By Liz Szabo, Sarah Jane Tribble, Arthur Allen and Jay Hancock
Americans die from thousands of COVID-19s, but efforts to increase the production of life-saving vaccines are hitting a brick wall.
Vaccine manufacturers Moderna and Pfizer-BioNTech operate their factories at full tilt and are under enormous pressure to expand production or work with other pharmaceutical companies to set up additional assembly lines. This pressure only increases as new viral variants of the virus threaten to launch the country into a more deadly phase of the pandemic.
President Joe Biden has said he intends to invoke the Cold War authority in the Defense Production Act to provide more vaccines to millions of Americans. Consumer advocates – who had called for Donald Trump to use the Defense Act more aggressively as president – are now asking Biden to do the same.
But even forcing companies to step up production will not provide much-needed doses soon. Expanding production lines takes time. The establishment of lines in reused installations can take months.
“The big problem is that even if you can get the raw material and install the infrastructure, how can you get a company that already produces at full capacity to exceed that maximum capacity?” said Lawrence Gostin, a professor of global health law at Georgetown University.
Ordering companies to work 24/7 “would be a naive solution,” said Dr. Nicole Lurie, senior adviser to the Coalition for Innovation Coalition for Epidemic Preparedness, an international group that funds emerging disease vaccines. “I probably already do that as long as I have the raw materials.”
Lurie added: “If you look at people completely, mistakes happen. You need to balance speed with quality and safety. ”
The technological challenges involved are daunting, and companies have not commented on what is needed to overcome supply shortages.
“We do not know what the agreement is. Is it capacity? Raw material? People? Glass bottles? We just don’t know what the blockage is, ”said Erin Fox, senior director of drug information and care at the University of Utah’s health hospitals.
Forcing other companies to start making vaccines may not work, Gostin said.
“I’m not sure if Biden could ask a private company to transfer its technology to another company,” Gostin said. “This is extremely questionable from a legal point of view … President Biden’s maneuvering chamber is not as great as people think.”
Pharmaceutical companies define “trade secrets” broadly, Fox said. “In general, pharmaceutical companies don’t have to tell me who makes their product, where it’s manufactured, the location of the factory … That’s considered property.”
Part of the challenge is how these vaccines are made. The first two authorized products use lipid nanoparticles to deliver a fragment of coronavirus genetic material – called messenger RNA or mRNA – into cells. Viral genes teach our cells how to produce proteins that stimulate an immune response to the new coronavirus.
Messenger RNA is fragile and decomposes easily, so it must be handled with care, with specific temperatures and humidity levels.
Vaccines “are not widgets,” said Lurie, who served as assistant secretary for training and response at the Department of Health and Human Services during the Obama administration.
Every step, experts say, to introduce vaccines on the market has its complexities: obtaining raw materials; building facilities to precise specifications; purchase of disposable products, such as tubing and plastic bags for the stainless steel bioreactor line; and hiring employees with the necessary training and expertise. Companies must also pass safety and quality inspections and arrange transportation.
The law on defense production, for example, would allow the government to order a factory that already has a fermenter – there are a lot in the biotechnology industry – to expand production. But this is only the first step in making an mRNA vaccine, and even then it would take about a year to begin, said Dr. George Siber, a vaccine expert who is on the advisory board of CureVac, a German drug company. mRNA vaccines.
“Making vaccines is not like making machines, and quality control is paramount.”
– Dr. Stanley Plotkin
Companies should first do a thorough cleanup to prevent cross-contamination, Siber said. Next, it should fine-tune, calibrate and test equipment and prepare scientists and engineers to lead 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 unit is what it claims to be without testing it. on animals and humans.
“Making vaccines is not like making cars, and quality control is essential,” said Dr. Stanley Plotkin, a vaccine industry consultant credited with inventing the rubella vaccine. “We expect more vaccines in a few weeks, so it may be faster to get them up and running.”
However, even that will require patience. Johnson & Johnson, which is expected to announce the results of clinical trials this month, said it will not be able to deliver as many photos as planned due to manufacturing delays. The company did not confirm the production delay and refused to answer questions.
