By Liz Szabo, Sarah Jane Tribble, Arthur Allen, and Jay Hancock
Americans are dying by the thousands from COVID-19, but attempts to ramp up production of potentially life-saving vaccines hit a brick wall.
Vaccine manufacturers Moderna and Pfizer-BioNTech are running their factories at full speed and are under tremendous pressure to expand production or partner with other pharmaceutical companies to set up additional assembly lines. That pressure is only increasing as new viral variants of the virus threaten to plunge the country into a deadlier phase of the pandemic.
President Joe Biden has said he plans to appeal to the Cold War-era authority of the Defense Production Act to provide more vaccines to millions of Americans. Consumer advocates – who had called on 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 ramp up production isn’t going to deliver much-needed doses anytime soon. Expanding production lines takes time. Establishing lines in repurposed facilities can take months.
“The big problem is that even if you can get the raw material and set up the infrastructure, how do you get a company that is already producing at maximum capacity to go beyond that maximum capacity?” said Lawrence Gostin, a professor of global health law at Georgetown University.
Telling the companies to operate 24/7 “would be a naive solution,” said Dr. Nicole Lurie, senior advisor to the CEO of the Coalition for Epidemic Preparedness Innovations, an international group that funds vaccines for emerging diseases. “They probably already do that insofar as they have the raw materials.”
Lurie added, ‘When you exhaust people completely, mistakes happen. You have to balance speed with quality and safety. “
The technological challenges are daunting and the companies have not talked about what it takes to solve any supply shortages.
‘We don’t know what the delay is. 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 Health Hospitals.
Forcing other companies to make the vaccines may not work either, Gostin said.
“I’m not sure Biden can require a private company to transfer its technology to another company,” said Gostin. “Legally, that is highly questionable … President Biden’s room for maneuver is not as great as people think.”
Pharmaceutical companies broadly define “trade secrets,” Fox said. “Generally, pharmaceutical companies don’t have to tell me who makes their product, where it’s made, the location of the factory … That’s considered property.”
Part of the challenge relates to the way 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 – into cells. The viral genes teach our cells how to make proteins that stimulate an immune response to the new coronavirus.
Messenger RNA is fragile and breaks down easily, so it must be handled with care, with specific temperatures and humidity levels.
The vaccines “are not widgets,” said Lurie, who served as assistant secretary for preparedness and response in the Department of Health and Human Services during the Obama administration.
Every step, experts say, to getting vaccines to market has its complexity: obtaining raw materials; building facilities to precise specifications; purchasing single use products such as tubing and plastic bags to line stainless steel bioreactors; and hiring employees with the necessary training and expertise. Companies must also pass safety and quality checks and arrange transportation.
For example, the defense production law would allow the government to take possession of a factory that already has a fermenter – there are plenty in the biotech industry – to expand production. But that’s only the first stage in making an mRNA vaccine and even then it would take about a year to get going, said Dr. George Siber, a vaccine expert on the advisory board of CureVac, a German mRNA. vaccine company.
“Making vaccines is not like making cars, and quality control is paramount.“
– Dr. Stanley Plotkin
Businesses should do a breathtaking thorough cleanup first to avoid cross-contamination, Siber said. They then had to install, calibrate, and test equipment and train scientists and engineers to work with 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 it on animals and people to test.
“Making vaccines is not the same as making cars, and quality control is paramount,” said Dr. Stanley Plotkin, a consultant in the vaccine industry who reportedly invented the rubella vaccine. “We expect other vaccines in a few weeks, so it may be faster to put them to use.”
But even that requires patience. Johnson & Johnson, which is expected to release clinical trial results this month, has said it won’t be able to get as many shots as planned due to production delays. The company did not confirm a production delay and declined to respond to inquiries.
AstraZeneca’s vaccine, which is also partially funded by US taxpayers, is already in use in the UK and India, but the Food and Drug Administration has raised questions about the late-stage research, so it may not be here until spring available.
