[President Biden has promised enough doses for all American adults
by this summer. There’s not much even the Defense Production Act can
do to deliver doses before then.] [[link removed]]

WHY WE CAN’T MAKE VACCINE DOSES ANY FASTER  
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Isaac Arnsdorf and Ryan Gabrielson
February 19, 2021
ProPublica [[link removed]]

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_ President Biden has promised enough doses for all American adults
by this summer. There’s not much even the Defense Production Act can
do to deliver doses before then. _

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Why We Can’t Make Vaccine Doses Any Faster
_ProPublica is a Pulitzer Prize-winning investigative newsroom. Sign
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like this one in your inbox_.

Series: Coronavirus [[link removed]]
The U.S. Response to COVID-19
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President Joe Biden has ordered enough vaccines
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to immunize every American against COVID-19, and his administration
says it’s using the full force of the federal government to get the
doses by July
[[link removed]].
There’s a reason he can’t promise them sooner.

Vaccine supply chains are extremely specialized and sensitive, relying
on expensive machinery, highly trained staff and finicky ingredients.
Manufacturers have run into intermittent shortages of key materials,
according to the U.S. Government Accountability Office
[[link removed]]; the combination of
surging demand and workforce disruptions from the pandemic has caused
delays of four to 12 weeks for items that used to ship within a week,
much like what happened when consumers were sent scrambling for
household staples like flour
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chicken wings
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and toilet paper
[[link removed]].

People often question why the administration can’t use the mighty
Defense Production Act — which empowers the government to demand
critical supplies before anyone else — to turbocharge production.
But that law has its limits. Each time a manufacturer adds new
equipment or a new raw materials supplier, they are required to run
extensive tests to ensure the hardware or ingredients consistently
work as intended, then submit data to the Food and Drug
Administration. Adding capacity “doesn’t happen in a blink of an
eye,” said Jennifer Pancorbo, director of industry programs and
research at North Carolina State University’s Biomanufacturing
Training and Education Center. “It takes a good chunk of weeks.”

And adding supplies at any one point only helps if production can be
expanded up and down the entire chain. “Thousands of components may
be needed,” said Gerald W. Parker, director of the Pandemic and
Biosecurity Policy Program at Texas A&M University’s Scowcroft
Institute for International Affairs and a former senior official in
the Department of Health and Human Services office for preparedness
and response. “You can’t just turn on the Defense Production Act
and make it happen.”

The U.S. doesn’t have spare facilities waiting around to manufacture
vaccines, or other kinds of factories that could be converted the way
General Motors began producing ventilators
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last year. The GAO said the Army Corps of Engineers is helping to
expand existing vaccine facilities, but it can’t be done overnight.

Building new capacity would take two to three months, at which point
the new production lines would still face weeks of testing to ensure
they were able to make the vaccine doses correctly before the
companies could start delivering more shots.

“It’s not like making shoes,” Dr. Anthony Fauci, director of the
National Institute of Allergy and Infectious Diseases, said in an
interview with ProPublica. “And the reason I use that somewhat
tongue-in-cheek analogy is that people say, ‘Ah, you know what we
should do? We should get the DPA to build another factory in a week
and start making mRNA.’ Well, by the time a new factory can get
geared up to make the mRNA vaccine exactly according to the very, very
strict guidelines and requirements of the FDA ... we already will have
in our hands the 600 million doses between Moderna and Pfizer that we
contracted for. It would almost be too late.”

Fauci added that the DPA works best for “facilitating something
rather than building something from scratch.”

The Trump administration deployed the Defense Production Act last year
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manufacturers priority in accessing crucial production supplies before
anyone else could buy them. And the Biden administration used it to
help Pfizer obtain specialized needles that can squeeze a sixth dose
from the company’s vials, as well as for two critical manufacturing
components: filling pumps and tangential flow filtration units. The
pumps help supply the lipid nanoparticles that hold and protect the
mRNA — the vaccines’ active ingredient, so to speak — and also
fill vials with finished vaccine. The filtration units remove unneeded
solutions and other materials used in the manufacturing process.

These highly precise pieces of equipment are not typically available
on demand, said Matthew Johnson, senior director of product management
at Duke University’s Human Vaccine Institute, who works on
developing mRNA vaccines, but not for COVID-19. “Right now, there is
so much growth in biopharmaceuticals, plus the pinch of the
pandemic,” he said. “Many equipment suppliers are sold out of
production, and even products scheduled to be made, in some cases,
sold out for a year or so looking forward.”

In the meantime, the shortage of vaccines is creating widespread
frustration and anxiety as eligible people struggle to get
appointments and millions of others wonder how long it will be before
it is their turn. As of Feb. 17
[[link removed]], the U.S. had
distributed 72.4 million doses and administered 56.3 million shots,
but fewer than 16 million people have received both of the two doses
that the Pfizer and Moderna vaccines require for full protection.

