By Liz Szabo, Sarah Jane Tribble, Arthur Allen and Jay Hancock
Americans die a thousand to COVID-19, but efforts to increase the production of potentially life-saving vaccines hit a brick wall.
Vaccine manufacturers Moderna and Pfizer-BioNTech are operating their factories and are under tremendous pressure to expand production or collaborate with other pharmaceutical companies to set up additional assembly lines. This pressure only increases as new virus variants of the virus threaten to start the country in a more deadly phase of the pandemic.
President Joe Biden has said he plans to call on the Cold War government to defend more vaccines to millions of Americans. Consumer advocates – who called on Donald Trump to use the Defense Production Act more aggressively as president – are asking Biden to do the same.
But even forcing companies to leverage their production will not soon deliver much-needed doses. Expanding production lines takes time. It can take months to establish lines in reusable facilities.
“The big problem is that even if you can get the raw material and set up the infrastructure, how do you get a business that is already producing at maximum capacity beyond the maximum capacity?” says Lawrence Gostin, a professor of global health law at Georgetown University.
‘This is a naive solution to order the companies to work 24/7,’ says dr. Nicole Lurie, senior adviser to the CEO of the Coalition for Epidemic Preparedness Innovations, an international group that funds vaccines for emerging diseases. “They’re probably already doing it to the extent that they have the raw materials.”
Lurie added, ‘If you wear people out completely, mistakes happen. You need to balance speed with quality and safety. ”
The technological challenges involved are frightening, and the businesses have not yet taken note of what is needed to overcome any supply shortages.
“We do not know what the hold is. Is it capacity? Raw materials? People? Slides of glass? We just do not know what the bottleneck is, ”said Erin Fox, senior director of medical information and support services at the University of Utah Health Hospitals.
Forcing other companies to start making the vaccines may not work either, Gostin said.
“I’m not sure if Biden can require a private company to transfer its technology to another company,” Gostin said. “It’s legally questionable … President Biden’s room for maneuver is not as large as people think.”
Medicine companies define “trade secrets” broadly, Fox said. “In general, drug companies do not have to tell me who makes their product, where it is made, the location of the factory … it is considered their own.”
Part of the challenge has to do with how these vaccines are made. The first two approved products use lipid nanoparticles to deliver a fragment of the coronavirus’s 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 of state for preparedness and response during the Obama administration’s response to the Department of Health and Human Services.
Every step, according to experts, to get vaccines on the market has its complexity: the acquisition of raw materials; build facilities according to exact specifications; buy disposable products, such as tubes and plastic bags to feed stainless steel bioreactors; and hiring employees with the necessary training and expertise. Businesses must also pass safety and quality inspections and arrange transportation.
The Defense Production Act, for example, would allow the government to set up a plant that already has a fermentation – there are many in the biotechnology industry – to expand production. But this is only the first phase in making an mRNA vaccine, and even then it will take about a year to get started, said Dr. George Siber, a vaccine expert, told 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
Siber will first need to do a breathtaking cleaning job to prevent cross-contamination. Next, they will need to set up, calibrate and test equipment, and train scientists and engineers to manage it. Finally, Siber said, unlike a drug whose components can be tested for purity, there is no way to be sure that a vaccine produced in a new plant, according to him, is without it on animals and people to test.
“Making vaccines is not like making cars, and quality control is of the utmost importance,” said Dr. Stanley Plotkin, a vaccine industry consultant, admits he invented the rubella vaccine. “We are expecting other vaccines within a few weeks, so it may be quicker to put them to use.”
However, even that will require patience. Johnson & Johnson, which is expected to announce the results of clinical trials this month, said they would not be able to deliver as many shots as planned due to manufacturing delays. The company did not confirm a delay in production and declined to comment.
The AstraZeneca vaccine, which is also partly funded by US taxpayers, is already in use in the UK and India, but the Food and Drug Administration has asked questions about the late trial, so it will only be available here in the spring.
