FDA’s COVID-focused vaccines adcomm: A preview
On 22 October, the US Food and Drug Administration (FDA) will convene the first COVID-19-focused meeting of its Vaccines and Related Biological Products Advisory Committee (VRBPAC).The meeting is not reviewing information about a specific vaccine; rather, the committee is convening “to discuss, in general, the development, authorization and/or licensure of vaccines to prevent COVID-19,” according to the agenda. The committee is tasked with sorting through much technical detail of how an authorization or approval would be executed, but members will also weigh in on much broader ethical issues.
The advisory committee’s 18 members will be joined – virtually, as all attendees are participating via webcam – by seven temporary voting members. The agency usually also live-streams its advisory committee meetings for registered attendees; for this meeting, FDA has taken the unusual step of adding live streaming via YouTube in anticipation of high numbers of viewers.
Among the presentations slated for the meeting, which kicks off at 10 am ET, are talks by staff members of the Centers for Disease Control and Prevention (CDC) on its plans for vaccine safety and effectiveness monitoring after a vaccine or vaccines are licensed, as well as plans should any vaccines receive emergency use authorization (EUA).
FDA’s Center for Biologics Evaluation and Research (CBER) will also weigh in on postmarketing surveillance plans.
CDC is also presenting information on operational aspects of distributing and tracking COVID-19 vaccines. Supply chain and distribution issues have been a topic of concern for months, since it became known that two of the leading candidates, the messenger ribonucleic acid (mRNA) vaccines from Pfizer/BIoNTech and Moderna, require transport and storage at temperatures well below those maintained by most commercial freezers and freezer trucks.
The afternoon includes a pair of presentations from CBER officials addressing considerations for chemistry, manufacturing and controls (CMC) and clinical considerations in weighing licensure or EUA of vaccines against COVID-19.
A full 90 minutes is allotted to an open public hearing that immediately precedes the committee’s discussion and generation of recommendations. Items for discussion were posted by FDA the day before the hearing. The agency is seeking the advisory committee’s perspective on FDA’s approach to safety and effectiveness that it laid out in a pair of guidance documents, one addressing considerations for approval of a vaccine against COVID-19 and the other outlining what might be required for a vaccine EUA.
The latter guidance document was the subject of considerable controversy, since it had been stalled with the White House. FDA published the substance of the EUA guidance in announcing the 22 October meeting, but then also published the EUA guidance itself the same day. (RELATED: FDA issues COVID-19 vaccine EUA guidance after clash with White House, Regulatory Focus 6 October 2020)
Also on the committee’s discussion agenda is the thorny question of whether to unblind Phase 3 clinical trials in the event of an EUA for an investigational COVID-19 vaccine, so that placebo arm participants may be afforded the opportunity for vaccination. Doing so could seriously hobble data collection to support full authorization of a vaccine.
Standing against this, however, are ethical considerations for keeping healthy study participants from knowing their immunity status mid-pandemic, if a vaccine might be available to them. It is not clear that this question was addressed – or even anticipated – when study protocols were drawn up and the first subjects were enrolled into vaccine trials. Since then, vaccine development has progressed at an unprecedented pace and the pandemic’s resurgence means more individuals than ever are at risk of infection.
“FDA does not consider availability of a COVID-19 vaccine under EUA, in and of itself, as grounds for stopping blinded follow-up in an ongoing clinical trial,“ said the agency in its EUA guidance. Both the Biotechnology Innovation Organization (BIO) and Pfizer, sponsor of a leading vaccine candidate, are seeking clarification of this stance, according to comments they have submitted to the public docket.
“It is our position that while ensuring the blinded nature of the study as long as possible, Pfizer and BioNTech nevertheless would have an ethical responsibility to inform all study participants about the availability of an Emergency Authorized Vaccine, if authorized, and the eligibility requirements for such a vaccine,” said the pharmaceutical company. Pfizer proposes an amendment that would allow placebo participants to cross over to the active vaccine arm.
“As an industry, we have an ethical obligation to make our trial participants aware that a vaccine may be available,” commented BIO. The association is advocating for consideration of safety and pharmacovigilance, but also that the decision include “input from a variety of stakeholders, including regulators as well as experts in ethics, clinical trial design, and statisticians.”
Finally, FDA is asking the committee to address post-licensure or post-EUA safety and effectiveness, with specific attention to which immune markers should be tracked, and how to address safety and efficacy endpoints in specific populations.
None of the discussion items are up for a vote. FDA officials have repeatedly said they are prepared to schedule additional VRBPAC meetings on short notice to receive EUA applications.
FDA