PORTAGE, Mich. - The first attempt to produce industrial-scale quantities of the experimental vaccine that has played a central role in arresting the coronavirus pandemic in the United States was a total failure.
Operators at a Pfizer plant outside Kalamazoo hoped the trial run could provide quick validation of the company's gamble on a newfangled mRNA technology. It also was an early test of Pfizer's strategy of refusing government aid to develop and rapidly ramp up commercial scale production of its vaccine.
But as soon as pressure built in the array of pumps, tubes and tanks at the plant on Sept. 11, it became clear something was wrong, Pfizer team leaders told The Washington Post in the most detailed public accounting of the company's efforts to produce mass quantities of vaccine.
When operators checked a vat at the end of the production run, most of the key ingredient - the fat molecule encasing the messenger RNA - was missing.
"Our first engineering trial . . . was an absolute and utter failure," said Pat McEvoy, Pfizer's senior director of operations and engineering at the Kalamazoo plant.
Pfizer had evidence the mRNA vaccine could stop the virus. The vaccine is composed of a lipid nanoparticle, a sphere of fat molecules encapsulating a strand of messenger RNA, which instructs human cells to make proteins that trigger antibodies and prime the immune system against future viral invasions.
But it would do little good unless Pfizer could rapidly take the new nanoparticle technology from lab to mass production - a feat never before accomplished - making immunizations available in America and around the world.
The company and its vaccine partner BioNTech would ultimately master the job of churning out large batches of mRNA vaccine, making it the clearest winner among drug companies to emerge from the pandemic. The company is producing vaccine in greater quantities than any other company and has secured an advantage in the quest to use next generation mRNA technology for treatments of other diseases.
But the failed September test shows that success was far from a foregone conclusion. Pfizer's ambitious production objective ultimately forced the company to accept government help to procure vital supplies, defeating its earlier efforts to avoid a closer partnership with federal health authorities.
The company also has been criticized for selling most of its early supply to the wealthiest nations, which paid the highest prices, fueling severe global inequities. Pfizer was able to fill President Biden's order this month for 500 million doses that will be distributed to low-income countries, but advocates point out that pledge is still just a fraction of global need.
"The weight of the world was on us. We have the manufacturing capability for a solution to the pandemic, and we knew we couldn't go fast enough," said Chaz Calitri, Pfizer's vice president of operations for injectable drugs in the United States and Europe.
Pfizer's spigot opened wide in March of this year, stemming the toll of death in the United States and allowing the economy to enter a strong rebound. The breakthroughs are fueling investment in the new technology.
The company says it expects to make enough for 3 billion shots in 2021, twice as much as initial projections and enough of the two-dose immunization for 1.5 billion people. It has said it will make $26 billion in vaccine sales in 2021, which would make it the biggest-selling medicine ever.
Pfizer and other companies are building mRNA vaccine pipelines for influenza, HIV, tuberculosis, rabies, rotavirus, malaria, and Zika, according to an analysis by the investment advisory firm Berenberg Capital Markets. BioNTech and Moderna are conducting extensive work on the use of mRNA against cancer.
"This is about as disruptive as it gets when it comes to a new medicine," said Pieter Cullis, a researcher at the University of British Columbia who helped pioneer the use of lipid nanoparticles to deliver drugs into the human body. "It's a fantastic time."
Success wasn't quick or easy
What looks like success now was not clear at all on March 20, 2020, when McEvoy received an email from his boss, Calitri.
Three days earlier, Pfizer had announced its partnership with the German biotech company BioNTech to develop and manufacture its experimental coronavirus vaccine. BioNTech had already identified how it would make an mRNA vaccine to fight coronavirus, but it needed a big production partner with the engineering and distribution expertise to make vaccine on a global scale.
Calitri was among Pfizer executives who picked the Kalamazoo plant and McEvoy's team to formulate doses, fill vials, and ship boxes of vaccine packed with dry ice.
"I confirmed you a moment ago. Are you good with this?" Calitri wrote to McEvoy.
McEvoy's simple reply came seven minutes later: "Chaz, 100 percent."
It would require a huge commitment of resources and workers in Kalamazoo, where drug manufacturing began in the 19th century under Upjohn, a company name that is intertwined with the community's history.
Through mergers, Pfizer in 2003 acquired UpJohn's 1,300-acre manufacturing campus, built in 1948 south of town, out past the county airport. It has 2,800 employees and mostly churns out generic drugs and bulk pharmaceutical ingredients, from birth control injections to coral snake antivenom. It is one of the largest manufacturers of steroids in the world. The building where most of the coronavirus vaccine production happens is a quarter-mile long.
As he assembled a team to lead a Michigan vaccine workforce that now numbers 600 and is expected to reach 1,000 employees, McEvoy learned that key production steps would have to be built from scratch. Large machines to mix together lipid nanoparticles and filter the finished product did not exist.
"We built this out of the Erector Set we had," McEvoy said.
First deal: 100 million doses
In July, the same month Pfizer cut its first deal to sell the United States 100 million doses of vaccine for $1.95 billion, McEvoy and other Pfizer executives brought the leaders of then-President Donald Trump's Operation Warp Speed for a factory tour. McEvoy showed Moncef Slaoui, an experienced pharma executive recruited by Trump to advise OWS, and Army Gen. Gustave Perna, who managed OWS logistics, a cavernous empty space.
Here's where the hundreds of freezers will maintain finished vials of vaccine at minus-70 degrees Celsius, McEvoy told them. Here's where the vaccine will be packed. Prefabricated manufacturing suites would be rolled in off trucks from a Texas contractor and filled with gleaming new vats, pipes, and pumps.
Slaoui, in an interview, said he came away impressed with Pfizer's commitment. It was apparent Pfizer planned to use its enormous, global size, vast amounts of cash, and swarms of engineers in a "bulldozer, brute-force" strategy to make billions of mRNA-ferrying nanoparticles, he said.