Novavax, another US-funded vaccine maker, is plagued by 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 Monday that it would scrap its two candidates after failing to provide adequate immune response to early tests.
“None of the vaccine manufacturers manufacture at the volume they ultimately want to be,” Lurie said. “They all have production delays.”
Pfizer, which dedicated 200 million doses to the U.S. government by the end of July, said last week it expects “no interruptions” from deliveries from its primary U.S. COVID plant in Kalamazoo, Michigan. Pfizer spokeswoman Sharon Castillo said the company had expanded manufacturing facilities and added more suppliers and contract manufacturers. These efforts, and the company’s announcement that its five-dose vials contain an extra dose, mean that “by the end of 2021, we could potentially be delivering around 2 billion doses worldwide.”
The US government also has an option to obtain another 400 million doses of Pfizer-BioNTech vaccine, although the company declined to comment on the option when contacted.
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 U.S. contracts, but that would be politically risky’, as other countries could retaliate by stockpiling supplies. Although Pfizer is a US company, it has co-developed a COVID vaccine with BioNTech, Germany. “It will lead to a global mess.”
Trying to turn the world market for vaccine ingredients or supplies upside down will make experts look bad, as the United States just joined Covax this week, an international vaccine-sourcing and distribution company, in an effort to secure that poor countries do not lag behind. .
Paradoxically, the rush to get vaccines on the market could potentially result in a less efficient manufacturing process.
Vaccination companies usually spend months getting their factories working as efficiently as possible, as well as finding the ideal dose and the most effective intervals, Lurie said. However, due to the urgency of the pandemic, they delayed parts of this process and began mass production directly.
‘The US may not necessarily have easy access to things held in other countries for vaccinations.”
– Nicole Lurie
Pfizer angered European countries last week when it disrupted vaccine production at a Belgian plant to improve its capacity. Pfizer said the closure of the week would reduce vaccine deliveries to Europe for three to four weeks before stock increases in February. The move has no effect on U.S. vaccine supplies.
“The US may not necessarily have easy access to things that are being held in other countries for vaccinations,” Lurie said.
And forcing other companies to make COVID vaccines could jeopardize the production of other important shots, such as measles, Drs. Amesh Adalja, a senior scholar at the Johns Hopkins Center for Health Safety, said. Routine vaccination rates in children declined during the pandemic, increasing the risk of epidemics.
The use of the law to prioritize the production of COVID vaccines has already disrupted the supply of at least one drug. In December, Horizon Therapeutics warned doctors and patients to anticipate a shortage of a drug called Tepezza, which is used to treat thyroid-related eye disease, as its manufacturer was ordered to prioritize COVID shots.
Consumer lawmakers and advocates like Public Citizen are urging the government to use the Defense Production Act more aggressively. In a letter sent earlier this month, Senator Elizabeth Warren (D-MA) and Representative Katie Porter (D-CA) said that Moderna should share its technique to stabilize its vaccine at normal refrigerator temperatures, without an ‘ultra-cold’ freezer.
Modern officials said the intrinsic differences in the two companies’ mRNA material make it difficult to share the technology. Besides, they say, Pfizer refused to share data with Moderna. Pfizer declined to comment on the issue.
Since the Moderna effort is federally funded, the government presumably has marching rights and could take over production, Mike Watson, former president of the Moderna subsidiary Valera, said in an email. “The reality is that no matter how far you use production capacity, sooner or later you will reach a bottleneck.”
Experts believe that it is not as simple as demanding that the glass manufacturer Corning act and make glass bottles, for example. Of course, the vials must meet strict requirements. But there it is, too: the US faces a shortage of mined sand, the most important component needed to make glass bottles.
KHN (Kaiser Health News) is a non-profit news service that covers health issues. This is an editorially independent program of KFF (Kaiser Family Foundation) which is not affiliated with Kaiser Permanente.