To deal with the next pandemic, the FDA needs an Office of Preparedness and Response

New evidence of the spillover of the avian flu virus, known as H5N1, to some mammals is again raising alarm bells, though for experts familiar with the virus, “none of them ever stopped worrying about H5N1.”

The recent death of a Cambodian girl from bird flu is a reminder that much is at stake. If H5N1 were to cross over to humans and ignite another pandemic, could the United States do it all over again? Could it get to a vaccine in just eight months, as with Covid-19? Does the country have the capabilities and resilience to do so?

As it stands, this is doubtful. Something must change.

The FDA’s response to SARS-CoV-2, the virus that causes Covid-19, was unprecedentedly fast. The previous administration’s Operation Warp Speed public-private partnership was instrumental to this, saving an enormous number of lives. To facilitate the expedited authorization of the Operation Warp Speed vaccines, the regulatory bandwidth within the FDA’s Center for Biologics Evaluation and Research (CBER) was massively heightened, with staff working around the clock to review submissions in real time, which was made possible only because of the dedication and personal sacrifice of individual reviewers.

The U.S.’s usual, reactive approach to disease — wait for it to spring up before starting the work — is not a sustainable model.

Today, FDA staffers are fatigued, and the agency’s attention is now focused on alleviating the immense backlog that piled up while prioritizing Operation Warp Speed vaccines, drugs, and diagnostics and handling the pandemic. Should the current situation with H5N1 result in a human epidemic, it would be naive to think that the FDA as it stands could muster a similar response as it did three years ago. Even then, beginning in late 2020, there was significant controversy over the pace of the emergency authorization review of the first Covid-19 vaccines, a result of factors including manpower (staff “were eating turkey sandwiches on Thanksgiving while reviewing documents”) and the FDA’s particularly strict requirements for safety data.

Timelines for new tools against Covid-19 are worrisome: a new interferon drug that cut hospitalizations in half for all known variants in a large trial may still have to wait years for licensure by the FDA.

Epidemics don’t pay heed to the burnout of agencies nor their review timelines. Viral threats, like H5N1, are not expected to subside anytime soon. In fact, the likelihood of another pandemic similar to Covid-19 in impact could increase threefold over the coming decades. If CBER’s Operation Warp Speed successes are to be replicated as part of a sustainable model, there is an urgent need to overturn the FDA’s fundamentally reactive approach to authorization. As much work as possible should be done ahead of time.

We propose that CBER develop an Office of Preparedness and Response to support the development and eventual authorization of medical countermeasures, particularly vaccines, to protect Americans against future outbreaks. The office would facilitate and review safety studies and related research in advance for innovations that could feasibly be of use in a future pandemic. This could include testing for safety and immunogenicity, in some cases with human challenge studies, for pandemic-potential pathogens. To this end, the office would institutionalize the regulatory successes of Operation Warp Speed while strengthening the FDA’s surge capacity on a more long-term basis.

While the FDA’s Office of Counterterrorism and Emerging Threats plays a pivotal role in terms of leading and overseeing the agency’s emergency response, Covid-19 demonstrated how essential it is to have robust capacity to evaluate evidence for medical advances within the FDA’s constituent centers.

CBER’s Office of Preparedness and Response would not only be capable of increasing reviewer capacity in the event of a public health emergency, but would also support vaccine developers in anticipation of such outbreaks through the proactive publication of guidance documents. Setting out CBER’s requirements for what a vaccine needed to achieve was pivotal to the rapid development and authorization of the Covid-19 vaccines. This model is ripe for replication for prototype medical countermeasures in anticipation of future outbreaks — a perfect example being an H5N1 vaccine.

While there are already FDA-approved vaccines for H5N1, all but one rely on egg-based manufacturing, where the target virus is cultivated within fertile chicken eggs. Despite being by far the most popular approach for producing influenza vaccines, a production method that depends on the supply of chicken eggs is not conducive to rapid scaling. In the case of H5N1, ironically, the supply of eggs could be threatened by the disease itself as it kills hens (one of the reasons egg prices have skyrocketed in the last year). While the U.S. government does make provisions for such scenarios through its strategic egg supply programs, reducing the reliance on egg supply is clearly a preferable route.

Current H5N1 vaccines are expected to take several months to scale. Against a pandemic with the potential to eclipse Covid-19, this would be far too late.

A more promising approach would be mRNA vaccines, which proved incredibly versatile for rapid scaling during Covid-19, as well as outshining other technologies in terms of effectiveness. At present, there are no authorized mRNA-based H5N1 vaccines. Several unique efforts are currently underway, however, including attempts toward a universal influenza mRNA vaccine.

The opportunities presented by these new technologies are heartening. But unless regulators provide developers with a clear pathway for success, there is a risk that these opportunities will be squandered. An Office of Preparedness and Response would remove some of the regulatory uncertainties that hinder vaccine development.

We estimate that an annual appropriation worth $15 million would be sufficient to support the core functions of an Office of Preparedness and Response within CBER, including around 25 full-time staff consisting of reviewers and liaison officers. Should the pilot office within CBER prove successful, similar offices could be adopted over time by the FDA’s Center for Drug Evaluation and Research and the Center for Devices and Radiological Health.

Bearing in mind the immense economic value of the Covid-19 vaccines, an Office of Preparedness and Response has the potential to be extremely cost effective. Furthermore, the upcoming reauthorization of the Pandemic and All-Hazards Preparedness Act — provisions for which will expire at the end of this fiscal year — serves as the perfect opportunity to secure the necessary federal support.

Others have convincingly argued that the impact of regulatory flexibility and innovation on vaccine development is profound, with the potential to safely accelerate the arrival of life-saving vaccines at a much lower cost than by other means. Operation Warp Speed laid out the critical path for achieving this — the FDA needs only to replicate it.

Robert Kadlec is a former assistant secretary of Health and Human Services. Enlli Lewis is the regulatory policy and research coordinator at 1Day Sooner.