The Biden administration has said it is increasing vaccine shipments
to states by 20%, to 13.5 million doses a week, and encouraged states
to give out all their shots instead of holding on to some for second
doses. But now that second-dose appointments are coming due, many
jurisdictions are having to focus on those and stepping back from
vaccinating uninoculated people. Even as the total number of
vaccinations increased last week, the number of first doses fell to
6.8 million people, down from 7.8 million three weeks ago, according
to Centers for Disease Control and Prevention data.

At best, it will take until June for manufacturers to deliver enough
doses for the roughly 266 million eligible Americans age 16 and over,
according to public statements by the companies.

That includes expected deliveries of Johnson & Johnson’s one-dose
vaccine, which is widely expected to win emergency authorization from
the FDA shortly after a public advisory committee meeting on Feb. 26.
But Johnson & Johnson has fallen behind in manufacturing. The company
told the GAO [[link removed]] it will have
only 2 million doses ready to go by the time the vaccine is
authorized, whereas its $1 billion contract
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with HHS scheduled 12 million doses by the end of February. It’s not
clear what held up Johnson & Johnson’s production line; the company
has benefited from first-priority purchases thanks to the DPA,
according to a senior executive close to the manufacturing process. A
Johnson & Johnson spokesman declined to comment on the cause of the
delay, but said the company still expects to ship 100 million U.S.
doses by July.

Moderna declined to comment on “operational aspects” of its
manufacturing, but “does remain confident in our ability to meet
contracted quantities” of its vaccine to the U.S. and other nations,
a spokesperson said in a statement. Pfizer did not respond to
ProPublica’s written questions.

Ramping up production is especially challenging for Pfizer and
Moderna, whose vaccines use an mRNA technology that’s never been
mass-produced before. The companies started production even before
they finished trials to see if the vaccines worked, another historic
first. But it wasn’t as if they could instantly crank out millions
of vaccines full blast, since they effectively had to invent a novel
manufacturing process.

“Putting together plans 12 months ago for a Phase 1 and 2 trial, and
making enough to dose a couple hundred patients, was a big deal for
the raw material suppliers,” said Johnson, the product manager at
Duke University’s vaccine institute. “It's just going from dosing
hundreds of patients a year ago to a billion.”

Raw materials for the Pfizer and Moderna vaccines are also in limited
supply. The manufacturing process begins by using common gut bacteria
cells to grow something called “plasmids” — standalone snippets
of DNA — that contain instructions to make the vaccine’s genetic
material, said Pancorbo, the North Carolina State University
biomanufacturing expert.

Next, specific enzymes cultivated from bacteria are added to cause a
chemical reaction that assembles the strands of mRNA, Pancorbo said.
Those strands are then packaged in lipid nanoparticles, microscopic
bubbles of fat made using petroleum or plant oils. The fat bubbles
protect the genetic material inside the human body and help deliver it
to the cells.

Only a few firms specialize in making these ingredients, which have
previously been sold by the kilogram, Pancorbo said. But they’re now
needed by the metric ton — a thousandfold increase. Moderna and
Pfizer need bulk, but also the highest possible quality.

“There are a number of organizations that make these enzymes and
these nucleotides and lipids, but they might not make it in a grade
that is satisfactory for human consumption,” Pancorbo said. “It
might be a grade that is satisfactory for animal consumption or
research. But for injection into a human? That’s a different
thing.”

Johnson & Johnson’s vaccine follows a slightly more traditional
method of growing cells in large tanks called bioreactors. This takes
time, and the slightest contamination can spoil a whole batch. Since
the process deals with living things, it can be more like growing
plants than making shoes. “Maximizing yield is as much of an art as
it is a science, as the manufacturing process itself is dependent on
biological processes,” said Parker, the former HHS official.

The vaccine developers are continuing to find tweaks that can expedite
production without cutting corners. Pfizer is now delivering six doses
in each vial instead of five, and Moderna has asked for permission to
fill each of its bottles with 15 doses, up from 10. If regulators
approve, it would take two or three months to change over production,
Moderna spokesman Ray Jordan said on Feb. 13.

“It helps speed up and lighten the logistical side of getting
vaccines out,” said Lawrence Ganti, president of SiO2, an Alabama
company that makes glass vials for the Moderna vaccine. SiO2 expanded
production with $143 million
[[link removed]]
in funding from the federal government last year, and Ganti said there
aren’t any hiccups at his end of the line.

Despite the possibility of sporadic bottlenecks and delays in the
coming months, companies appear to have lined up their supply chains
to the point that they’re comfortable with their ability to meet
current production targets.

Massachusetts-based Snapdragon Chemistry received almost $700,000 from
HHS' Biomedical Advanced Research and Development Authority to develop
a new way of producing ribonucleoside triphosphates (NTPs), a key raw
material for mRNA vaccines. Snapdragon’s technology uses a
continuous production line, rather than the traditional process of
making batches in big vats, so it’s easier to scale up by simply
keeping production running for a longer time.

Suppliers have told Snapdragon that they have their raw materials
covered for now, according to Matthew Bio, the company’s president
and CEO. “They’re saying, ‘We have established suppliers to meet
the demand we have for this year,’” Bio said.

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