision, FDA officials appeared on news channels and made pointed comments, including suggesting Moderna show "humility." This public relations offensive is unusual for a regulatory agency and serves as a warning to the industry, reflecting a newly adversarial relationship with developers.
Industry sentiment on the FDA is not monolithic. A recent survey reveals that while biotechs largely maintain confidence in the agency's hardworking staff and their day-to-day interactions, there is deep concern and a lack of trust in the agency's top leadership. This nuanced view highlights that the perceived problems are rooted in politicization and leadership competence, not frontline operations.
