Billions will be clamoring for a coronavirus vaccine once one is ready, putting pressure on drugmakers and federal regulators to ramp up a production process that will likely take months or even years to meet global demand.
Roughly a half dozen vaccine candidates are being readied for human testing in the U.S. by the end of 2020. But regulatory and logistical hurdles will affect the timeline for when average Americans can get the shot, according to health-care regulatory lawyers.
“It’s not just inventing the vaccine, but how do you scale up to get enough doses out,” said Jim Johnson, a partner with Hogan Lovells who focuses on FDA regulatory issues.
Drugmakers will have to work with the Food and Drug Administration to navigate a web of regulations to ensure vaccine vials and production facilities are safe before manufacturing can adequately scale up for a vaccine to be widely distributed.
The biggest challenge is with the FDA’s regulations for approving facilities to manufacture vaccines, which are a more complex biological product than a traditional small-molecule drug, said Kathleen Sanzo, the FDA practice leader at Morgan Lewis.
“One of the issues for the U.S. industry is there’s just not a lot of those sites around,” Sanzo said. “To the extent that we need additional capacity, you can’t just take a site that makes small molecule drugs and convert it into a biologic manufacturing site.”
The FDA doesn’t approve a company’s vaccine until the facility where it will be produced passes a pre-approval inspection, which can take months under normal circumstances, she added.
The FDA is likely to use every tool available—including emergency use authorizations—to speed the process, said Tom DiLenge, president of advocacy, law, and public policy for biopharmaceutical lobbying group BIO. However, with the whole world awaiting the vaccine, it’s likely drugmakers in the U.S. and other countries don’t have enough existing manufacturing capacity to meet demand.
“In this situation, where you know you need millions and millions of doses, you’re going to need multiple facilities” to produce enough vaccine, said Ha Kung Wong, a partner at Venable LLP.
Expanding into existing production facilities would likely add months to the global waiting period, and current slowdowns in that approval process could compound the time it takes to get a new vaccine to everyone who needs it.
Building new facilities that meet U.S. requirements for producing a new vaccine would add years to the wait, Wong said.
The FDA’s process for inspecting and approving new vaccine production facilities is complex, “but there’s a danger when you cut corners,” Wong said.
As biologic products, most vaccines are dead or weakened viral strains, which can be dangerous if they aren’t manufactured responsibly, he said.
Even more dangerous are newer mRNA vaccines, which use Messenger RNA—a single strand molecule that is complementary to a DNA strand in a gene, Wong said. Those mRNA vaccines make the body produce an antigen, and then the body will create antibodies against the virus, he said. If handled improperly, they could be harmful to humans, Wong said.
The FDA’s role is critical to ensuring that any coronavirus vaccine will protect against the virus without creating new health problems. It needs to inspect every aspect of the manufacturing process and facilities where the vaccines will be produced.
“The FDA is the gold standard when it comes to approving products,” Wong said. “As much as we like to hate on them for taking too much time, we forget that drugs get approved faster in other jurisdictions and they have problems.”
The FDA likely will try to speed up the approval process for additional manufacturing facilities, given the global problem Covid-19 poses.
“There’s ways that FDA could create SWAT teams to inspect a facility and pull people from the pharmaceutical and biologic teams that they have there” to speed approvals, Sanzo said.
Still, “there’s a limited supply of people who know how to do this in the U.S., and that’s going to take time to ramp up,” she added.
The FDA is aware of the “urgent need” surrounding a Covid-19 vaccine, spokesman Michael Felberbaum said.
“We’ve made clear that the FDA will make use of all appropriate regulatory authorities to expedite the development and availability of a Covid-19 vaccine and will discuss matters related to production of any potential vaccine candidate with sponsors as needed,” he said.
Some regulatory lawyers are optimistic that companies with the most promising vaccines will start the manufacturing approval process in parallel to their research work, saving time.
“There’s nothing that says you can’t get a manufacturing process up and running while they’re developing the vaccine,” Wong said. “The problem is if there’s an issue with the vaccine and you have to change something in the manufacturing process. Then you have to start all over.”
However, due to social distancing measures, the FDA is “not doing on-site inspections right now unless it’s mission critical, and one step to approval is a pre-approval or pre-license inspection,” Johnson said.
“One thing the regulators will need to juggle is, can they approve a product if they’re not having on-site inspections? Will they have the flexibility to say this is mission critical?” he added.
Johnson said it’s highly likely that the FDA will designate on-site inspections for vaccine manufacturing facilities as mission critical. However, if a drugmaker in another country is the first to invent a new vaccine, the product won’t be allowed in the U.S. until the FDA is able to access and inspect those international facilities, he said.
“One thing FDA can’t control is if that country will let you in,” Johnson said. “The U.S. has the highest rate of Covid-19 cases. You can’t travel internationally right now. How do you approve products if you can’t be on-site?”
Beyond that, approvals are also required for the vials and stoppers that will hold the vaccines, and drugmakers will have to compete for that limited supply.
“You also have to show that the container and enclosure that you use doesn’t have an adverse effect on the product—that’s particularly true for biologics,” Johnson said. “Those are studies that need to be done. It’s not like you’re going to a wholesaler and building a house and just buying various kinds of nails or boards. You have to have your enclosure approved by the FDA.”
Ultimately, the world may need to get used to the idea that inventing an effective vaccine doesn’t mean everyone will have access to it right away. However, the FDA has a record of ensuring the final product will be safe, said Patrick Gallagher, a partner with Duane Morris and chair of the firm’s pharmaceuticals and biopharmaceuticals litigation and regulatory group.
“Everyone is incentivized to get product out as quickly as possible, but it would be really bad to have distribution of products that could be harmful to people,” he said.