By Jared S. Hopkins, Joel Eastwood and Dylan Moriarty 

Pfizer Inc. and partner BioNTech SE did the unimaginable when they developed a Covid-19 vaccine in less than a year. Previously, the quickest vaccine development program was the four years it took to make the mumps vaccine, licensed in 1967.

A big reason for the speedy success: a new gene-based technology involving messenger RNA, the molecules that carry genetic instructions. Yet that technology has also complicated manufacturing, forcing companies to redo how shots get made.

Bottlenecks have emerged, manufacturing experts say, because some steps are difficult to scale up quickly or because they simply haven't been done before.

mRNA vaccines instruct cells to make a harmless version of the spike protein that juts from the new coronavirus. Production of the protein trains the immune system to recognize the real coronavirus -- and fight it.

To make mRNA vaccines, Pfizer assembled a bespoke manufacturing network that the company projects will make 2 billion doses this year.

Here's how the vaccine is made and why manufacture is so hard to scale up:

Step 1: Duplicate DNA

In a plant near St. Louis, Pfizer scientists synthesize DNA, the key to creating this kind of vaccine. This step in the process isn't new to the drug industry, but Pfizer needed to scale it up fast.

The resulting solution is portioned out into clear 1-gallon bottles, which are then frozen, packed into special plastic bags and shipped to Andover, Mass.

Step 2: Convert DNA to mRNA

Next, the manufacturer turns the DNA into messenger RNA. The mRNA carries the instructions that tell cells to make proteins mobilizing immune defenses against the new coronavirus. At its plant in Andover, Pfizer is performing this step at a much larger scale than research labs have done before to meet the heavy demand for Covid-19 vaccines.

The mRNA is packed into plastic bags the size of a large shopping bag, each containing 5 million to 10 million doses. It undergoes quality checks and is frozen for shipment to Michigan.

Step 3: Add fat

The biggest bottleneck in producing mRNA vaccines, manufacturing experts say, is the formulation process: Putting the synthesized mRNA in a fatty envelope to reach its cellular destinations.

Few companies make lipids, the tiny fat particles that wrap around the mRNA and safeguard it during its journey through the body. Pfizer contracted with suppliers to receive lipids and has begun making them in-house.

At a Pfizer plant in Michigan, a formulation suite designed by the drugmaker -- the size of a one-car garage -- is crisscrossed by pumps and pipes, and crowded with tanks, filtration units and half-dollar size jet mixers. This is where the mRNA is encapsulated in the lipids.

The Michigan plant uses about 100 mixers for the formulation, which happens continuously over 30 hours to make about 3 million doses.

Step 4: Test and package

This final step packages the mRNA vaccine for shipment, in a process known as fill-finish.

Pfizer does the work at the same plant in Michigan, filling hundreds of vials a minute, with six doses in each tiny container. The company caps, labels and packs the vials into containers the size of pizza boxes. It takes about two days to complete a batch of more than a million doses.

Then the batches must undergo inspections and two weeks of sterility testing to make sure they aren't contaminated, meet additional quality specifications and won't leak.

The vials that clear inspection and testing are stored in subzero freezers and await shipment to trucks or airplanes for distribution.

Pfizer last month said it would help boost production in the U.S. by incorporating more plants and bringing on two contract manufacturers.

Johnson & Johnson's newly authorized vaccine also uses a new gene-based technology, but not mRNA. To boost production, Merck & Co. will help make the vaccine.

Graphics sources: Pfizer; Matthew Johnson, Duke University; Jennifer Pancorbo, North Carolina State University.

Write to Jared S. Hopkins at jared.hopkins@wsj.com

 

(END) Dow Jones Newswires

March 03, 2021 08:14 ET (13:14 GMT)

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