Novavax, another US-funded vaccine maker, is plagued with delays and has only recently started recruiting volunteers for its big trial. Merck, the most recent company to receive federal support for COVID vaccines, announced on Monday that it would drop its two candidates after failing to produce an adequate immune response in early testing.
“None of the vaccine makers are producing at the volume they ultimately want,” said Lurie. “They all have production delays.”
Pfizer, which pledged 200 million doses to the US government in late July, said last week that it expected “no interruptions” in shipments from its primary US COVID plant in Kalamazoo, Michigan. Pfizer spokesperson Sharon Castillo said the company has expanded manufacturing facilities and added more suppliers and contract manufacturers. Those efforts, and the company’s announcement that the five-dose vials will actually contain an additional dose, mean that “by the end of 2021 we could potentially deliver approximately 2 billion doses worldwide.”
The US government also has an option to purchase an additional 400 million doses of the Pfizer-BioNTech vaccine, although the company declined to provide details about that option upon request.
But countries around the world 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,” as other countries could retaliate by hoarding supplies. Although Pfizer is a US company, it has partnered with Germany’s BioNTech to make its COVID vaccine. “That would lead to a worldwide mess.”
Trying to conquer the global market for vaccine ingredients or supplies would look bad, experts say, as the United States this week joined Covax, an international company that purchases and distributes vaccines, in an effort to ensure that poor countries are not left behind. .
Paradoxically, the rush to bring vaccines to market may have resulted in a less efficient manufacturing process.
Vaccination companies typically spend months running their factories as efficiently as possible, and finding an ideal dose and the most effective interval between doses, Lurie said. However, given the urgency of the pandemic, they slowed down parts of this process and immediately began mass production.
“The US does not necessarily have easy access to stuff kept for vaccines in other countries.“
– Nicole Lurie
Last week, Pfizer angered European countries when it shut down vaccine production at a Belgian factory to increase capacity. Pfizer said the one-week shutdown would cut supplies of vaccines to Europe for three to four weeks, before increasing supplies in February. The move will not affect the US vaccine supply.
“The US doesn’t necessarily have easy access to stuff that’s kept for vaccines in other countries,” Lurie said.
And forcing other companies to make COVID vaccines could jeopardize the production of other major injections, such as measles, said Dr. Amesh Adalja, a senior scholar at the Johns Hopkins Center for Health Security. The number of routine immunizations in children has fallen during the pandemic, increasing the risk of epidemics.
Using the law to prioritize the production of COVID vaccines has already disrupted the supply of at least one drug, Fox noted. In December, Horizon Therapeutics warned doctors and patients to expect a shortage of the drug Tepezza, which is used to treat thyroid-related eye conditions, as the manufacturer was instructed to prioritize COVID injections.
Lawmakers and consumer advocates, such as Public Citizen, called on the government to be more aggressive with the Defense Production Act. In a letter sent earlier this month, Sen. Elizabeth Warren (D-MA) and Rep. Katie Porter (D-CA) that Moderna should share his technique for stabilizing its vaccine at normal refrigerator temperatures, without “ultra-cold” freezers.
Moderna officials have said the intrinsic differences in the mRNA material of the two companies make it difficult to share this technology. In addition, they say, Pfizer has refused to share data with Moderna. Pfizer has declined to comment on the matter.
Since Moderna’s efforts are federally funded, the government presumably has marching-in rights and could take over the production, Mike Watson, former president of Moderna subsidiary Valera, said in an email. “The reality is that no matter how far you push production capacity, sooner or later you’ll hit a bottleneck.”
Experts say it is not as simple as demanding that glass manufacturer Corning go a step further and make glass bottles, for example. The bottles must of course meet strict requirements. But there is also this: the US is running out of mined sand, the most important part needed to make glass bottles.
KHN (Kaiser Health News) is a non-profit news service about health issues. It is an editorial independent program from KFF (Kaiser Family Foundation) which is not affiliated with Kaiser Permanente.