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

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.

Everything You Need to Know about COVID-19 Booster Shots

Every year, you get your flu shot.  Will the same be said for COVID-19 shots?  No one knows for sure, but federal officials and public health experts are weighing in on whether certain people might need COVID-19 booster shots as soon as this fall.  With questions about the longevity of vaccine-induced immunity and the potential for vaccine-eluding variants still unanswered, it certainly does not hurt to prepare.

What Is the Administration Planning?

On May 11, David Kessler, MD, Chief Science Officer of the White House COVID-19 Response Team, told a Senate panel that the Biden Administration is preparing for the possibility of booster shots for people who do not have a robust or long-lasting immunity, or if new variants evade protection from previously-administered vaccines.  Kessler said the booster shots would likely be a third shot of Pfizer or Modern’s mRNA vaccine rather than a new shot tailored to emerging variants.  He also confirmed that the booster shots would be free to Americans and funded by congressional appropriations through the end of Fiscal Year (FY) 2021.  Since Kessler’s testimony, the Administration purchased 200 million additional doses of Moderna’s COVID-19 vaccine in June to vaccinate children or to serve as a booster shot for adults.  Any decision to use booster shots would be up to the Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC).

Kessler’s testimony was not the first time someone raised the possibility that people vaccinated against COVID-19 could need booster shots in the future.  In February, Johnson & Johnson CEO Alex Gorsky said COVID-19 booster shots may be needed annually, like flu shots.  Similarly, Pfizer CEO Albert Bourla said in April that people will likely need a third dose of a COVID-19 vaccine within 12 months of being fully vaccinated. 

How Long Does Immunity from Vaccines Last?

Since the vaccines were just developed in 2020, experts say only time will tell how long protection from the vaccines will last.  Of the few studies conducted so far, research from the New England Journal of Medicine published in April 2021 found Moderna’s COVID-19 vaccine can produce strong antibody protection for at least six months following the second dose.  Pfizer also announced research findings in April confirming its vaccine’s efficacy six months after the second dose.  

However, new research suggests it could be for a year or longer.  A pair of studies published in May 2021 found that the B-cells of people infected with COVID-19 still continued to mature and strengthen one year after infection, suggesting some type of immune response.  More recently, a study published in the journal Nature in June suggested immunity from mRNA vaccines could last for years.

What about the Variants?

However, many of these studies were conducted before the Delta variant became more prevalent.  Public health experts say the Delta variant, which was first discovered in India in October 2020, is 43-90% more transmissible than previous COVID-19 variants, leading some to believe that currently-approved vaccine are less efficacious against the  Delta variant.  A recent study said the Delta variant could become dominant in the US by mid-July.

Fortunately, the vaccines still offer strong protection.  According to a study by Oxford University researchers, two doses of the Pfizer vaccine appears to provide 79% protection against the Delta variant, compared to 92% against the Alpha variant, which is currently the dominant variant in the US, and was first discovered in the United Kingdom in September 2020.  Since the Moderna vaccine uses the same mRNA technology as Pfizer’s, it can be inferred that two Moderna doses offer the same levels of protection as the Pfizer vaccine provides against the Delta variant. 

But what about the Johnson & Johnson vaccine?  Compared to its Moderna and Pfizer counterparts, the single-dose vaccine has been administered far less, meaning public health officials have little data regarding its effectiveness against the Delta variant.  However, experts say a Johnson & Johnson vaccine is better than no vaccine at all, and that one dose is likely effective at protecting a recipient against serious illness or death.  Additionally, former Senior Advisor to the COVID-19 Response Coordinator Andy Slavitt has said that recipients of the Johnson & Johnson could take a single mRNA booster shot now for added protection.

Nonetheless, just because the current vaccines remain effective against the Delta variant does not  mean they are  necessarily guaranteed to be effective against future variants.  As explained by CDC Director Rochelle Walensky on June 22, the Delta variant represents a “set of mutations” of COVID-19, and future mutations could produce a variant that evades protection from vaccines.  However, scientists say it’s unlikely a variant will arise that will make COVID-19 vaccines totally unless.  While vaccines appear to offer diminishing protection from being infected from newer COVID-19 variants, they still appear effective at preventing hospitalization and death.    

The Jury Is Still Out

The point of vaccines is to protect people from serious illness and death, and until fully vaccinated individuals are finding themselves with infections severe enough to require hospitalization, is it difficult to predict when booster shots will be needed and how often.  In an interview on May 21, National Institute of Allergy and Infectious Diseases Director Dr. Anthony Fauci said the need for booster shots is still unclear.  The CDC Advisory Committee on Immunization Practices reached a similar conclusion on June 24, saying there currently is not enough data to determine booster shots are needed, although the panel did not rule out the possibility of requiring booster shots if immunity wanes or new variants render existing vaccines less effective.  Considering this risk, the evolving nature of the virus, and the pain the world has already experienced at the hand of COVID-19, the US government has every reason to prepare for the worst and continue this conversation around COVID-19 booster shots.

