FDA

Will We Need More Booster Shots?

by Matt Gontarchick

People will only need annual COVID-19 booster shots after getting their third vaccine dose, according to a top Food and Drug Administration (FDA) official at the 2022 Innovation in Regulatory Science Summit in January 2022.  Since then, however, mounting evidence over waning immunity plus the potential of a new wave of COVID-19 are feeding calls for people to get their fourth vaccine doses sooner rather than later.  Does that mean Americans can expect to get a second booster shot in the coming months?

First, some Americans are already able to get a second booster shot.  According to guidance from the Centers for Disease Control and Prevention (CDC), people ages 12 years and older who are moderately or severely immunocompromised should receive a total of four mRNA vaccine doses.  This includes transplant patients and those undergoing chemotherapy for cancer.

Drug manufacturers are already asking for approval on second boosters for additional populations.  In mid-March, Pfizer and Moderna submitted applications to the FDA for an emergency use authorization (EUA) for a second booster dose of their respective COVID-19 vaccines.  While Pfizer is specifically seeking an EUA for adults over age 65, Moderna is requesting an EUA for anyone over 18 years of age. 

The submission of both applications came just days after Pfizer CEO Albert Bourla said a fourth vaccine dose will probably be needed for everyone.

  • One reason for this is mounting data that shows protection acquired from a third COVID-19 vaccine dose wanes over time.  According to CDC data, a booster shot’s effectiveness in protecting against hospitalization dropped from 91% to 78% between August 2021 and January 2022 – a timeframe that includes both the Delta and Omicron variants. 
  • Another reason for a fourth shot is a need to protect Americans ahead of a new wave of COVID-19 cases.  In recent weeks, a new Omicron subvariant known as BA.2 has driven an increase in cases across Europe, which many experts say could foreshadow an increase in cases in the US within the coming weeks.  Although BA.2 is roughly 30% more transmissible than the original Omicron strain, it does not appear to be more severe or lead to more hospitalizations.  While overall COVID-19 case numbers are still trending downward in the US, 10 states have reported an increase in case numbers over the last 14 days. 

Due to these concerns over waning immunity and growing case numbers, nearly a dozen countries including Australia, Belgium, Denmark, Israel, Poland, Sweden, and the United Kingdom have already begun offering fourth doses, albeit eligibility is limited to seniors and medically vulnerable people in most cases.  Additionally, reports suggest the FDA could authorize second boosters for all adults over age 50 as soon as March 29.  However, that doesn’t necessarily mean the government will follow suit in recommending a fourth mRNA vaccine dose to every individual age 12 and up who’s already cleared to get a third dose anytime soon, as a couple issues stand in the way.  These include:   

  • Regulatory approval.  The FDA’s vaccine advisory committee will meet on April 6 to discuss the need for additional COVID-19 booster shots.  However, the advisory panel will NOT be reviewing any EUA applications from Pfizer or Moderna or taking a vote on recommendations – instead, the committee will discuss the timing and populations for additional doses in the coming months.  The April 6 agenda is a sign of the federal government’s cautious approach to boosters, which means it might take some time for federal regulators to sign off on additional doses, especially for the broader population.  In September 2021, for instance, a CDC advisory panel declined to recommend third doses for people who work in “high-risk” settings like health care practitioners and teachers – a decision which was ultimately overruled by CDC Director Rochelle Walensky.
  • Data.  Even though a number of countries have already cleared fourth shots for certain populations, the jury’s still out on whether a second booster will make a difference for non-elderly adults who are not considered medically vulnerable.  Preliminary results from a study involving 154 health care workers in Israel found that a fourth mRNA dose is only “partially effective” in protecting against the Omicron variant.  Without any strong evidence of the effectiveness of a fourth shot, US regulators are likely to continue to take a cautious approach on recommending additional boosters for the broader population.
  • Funding.  Lawmakers dropped $15 billion in additional COVID-19 funding from the Fiscal Year (FY) 2022 omnibus appropriations bill, and so far, congressional leaders are locked in a stalemate on passing separate legislation on additional COVID-19 support.  Without additional funding, Biden administration officials have warned that they won’t have enough money to purchase a potential fourth vaccine dose for even 70% of all Americans.  And barring additional funding, the federal government will no longer be able to cover the cost of vaccinations for uninsured people starting on April 5, which means uninsured immunocompromised Americans may not be able to afford a booster if they need one.

Ultimately, the trajectory of the COVID-19 pandemic may ultimately inform whether additional boosters are necessary for Americans, and in turn, whether Congress decides to allocate enough money to pay for additional vaccine doses.  While White House Chief Medical Advisor Anthony Fauci has acknowledged that the BA.2 subvariant is likely to cause cases to rise in the US, he doesn’t anticipate new cases will culminate in a major surge that results in high levels of hospitalizations. 

