Why is the FDA Taking So Long to Review a COVID-19 Vaccine?

Coronavirus Question_Compressed

The pharmaceutical industry has battled COVID-19 since the moment members learned of it. The U.S. declared war on COVID and sacrificed large swathes of its economy to prevent the spread of this dreaded disease. Yet, despite the push, the UK is set to administer the first Western vaccine before the FDA’s vaccine review committee even meets, leaving an increasingly skeptical public wondering why.

Twenty days will have elapsed between the time Pfizer submitted its request for Emergency Use Authorization (EUA) and the time the Vaccines and Related Biological Products Advisory Committee (VRBPAC) meets December 10. (A live web conference and a recorded YouTube broadcast will be available.) For Moderna, the lag is 17 days.

To industry insiders, that’s as it should be.

According to the FDA, “This amount of time will allow the FDA to thoroughly evaluate the data and information submitted in the EUA request before the meeting and to be prepared for a robust public discussion with the advisory committee members.”

“The FDA isn’t delaying,” Anna Durbin, M.D., professor of international health at the Bloomberg School of Public Health, Johns Hopkins University, told BioSpace. “Unlike some European committees, the FDA reviews the raw data,” which requires a longer timeframe than reviewing topline data.

“The submitting company has to provide the FDA with all the data (typically hundreds of pages), and the experts need time to review that data before the committee meets,” she said. “Members may have questions for the company during the review process. The advisory committee also is reviewing enormous amounts of data, independent of the EUA application. That may include background papers and additional data sets, such as data about attack rates of COVID and safety data for subpopulations (such as the elderly or those with comorbidities), to determine whether the efficacy data is sufficient.”

A short public comment period also occurs before the meeting.

The Phase III trials that involve 44,000 patients (Pfizer) or 30,000 people (Moderna) aren’t adequate for a simple yes or no response. In normal times, Durbin explained, “Phase I trials typically involve 10 to a couple hundred people. The results are reviewed, analyzed and published. Phase II trials involve hundreds to a few thousand people. Results are collected and analyzed.”

For the COVID-19 vaccines, Pfizer and Moderna are still collecting data from Phases I and II. Phase III trials for COVID-19 vaccines are scheduled to run for about two years, although some trials are longer.

“Because those Phase I, II and III trials aren’t complete, (robust) reviews haven’t happened,” she said. “Safety and efficacy data were reviewed a few weeks after the initial vaccinations, but VRBPAC probably will have additional efficacy data when it meets.”

VRBPAC is one of 31 FDA advisory committees. Although the Agency has a staff of about 17,000, “It can’t have experts for every single disease,” Durbin said. So, to expand its expertise, it relies on external experts on specialty committees.

VRBPAC’s 15 voting members represent expertise in the field of immunology, molecular biology, rDNA, virology; bacteriology, epidemiology or biostatistics; vaccine policy, vaccine safety science, federal immunization activities; and vaccine development including translational and clinical evaluation programs, allergy, preventive medicine, infectious diseases, pediatrics, microbiology and biochemistry. Ad hoc members are called on as needed.

After discussing the application and any concerns, the FDA presents questions and the committee votes on each question.

Durbin said that the advisory committee generally makes a decision the same day. FDA review of its recommendations often takes months but, for a COVID-19 vaccine, the FDA is expected to make its decision to grant or deny an EUA very quickly.

“Everybody expects the decision within days,” Durbin said.

In the case of COVID-19 vaccines, such speed is a blessing, but it also makes people nervous.

“We have a very skeptical public now,” Durbin said. “Most vaccines take 20 to 30 years to be licensed. To have multiple vaccines licensed within a year of the pathogen being discovered is unprecedented.

Such speed doesn’t imply negligent science. Instead, Operation Warp Speed, enacted by President Trump, enabled efficiencies that shortened the usual timelines – conducting trials in parallel rather than sequentially, and arranging for manufacturing before the formulation is finalized, for example.

Earlier in the year, “There was great concern that the government would pressure the FDA to make a decision before the process worked itself out,” she said. “That would have been detrimental to the public’s confidence in the vaccine.”

Therefore, the robustness and independence of FDA review – even under an EUA – is an important factor in encouraging a skeptical public to accept COVID-19 vaccinations.

“The FDA must be viewed as independent,” Durbin emphasized. “The external review committee supports that independence.”

Regulators must “move as quickly as possible, but not so quickly as to erode confidence,” she continued. The clinical hold placed on two of the three vaccines – one of which has been removed – is evidence that the FDA still maintains its rigorous standards.

“The people who enrolled in Phase II studies will be followed for two years. After an EUA is granted, Phase IV post-licensure studies will follow large numbers of people to ensure the vaccines work in real world settings,” Durbin said.“If there is a perception that corners were cut, that will be extremely detrimental to vaccine uptake.”

Therefore, it’s very important that the vaccines are seen, through external vetting, not to have cut corners.

“The process is working the way it should,” Durbin said.

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