Thousands of Americans are dying from COVID-19, but efforts to increase production of potentially life-saving vaccines are at a dead end.
Moderna and Pfizer-BioNTech, the makers of the two vaccines available so far, are operating at full throttle, under enormous pressure to expand production or collaborate with other pharmaceutical companies to establish additional assembly lines.
This pressure is mounting as new strains of the virus threaten to put the country in a deadlier pandemic wave.
President Joe Biden has said he plans to invoke the Defense Production Act, a Cold War-era rule, to provide more vaccines to millions of Americans.
Consumer advocates, who had asked Donald Trump to use this law more aggressively as president, are now asking Biden to do the same.
But even forcing companies to speed up production won’t deliver much-needed doses any time soon. Expanding production lines takes time, months.
“The big problem is that even if you can source the raw materials and configure the infrastructure, how do you get a company that is already producing at full capacity to exceed that limit?” Said Lawrence Gostin, professor of global health law. at Georgetown University.
Ordering companies to work 24/7 “would be a naive solution,” said Dr. Nicole Lurie, senior advisor to the Coalition for Epidemic Preparedness Innovations, an international group that funds vaccines for emerging diseases. . “They are probably already doing it as long as they have raw materials.”
Lurie added: “If you completely wear people out, mistakes happen. You have to balance speed with quality and safety. “
The technology challenges involved are daunting, and companies have not communicated well what it takes to overcome supply shortages.
“We do not know what is the cause of the delay. Is it capacity? Raw Materials? People? Glass bottles? We just don’t know what the bottleneck is, ”said Erin Fox, senior director of drug information and support services at the University of Utah Hospital Network.
It also might not work forcing other companies to start making vaccines, Gostin said.
“I’m not sure if Biden could require a private company to transfer its technology to another company,” Gostin said. “It is very questionable legally … The president’s room for maneuver is not as great as people think.”
Drug companies define “trade secrets” broadly, Fox said. “Generally, they don’t have to tell me who makes their product, where it’s made, the location of the factory. That is considered property. “
Part of the challenge relates to how these vaccines are produced. The first two authorized use lipid nanoparticles to insert a fragment of the coronavirus’ genetic material, called messenger RNA or mRNA, into cells.
Viral genes teach our cells how to make proteins that stimulate an immune response to the new coronavirus.
Messenger RNA is fragile and easily decomposed, so it must be handled with care, with specific temperatures and humidity levels.
Vaccines “are not devices,” said Lurie, who served as an assistant secretary for preparedness and response at the Department of Health and Human Services during the Obama administration.
Experts explain that each step in bringing vaccines to market has its complexities: obtaining raw materials; build special facilities; buy one-time-use products, such as plastic tubes and bags for lining stainless steel bioreactors; and hire employees with the necessary training and experience.
Businesses must also pass safety and quality inspections and organize transportation.
The Defense Production Law, for example, would allow the government to take possession of a plant that already has a fermenter (there are many in the biotech industry) to expand production.
But that’s just the first stage in making an mRNA vaccine, and even then, it would take about a year to get started, explained Dr. George Siber, a vaccine expert who sits on the advisory board of CureVac, a German vaccine company. of mRNA.
Companies would first have to do an incredibly deep cleaning to avoid cross contamination, Siber said. Then they would have to configure, calibrate, and test equipment, and train scientists and engineers to use it.
Finally, Siber said that, unlike a drug whose components can be tested for purity, there is no way to be sure that a vaccine produced in a new facility is what it claims to be without testing it on animals and people.
“Making vaccines is not like making cars, and quality control is paramount,” said Dr. Stanley Plotkin, a vaccine industry consultant who is credited with inventing the rubella vaccine.
Johnson & Johnson, which is expected to announce the results of the clinical trials in the coming days, has said it will not be able to administer as many injections as planned due to manufacturing delays. The company declined to answer questions.
AstraZeneca’s vaccine, also funded in part by US taxpayers, is already in use in the UK and India, but the Food and Drug Administration (FDA) has raised questions about its phase 3 trial, making it May not be available here until spring.
Pfizer, which has committed 200 million doses to the US government by the end of July, said it did not expect “disruptions” in shipments from its main US COVID-19 manufacturing facility in Kalamazoo, Michigan. .
The United States government also has the option to purchase another 400 million doses of the Pfizer-BioNTech vaccine, although the company declined to provide details on that option.
But all countries compete for the same supplies and raw materials, Gostin said.
Biden could use the Defense Production Act “to force Pfizer to prioritize US contracts, but that would be politically risky” since other countries could retaliate by stockpiling supplies.
Although Pfizer is an American company, it has partnered with BioNTech of Germany to manufacture the vaccine. “That would lead to a global disaster.”
Attempting to corner the global market for vaccine ingredients or supplies would look bad, experts say, even more so now that the United States has just teamed up with Covax, an international company to source and distribute vaccines, in an effort to ensure poor countries are not get left behind.
And forcing other companies to make COVID-19 vaccines could jeopardize the production of other important vaccines, such as measles, said Dr. Amesh Adalja, principal investigator at the Johns Hopkins Center for Health Security.
Routine childhood vaccination rates have decreased during the pandemic, increasing the risk of epidemics.
Using the law to prioritize vaccine manufacturing has already disrupted supplies of at least one drug, Fox said. In December, Horizon Therapeutics warned doctors and patients to expect a shortage of a drug called Tepezza, which is used to treat thyroid-related eye disease, because its manufacturer was ordered to prioritize covid-19 vaccines.
Legislators and consumer advocates like Public Citizen called on the government to use the Defense Production Act more aggressively.
In a letter sent earlier this month, Sen. Elizabeth Warren (D-Massachusetts) and Rep. Katie Porter (D-California) said Moderna should share her technique for stabilizing her vaccine at normal refrigerator temperatures, without “ultra-cold freezers. ”.
Moderna officials have said that intrinsic differences in the mRNA material of the two companies make that technology difficult to share. Furthermore, they say, Pfizer has refused to share data with Moderna. Pfizer has declined to comment on the matter.
Given that Moderna’s effort is federally funded, the government presumably has access rights and could take over production, Mike Watson, former president of Moderna’s subsidiary Valera, said in an email.
“The reality is that, no matter how much production capacity is boosted, sooner or later a bottleneck is reached,” he added.
Experts say it’s not as simple as asking glass maker Corning to make vials (glass tubes). Of course, the tubes will have to meet stringent requirements. But there is another problem: The United States faces a shortage of mined sand, the main component needed to make these pipes.
By Lis Szabo, SJ Tribble, Arthur Allen and Jan Hancock
KHN (Kaiser Health News) is a non-profit news service that covers health topics. It is an editorially independent program from KFF (Kaiser Family Foundation) that is not related to Kaiser Permanente.
Original English version: https://bit.ly/36dSevu