Safeguarding sound decision-making at FDA: Guest Commentary

Political interference in product reviews threatens to undermine FDA’s credibility

Recent delays and confusion surrounding the approval of Novavax’s updated COVID-19 vaccine offer a case study in how missteps at the political level can undermine public health goals. Shifting standards and late-stage demands for new data — based on faulty scientific assumptions — erode trust, delay access to important tools, and discourage developers from advancing vaccine innovation.

More than five years into the COVID-19 pandemic, nearly everyone, vaccinated or not, has been infected with SARS-CoV-2 multiple times. As a result, most people are protected from severe disease, and the primary benefit of additional vaccine boosters is short-term protection from infection. Despite widespread population immunity, COVID-19 continues to kill roughly 40,000 Americans each year, mostly older adults who have not been recently vaccinated. In this vulnerable population, boosters can reduce the risk of hospitalization by about 45%.

In this setting, the Novavax vaccine has significant promise. Because it is an adjuvanted protein vaccine, it has the potential to provide broader and more durable protection, and be more resilient to evolution of new SARS-CoV-2 variants, than mRNA vaccines. It may also have fewer side effects than mRNA vaccines. Some people who are weary of mRNA vaccines due to the deluge of misinformation advanced by vaccine skeptics might be more likely to take a protein vaccine.

In 2021, before he became FDA commissioner, Marty Makary said the Novavax product might be “the best COVID vaccine to date.”

Simply put, this vaccine has the potential to reduce deaths due to COVID.

Based on user fee deadlines that FDA has always met for vaccine license applications, the medical community was expecting Novavax’s vaccine to be approved by April 1. Last week, Novavax announced that, instead of approving its vaccine, FDA was requesting a new post-marketing study to evaluate vaccine effectiveness.

Although post-marketing means after approval, HHS followed up with a statement that seemed to leave open the possibility of delaying approval until such studies are completed. HHS stated that “…the public deserves clear answers about [the Novavax vaccine’s] efficacy and if its benefits outweigh the risk. Trials from four years ago conducted in people without natural immunity no longer suffice…”

We have no financial stake in Novavax or its products. As former public health officials, we have decades of experience in the oversight of vaccines.

We are concerned because the HHS announcement suggests political interference in scientific decisions that normally are made by the objective and highly trained experts at FDA. These experts had already recommended approval of the product based on a combination of data that included very strong immune responses induced by the vaccine against new variants, and clinical efficacy data obtained both with the original vaccine and subsequent variant vaccines.

Moving the goalposts like this has a chilling effect on the entire biotech community and reduces appetite to develop critically needed new drugs and biologics in areas beyond just vaccines, including immunotherapies and cancer treatments. Further, interference from HHS reduces the credibility of FDA and makes it much more difficult for the commissioner to do his job. Indeed, availability of investment capital for biotechnology is declining, likely in part because investors plainly see that politics are trumping science.

Current U.S. recommendations to vaccinate the entire population against COVID are out of step with the rest of the world, where boosting is generally limited to the elderly and otherwise highly vulnerable populations. However, vaccine recommendations are not determined by the FDA or tied to product approval. The CDC’s Advisory Committee on Immunization Practices (ACIP) is expected to consider narrower recommendations for COVID vaccination in June.

Obtaining better data on the populations who most need the vaccine is essential to ensuring that recommendations align with the public health need. The problem is thus not that there is an interest in obtaining additional data to guide vaccine use or to account for changes in product efficacy. Post-marketing studies for all COVID-19 vaccines are a critical part of that effort. The real questions are when and by whom these studies should be conducted. These crucial data are more efficiently and accurately collected after approval, in the broader post-marketing setting, and not by a single developer. Saddling a single manufacturer with a post-marketing study is unlikely to yield useful results and, in the meantime, the requirement only serves to delay the availability of an important vaccination option.

A clear picture of the efficacy of COVID vaccines against severe disease (the main reason we vaccinate in the first place) in different subgroups in the current era of high background immunity can only be obtained by performing multiple studies in large databases that are generally not accessible to product manufacturers. For example, in its recent review of COVID vaccine efficacy, CDC performed studies in its VISION and IVY networks, spanning over 300 emergency rooms, 26 hospitals, and over 20 states. Additional study, for example, in the Medicare database, might provide even more useful information, but this database is not available for non-government use.

Additional important data might also be obtained in studies performed by NIH grantees, to the extent that these grants have not been cancelled. And it’s only by studying all of the vaccines together that it will be possible to understand the strengths and limitations of each one.

FDA should stick to its normal processes and trust its review teams. Where it is believed that a review team needs to be overruled, there should be an explicit explanation of the defects in the review team’s reasoning and substantial external support (for example, concurrence from an advisory committee) for such a decision. Anything less erodes the agency’s credibility and undermines its ability to guide the thoughtful development of new biotechnology products, including vaccines, for the benefit of all.

Phil Krause, an independent consultant, is the former deputy director of FDA’s Office of Vaccines Research and Review. Luciana Borio, a venture partner at ARCH Venture Partners, has served in a number of government positions, including FDA acting chief scientist and director for medical and biodefense preparedness policy at the National Security Council. 

Signed commentaries do not necessarily reflect the views of BioCentury.