In-Depth: How the FDA will expedite booster shots against variants

Approval based on bloodwork, not a Phase 3 trial
Covid Vaccine Protocol
Posted at 4:40 PM, Feb 23, 2021
and last updated 2021-04-18 22:59:12-04

SAN DIEGO (KGTV) -- Vaccine makers will not have to go through another long round of clinical trials to develop updated COVID-19 vaccines against viral variants, the Food and Drug Administration announced this week.

With the South Africa variant showing signs of partial resistance to the current generation of vaccines, the FDA unveiled new guidelines Monday that will allow drug companies to submit applications based on bloodwork analyses from a small group of volunteers.

The agency said the currently authorized vaccines remain effective in the U.S. “at this time.”

“The FDA is committed to identifying efficient ways to modify medical products that either are in the pipeline or have been authorized for emergency use to address emerging variants,” said Acting FDA Commissioner Janet Woodcock in a statement. “By issuing these guidances, we want the American public to know that we are using every tool in our toolbox to fight this pandemic, including pivoting as the virus adapts.”

To understand this regulatory shortcut, you have to go back to the large, randomized controlled trials last year.

Pfizer and Moderna recruited tens of thousands of volunteers for three phases of clinical testing. In the final Phase 3 stage, half of the volunteers got vaccine and half got a saltwater placebo. Then the companies waited for volunteers to encounter the virus in their daily lives and compared the outcomes.

The Phase 3 stage took 4.5 months, roughly half of the time it took from the start of Pfizer's clinical trials to FDA authorization.

“In the accelerated version, you basically don't wait for people to get disease. You just look at antibody response,” explained Dr. Peter Chin-Hong, an infectious disease specialist at the University of California San Francisco.

Under the expedited framework announced by the FDA, vaccine makers will administer shots to a few hundred volunteers and then take blood samples. They’ll measure the levels of a specific kind of antibody -- one that can neutralize the targeted variant. This is similar to a Phase 2 clinical trial.

If the updated vaccine produces similar neutralizing antibody levels to the first-generation “prototype” vaccine, it’ll be considered a success. The FDA is essentially allowing companies to estimate or project the efficacy of booster shots based on antibody levels, rather than prove them.

“By not waiting for people to get the disease or go to the hospital, you can actually just study hundreds of people instead of tens of thousands of people,” Dr. Chin-Hong said.

The FDA said the process should take a few months.

The new guidelines say companies must use identical manufacturing processes for the updated vaccines.

“That's where the FDA says, ‘Look, you're not changing that much except for just a tiny little piece of the message that goes inside that mRNA vaccine, so you don't need to start from scratch,’” said infectious disease Dr. Christian Ramers of Family Health Centers of San Diego.

The accelerated procedure is similar to the way flu vaccines are retooled each year for new variants. Unlike with flu, however, scientists are less certain about the levels of coronavirus antibodies needed to fend off the virus.

Still, both Chin-Hong and Ramers said they were comfortable with the FDA approach.

“There's really not much that's changing other than just a very tiny little tweak, so I don't anticipate that there's going to be any new safety signals,” Dr. Ramers said. “To be honest, it has to be this approach because the variants are going to move too fast.”

The variants aren’t just affecting vaccines.

The FDA released new guidelines Monday for the development of updated drugs like monoclonal antibodies and diagnostic tests.

The agency said further mutations could make diagnostic tests less reliable. So far, the agency said “a few” tests have been affected by emerging viral mutations, but at the moment the impacts do “not appear to be significant.”

“I think what the FDA is doing is just preparing us for the fact that there may be a new strain, or a new variant, that looks so different from what we know now that our current testing and therapeutics may not work,” said Dr. Chin-Hong.