Last week, the U.S. Food and Drug Administration (FDA) published its new guidance on the Development and Licensure of Vaccines to Prevent COVID-19 (the “Guidance”). FDA provided a preview of a new COVID-19 vaccines guidance back in March 2023, when it announced that the current policy on Emergency Use Authorizations (EUAs) for COVID-19 vaccines would expire on November 7, 2023, unless superseded by another policy before that date. While the Guidance does not indicate that it replaces the previous EUA guidance, it is significant because FDA does clearly state that, “At this time, the goal of new vaccine development programs to prevent COVID-19 should be to pursue traditional approval[.]”
The Guidance provides extensive recommendations on how to conduct pre-clinical and clinical studies and what FDA expects from sponsors regarding the data to support their Biologics License Application (BLA) submissions. Some of the noteworthy aspects of the Guidance include the following:
- The Guidance suggests that because the immunogenicity of COVID-19 is still not well understood, developers should focus on vaccine efficacy in their trials.
FDA recommends late phase trials with thousands of participants and at least six months of monitoring.
FDA also takes important steps in the Guidance to address health inequities related to vaccine trials and the effects of COVID-19, noting that the agency “strongly encourages” enrollment of racial and ethnic minorities. FDA also encourages vaccine developers to include pregnant women in trials.
FDA encourages sponsors to consider more innovative clinical trial designs that may speed up the development process, such as adaptive trials and seamless trials.
To facilitate the ability to make comparisons across vaccines, FDA recommends the standardization of efficacy endpoints across trials.
Screening trial participants and evaluating the efficacy of trials will require high quality in vitro diagnostic testing to accurately detect infection. However, the Guidance merely states that the testing should be “sensitive and accurate” and “validated before use in pivotal clinical trials” without further specifying a standard or regulatory status of the testing to be used.
The Guidance also provides that accelerated approval may be appropriate for a vaccine that can more fully protect against COVID-19, but FDA will require a better understanding of COVID-19 immunology.
Overall, it appears that FDA is taking steps to ensure that some of the criticisms of the government’s response to COVID-19 are addressed, for example, by encouraging diverse trials in acknowledgment of the health inequities of those populations who have been most affected by COVID-19. FDA also continues to recognize the need for public transparency regarding the standards of vaccine approval and the importance of establishing rigorous standards for the approval of COVID-19 vaccines. However, it seems that other criticisms, such as the concern among many in the public that the vaccines do not prevent diseases, will remain unaddressed for now. Until the immunology of COVID-19 is better understood, we will likely continue to see members of public skeptical of future vaccines because they do not prevent infection.
As an administrative law matter, it is noteworthy that FDA issued the Guidance without prior comment, invoking the provisions of FDA’s statutes and regulations that say a guidance can be immediately implemented without public comment when a public comment period is not feasible or appropriate. Most of FDA’s COVID-19 guidance publications have been immediately issued without the opportunity for public comment, given the exigencies of the COVID-19 pandemic. However, with the Public Health Emergency no longer in place, it is unclear what FDA’s basis was for immediate publication of the Guidance, and FDA did not provide any explanation.