How Pfizer Makes Its Covid-19 Vaccine



Inside this facility in Chesterfield, Missouri, trillions of bacteria are producing tiny loops of DNA containing coronavirus genes — the raw material for the Pfizer-BioNTech vaccine.

It’s the start of a complex manufacturing and testing process that takes 60 days and involves Pfizer facilities in three states. The result will be millions of doses of the vaccine, frozen and ready to ship.

STEP 1

Pull DNA from Cold Storage

A scientist removes vials of DNA from the master cell bank, the source of every batch of Pfizer’s Covid-19 vaccine. The vials are kept at –150°C (–238°F) or below, and contain small rings of DNA called plasmids.






Coronavirus

spike protein

gene

Coronavirus

spike proteins

Coronavirus

spike protein

gene

Coronavirus

spike proteins


Each plasmid contains a coronavirus gene, the genetic instructions for a human cell to build coronavirus proteins and trigger an immune response to the virus.

“This kind of reminds me of September 11th. It’s that same feeling of: What were you doing at the time?”– Amy Barnessenior scientist

Scientists thaw the plasmids and modify a batch of E. coli bacteria to take the plasmids inside their cells.







A single vial can eventually produce up to 50 million doses of the vaccine.

STEP 2

Grow the Cells

“Rarely do you work on something in the lab and go home and turn on your TV and see the top 10 headlines are about the thing that you were working on today.”– Katherine Calhounassociate scientist

The vial of modified bacteria is swirled into a flask of amber-colored growth medium, a sterile and warm environment that encourages the bacteria to multiply.







STEP 3

Ferment the Mixture

The bacteria are allowed to grow overnight and then moved into a large fermenter that contains up to 300 liters of a nutrient broth.







The bacterial broth spends four days in the fermenter, multiplying every 20 minutes and making trillions of copies of the DNA plasmids.

STEP 4

Harvest and Purify the DNA

When the fermentation is complete, scientists add chemicals to break open the bacteria and release the plasmids from their enclosing cells.







The mixture is then purified to remove the bacteria and leave only the plasmids.

STEP 5

Test for Quality

The plasmids are tested for purity, and compared against previous samples to confirm that the coronavirus gene sequence has not changed.






Linear DNA

for comparison


STEP 6

Cut the Plasmids

If the plasmids pass the quality checks, proteins called enzymes are added to the mixture. The enzymes cut the circular plasmids and separate the coronavirus genes into straight segments, a process called linearization that takes about two days.






Enzymes

cutting the

plasmids

Enzymes

cutting the

plasmids


STEP 7

Filter the DNA

Any remaining bacteria or plasmid fragments are filtered out, leaving one-liter bottles of purified DNA.







The DNA sequences are tested again, and will serve as templates for the next stage of the process. Each bottle of DNA will produce about 1.5 million doses of the vaccine.

The Chesterfield facility is Pfizer’s only source of plasmids for its Covid-19 vaccine. But finishing the vaccine requires several more steps in two other facilities.

STEP 8

Freeze, Pack and Ship

Each bottle of DNA is frozen, bagged, sealed and packed with a small monitor that will record its temperature in transit.

“What we do is so important because we basically control everything that gets shipped. Every vial that goes to every person goes through us first.”– Sahar Gholamilab technician

Up to 48 bottles are packed in a container with enough dry ice to keep them frozen at –20°C (–4°F). The containers are locked to prevent tampering and shipped to a Pfizer research and manufacturing facility in Andover, Mass.

The Andover plant will process the DNA into messenger RNA, or mRNA, the active ingredient of the Pfizer-BioNTech vaccine.






Other bottles are flown to BioNTech facilities in Mainz, Germany, where they are processed for Europe and other markets.

STEP 9

Transcribe the DNA into mRNA

Inside the Andover facility, yellow walls mark the mRNA suite. Five bottles of DNA are thawed for a day, then mixed with the building blocks of messenger RNA.

Over several hours, enzymes pry open the DNA templates and transcribe them into strands of mRNA. The finished vaccine will carry the mRNA into human cells, which will read the coronavirus gene and begin producing coronavirus proteins.






Transcribing

DNA into mRNA

Transcribing

DNA into

mRNA


The mixture is moved into a holding tank, then filtered to remove any unwanted DNA, enzymes or other impurities. Each batch will eventually yield up to 7.5 million doses of the vaccine.

STEP 10

Test the mRNA

“This new RNA lipid nanoparticle was new to us, but we could take our tried-and-true tools out and understand it, and analyze it, and figure out how to make it high quality.”– Meg Rueschvice president for research and development

The Pfizer-BioNTech vaccine was the first mRNA vaccine to be authorized for emergency use in people.

Analytical scientists repeatedly test the filtered mRNA to verify its purity and confirm the genetic sequence is correct.







The result is 10 bags of coronavirus mRNA. Each bag holds 16 liters and represents the raw material for about 750,000 doses of the vaccine.

STEP 11

Freeze, Pack and Ship (Again)

The bags of mRNA are frozen to –20°C (–4°F) and shipped to a Pfizer facility in Kalamazoo, Mich., where they will be processed into the finished vaccine and packaged in vials. Samples are also sent back to Pfizer’s Chesterfield facility, where they are tested again.






The Andover plant can produce two batches of mRNA a week, each about 10 bags. The facility made its first test batch last July, and recently doubled its mRNA capacity by adding a second suite.

A parallel process in Mainz, Germany, processes DNA from the Chesterfield facility and sends bags of filtered mRNA to Puurs, Belgium.

STEP 12

Prepare the mRNA

“There’s no weekend breaks. There’s no whitespace in the project plan. You hire people, you put everyone you can on. But the quality built in is the same as we’d do for any vaccine.”– Meg Rueschvice president for research and development

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