What does full FDA approval of COVID-19 vaccines actually mean?

The development and deployment of the mRNA vaccines against COVID-19 has been an amazing success story in science and this technology has the potential to revolutionize future vaccines and treatment for many diseases, including cancer. But the real superstar is actually the process that was used to get us to this point.

Fundamentally, we have pressure tested the Emergency Use Authorization (EUA) process and it has passed with flying colors. For this, the Food and Drug Administration (FDA) should be commended. Imagine a process that took less than nine months from the first in-human administration of a candidate mRNA vaccine to the FDA granting an EUA. Since then, according to the CDC COVID-19 Vaccine Tracker, over 159 million shots of the Pfizer-BioNTech and over 124 million shots of the Moderna vaccine have been administered in the U.S. with great efficacy and very limited adverse reactions.

On Jan. 31, 2020, when COVID-19 was first declared a public health emergency by then-HHS Secretary Alex Azar, who could have foreseen the challenges that lie ahead? We were in crisis and there was much disagreement around approaches to exactly what was going to help us dig out of this pandemic. But one thing most of the top experts agreed upon was that one or even more vaccines were desperately needed and would have to be administered to a large swath of the population if we were to stop SARS-CoV-2 transmission.

The vaccines needed to be developed and approved at pandemic speed. To support this, the FDA had a process solution already worked out called the Emergency Use Authorization. Even though it had never been utilized at the scale of this pandemic, it was a process that had proven itself at smaller scale many times and frankly it was perhaps our best opportunity to begin making headway against the pandemic.

This particular use of the EUA process shows what can be done when our backs are against the wall, but what could it mean in other applications? I think it could mean even more lives saved in a host of other areas of medicine. Given this, it is my hope and the hope of many colleagues and experts I have spoken to, that this experience is not taken for granted. We should not need a pandemic to drive this level of collaboration and action. Steps need to be taken to identify how a process similar to the EUA can be applied more often and more widely, as appropriate.

The process itself is still incredibly rigorous and safe. For an EUA to be issued, companies need to present to the FDA evidence that they have adequate manufacturing capacity to ensure the vaccine quality, consistency and efficacy analysis from a Phase 3 trial or an interim analysis of the trial and safety data with a median follow-up of at least two months. In contrast, for a Biologic License Application (BLA) safety and efficacy data from at least six months is required. Thus, a major difference between an EUA and a BLA is in the length of follow up that is required around both efficacy and safety. Both processes have a place in the system.

A Biologic License Application is a request for permission to introduce, or deliver for introduction, a biologic product into interstate commerce. After careful review of the information submitted, the FDA decides if the drug will be approved (also known as to license) for its use in the United States.

Regardless of any increased use of the EUA process, obtaining full FDA approval will always be important. It should remain the threshold that among other things allows companies to initiate direct to consumer marketing, it will allow for the vaccines to remain in the market once there is no longer a public health emergency, and it will also allow many businesses and institutions to feel more comfortable requiring employees to be vaccinated.

And today, this process is continuing to play out. On May 7, Pfizer-BioNTEch announced the initiation of a Biologic License Application with FDA for approval of their COVID-19 vaccine for persons 16 years and older. Moderna announced on June 1 that they had initiated their Biologic License Application to the U.S. FDA seeking approval of their vaccines for people 18 years and older. Once their application is received by the FDA, scientists will begin the review process of the submitted data. This review can take as long as 10 months, it is possible that for the COVID-19 it may be shorter, but it can still be as long as six months.

Ironically, as the BLA review process is occurring with these two vaccines, roughly half of the U.S. population have already received at least one dose of one of the COVID-19 vaccines. In fact, by the time the FDA issues its full approval, it is likely that the great majority of the U.S. population could have already been vaccinated. Full licensure may still help in convincing some persons who are hesitant to receive COVID-19 vaccines to be vaccinated. However, the major problem is globally where lack of access to approved vaccines is the reality for the majority of the population. Thus, the FDA approval of the mRNA vaccines may have a profound impact on the global pandemic in helping regulatory agencies around the world, proceed quickly to approve these vaccines.

There are many challenges for the global availability of the mRNA vaccines, including scaling up manufacturing capacity. While we need to overcome these challenges, a major advantage of mRNA COVID-19 vaccines is their proven efficacy against SARS-CoV-2 variants of concern. Data on the Pfizer-BioNTech vaccine suggests an estimated effectiveness of 87 percent against the Alpha (B.1.1.7 also known as the U.K. variant) and 72.1 percent against the Beta (B.1.351 also known as the South Africa variant). Moderna has reported in vitro data suggesting neutralizing titers against these two variants. Nevertheless, both companies are already working on “booster shots” against these and other variants, which would be relatively easy to do given their “plug and play” technology, should boosters be necessary.

There is so much to learn from the pandemic, and we will be peeling back the layers on this crisis for years to come. But the one learning that we can take a hard look at is the application of the EUA process and hope it can help physicians like myself and other colleagues across the U.S. save more lives from other conditions that have not reached pandemic situations, yet still threaten the lives of so many.

Carlos del Rio, M.D., FIDSA, is vice president of the Infectious Diseases Society of America. He is a professor of medicine at Emory University School of Medicine and of global health and epidemiology at Emory’s Rollins School of Public Health, principal investigator and co-director of the Emory Center for AIDS Research, and co-principal investigator of the Emory-CDC HIV Clinical Trials Unit and Emory Vaccine and Treatment Evaluation Unit. He is also the international secretary of the National Academy of Medicine and the Chair of the PEPFAR Scientific Advisory Board.