HELP Hearing Explores Ways to Rebuild Public Health Workforce

The COVID-19 pandemic represents an “unmitigated attack” on providers and first responders, which has left workers “fatigued emotionally and physically” according to public health experts at a March 9 hearing of the Senate Health, Education, Labor, and Pensions Committee on the COVID-19 response.

The nation’s public health system had been “hollowed out over the past 10 years” said Ashish Jha (Brown University) due to years of underinvestment and chronic personnel shortages.  

As a result, the challenges facing front-line health care workers according to Mary Ann Fuchs (Duke University) include a lack of access to personal protective equipment, confusion over changing policies, and exhaustion from surge staffing.  Fuchs also described the growing toll on health care workers’ emotional well-being due to fears of exposing family members to the virus and the trauma of constantly treating critically ill patients.  Washington State Secretary of Health Umair Shah similarly observed “compassion fatigue” among behavioral health providers as they face their own mental health pressures, and he noted outdated information technology systems such as faxes have complicated workers’ response efforts.  The result of these pressures, explained Fuchs, is the exacerbation of high rates of depression, burnout, addiction, and suicide among providers that existed before COVID-19.  As a consequence, Fuchs said the pandemic threatens to increase already-high turnover rates among health care workers.

To tackle stressors on the health workforce, the panelists recommended:

  • greater access to behavioral health resources that provide assessment and short-term counseling for providers
  • more support of workplace violence initiatives
  • new ways for paying primary care physicians
  • focus on diversity and equity to ensure workers represent the communities they serve
  • expansion of the public health workforce to include specialists and paraprofessionals

The panel underscored that rebuilding the nation’s public health system is essential to prepare for the next pandemic.  As described by Jha, economic development, climate change, and globalization are thrusting the world into a new “age of pandemics,” which underscores the need to continue to invest in the public health workforce even after the COVID-19 public health emergency ends. 

Hospitals Face Looming Deadline on Advance Medicare Payments

Hospitals face a fast-approaching deadline to pay back loans from the Medicare Accelerated and Advance Payment (AAP) programs towards the end of March. However, lawmakers who provided little assistance for hospitals in the way of additional relief funding in the most recent COVID-19 relief bill seem just as unlikely to adjust the loan repayment date.

The Medicare AAP programs, which predates the COVID-19 public health emergency, were designed to help hospitals and other providers withstand cash flow disruptions during emergencies.   The programs provide loans paid out of the Medicare Hospital Insurance (Part A) and the Supplementary Medical Insurance (Part B) trust funds and include timelines and terms for repayment.  Enacted on March 27, 2020, the CARES Act (P.L. 116-136) greatly expanded the Medicare AAP programs to include a broader swath of health care providers.  Of the $100 billion in Medicare advance payments loaned to providers in 2020, nearly 80% went to hospitals, while the remainder went to skilled nursing facilities, critical access hospitals, home health providers, and other types of providers and suppliers. 

While repayment for the AAP loans was originally set to begin in August 2020, Congress delayed the repayment start date to March 27, 2021 under the Continuing Appropriations Act, 2021 (P.L. 116-159).  Signed into law on October 1, 2020, the Continuing Appropriations Act also revised the repayment terms for AAP loans to allow Medicare to begin automatically recouping 25% of Medicare payments to the outstanding loan balance in the first 11 months following the March 27, 2021 repayment deadline and 50% of Medicare payments in the subsequent six-month period.

Hospitals are again requesting a delay in the repayment schedule and other changes to AAP programs due to concerns over continued revenue losses associated with the pandemic.  According to an analysis commissioned by the American Hospital Association (AHA), hospitals could stand to lose between $53-122 billion in revenue in 2021 due to costs related to COVID-19 vaccine distribution and the potential for future surges in case numbers to cause elective procedures to drop.  As such, America’s Essential Hospitals has urged congressional leadership to delay the AAP loan deadline and lower interest rates in a February 17 letter.  The AHA has gone a step further in asking the federal government to outright forgive the loans per a November 2020 fact sheet.

However, Congress has yet to deliver further.  In the American Rescue Plan Act of 2021, the latest COVID-19 relief bill that could be signed into law within days, lawmakers did not make any changes to the AAP program.  Congress also notably came up short on hospitals’ request to provide $35 billion in additional funding for the Provider Relief Fund.  Instead of more fully replenishing relief funds, the American Rescue Act only provides $8.5 billion in assistance, and specifically designates the monies for rural hospitals.

One reason lawmakers may be hesitant to make significant changes to AAP loans is the implications for the Medicare trust funds.  The Congressional Budget Office projects the Part A trust fund and Part B trust fund will become insolvent by 2026 and 2024 respectively.  Further changes to AAP programs that would protract repayment or forgive the loans outright would ramp up the timeline for the trust funds to run dry.

At the moment, Congress is carefully monitoring whether to legislate any additional financial help for hospitals, whether it be in the form of a delayed loan repayment date or grants from the Provider Relief Fund, taking a pass for now in the American Rescue Plan.