The emergency nature of the pandemic and the rapidly accelerating nature of the fatalities tipped the agency’s risk/benefit scale and created an environment which necessitated greater regulatory flexibility for those therapies with potential to treat COVID-19. Lessons learned from the pandemic thus far are likely to influence all drug and biologic reviews and approvals in the future. Commissioner Hahn recently asked FDA staff to consider which approaches could continue beyond COVID-19.

The Evolution of FDA Guidance for Sponsors Developing COVID19 Therapies

As the magnitude of the global pandemic became apparent, FDA announced the opportunity to use Emergency Use Authorization (EUA) for drugs and biologics to be deployed against COVID-19. EUAs allow unapproved medical products or medical products currently approved for other conditions to be used in a medical emergency. This immediate response was established to address the emerging threat and ensure unnecessary regulatory barriers were not harming or slowing access to medications for critical ill patients. Earlier in the pandemic, EUAs were issued alongside other regulatory actions taken for COVID-19 therapeutics such as New Drug Applications (NDAs). Resources at FDA were redeployed to accommodate the needs for Agency engagement in the development of new COVID-19 countermeasures and the Coronavirus Treatment Acceleration Program (CTAP) was established.

As information on the disease COVID-19, the virus SARS-CoV-2, and the spread of the virus accumulated, FDA reassessed the situation and modified responses according to the information coming in. Various government agencies initiated collaborative efforts to accelerate COVID-19 therapies such as the Accelerating Covid-19 Therapeutic Interventions and Vaccines (ACTIV) partnership by the National Institutes of Health (NIH) and Operation Warp Speed by the Administration. Two months after use of EUAs for COVID-19 therapeutics was first initiated, FDA announced an updated and streamlined process for sponsors studying COVID-19 products. Alongside this announcement, FDA released guidance recommending that sponsors submit a pre-Investigational New Drug (IND) request rather than a pre-EUA request. This shift from EUA to NDA/Abbreviated NDA (ANDA), helps normalize the process, but does not answer the question as to the most expeditious and efficient regulatory route to approval. FDA has also implemented processes to adjust to measures intended to control the pandemic, as evidenced by the release of the COVID MyStudies to obtain electronic informed consent from patients on clinical trials for COVID-19 therapies.The timeline in Figure 1 demonstrates actions the agency has taken throughout the pandemic.

Manufacturer Considerations

There are many different approaches to getting a COVID-19 therapeutic on to the market in the US and each has very specific advantages and disadvantages in terms of data expectations and timelines. As important as the FDA approval is how the product will ultimately be deployed within the health care system and by whom. As such for each possible regulatory pathway, there are downstream implications for commercialization that sponsors should consider right at the beginning of their development plan. Making these decisions early will be of upmost importance to ensure a strong market access strategy post approval, and an ability to recoup any investments. Direct engagement with FDA by sponsors will also be invaluable, but the Agency’s expectation is to comment on data, and it will not design a development program for a company. It will however make constructive recommendations and provide substantial input to thoughtful product development programs. Careful consideration should also be given to scale up and manufacturing at commercial scale given that an approval serves little value if adequate amounts of the product cannot be manufactured and made available in a timely manner. FDA expectations can be expected to continue to evolve.

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