Indeed, a good portion of the US population has acquired some degree of immunity through infection, vaccination, or both over the last two years of the pandemic, which could protect Americas from the worst consequences if case numbers continue to rise over the next few weeks.  However, if hospitalizations suddenly spike across multiple populations, it may be too late for the federal government to act swiftly on additional boosters.

FDA

What’s Taking FDA So Long to Fully Approve Pfizer’s COVID-19 Vaccine?

by Matt Gontarchick

It took the Food and Drug Administration (FDA) just three weeks to issue an emergency use authorization (EUA) for Pfizer’s COVID-19 vaccine in December 2020 when Pfizer submitted the request.  In contrast, it’s been over two months since Pfizer initiated a “rolling submission” of its biologics license application (BLA) for its vaccine on May 7, and FDA has yet to comment on its timeline for approval.  Amid growing calls for FDA to fully approve Pfizer’s vaccine, what’s making the review process take so long?

Why the Push for Full Approval?

Many people believe full approval of Pfizer’s COVID-19 vaccine will help get more shots into arms, which is seen as vital to protecting Americans from the rapidly spreading Delta variant.  According to data from the Centers for Disease Control and Prevention posted on July 6, the Delta variant makes up 51% of new COVID-19 cases in the US.  Additionally, studies show the Delta variant is at least 40% more transmissible than the Alpha variant, which was previously the country’s dominant variant.  The surge in the Delta strain comes as many Americans remain vulnerable to COVID-19, as only 67% of Americans have received at least one COVID-19 shot, and the pace of vaccinations has dropped off considerably in recent weeks. 

Full approval of the COVID-19 vaccine is one way public health experts believe could convince more Americans to roll up their sleeves, which addresses vaccine hesitancy, a sentiment echoed by several major elected officials.   In June, President Joe Biden said going from “temporary approval to full approval” would “increase the number of people” willing to get vaccinated.  Similarly, Arkansas Governor Asa Hutchinson, whose state has some of the nation’s lowest vaccination rates, remarked in June that full approval is needed to combat vaccine hesitancy.  According to a Kaiser Family Foundation poll from May 2021, 32% of unvaccinated adults said full approval of one of the currently authorized vaccines would make them more likely to get vaccinated.

Furthermore, fully approving the vaccine will allow for more businesses and organizations to mandate the COVID-19 vaccine, which could help increase vaccination rates.  While several hospitals and health systems such as Houston Methodist and Trinity Health have mandated the vaccine for their employees, some health systems like Beth Israel Leahy Health in Boston are holding off until a vaccine is fully FDA-approved.  Even though lawsuits against vaccine mandates have so far held up in court, many employers and organizations seem to be holding off on mandating  employees to get the vaccine out of fear of litigation.   Even the US Army has communicated to servicemembers that vaccination won’t be mandated until “full FDA licensure.”

What’s the Hold Up?

The reason for FDA’s longer process for fully-approving Pfizer’s COVID-19 vaccine is due to the fact that the business of issuing a BLA is more intensive than an EUA.   For an EUA to be issued, companies need to provide the FDA data that demonstrates efficacy and safety from a Phase 3 trial with a median follow-up period of at least two months.  In contrast, a BLA requires FDA to look through at least six months of clinical trial data as well as a close examination of the company’s manufacturing process, both of which take additional time.  Dr. Paul Offitt, a member of FDA’s Vaccines and Related Biological Products Advisory Committee,  commented in December 2020 that Merck’s BLA submission for its 70,000-person rotavirus vaccine trial contained enough pages to exceed the height of the Sears Tower, a 1,450-foot skyscraper in Chicago currently known as the Willis Tower.

There are benefits for drug manufacturers in getting their products fully approved.  According to former FDA Commissioner Dr. Robert Califf, a BLA would allow Pfizer to being marketing its vaccine directly to consumers.  Additionally, full approval would open the door to Pfizer increasing the price of its vaccine post-pandemic, potentially generally billions of dollars for the company.

When Will the Vaccine Be Fully Approved?

Unfortunately, FDA has yet to shed any light on its timeline for fully approving the Pfizer vaccine.  In late June, an FDA spokesperson  told The Hill that the agency “cannot comment on individual applications before it.”  More recently, the FDA told Army Times on July 2 that timelines for approval “may vary depending on a number of factors.” 

While fully approving a vaccine normally takes between 8-12 months, there is reason to believe Pfizer will receive a decision from the FDA soon. Former FDA scientist Jesse Goodman said in June that the FDA might not complete its review process for another 3-4 months, meaning a BLA might not come until  September or October.  Notably, Goodman cautions against fully approving the vaccine too quickly, as it could “undermine confidence” in the vaccine. 

Ultimately, FDA is in a tough position.  As a full review of the Pfizer vaccine continues, the agency must strike a balance between ensuring the American people can benefit from a fully approved vaccine in a timely manner without giving off the sense that the BLA was issued too quickly.  Absent any communication from FDA, however, vaccine observers have no choice but to sit and wait.