The AstraZeneca vaccine, also funded by US taxpayers, is already in use in the UK and India, but the Food and Drug Administration has raised questions about its late-stage study, so it may not be available here until spring.
Novavax, another US-funded vaccine manufacturer, has been affected by delays and has only recently begun recruiting volunteers for its big trial. Merck, the latest company to obtain federal support for COVID vaccines, announced Monday that it is canceling its two candidates after failing to produce an adequate immune response to early testing.
“None of the vaccine manufacturers manufacture at the volume they want to be in the end,” Lurie said. “Everyone has manufacturing delays.”
Pfizer, which committed 200 million doses to the U.S. government by the end of July, said last week that it expects “no interruptions” in deliveries from its main COVID production plant in Kalamazoo, Michigan. Pfizer spokeswoman Sharon Castillo said the company has expanded production facilities and added more contract suppliers and contractors. These efforts and the company’s announcement that its five-dose vials actually contain an additional dose means “that we can deliver approximately 2 billion doses worldwide by the end of 2021.”
The US government also has an option to purchase another 400 million doses of Pfizer-BioNTech vaccine, although the company declined to provide details on 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 this would be politically risky,” as other countries could retaliate by accumulating supplies. Although Pfizer is an American company, it collaborated with BioNTech, from Germany, to make its COVID vaccine. “That would lead to a global mess.”
Attempting to confuse the global market with vaccine ingredients or supplies would look bad, experts say, given that the United States joined Covax, an international vaccine supply and distribution company, this week in an effort to ensure that poor countries are not left behind.
Paradoxically, the rush to launch vaccines could have led to a less efficient manufacturing process.
Vaccine companies usually spend months making factories operate as efficiently as possible, finding an ideal dose and the most effective dose interval, Lurie said. However, given the urgency of the pandemic, they delayed certain parts of this process and launched directly into mass production.
“The US cannot necessarily access things that are held for vaccines in other countries.”
– Nicole Lurie
Pfizer upset European countries last week by shutting down vaccine production at a Belgian plant to improve capacity. Pfizer said the one-week shutdown will reduce vaccine deliveries in Europe for three to four weeks before supplies rise in February. The move does not affect the US vaccine supply.
“The US can’t necessarily access things that are held for vaccines in other countries,” Lurie said.
And forcing other companies to make COVID vaccines could jeopardize the production of other major outbreaks, such as measles, said Dr. Amesh Adalja, a senior researcher at the Johns Hopkins Center for Health Security. Routine immunization rates in children decreased during the pandemic, increasing the risk of epidemics.
The use of the act to prioritize the manufacture of COVID vaccine has already disrupted the supply of at least one drug, Fox said. In December, Horizon Therapeutics warned doctors and patients to expect a lack of a drug called Tepezza, used to treat thyroid-related eye disease, because its manufacturer was ordered to prioritize COVID photos.
Parliamentarians and consumer advocates, such as Public Citizen, have called on the government to use the Defense Production Act more aggressively. In a letter earlier this month, Senator Elizabeth Warren (D-MA) and Rep. Katie Porter (D-CA) said Moderna should share its vaccine stabilization technique at normal refrigerator temperatures without freezers. ” ultracold ”.
Moderna officials said that the intrinsic differences in the mRNA material of the two companies make this technology difficult to share. In addition, they say, Pfizer refused to share data with Moderna. Pfizer declined to comment.
As Moderna’s effort is federally funded, the government is likely to have entry rights and could take over production, Mike Watson, former president of Moderna Valera’s subsidiary, said in an email. “The reality is that no matter how hard you push production capacity, you will sooner or later reach a deadlock.”
Experts say it’s not as simple as requiring glassmaker Corning to step up and make glass bottles, for example. Of course, the vials will have to meet rigorous requirements. But there is also this: the US is facing a shortage of extracted sand, the main component needed for the manufacture of glass bottles.
KHN (Kaiser Health News) is a non-profit news service that covers health issues. It is an editorially independent program of the KFF (Kaiser Family Foundation) which is not affiliated with Kaiser Permanente.