On the menu today: why the Biden administration’s recent use of the Defense Production Act for vaccines is less than meets the eye, the WHO investigation in Wuhan can’t tell us anything other than they trust China’s denials of a lab accident, and South Africa decides to start using the Johnson & Johnson vaccine.
Why We Can’t Just ‘Make More Vaccines Faster’
Between impeachment, the Congressional wrangling over the relief package, and the Super Bowl, it was easy to miss the Biden administration’s announcement Friday that they are invoking the Defense Production Act — as the Washington Post put it, “to speed vaccinations and production of protective equipment.”
“Speed vaccinations” is a generous assessment; it is more like the Defense Production Act is being preemptively invoked to prevent any disruptions early in the supply chain of vaccine production. The DPA will ensure Pfizer has first priority to needed supplies — as well as instructing other companies to manufacture more gloves and coronavirus tests. But the DPA can’t simply be used to make Pfizer or Moderna make more vaccines, or, as some not-well-informed governors such as Minnesota’s Tim Walz contend, force other companies to make the vaccine:
Walz said other governors are wondering if more can be done with facilities used for vaccine development efforts that hit dead ends.
“The question is, ‘why can’t we use their facilities, the Defense Production Act and have every pharmaceutical company producing vaccines and get us 300 million doses by May?’ The White House’ response was ‘We’re exploring everything. Those are possibilities,’” Walz said.
No, they are not. Invoking the Defense Production Act to tell other pharmaceutical companies to make the Pfizer, Moderna, or some other vaccine is like instructing fireworks factories to start manufacturing thermonuclear weapons. Or, if you feel the comparison to nuclear fusion is hyperbole, instructing the Ford Focus plant in Wayne, Ind., to start manufacturing Lamborghinis. You would have to tear out almost all of the existing equipment, retrain the workers, and start over, if not quite from the ground up, then only a bit above it.
A week ago, this newsletter laid out how the equipment used to make the vaccine is custom-made; you can’t just tweak existing equipment or substitute out one part. Recall Derek Lowe’s description in Science Translational Medicine, that each step requires
. . . special-purpose bespoke machines, and if you ask other drug companies if they have one sitting around, the answer will be, “of course not”. This is not anything close to a traditional drug manufacturing process. And this is the single biggest reason why you cannot simply call up those “dozens” of other companies and ask them to shift their existing production over to making the mRNA vaccines. There are not dozens of companies who make DNA templates on the needed scale. There are definitely not dozens of companies who can make enough RNA. But most importantly, I believe that you can count on one hand the number of facilities who can make the critical lipid nanoparticles. That doesn’t mean that you can’t build more of the machines, but I would assume that Pfizer, BioNTech, Moderna (and CureVac as well) have largely taken up the production capacity for that sort of expansion as well.
Recall Kevin Williamson’s First Law: “Everything is simple when you don’t know a thing about it.” Here are a trio of experts politely laying out that Walz has no idea what he is talking about:
But the idea that any company, even another pharmaceutical company, can simply start producing the vaccines is easier than it sounds, according to some experts. Barry Bloom, a leading infectious disease expert at Harvard University, said it’s “one of the delusions I think people have.”
“This is a really complicated business that requires highly skilled people that you can’t go by, with a Defense Production Act, to make vaccines tomorrow,” he said.
“This is a really complex business,” Bloom added, in a recent interview.
NYU Langone Health vaccine expert Dr. Arthur Caplan said vaccines are “a pain in the neck” because unlike other pharmaceutical products, they rely on incubating biological ingredients.
“Sometimes what you’re trying to grow in an incubator doesn’t grow well, and you don’t know why. Historically, vaccine rollouts . . . have had some delay because the factory gets in trouble,” Caplan said.
Baylor College of Medicine’s Dr. Peter Hotez, another top vaccine expert, said the current demand is pushing the limits of manufacturing a brand new technology, messenger RNA, at scale.
“We knew the mRNA vaccines were not going to be the workhorse of this epidemic. It’s a new technology, it doesn’t have that capacity for scale like other technologies do,” Hotez said.
Pfizer does not have any unused production capacity sitting idle. The company is already working 24-7 to make their vaccine:
This is where the frozen mRNA is turned into a vaccine and vials are filled for distribution.
The process happens in Building 41 at Pfizer’s enormous Kalamazoo plant.
