Concerned public health experts suggest that if the US Food & Drug Administration’s recent overriding of standard regulatory processes regarding its review of the Novavax vaccine BLA is a precedent, this does not bode well for future product research and development – or indeed, for patients.
In their viewpoint in JAMA Network, Patricia Zettler, Stephen Cha, Sarah Despres and Peter Lurie write that in 2024, Novavax submitted a biological license application (BLA) to the US Food and Drug Administration (FDA), seeking full approval of its Covid-19 vaccine for people aged 12 or older.
The product had been marketed since 2022 for this population under an emergency use authorisation, a mechanism for the FDA to allow use of unapproved products during public health emergencies.
The FDA was under a deadline to take action on the Novavax BLA by 1 April this year, but missed that deadline, delaying action until 16 May 2025.
Even though the FDA occasionally misses such targets, career review staff at the Centre for Biologics Evaluation and Research reportedly determined, before the 1 April deadline, that the Novavax BLA should be approved for the requested population.
But the FDA’s Office of the Commissioner paused the decision.
In an interview a few days after the pause, Secretary of the US Department of Health and Human Services (DHHS) Robert F. Kennedy Jr, said the delay reflected the DHHS’ “shifting (its) priorities to multiple-antigen vaccines”, a departure from the FDA’s practice to review all applications regardless of the DHHS’ priorities.
Novavax then said that it had agreed to conduct a clinical trial after the product was approved, while statements from the FDA commissioner and the DHHS communications staff hinted that a trial may be required before approval.
It turned out to be both. The FDA’s approval on 16 May 2025 does require that the company conduct several post-market studies. But it also licensed Novavax’s Covid-19 vaccine for a narrower population than the company had requested.
The FDA licensed the product for people aged 65 or older, but those who are 12 to 64 are required to have a condition that puts them at high risk of severe Covid-19 outcomes.
In an article published a few days after the approval, the FDA said it would now require new placebo-controlled clinical trial data for all Covid-19 boosters for healthy adults under 65.
As both former political appointees at the DHHS and career staff at the FDA, in this Viewpoint, we consider the implications of this chain of events for FDA product approval policy.
The FDA’s review process for Novavax’s BLA, and for communicating with the company and the public, has differed from standard practices in key ways. To be sure, it is worthwhile to consider changes to the FDA’s traditional practices, such as improving transparency by disclosing the FDA’s rationale for declining to approve products.
But the deviations from the standard process for Novavax’s BLA – if the FDA begins to conduct other product reviews similarly – would create confusion rather than transparency and raise questions about the FDA’s commitment to regulatory integrity.
One notable deviation was the involvement of the FDA’s Office of the Commissioner (and possibly the DHHS) in the Novavax review process. Under existing FDA policies, product approval decisions are delegated to the expert staff at the relevant centre.
Although the Trump administration has now placed at least one political appointee within the Centre for Biologics Evaluation and Research (who is also the special assistant to the FDA commissioner and was involved in the Novavax review), historically, the FDA’s Office of the Commissioner has included a small number political appointees, and the FDA’s centres have had none.
Centre staff might share information with the FDA’s Office of the Commissioner to prepare for communications about a decision, but the Office of the Commissioner generally has weighed in only in very rare circumstances to resolve internal scientific disagreements.
Commissioners across presidential administrations for both political parties have recognised the importance of, and generally followed, this practice – and political appointee involvement in application review has been rare.
In one circumstance that drew attention precisely because of its rarity, an FDA commissioner explained, when declining to overturn a centre director’s controversial approval decision, that medical product application reviews “are most appropriately vested in the Centres and only the most unusual circumstances would warrant overturning the decision of a Centre”.
These procedures are part of the reason FDA approvals have been considered an international gold standard. They help ground approval decisions in scientific evidence and ensure that established regulatory policy is followed, preventing political influence.
Political interference, or even the perception of political interference, in the FDA’s approval decisions could undercut public confidence. Particularly with the Covid-19 vaccines, public distrust of the FDA and other public health agencies has undermined uptake, with adverse consequences for community immunity and public health.
