By Liz Szabo, Sarah Jane Tribble, Arthur Allen and Jay Hancock
Americans are dying of COVID-19 by the thousands, but efforts to increase production of potentially life-saving vaccines are hitting a brick wall.
Vaccine manufacturers Moderna and Pfizer-BioNTech are operating at full steam and under enormous pressure to expand production or collaborate with other pharmaceutical companies to establish additional assembly lines. This pressure is only growing as new viral variants of the virus threaten to launch the country into a more deadly phase of the pandemic.
President Joe Biden said he plans to invoke the Cold War era authority of the Defense Production Act to provide more vaccines to millions of Americans. Consumer advocates – who had asked Donald Trump to use the Defense Production Act more aggressively as president – are now asking Biden to do the same.
But even forcing companies to increase production will not provide much-needed doses anytime soon. Expanding production lines takes time. Establishing lines in reused facilities can take months.
“The big problem is that even if you get the raw material and set up the infrastructure, how can a company that is already producing at maximum capacity go beyond that maximum capacity?” said Lawrence Gostin, professor of global health law at Georgetown University.
Telling companies to work 24 hours a day, 7 days a week “would be a naive solution,” said Dr. Nicole Lurie, senior consultant to the CEO of Coalition for Epidemic Preparedness Innovations, an international group that funds vaccines for emerging diseases. “They are probably already doing this to the extent that they have the raw materials.”
Lurie added: “If you tire people out completely, mistakes happen. You have to balance speed with quality and safety. “
The technological challenges involved are daunting, and companies have not been open about what is needed to overcome any supply shortages.
“We don’t know what the delay is. Is it capacity? Raw material? 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 Health Hospitals.
Forcing other companies to start producing vaccines may also not work, said Gostin.
“I’m not sure if Biden can require a private company to transfer his technology to another company,” said Gostin. “This is highly questionable legally … President Biden’s room for maneuver is not as great as people think.”
Pharmaceutical companies broadly define “trade secrets”, Fox said. “In general, pharmaceutical companies don’t have to tell me who is making their product, where it is made, the location of the factory … This is considered to be proprietary.”
Part of the challenge is related to how these vaccines are made. The first two authorized products use lipid nanoparticles to deliver a fragment of the coronavirus genetic material – called messenger RNA, or mRNA – to cells. Viral genes teach our cells to produce proteins that stimulate an immune response to the new coronavirus.
The messenger RNA is fragile and decomposes easily, therefore, it must be handled with care, with specific temperatures and humidity levels.
Vaccines “are not widgets,” said Lurie, who served as an assistant secretary for preparedness and response at the Department of Health and Human Services during the Obama administration.
Each step, experts say, to put vaccines on the market has its complexities: obtaining raw materials; build facilities to precise specifications; purchase of disposable products, such as tubes and plastic bags for coating stainless steel bioreactors; and hiring employees with the necessary training and experience. Companies must also pass safety and quality inspections and arrange transportation.
The Defense Production Law, for example, would allow the government to run a plant that already has a fermenter – there are many in the biotechnology industry – to expand production. But this is only the first stage in the production of an mRNA vaccine and it would still take about a year to start, said Dr. George Siber, a vaccine specialist who serves on the advisory board of CureVac, a German company of mRNA vaccines.
“Making vaccines is not like making cars, and quality control is key.“
– Dr. Stanley Plotkin
Companies would first have to do a breathtaking thorough cleaning to avoid cross-contamination, said Siber. Then, they would need to configure, calibrate and test equipment and train scientists and engineers to operate 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 key,” said Dr. Stanley Plotkin, a consultant to the vaccine industry who was credited with inventing the rubella vaccine. “We expect other vaccines in a matter of weeks, so it may be quicker to put them to use.”
However, even that will require patience. Johnson & Johnson, which is due to announce the results of clinical trials this month, said it would not be able to deliver the planned number of shots due to manufacturing delays. The company did not confirm a manufacturing delay and refused to answer questions.
