FDA Vaccines Advisory Committee Reviews EUA Requirements, Postmarket Studies

The FDA’s Vaccines and Related Biological Products Advisory Committee took no action Thursday after a lengthy discussion of the agency’s COVID-19 vaccine requirements, considerations for continuing blinded phase 3 trials after an Emergency Use Authorization (EUA) is issued and postmarket studies.

While some members on the 18-member panel lauded the agency’s EUA guidance and said it should be supported, others said the guidance’s requirements for a minimum of two months of follow-up after an EUA is granted don’t go far enough and questioned aiming for an EUA first instead of a full approval under a biologics license application (BLA).

Philip Krause, the deputy director for the Center for Biologics Evaluation and Research (CBER)’s Office of Vaccines Research and Review, pointed out that EUAs, while they are close to BLAs in terms of having stringent requirements, still represent investigational products that don’t yet meet the standards for full approval. Additionally, BLAs involve a more extensive review process, he said.

“I don’t want you to underestimate the importance of the FDA review that goes along with a BLA too, because under BLA, the FDA has actually carefully reviewed essentially every single person that’s been in those trials and looked at what happened to them, and has carefully looked at the manufacturing process and all the ways in which [it] is controlled to make sure this product can be consistently made,” Krause said.

Paul Offit, director of the Vaccine Education Center at Children’s Hospital of Philadelphia, said he believes the public may have a misunderstanding about EUAs as having a significantly lower standard for vaccines than a full approval due to the wording of the term.

“I think we have a language problem. I think when people hear the term EUA, what they hear is not necessarily approved or authorized product, they hear a permitted product, which is to say that you are permitted to use it as you would any investigational new drug, which is a very low bar,” he said. “People think that there are critical safety guidelines or efficacy guidelines [that] are being curtailed, but that’s really not the story.”

Members of the expert panel also expressed concerns about making sure minority and pediatric populations will be adequately represented in COVID-19 vaccine trials. Cody Meissner, chief of Pediatric Infectious Diseases at Tufts Children’s Hospital, called for pediatric patients to be evaluated as a distinct group because the disease impacts them differently.

The committee also considered the continuation of blinded phase 3 trials — which involve the randomized use of placebos — with most members believing doing so is essential, while some said there are ethical considerations.

Luigi Notarangelo, head of the National Institute of Allergy and Infectious Diseases’ laboratory of clinical immunology and microbiology, said that the “continuation of blinded phase 3 trials is absolutely critical, and we should do all that we can to make sure that they continue.”

Acting Committee Chairman Arnold Monto, an epidemiology professor at the University of Michigan, echoed the same sentiments, arguing that “unblinding destroys the whole purpose of a randomized trial.” He did, however, acknowledge the ethical dilemma of granting an EUA while continuing to give trial participants placebos.

Lastly, the committee discussed postmarket studies that should be conducted following an EUA or BLA that would continue to assess a vaccine’s safety, effectiveness and immune markers for protection, as well as the safety and efficacy in specific populations.

Meissner again stressed the importance of extensively evaluating COVID-19 vaccines in pediatric and adolescent patients before they’re recommended for vaccination.

CBER Director of Office of Biostatistics and Epidemiology Steven Anderson said the FDA is currently developing master protocols for safety and effectiveness outcomes it intends to study for coronavirus vaccines. It will post the draft versions of those protocols for public comment, and will eventually publish the final versions and final study reports online. The agency plans to identify and monitor 10 to 20 safety outcomes of interest, which will be done alongside the CDC and other government partners, he said.

Pfizer is likely leading the COVID-19 vaccine race, with its CEO Albert Bourla announcing last week that the company will likely file for an EUA in late November (DID, Oct. 19). — James Miessler