Approval may be easy. Then the hard part

Panel: Challenge to prep for various candidates

USA TODAY’s vaccine panel of experts say we’re likely to see at least one candidate approved possibly as early as December, but what’s most worrisome now is the complexity of distribution. The two leading candidates have to be delivered in different ways, and both require two doses. “It’s going to be hard,” one of our panelists says.

Science is making incredible progress toward a COVID-19 vaccine, but as approval nears – potentially as early as December – worry has shifted to the complexity of distribution.

Overall, hopefulness was the theme of USA TODAY’s vaccine panel this month. After five months, the panel’s countdown clock to a widely available vaccine skipped forward another hour, to 8 a.m.

Companies and observers generally expect at least one candidate vaccine soon will receive a regulatory thumbs up. Francis Collins, director of the National Institutes of Health, told NPR he was “guardedly optimistic” one or more of the candidates will be judged safe and effective by the end of the year.

But reality is setting in about how hard it will be to get an approved vaccine into the arms of everyone who wants it – twice.

“The initial vaccine supply and the distribution and vaccination programs will not live up to the public’s desire for immediate, widespread access to a safe and effective vaccine,” said Kelly Moore, associate director of immunization education at the Immunization Action Coalition.

Health care workers and first responders are likely to be prioritized for an approved vaccine, followed by highrisk elderly.

Even those limited groups account for as many as 150 million Americans, said Paul Offit, a vaccine expert at Children’s Hospital of Philadelphia. Unless three vaccines win approval simultaneously, it’s unlikely enough doses will be available right away.

The two leading vaccine candidates have to be delivered in different ways, adding to the difficulty of getting the right vaccine into the right person. Both

“From my interactions with some county and state public health agencies, they are trying to get their plans organized. But without knowing which or how many vaccines will make it successfully though, it is a challenge to plan.” Sandra Crouse Quinn Senior associate director of the Maryland Center for Health Equity

require two doses, but the Pfizer-BioNTech vaccine shots are given 21 days apart, while Moderna’s second shot is delivered at 28 days.

Moderna’s vaccine must be kept frozen. Pfizer’s has to be kept even colder – at minus-78 degrees Fahrenheit, the temperature of dry ice – meaning it needs different shipping and storing protocols.

Another variable is whether the vaccines will be equally effective in groups such as the elderly. Studies underway may show one vaccine is more effective than another among high-risk populations.

“It’s going to be hard,” Offit said, to get the right vaccine into the right person’s arm at the right time. And then to do it again with a second dose.

Making progress

For the past five months, USA TODAY has asked a dozen or more experts in vaccine development to gauge progress.

We asked panel members to place vaccine development on a 12-hour clock, on which midnight, the starting point, is the moment in early January when the world became aware of the virus known as SARS-CoV-2, and noon is the time a vaccine will become widely available.

In late June, panelists put the time at 4 a.m., one-third of the way – a stunning amount of progress considering the short time frame.

By July, the panel’s estimate crept to 5 a.m. as the launch of large clinical trials fueled optimism, tempered by concern that “a lot had to go right.”

August and September each saw the clock advance an hour. There were no major setbacks, and plans began to fall into place for distributing a vaccine.

This month, panelists moved the clock another hour closer to a broadly available vaccine. Some said we’re still in the very early morning hours. Others said we’re closing in on the goal.

For October, the midway point among our experts’ times was 8 a.m., nearing three-quarters of the way there.

First generation versus next-gen

All six candidate vaccines backed by U.S. taxpayers were developed this spring. They received government financing for development, manufacturing or both, so they could be made faster than conventional vaccines, which have taken a minimum of four years and often far longer to develop.

All the companies are contractually obligated to produce at least 100 million doses of vaccine in return for funding. All those doses won’t be available the first day a vaccine gets a thumbs up from the U.S. Food and Drug Administration.

“For the two or three lead candidates, we may have a few million stockpiled doses and a clear production plan for the first couple of hundred million doses,” said Prashant Yadav, a medical supply chain expert and senior fellow at the Center for Global Development.

If none of the front-runners pans out, things get less clear, he said.

Two of the leaders, Pfizer and Moderna, use messenger RNA platforms never before used for an approved vaccine, noted Duke University Law School professor and health law expert Arti Rai.

Even if one or more works, there might be better vaccines to come – requiring just one dose or proving more effective in older or more vulnerable people. Once a vaccine is secured, it may be

difficult to convince tens of thousands of people to volunteer to test a 2.0 or 3.0 version.

As infections hopefully drop once a vaccine becomes available, it will be harder to find volunteers in the USA likely to contract COVID-19. The trials include 30,000 people, and at least 150 of them need to get sick to statistically prove whether a vaccine is effective. Fewer infections means it will take longer to reach that number.

Virtually all the USA TODAY panelists said they expect it will be difficult to improve on first-generation vaccines.

Waning public interest after a first COVID-19 vaccine is approved could mean that “some of these vaccine trials trailing behind will have to close,” said Monica Gandhi, a professor of medicine and infectious disease expert at the University of California-San Francisco.

Bringing multiple vaccines across the finish line will be crucial for ensuring everyone, regardless of age, ethnicity, health status and other variables, has a safe and effective vaccine available, said Dr. Michelle McMurry-Heath, president and CEO of Biotechnology Innovation Organization.

“It’s why having diversity among the volunteers in clinical trials is so important, so researchers can follow the data to know precisely how vaccines work in different populations,” she said. “The more solutions we have, the better prepared we will be to end this global pandemic.”

Distribution and other concerns

Sandra Crouse Quinn, senior associate director of the Maryland Center for Health Equity, said she’s worried about

how state and local health departments will deal with the complexity of vaccinating so many people.

“From my interactions with some county and state public health agencies, they are trying to get their plans organized,” she said. “But without knowing which or how many vaccines will make it successfully though, it is a challenge to plan.”

There are tremendous logistical challenges ahead, said Gregory Poland, director of the Mayo Clinic’s Vaccine Research Group and editor-in-chief of the journal Vaccine.

“It will be confusing and likely chaotic,” he said.

Pamela Bjorkman, a structural biologist at the California Institute of Technology, said her “optimism was diminished” by holds put on two of the leading vaccine candidates.

AstraZeneca’s trial was paused in September after a British volunteer had a rare neurological complication. Although the trial in the U.K. was allowed to resume, the FDA continued the hold on the U.S. trial.

This month, Johnson & Johnson’s trial was paused after a participant came down with an “unexplained illness.”

Trial pauses are relatively routine, “so nothing necessarily to worry about in terms of vaccine safety,” Bjorkman said. “It shows, however, that testing vaccines should be done carefully and without skipping any safety standards.”

“It will be confusing and likely chaotic.” Gregory Poland Director of the Mayo Clinic’s Vaccine Research Group and editor-in-chief of the journal Vaccine