The AstraZeneca vaccine, also partly funded by United States taxpayers, is already in use in the United Kingdom and India, but the Food and Drug Administration has raised doubts about its latest testing stage, so it may not be available here until spring. .
Novavax, another US-funded vaccine manufacturer, has been delayed and has only recently started recruiting volunteers for its big trial. Merck, the latest company to obtain federal support for COVID vaccines, announced on Monday that it was discarding its two candidates after they failed to produce an adequate immune response in the first tests.
“None of the vaccine manufacturers are manufacturing at the volume they are targeting,” said Lurie. “They all have manufacturing delays.”
Pfizer, which committed 200 million doses to the United States government by the end of July, said last week that it did not expect “interruptions” in shipments from its main US COVID plant in Kalamazoo, Michigan. Pfizer spokesman Sharon Castillo said the company expanded its manufacturing facilities and added more suppliers and contract manufacturers. These efforts, and the company’s announcement that its five-dose vials actually contain an extra dose, mean that “we can potentially deliver around 2 billion doses worldwide by the end of 2021”.
The US government also has the option to purchase another 400 million doses of the Pfizer-BioNTech vaccine, although the company declined to provide details about this option when requested.
But countries around the world are competing 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”, as other countries could retaliate by accumulating supplies. Although Pfizer is an American company, it has partnered with BioNTech, from Germany, to manufacture its COVID vaccine. “It would lead to global confusion.”
Trying to monopolize the world market for vaccine ingredients or supplies would be bad, experts say, since the United States just this week joined Covax, an international company to supply and distribute vaccines, in an effort to ensure that poor countries do not. be left behind.
Paradoxically, the rush to market vaccines may have resulted in a less efficient manufacturing process.
Vaccine companies typically spend months making their plants run as efficiently as possible, as well as finding the optimal dose and the most effective interval between doses, said Lurie. Given the urgency of the pandemic, however, they delayed parts of that process and started mass production.
“The US cannot necessarily readily access the things that are being maintained for vaccines in other countries.“
– Nicole Lurie
Pfizer angered European countries last week when it halted vaccine production at a Belgian factory to increase its capacity. Pfizer said the one-week closure would slow vaccine deliveries to Europe by three to four weeks before increasing supplies in February. The change does not affect the US vaccine supply.
“The US cannot necessarily readily access the things that are being maintained for vaccines in other countries,” said Lurie.
And forcing other companies to produce COVID vaccines could hamper the production of other major vaccines, like measles, said Dr. Amesh Adalja, a senior scholar at the Johns Hopkins Center for Health Safety. Routine childhood vaccination rates fell during the pandemic, increasing the risk of epidemics.
Using the law to prioritize the manufacture of the COVID vaccine has already stopped supplying at least one drug, Fox noted. In December, Horizon Therapeutics warned doctors and patients to expect a shortage of a drug called Tepezza, used to treat eye diseases related to thyroid, because its manufacturer was forced to prioritize COVID injections.
Legislators and consumer advocates, such as Public Citizen, have called on the government to use the Defense Production Act more aggressively. In a letter sent earlier this month, Senator Elizabeth Warren (D-MA) and Congresswoman Katie Porter (D-CA) said Moderna should share its technique to stabilize its vaccine at normal refrigerator temperatures, without “ultracold freezers” ”.
Moderna officials said the intrinsic differences in the two companies’ mRNA material make this technology difficult to share. In addition, they say, Pfizer refused to share data with Moderna. Pfizer declined to comment.
Since Moderna’s effort is funded by the federal government, the government presumably has walking rights and can take over production, said Mike Watson, former president of Moderna Valera’s subsidiary, by email. “The reality is that no matter how much you push production capacity, sooner or later you get to a bottleneck.”
Experts say it is not as simple as requiring the glass maker Corning to introduce itself and make glass bottles, for example. Obviously, the bottles must meet strict requirements. But it also has this: the United States is facing a shortage of mining sand, the main component needed to make glass jars.
KHN (Kaiser Health News) is a non-profit news service that covers health issues. It is an independent editorial program from KFF (Kaiser Family Foundation) which is not affiliated with Kaiser Permanente.