Vaccine Booster Battle Reveals Rifts Among Regulators and Sponsors

Amidst political pressures and dissension on multiple fronts, FDA and its panel of vaccine experts weighed the evidence and worked to ensure a science-based decision on whether to authorize additional shots of Pfizer’s COVID-19 vaccine to further protect those that already received the recommended doses. The day-long meeting on Sept. 17, 2021 of FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) concluded with the panel recommending that a third dose of the Pfizer/BioNTech Comirnaty vaccine be authorized only for people over age 65, plus those at high risk of infection related to occupation, such as health care workers and teachers.

A formal recommendation from FDA on the Pfizer booster, likely to be issued today, will be considered this week by the Advisory Committee on Immunization Policy (ACIP) at the Centers for Disease Control & Prevention (CDC). That panel will advise practitioners and health agencies on when and where to administer any additional shots in ongoing efforts to curb the COVID-19 pandemic.

The FDA advisors agreed unanimously on the more limited booster plan after soundly rejecting Pfizer’s original request to authorize its third shot for everyone over age 16, as covered by the biologics license application (BLA) for the vaccine approved by FDA’s Center for Biologics Evaluation and Research (CBER). The panel felt there was insufficient data to support more widespread administration and that boosters could pose added risks for men under age 40, who have experienced rare cases of myocarditis following vaccination. A main point of discussion was whether waning immunity from the initial two-dose vaccine regimen was due to effects of the Delta variant or to limitations of the Pfizer vaccine itself. Pfizer researchers published a letter in the New England Journal of Medicine summarizing its research to support a booster dose, but that failed to convince the advisory panel of the need for widespread third shots.

The debate over the issue was intensified by the recent announcement of pending departures of leading FDA officials who had expressed dismay over earlier statements by President Biden backing booster shots in the United States while FDA was examining the issue. Marion Gruber, long-time Director of CBER’s Office of Vaccine Research & Review (OVRR), and OVRR Deputy Director Phillip Krause announced last month that they would both retire from FDA after many years of service, most recently shepherding through speedy emergency approvals for effective COVID-19 vaccines.

In addition, Gruber and Krause were prominent co-authors of a leading article published in The Lancet questioning booster shots while much of the world still awaited initial COVID-19 vaccines. The article by a group of vaccine scientists formed by the World Health Organization (WHO) argues that much uncertainty remains about the timing and value of extra shots, and that boosters for healthy adults should be delayed until at least 40% of the global population is vaccinated.

The debate within the Biden administration and FDA opened the door to widespread criticism and questioning of the booster shot policy. Leading House Republicans charged FDA officials with caving to White House pressure to speed access to booster shots and demanded that FDA Acting Commissioner Janet Woodcock provide them with all documents related to the study and implementation of a booster shot option plus communications between the agency and the White House on this issue.

Pfizer, Israeli data don’t convince

While the politicians look to make points over the policy debate, the VRBPAC panel weighed the scientific evidence presented at the September 17 session. That included current data on COVID-19 prevalence, infection and hospitalization rates from the CDC and from the United Kingdom. Of particular interest was a report on how a recent Pfizer vaccine booster program in Israel reduced infection rates and hospitalizations. Pfizer presented its own analysis on how protection by Comirnaty waned over six months after initial doses and how boosters could provide important added protection. But the advisors found the Israeli and Pfizer data too limited and unconvincing to approve boosters for the entire US population. The narrower recommendation to add shots for the elderly and immune-compromised is seen as a compromise to provide protection where most needed while sponsors gain added information.

A main issue for the international health research community is whether limited supplies of effective preventives should be provided to those already protected by authorized shots, while vaccines remain severely limited in many regions of the world. The advisory panel did not address that question directly, and ample vaccine supplies in the US appeared to offset the issue.

Members of the advisory panel and experts from CDC and FDA did agree that more widespread vaccination of the American public would do more to prevent high COVID-19 infection rates than booster shots for those already benefitting from protection. However, that possibility was further countered by the ranting of vaccine opponents about the safety and value of any COVID-19 preventive, as heard in multiple presentations during the usual one-hour public comment period at the VRBPAC meeting.

The debate will continue, as Moderna has announced it also will seek FDA approval of a third shot to its two-dose vaccine regimen, citing similar waning of antibodies six months after the second shot and no added safety concerns. Perhaps Moderna will consider closely the recent debate and target its booster plan to the higher-risk population, as recommended by the advisory panel for the Pfizer preventive.

About the author

Jill Wechsler is Pharmaceutical Technology's Washington editor.