FDA Authorizes Second COVID-19 Vaccine Booster

The space has become increasingly controversial, with varying new recommendations.

Without holding the customary advisory committee hearing, the Food and Drug Administration (FDA) recently authorized the fourth shot of Pfizer-BioNTech and Moderna’s COVID-19 vaccine.

FDA authorized the two mRNA vaccines as a second booster shot for people 50 years old and older and certain immunocompromised groups on March 29, leaving out the Janssen COVID-19 vaccine from the mix. Yet, Pfizer-BioNTech’s request was for people 65 years old and older.

The agency will continue evaluating data and information as these become available to consider the potential of authorizing a second booster dose for other groups.

Pfizer-BioNTech’s vaccine is marketed as Comirnaty, while Moderna’s vaccine is marketed as Spikevax. Both vaccines were FDA OK'ed to provide the second booster dose in a few days, as Pfizer-BioNTech and Moderna applied for this on March 15 and 17, respectively. The companies submitted safety, immune response, and effectiveness information as part of their applications to revise their emergency use authorizations for the additional booster dose. The FDA posted March 28 review memoranda on Pfizer-BioNTech’s and Moderna’s vaccines.

Some have lauded the FDA for reaching a seemingly timely decision to make a second booster available as the U.S. faced a wave of new cases with the more contagious omicron subvariant BA.2. But others have heavily criticized the FDA's decision, questioning whether the agency kept its promise to ensure the safety and effectiveness of its authorizations not just because of the larger age category but also because of the lack of an AdCom meeting.

"Current evidence suggests some waning of protection over time against serious outcomes from COVID-19 in older and immunocompromised individuals," said Peter Marks, director of FDA’s Center for Biologics Evaluation and Research. "Based on an analysis of emerging data, a second booster dose of either the Pfizer-BioNTech or Moderna COVID-19 vaccine could help increase protection levels for these higher-risk individuals. The data show that an initial booster dose is critical in helping to protect all adults from the potentially severe outcomes of COVID-19. So, those who have not received their initial booster dose are strongly encouraged to do so."

The FDA followed up by updating its guidance for industry on March 31, Emergency Use Authorization for Vaccines to Prevent COVID-19, superseding the May 25, 2021, version. This guidance was first issued and revised in October 2020 and February 2021, respectively. In the latest version, the agency added policies on the second booster dose under clinical data. This includes a new table on immune response comparisons and analyses to demonstrate the effectiveness of a modified COVID-19 vaccine administered as a second booster dose.

The document also set forth new guidance regarding alternate study designs for both boosters.

"Alternate study designs can be considered, for example a study in which subjects who have completed primary vaccination with other authorized (or approved) prototype vaccines are randomized to receive a booster dose with either the prototype vaccine or the modified vaccine," the FDA added to the section on the first booster dose. "Alternate study designs can be considered, for example a study in which subjects who have completed primary vaccination and first booster with any combination of authorized or approved (primary vaccination) and authorized (booster vaccination) prototype vaccines are randomized to receive a second booster dose with either the prototype vaccine or the modified vaccine," the agency wrote on the second booster dose.

The Center for Disease Control and Prevention (CDC) issued updated COVID-10 vaccine guidance in conjunction with the FDA to also include new information on the second booster. Yet, the CDC guidance specifies recommending the dose for people ages 12 years and older who are moderately or severely immunocompromised and adults ages 50 years and older who are not moderately or severely immunocompromised. Both groups "may choose to receive a second booster dose using an mRNA COVID-19 vaccine at least 4 months after the first booster dose."

The CDC also differed from the FDA in adding guidance that people between 18 and 49 years old who are not moderately or severely immunocompromised and who received Janssen's COVID-19 vaccine as both their primary series dose and booster dose may receive a second booster using an mRNA COVID-19 vaccine at least four months after the first Janssen booster.

The FDA, meanwhile, specifies that a second booster dose of Moderna’s COVID-19 vaccine to people may be administered to people 18 years of age and older with certain kinds of immunocompromise—people who have undergone solid organ transplantation, or who are living with conditions that are considered to have an equivalent level of immunocompromise—at least four months after the first booster dose of any authorized or approved COVID-19 vaccine.

The timing of the authorization coincides with a 100-day pledge Pfizer made last June at the G7 Summit. "We have built a process to develop, within 100 days, a new vaccine if needed," Pfizer CEO Albert Bourla said at the time. And the FDA's authorization of the second booster dose happened on day 99 since omicron was detected in every state across the country.

The issue came up during the Vaccines and Related Biological Products advisory committee meeting the FDA held on April 6. People who had received a first, second, and third dose brought to the FDA's attention long lists of symptoms and health conditions they had developed because of the vaccines, including tinnitus, neuropathy, hair loss, brain fog, and migraines, among others.

At the center of the issue was the need for releasing Vaccine Adverse Event Reporting System (VAERS) data in the interest of public health. Marks took this into account when discussing how to approach the potential for combatting future variants with additional vaccine authorizations.

The FDA created a new Q&A page on what happens to emergency use authorizations (EUA) when a public health emergency (PHE) ends. This covers whether EUAs continue after a PHE ends, what becomes of the medical products with an EUA, and how EUAs are terminated or revoked.