The ‘biggest challenge’ won’t come until after a coronavirus vaccine is found

“Probably the biggest challenge will be scaling up the actual vaccine. It’s one thing to have clinical trial samples and materials in lab quantities,” said George Zorich, a pharmacy expert and CEO of ZEDPharma. “It’s another challenge actually scaling that up effectively.”

Potentially making it even harder is that the U.S. is striking out on its own. The administration has snubbed an international collaboration spearheaded by the World Health Organization, while the president readies for a November election that could be a referendum on his coronavirus response.

The government is already trying to avoid the costly pitfalls that have hindered the development of vaccines for emerging threats like the Zika and Ebola viruses.

Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, alluded to those challenges during a talk in February. Major drugmakers have been “burned” in the past, he said, when they have raced to develop vaccines for crises like Ebola outbreaks and have spent millions to expand manufacturing without ever seeing their products used.

“You invest hundreds and hundreds and hundreds of millions of dollars to scale up on something that you hope might work. That’s the real glitch there,” Fauci said. “It is going to be a challenge to get a major company to do that.”

This time around, the government has given nearly a billion dollars to two experimental vaccines that are hurtling through human trials. Some of the funding will support the manufacture of doses of both vaccines, in the hopes that at least one will pan out.

Moderna Therapeutics, a Boston biotech company working with the National Institutes of Health on a completely new vaccine technology, has received $430.2 million in federal funds. The company said last week that it could begin phase three trials — the final, monthslong stage of vaccine development — by “early summer.” And the government gave $456.2 million to Johnson & Johnson for its experimental vaccine.

“There are a lot of resources needed, from the early stages, the pre-clinical and clinical trials, to the moment it gets injected into people’s arms,” said Howard Sklamberg, a former FDA official and attorney now at Arnold & Porter.

Just creating a successful vaccine within the year would be an unprecedented achievement, since the record for developing a vaccine is four years. On top of that, while vaccines have been developed for a range of other viruses, there has never been a coronavirus vaccine.

HHS has assembled an initiative under the name “Project Warp Speed” to accelerate vaccine development. Spearheaded by the experienced director of FDA’s vaccine unit, Peter Marks, the project nonetheless could face hurdles.

Speeding up the vaccine timeline means taking shortcuts. Some, such as letting vaccine makers forgo certain animal studies or do them in parallel with early human trials, are already underway. The government could also issue an emergency use authorization for a promising vaccine before it’s completed all the typical review steps, just as it’s done for some coronavirus tests and drugs.

Health officials are still wary of promising too much. At a Thursday Senate hearing on the pandemic, Gary Disbrow — acting director of the government’s vaccine funding unit, the Biomedical Advanced Research and Development Authority — resisted Sen. Mitt Romney’s (R-Utah) repeated questions about whether achieving a vaccine this year was reasonable.

“I’m not a betting person, but if we don’t set lofty goals we won’t achieve those goals,” said Disbrow, who took the role just weeks ago after his predecessor Rick Bright was abruptly ousted.

“The thing that is very important with vaccines is FDA has to be very sure that they are safe and effective. Unlike with drugs, you’re administering them to healthy people,” Sklamberg said. “So FDA is not going to cut corners and say, ‘We’re not sure of the safety of this one but we’re going to give it a ride.’”

Then there are the supplies needed to package and distribute the vaccine itself. Each dose requires a vial, stopper, cap and packaging that keeps it stable through shipping. While the glass used for vials does not affect the vaccine, the stoppers are tricky: Manufacturers have to choose the right material, usually rubber or latex, that will not interact with the sensitive chemicals inside the vial.

And in both cases, vials and stoppers, a vaccine manufacturer cannot just switch to a slightly different product or another brand. They typically have to run manufacturing changes by FDA first, which could make quick supplier changes to curb shortages a difficult prospect.

The FDA can decide how flexible it will be about this type of change, says Sklamberg. The agency said in a December 2017 draft guidance that companies could note some changes in their annual reports rather than waiting for approval, but it has not finalized the policy.

The ability to switch products could be crucial as the entire world readies for a possible vaccine and vies to secure their supplies. The stopper business is not a very crowded field. A Pennsylvania company called West Pharmaceutical Services is one of the dominant players, churning out millions of products a day at 25 sites worldwide. Another major producer, Schott, is based in Germany.

Both companies also make glass vials, a market with a bit more competition both in the U.S. and globally — India is a major producer, said Zorich.

But a medical glass shortage was already setting in before the Covid-19 pandemic emerged this year because of sand shortages in the U.S., Evercore analyst Vijay Kumar wrote in an investor note. Desert sand is too smooth to use, necessitating “angular” sand from river beds and mining that has been difficult to procure because of environmental laws and restrictions, he wrote.

Glass shortages are already on the U.S. government’s radar, according to ousted Bright’s 60-plus page whistleblower complaint against the administration. Bright alleges he warned of a looming global shortage of glass vials but administration officials did not heed his advice. He wrote that major glass producers have warned that a particular material, borosilicate tubing, is sold out and it could take up to two years to meet the U.S. vaccine need alone.

Some manufacturers are already preparing for this potential crunch: Moderna is exploring both single-use vials and those that can hold multiple vaccine doses, according to its regulatory filings. Neither Moderna nor Johnson & Johnson immediately responded to requests for comment.

A shortage of vials could interfere not just with the availability of a coronavirus vaccine but a range of other medicines, including sedatives and other drugs administered in hospitals. Government efforts to avert shortages would have to begin soon if they involve enlisting more manufacturers.

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