Sarah Liz Tribble, Arthur Allen, and Jay Hancock, by Liz Szabo
Thousands of Americans are dying of COVID-19, but efforts to increase production of potentially life-saving vaccines are hitting a brick wall.
Vaccine manufacturers Modern and Pfizer-BioNotech are running their factories fully and are under tremendous pressure to increase production or to establish additional assembly lines in collaboration with other pharmaceutical companies. This pressure is only increasing as new viral variants of the virus threaten to launch the country into a deadly phase of the epidemic.
President Joe Biden has said he plans to implement the Cold War-era Authority of Defense Production Act to provide more vaccines to millions of Americans. Consumer advocates — who had called Donald Trump as president to use the Defense Production Act more aggressively — are now asking Biden to do the same.
But even forcing companies should not give too much dose anytime soon. It takes time to expand production lines. The renovated facilities can take months to install lines.
“The big problem is that even if you can get the raw materials and set up the infrastructure, how can you find a company that is already producing at maximum capacity to go beyond the maximum capacity ? ” Said Lawrence Gostin, a professor of global health law at Georgetown University.
24/7 “ordering companies to work” would be a gullible solution, Drs. Nicole Lurie, a senior adviser to the CEO of the Alliance for Epidemic Preparation, is an international group that finances vaccines for emerging diseases. “They are probably already doing that they have the raw material.”
Lurie said, “If you completely wear people out, then mistakes happen. You have to balance speed with quality and safety.”
The technical challenges involved are daunting, and companies are not prepared for what is needed to overcome any supply shortage.
“We don’t know what the holdup is. What is this ability? raw material? People? Glass vials? 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.
Gostin said that forcing other companies to make vaccines may not work either.
“I’m not sure if Biden might need a private company to transfer his company to another company,” Gostin said. “It’s legally highly questionable … President Biden’s room for maneuvers is not as great as people think.”
Pharmaceutical companies broadly defined “trade secrets”, Fox said. “In general, pharmaceutical companies do not have to tell me who is making their product, where it is made, the location of the factory … It is considered financially important.”
Part of the challenge is how these vaccines are made. The first two authorized products use lipid nanoparticles to deliver coronovirus genetic material – messenger RNA, or mRNA – into cells a snippet. Viral genes teach our cells how they make proteins that stimulate the immune response to novel coronoviruses.
Messenger RNA is fragile and breaks easily, so it needs to be taken care of with specific temperature and humidity levels.
The vaccine is “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, has its complexities in the market for vaccines: obtaining raw materials; Construction of facilities to exact specifications; Purchase single-use products, such as tubing and plastic bags, to line stainless steel bioreactors; And hiring employees with the requisite training and expertise. Companies should also pass safety and quality inspections and arrange for transportation.
The Defense Production Act, for example, would allow the government to hand over the command of a plant that already has a fermenter – many in the biotech industry – to expand production. But this is just the first stage of making an mRNA vaccine and even then, it will take about a year to achieve, a vaccine expert, Dr. Georg Sieber, who is on the advisory board of CureVac, a German mRNA vaccine company.
“Making vaccines is not the same as making a car, and quality control is paramount.“
– Dr. Stanley Plotkin
Siber said companies would first have to do a thorough cleaning to prevent cross-contamination. They will then need to install it, test and install test equipment and train scientists and engineers. Finally, Siber said, unlike a drug whose components can be tested for purity, there is no way to ensure that there is a vaccine produced in a new facility without testing it on animals and people Claims to be.
“Making a vaccine is not the same as making cars, and quality control is paramount,” said Dr. Rubella, a vaccine industry consultant credited with inventing the vaccine. Stanley Plotkin gave. “We are expecting other vaccines in a few weeks, so it may be faster to use them.”
However, even patience will be required. Johnson & Johnson, expected to announce the results of the clinical trial this month, said it would not be able to deliver as many shots as scheduled due to manufacturing delays. The company did not confirm manufacturing delays and refused to answer questions.