The COVID-19 vaccine uses most of the 1 million-square-foot building as it goes from start to finish. Three shifts of 30 to 40 people work 24 hours a day, seven days a week. The lines are continuously staffed and didn’t stop for the holidays.
Just to get into the formulation portion of the plant, workers must first change into scrubs, then enter the facility and completely strip, donning an aseptic gown and finally gear that resembles spacesuits.
That’s from a detailed and valuable USA Today feature that explores how the Pfizer vaccine is created, step by step. It’s worth reading the whole thing, but the abbreviated version is that at the Pfizer plant in Chesterfield, Mo., plasmids are grown in giant vats, placed into bags, and then frozen. From there the vaccine material is sent to Pfizer’s plant in Andover, Mass., where it is further refined and the lines of DNA are transcribed into messenger RNA. After a lot of quality testing, the purified and refrozen mRNA is put into bags and shipped to Kalamazoo, Mich., where “fragile strands of mRNA are enclosed in tiny balls of fat known as lipid nanoparticles” and the vaccine is put into vials for final shipping.
Pfizer has already figured out how to cut production time from 110 days to 60 days. Each batch can make anywhere from 1 to 3 million doses of vaccine per production run. The vaccines being used last week were started before Halloween.
None of this is simple or easy, and governors running around suggesting that pharmaceutical company production lines for Lipitor, Albuterol, or Prilosec can be quickly or easily retooled to make vaccines is so spectacularly dumb it can cause a headache.
WHO: The Only Scenario We Can Rule Out Is the One That China’s Rulers Deny
To sum up, a WHO team spent four weeks in Wuhan, China, and after their initial investigation, they can tell us absolutely nothing more about the origin of SARS-CoV-2. They’re certain it came from an animal but can’t yet identify which animal. No one has ever found this particular virus in any bats, or in any pangolins, or in any other animals. Other than the theorized original case of the virus jumping from an animal to a human being, the only case of animals catching the virus and spreading it to humans are minks in Denmark, months later.
But the one thing that the WHO team learned on this trip is that they’re certain that this pandemic did not stem from a lab accident from either the Wuhan Institute of Virology or the Wuhan Centers for Disease Control and Prevention, both of which were researching coronaviruses in bats.
In fact, the WHO team is now floating the theory that the virus did not originate in China:
Another member of the WHO team, Peter Daszak, went further, telling reporters after the press conference that the focus of the investigation was shifting toward countries—especially in Southeast Asia—that could have been the source of animals or animal products sold in Wuhan’s Huanan Market.
“We’ve done a lot of work in China and if you map that back, it starts to point towards the border and we know there is very little surveillance on the other side in the whole region of Southeast Asia,” he said. “I think our focus needs to shift to those supply chains to the market, supply chains from outside China, even.”
Oh, and they also said “it was also possible that the virus may have been transmitted to humans through imported frozen food, a theory heavily promoted by Beijing.”
Hey, FDA Guys, How’s That Johnson & Johnson Evaluation Coming?
Six days ago, Johnson & Johnson submitted its Emergency Use Authorization paperwork for its new vaccine to the FDA. As a layman, I won’t pretend to know what a proper amount of time for a sufficient FDA review is. I have heard experienced doctors and medical researchers argue it can be done in 24 to 48 hours without cutting corners. I am sure there are other doctors and medical researchers who strongly disagree. But I figure there’s “expedited” and then there’s “more-than-3,000-people-are-dying-from-this-virus-a-day expedited.”
It shouldn’t take that much longer, right? One week ago, Dr. Anthony Fauci said on national television, “We could see literally within a week or so that they wind up getting the kind of emergency use authorization. I don’t want to get ahead of the FDA, but I would not be surprised if this happens within the next week or two.”
The South African government, currently fighting a particularly contagious variant, just decided to give the Johnson & Johnson vaccine to frontline workers, saying they’ve seen enough from the 44,000-participant study.
Is our FDA going to come to a dramatically different conclusion from the South Africans?
ADDENDUM: The Gallup organization:
As the Biden administration begins to grapple with the COVID-19 situation, two-thirds of Americans say they are not satisfied with the way the vaccination process is going in the U.S. This includes 21 percent who are ‘very dissatisfied.’ At the same time, 34 percent are satisfied, with 4 percent of them ‘very satisfied.’