FDA aims to shore up trust at event

Agency released new guidelines for vaccines

A day after President Donald Trump promised Americans a coronavirus vaccine “momentarily,” the U.S. Food and Drug Administration released new guidelines Tuesday on what it expects from drug companies as they push for approval of their vaccines.

The FDA guidelines appear to reject White House pressure for lower standards intended to push out vaccines quickly.

Atop FDA director said the guidelines aim to restore public confidence in coronavirus vaccines by increasing data transparency, establishing an independent advisory committee to review clinical trial outcomes, and recruiting massive numbers of human participants for those trials.

“We’ll need to see data from a large, well-designed, stage-three clinical trial that shows clear and compelling efficacy of a vaccine,” said Peter Marks, the FDA’s director of the Center for Biologics Evaluation and Research. “That’s what will get vaccines over the hump; those

large trials. We’ll have the data and we’ll vet them in a public venue ... and make sure they meet quality standards.”

Marks’ remarks came during an online symposium organized Tuesday afternoon by the Johns Hopkins University and the University of Washington. The symposium focused on preserving the scientific integrity of COVID-19 vaccine development and allocation.

The FDA’s action and the symposium eased concerns that politics might overtake science in the approval process. Trump has repeatedly predicted that a vaccine would be available much more rapidly than his top health officials and drug company executives have estimated, perhaps as early as the Nov. 3 election.

Several media outlets reported Monday that the White House would block the new FDA guidance that vaccine makers should monitor trial participants for at least two months to rule out safety problems before seeking emergency approval. That would guarantee that a vaccine will not be ready before the presidential election.

Several vaccine candidates have reached the third stage of clinical trials, which is considered the last and longest step before researchers can determine their effectiveness.

Panelists at Tuesday’s symposium said at least two candidates — Moderna’s and Pfizer’s — could report results within the next seven weeks. Both mRNA vaccines are intended to provide the body with antibodies to defend against exposure to COVID-19 and the ongoing trials are looking to recruit as many as 30,000 participants — about twice as many as the normal vaccine process.

Marks’ comments reflect the language used in the new FDA guidelines, which recommend the two-month follow-up period to offset concerns about submitting vaccines for the agency’s Emergency Use Authorization. Those emergency standards differ somewhat from those for traditional vaccines, which must apply for FDA approval under a more rigorous and scientifically sound biologics license application.

Emergency use allows products to meet lower standards if the known and potential benefits of the vaccine or treatment outweigh the risks of not releasing it, Marks said. He acknowledged that the emergencyuse threshold will not help reassure the masses about a potential vaccine’s safety or efficacy.

“We’ll have a narrower amount of safety data than normal, we can’t deny that,” he said. “But we are in the middle of a pandemic. There needs to be some balancing out here.”

Marks said the FDA recommended two months because that length of time tends to be the median for when drugs start to show adverse side effects. He said a publicly available dataset of claims made against the vaccine on the FDA’s website will provide “active surveillance,” and open-source data on the clinical trials will provide “passive surveillance,” which could provide for a more complete picture of a given vaccine’s effectiveness and security.

A public advisory committee staffed by an independent panel of experts will review any vaccine that reports efficacy, and the discussion will be broadcast publicly, Marks said. The committee’s determination will not necessarily influence the FDA’s final decision to give approval to a candidate, Marks said, but should help further allay public misgivings.

“We want that to be a public enough process so people can see these are independent experts, and at the end of the day, if that committee recommends we authorize something, we’ll take that back and decide what to do,” he said.

In the meantime, other symposium panelists said, the FDA will be more active and assertive in highlighting its role as a neutral arbiter designed to operate outside of commercial and political constraints.

“There are a few moments I can think of where political dust was created for no actual effect,” said Kathy Neuzil, director of the University of Maryland School of Medicine’s vaccine development center.

The process must be free of political interference to yield maximum confidence in a vaccine, Neuzil said. Rushing through the process could create long-lasting distrust and dissuade people from getting vaccinated and returning to work.

Dr. Joshua Sharfstein, a vice dean in the Johns Hopkins Bloomberg School of Public Health, said confidence must be restored among vaccine users and physicians so that people who receive the vaccine can go home and recruit their neighbors and friends to “roll up their sleeves” to reach the critical mass of participants.

“In the past, the say-so of FDA has been enough to give confidence,” said Sharfstein, a former state health secretary and Baltimore City health commissioner. “But that’s not the environment we get today.”

Trump’s rhetoric, according to recent polls, has inspired a majority of wary Americans to predict that he will compel the FDA to authorize a vaccine without enough evidence that it’s safe and effective.

Even if some vaccine candidates report favorable outcomes by the end of the year and gain FDA approval, manufacturing and distribution hurdles remain, said Moncef Slaoui, the scientific head of Operation Warp Speed, which is a private-public partnership created by the Trump administration to expedite a vaccine.

“It’s useless to have lots of vaccine doses and no clinical efficacy, or to have clinical efficacy and it doesn’t meet expectations for the population,” Slaoui said. “Producing millions, or tens or hundreds of millions of vaccines, where you make sure the first dose and the last are the same, is a very different story.”

Slaoui said if Moderna or Pfizer were approved in November, very few doses would be available immediately, though Operation Warp Speed has invested in the companies’ scaling and manufacturing speed. The public needs to be aware of those distribution challenges, he said, and recognize that the vaccination process could lead far into 2021.

No matter the outcome of the current stage-three candidates, the subsequent vaccines in the pipeline will benefit from mass trial and error, said Dr. Larry Corey, a University of Washington professor in the departments of medicine and laboratory medicine. He called it “imperative” to resume the other trials and recognize the potential immunological diversity of the vaccine platforms.

Corey also stressed enrolling Black, Latino, indigenous and tribal communities in clinical trials to evaluate vaccines in the settings of the people at the greatest risk. People of color, overwhelmingly categorized as essential workers without much freedom to social distance, have been disproportionately affected by the coronavirus and could be among the first communities to qualify for vaccinations.