The AstraZeneca vaccine, partially funded by US taxpayers, is already in use in the United Kingdom and India, but the Food and Drug Administration has raised questions about its late trial, so it will be out by spring May not be available here.
Novavax, another US-funded vaccine manufacturer, has suffered from delays and recently began recruiting volunteers for its larger trial. Merck, the most recent company to receive federal assistance for COVID vaccines, announced on Monday that it was scrapping two of its candidates, as they failed to produce a sufficient immune response in early trials.
“None of the vaccine manufacturers are manufacturing the volume they ultimately want,” Lurie said. “They all have manufacturing delays.”
Pfizer, which has given the US government 200 million doses as of the end of July, said last week it expected “no interruptions” in shipments from its primary US COVID manufacturing plant in Kalamazoo, Michigan. Pfizer spokesman Sharon Castillo said the company had expanded manufacturing facilities and added more suppliers and contract manufacturers. Those efforts, and the company’s announcement that its five-dose vials actually included an additional dose, meant “we could potentially deliver around 2 billion doses worldwide by the end of 2021.”
The US government also has the option of receiving another 400 million doses of the Pfizer-BioNTech vaccine, although the company declined to provide details on that option when asked.
But countries around the world are competing for equal 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,” given that other countries could retaliate by hoarding supplies. Although Pfizer is an American company, it has partnered with BioNTech in Germany to manufacture its COVID vaccine. “This will cause a global mess.”
It would be bad to try to link the world market to vaccine ingredients or supplies, with experts saying the United States just joined Kovacs this week, an effort to ensure an international enterprise and vaccines to be distributed to source countries I am not leaving poor countries behind. .
Paradoxically, the haste to bring vaccines to market may result in a less efficient manufacturing process.
Vaccine companies typically spend months running their factories efficiently, as well as looking for an ideal dose and the most effective interval between doses, Lurie said. Given the urgency of the epidemic, however, he delayed parts of the process and began mass production directly.
“The US may not necessarily have easy access to the goods held for vaccines in other countries.“
– Nicole Lurie
Pfizer angered European countries last week when it stopped production of the vaccine at a Belgian plant to upgrade its capacity. Pfizer said that a week-long closure before increasing supply in February would reduce vaccine delivery to Europe by three to four weeks. The move does not affect US vaccine supply.
“America cannot necessarily use vaccines that can be easily held in other countries,” Lurie said.
And forcing other companies to produce COVID vaccines could jeopardize the production of other critical shots like measles, a senior scholar at the Johns Hopkins Center for Health Security, Dr. Amesh Adalja said. Regular childhood immunization rates have fallen during the epidemic, increasing the risk of the epidemic.
The use of the act to prioritize COVID vaccine manufacture has already disrupted at least one drug supply, Fox said. In December, Horizon Therapeutics warned doctors and patients to expect a shortage of a drug called thapiza, which was used to treat thyroid-related eye disease, as its manufacturer preferred COVID shots. Was ordered
Public citizens such as lawyers and consumer advocates called on the government to use the Defense Production Act more aggressively. In a letter sent earlier this month, Sen. Elizabeth Warren (D-MA) and rapist Katie Porter (D-CA) said Morden needed to stabilize her vaccine at normal refrigerator temperatures, without the “ultrahold” freezer Must share your technique.
Modern authorities have stated that internal differences in the mRNA content of the two companies make it difficult to share that technology. In addition, they say, Pfizer has refused to share data with Modern. Pfizer has declined to comment on the issue.
Since this modern-day effort is funded by the union, the government probably has march-in rights and can take over the production, said Mike Watson, former president of Modern subsidiary Valera, in an email. “The reality is that although you advance production capacity, you sooner or later get into the bottleneck.”
Experts say that it is not as simple that glassmakers demand a cornering step up and make glass vials for example. Of course, the vials will need to meet stringent requirements. But it is also: The US is facing a shortage of mined sand, the main ingredient needed to make glass vials.
KHN (Kaiser Health News) is a non-profit news service covering health issues. This is the editorial independent program of KFF (Kaiser Family Foundation) which is not affiliated with Kaiser Permanente.