Amidst growing global shortages of COVID-19 vaccine supplies, inaugural (by way of authorizations/approvals) COVID-19 vaccine maker Pfizer is addressing the issue by working to cut the manufacturing time of its vaccine by almost half.
A batch of Pfizer’s COVID-19 vaccine, BNT162b, developed in conjunction with Germany’s BioNTech, takes about 110 days to make. Pfizer is planning to reduce that time to an average of 60 days, cutting production time by almost 50 percent. For Pfizer-BioNTech’s vaccine, a batch consists of between one and three million doses of vaccine per production run.
The endeavor is being called “Project Light Speed” and “it’s called that for a reason,” said Chaz Calitri, Pfizer’s vice president for operations for sterile injectables, in an interview with USA Today. “Just in the last month we’ve doubled output.”
This in light of Pfizer having upped its production goal to two billion COVID-19 vaccine doses this year. The company is on track to fulfill the 200 million-dose order put in by the US government by May, but hopes to have more available as engineers improve systems on the go.
The increased production aims will be achieved through both improved manufacturing efficiency and increasing build capacity.
The drugmaker is targeting various steps in the manufacturing process, beginning right at the DNA stage, which is required as the template from which the mRNA for the SARS-CoV-2 spike protein in the vaccine is made.
In addition to enhancing process efficiencies, the company is also looking to increase overall output by adding new manufacturing lines at all three of its US plants.
The manufacturing time of Pfizer’s vaccine is already shorter than that of other vaccines including the flu shot, which takes about two months longer to make than the COVID-19 shot. Even longer is the Salk polio vaccine, which takes 18 months to make, said Robert Van Exan, a vaccine industry veteran expert who consults from Ontario, Canada now, in speaking to USA Today.
To put it in perspective, the Pfizer COVID-19 vaccine doses that are arriving now come from batches started just before Halloween.
Pfizer plans to get the time down to 60 days per batch for its COVID-19 vaccine by relying on its engineers who are tasked with the job of learning how to make the process more efficient. As soon as vaccine vials began coming off the production line, engineers started analyzing how production could be made faster and better.
Pfizer based its production system on how the vaccine was developed in the laboratory, Calitri said. He explained that typically engineers would spend years improving efficiencies and cost-effectiveness. But he says that’s not what happened with COVID-19. “We just went right to commercial production,” Calitri said. This is because the company did not have the luxury of time to perfect its manufacturing processes — something that can take several years — given the urgent need for a viable vaccine.
However, Calitri said Pfizer engineers have already “made a lot of really slick enhancements.”
How the Pfizer/BioNTech COVID-19 Vaccine is Made
The vaccine is made in three separate phases at three different Pfizer plants located in Chesterfield, Missouri; Andover, Massachusetts; and Kalamazoo, Michigan.
The USA Today got a peek into the process of making Pfizer’s mRNA vaccine and outlined the details in its report.
DNA Templates: The vaccine development process first begins with raw ingredients coming together at the Chesterfield plant. DNA templates that code for the exterior spike protein of SARS-CoV-2 are propagated and expanded to generate trillions of copies via DNA plasmids transfected into E. coli bacteria. The bacteria are grown in large vats, with the process taking two weeks.
The DNA copies are then purified and frozen in bags that are inspected to ensure they meet federal manufacturing guidelines. This involves testing and quality assurance of the DNA to make sure its integrity meets the strict vaccine requirements.
Vaccine mRNA: The DNA is then shipped 1,200 miles over to the Andover plant from which mRNA is synthesized. The RNA is transcribed from DNA in 40-liter vessels containing enzymes and chemicals over the course of three to four days.
“That one 40-liter batch, depending on sampling and things like that, can make up to 10 million doses of vaccine,” said Margaret Ruesch, Pfizer’s vice president for worldwide research and development, based at the Andover plant.
Given RNA’s instability and high susceptibility to degradation (due to RNAses from other organisms and those lurking in the general environment), the RNA is produced in an extremely high-tech manufacturing suite. According to the report, “The air is filtered, the equipment constantly tested and all employees wear head-to-toe cleanroom coveralls to ensure nothing is introduced into the vaccine as it’s made.”
The mRNA is purified and subjected to stringent quality control measures. Detailed records are maintained, which the FDA can access to ensure the plant is maintaining required standards. The Andover plant presently runs two batches a week, but is preparing to add more shortly, enough to make mRNA for 40 million doses per week.
Make and Fill: The manufactured, frozen mRNA is then finally shipped off to Pfizer’s Kalamazoo plant, where the mRNA is used to make the vaccine and vials are filled for distribution.
The mRNA is wrapped with lipid nanoparticles in the encapsulation process, which occurs in about 100 specially-produced hockey-puck-sized mixers, using “a maze of piping,” Calitri said. A single large mixer would be more efficient, but there was not enough time to build and optimize such a vessel.
The vaccine is then ready to be filled into vials using a high-speed vial filling machine that dispenses six doses into each container. The vials are inspected, packaged, labeled and frozen in a subzero -70 degrees C freezer.
While the process from make to fill only takes three days, quality control and testing processes take weeks, as each lot of the vaccine is tested to ensure product quality, with checks for identity, potency, purity and safety.
“People don’t understand, manufacturing vaccines is extremely complicated,” said AstraZeneca CEO Pascal Soriot at a recent news conference. By no means is making a vaccine like making orange juice, he added.
In addition to the US production arm, BioNTech and Pfizer had struck deals to have six global manufacturing sites, including a facility in Marburg, Germany that recently received manufacturing approval from German officials. It is expected to be up and running by the end of February with plans to make up to 750 million doses of the vaccine each year, according to German news outlet Hessenschau. BioNTech is also launching a factory upgrade in Puurs, Belgium.
Apart from its own contracted manufacturing facilities, unexpected production help has been coming in from rival drug-makers including Sanofi, Bayer and Novartis who are pitching in to produce millions more doses of BNT162b.
With multi-faceted efforts geared towards speeding up production of the vaccine — from manufacturing to the forging of inter-pharma partnerships — Pfizer, as well as other vaccine makers, could be on track to produce their promised doses of the COVID-19 vaccine.