Amid speculation that the White House had killed it, the FDA issued a promised guidance today on what it will take to get an emergency use authorization (EUA) for a COVID-19 vaccine.
The guidance sets a higher bar, in line with what FDA officials have already communicated, for a COVID-19 vaccine than what Congress set as the floor for granting an EUA for medical products intended to prevent, diagnose or treat serious or life-threatening conditions or diseases in the time of an emergency.
Speaking at a COVID-19 vaccine symposium when the news broke, Peter Marks, director of the FDA Center for Biologics Evaluation and Research, said that floor requires evidence that the product "may be effective." But vaccines need to do more than meet the statutory floor, Marks said.
To meet the higher standard, a COVID-19 vaccine must have adequate manufacturing information to ensure its quality and consistency and the FDA must determine that its benefits outweigh its risks based on data from at least one well-designed phase III trial that demonstrates its safety and efficacy in a clear and compelling manner.
For a preventive COVID-19 vaccine to be potentially administered to millions of people, sponsors will have to support an EUA request with adequate data to inform an assessment of the vaccine’s benefits and risks, with efficacy of at least 50%, according to the guidance.
Safety data from phase III studies should include a median follow-up duration of at least two months after completion of the full vaccination regimen. “Ideally, you’d like to have longer-term safety follow-up,” Marks said, but the duration of safety data has to be balanced against the cost of waiting as more people die every day from COVID-19.
Marks noted that generally most adverse events in vaccine trials occur within two to three months, so requiring at least a two-month follow-up is “reasonably aggressive,” especially since safety monitoring will be ongoing.
Additionally, the FDA doesn’t expect development to stop once an EUA has been granted. According to the guidance, an EUA request should include strategies to ensure that ongoing trials of the vaccine are able to assess long-term safety and efficacy in a sufficient number of participants to support a BLA. Those strategies will need to address how the ongoing trials will handle loss of follow-up data for participants who choose to withdraw from the study so they can receive the vaccine under the EUA.
The guidance also commits to FDA Commissioner Stephen Hahn’s promises that the Vaccines and Related Biological Products Advisory Committee will be asked to weigh in on each vaccine candidate before the agency decides to grant an EUA.
Marks said the adcom meetings will allow independent experts to vet the data in a public venue to ensure the evidence meets the FDA’s quality and manufacturing standards and to ensure the data are there to support efficacy and safety. Recognizing the need to build public trust and confidence in a vaccine, the agency wants the EUA process to be as public as possible, Marks added.
The vaccines adcom is scheduled to meet Oct. 22 to discuss the general development, authorization or licensure of COVID-19 vaccines. No particular vaccine candidate is on the agenda for that meeting, but the FDA said it’s prepared to quickly schedule additional committee meetings as it receives requests for an EUA or submissions of BLAs for COVID-19 vaccines.
The guidance reiterates that any assessment regarding an EUA will be made on a case-by-case basis that considers the target population, the characteristics of the vaccine, the preclinical and clinical study data and the totality of the available relevant scientific evidence.