Adhering to the FDA’s long-standing procedures also helps ensure that decisions are made consistently with the law.
Although there is no bar on political appointees making product approval decisions (the statute technically vests approval authority with the DHHS secretary, who has, for decades, delegated this authority to the FDA), the decision to approve or reject any application must be made based on the FDA’s statutory standard of substantial evidence of effectiveness.
“Shifting DHHS priorities”, for example, is not a factor that the FDA may consider. And in some instances, such as in the litigation over the DHHS’s extremely unusual over-riding of the FDA’s decision-making on an application for a non-prescription emergency contraceptive, courts have pointed to political interference and process deviations as evidence that the government acted arbitrarily or otherwise failed to follow the statute.
In addition to the review process itself, how the FDA communicated about that process, including the extent of DHHS involvement, was another deviation.
Novavax’s BLA included an update to its emergency use authorised–Covid-19 vaccine to match the strains of the virus anticipated for the upcoming respiratory virus season.
In press statements before Novavax’s BLA approval, the FDA commissioner described the vaccine as a “new product” and noted that “new products require new clinical studies”.
The DHHS made similar statements. This created confusion for several weeks, with certainty only coming after the FDA licensed Novavax’s BLA and published the agency’s revised approach to Covid-19 vaccine approval as a journal article, without the expert, public, and other stakeholder engagement that typically accompanies such a policy change.
Novavax’s existing Covid-19 jab, like the great majority of the original versions of marketed vaccines, is supported by evidence on clinical outcomes from placebo-controlled clinical trials.
The evidence necessary to support vaccines based on strain updates for each year’s respiratory season has typically taken the form of demonstrating immunity to expected strains, which in turn is based on correlations between immunogenicity and clinical protection in prior studies.
This standard approach facilitates rapid approval of product updates to mirror the mutation rates of viruses. To require annual placebo-controlled trials raises substantial questions about feasibility, timeliness, and ethics because individuals will be denied access to vaccines already shown to be effective.
The FDA can and should update its recommendations regarding evidence generation for medical products as the science evolves and health threats emerge or subside. But substantive changes to the FDA’s approach usually would be developed through a policy process, rather than announced via media statements or journal articles regarding a specific product.
Indeed, the FDA’s good guidance practices regulation requires that the FDA use guidance documents to describe agency policies on various topics, including application evaluation.
Guidance documents allow the FDA to outline at length its current thinking, giving product developers predictability and certainty. In addition, the process for issuing guidance, perhaps combined with advisory committee or other public meetings, provides the public and all other stakeholders with a chance to comment on the FDA’s approach, including opportunities to share views on the trade-offs of any policy.
Regardless of the merits of the FDA’s decision on the Novavax BLA, the process by which regulatory decisions are made matters. What is publicly known about the review process for the BLA is troubling, and there is also reason to be concerned about the formulation of vaccine policy more broadly.
On 29 May, after direction from the DHHS secretary, the CDC removed mention of pregnant women from the routine immunisation recommendation and changed the recommendation on the childhood schedule to shared clinical decision-making.
But it is still in the early days for the new leadership at the FDA and the DHHS, and, aligned with the DHHS’s stated goals of transparency and gold standard science, we hope that the regulatory process for the Novavax BLA will not prove to be a precedent.
If, however, the Novavax BLA represents a new normal process at the FDA, it portends potential trouble ahead for Covid-19 vaccines – and the nation’s ability to weather the upcoming respiratory season. Beyond vaccines, infusing political considerations and political appointees into individual product decisions imperils public health and innovation.
Uncertain approval processes with unpredictable approval standards that shift with the political winds could make long-term investment riskier for the research and development that medical product manufacturers must undertake, potentially diminishing biomedical innovation – all to the detriment of patients.
See more from MedicalBrief archives:
US reverses Covid vaccine guideliness, calls for new scientific evidence
Novavax Covid jab gets US nod, despite myocarditis concerns
Novavax trials in SA and UK confirm high efficacy against original and variants