COVID-19 vaccine makers are under intense pressure to rev up production, but the scale of the challenge is unprecedented — and the speed of production is limited.

Why it matters: Even with help from the federal government and outside companies, vaccine-making is a complex, time-consuming biological process. That limits how quickly companies like Pfizer and Moderna can accelerate their output even during a crisis.

The big picture: With new, more transmissible variants emerging, we're in a race to get shots into more people's arms. What would normally take years to set up is being compressed into less than a year, leaving engineers to adapt manufacturing processes on the fly.

• "The bottlenecks keeps moving. It keeps changing," said Chaz Calitri, who leads the COVID-19 vaccine program at Pfizer's Kalamazoo, Mich., facility.
• "It's a dream project, but at the same time, it’s the weight of the world," he tells Axios.

Between the lines: Making vaccines is complex, and the process can be hindered at different steps.

• "There's a lot of science and engineering that goes into the manufacturing of any vaccine," adds Margaret Ruesch, a vice president of Worldwide Research and Development at the company. "It’s molecular biology at a large scale."

How it works: Axios got a deep dive into the making of Pfizer's vaccine, a three-phase process that takes weeks from start to finish and involves three different facilities.

1) DNA manufacturing: At a plant near St. Louis, Mo., Pfizer produces DNA that encodes messenger RNA — instructions for cells to make part of the spike protein on the surface of the coronavirus. That primes the immune system to defend against future encounters with the virus.

• The DNA is produced by bacterial cells, then purified, frozen and shipped to another Pfizer facility in Andover, Mass.

2) Making the mRNA: In Andover, the template DNA is incubated with messenger RNA building blocks in a reactor to make the mRNA. Pfizer has been making two, 40-liter batches per week — up to 10 million doses worth — but expects to double that to four batches per week.

• After purification and quality checks, the frozen mRNA is shipped to a Pfizer plant in Kalamazoo, Mich.

3) Formulating the vaccine: In Kalamazoo, the mRNA and lipid nanoparticles (oily envelopes that deliver mRNA to cells in the body) are combined and go through a series of filtrations.

• The bulk vaccine is then transferred to sterile vials, capped, inspected, labeled and packed into containers the size of pizza boxes. Those containers are then stored in sub-zero freezers to await shipment to vaccine distribution sites.

Where it stands: Both Pfizer and Moderna say they're on track to meet their commitments to deliver 200 million doses each to the U.S. over the first half of the year.

• The Biden administration yesterday announced it had secured deals for another 200 million doses, bringing the total to roughly 600 million doses, enough to fully vaccinate 300 million Americans by the end of July.
• Pfizer and its German partner BioNTech recently upped supplies 20% by getting FDA approval to squeeze a sixth dose (instead of five) out of every vial.
• Yes, but: Extracting a sixth dose requires the use of specialized syringes, which have their own production constraints, as Reuters explained.

The latest: The Biden administration said last week that it will use its wartime powers under the Defense Production Act to give Pfizer priority access to critical components such as filling pumps and filtration units to try to help address bottlenecks.

• Meanwhile, Pfizer continues to tweak its processes to boost output and says it is adding more suppliers and contract manufacturers to the vaccine supply chain.
• Novartis, Sanofi and Merck KGaA are among 10 contract manufacturers that will help the company manufacture more doses, a Pfizer spokesman tells Axios.
• Pfizer and BioNTech will still do most of the work in their facilities, but contract manufacturers will help with specific tasks like formulating lipid nanoparticles, sterile filling, inspection and packaging.

Ordering other drug manufacturers to stand up manufacturing lines to whip up extra batches of Pfizer's or Moderna's vaccines is not an efficient or practical way for the federal government to quickly increase supplies, some experts say.

• “Making vaccines is not like making cars, and quality control is paramount,” Stanley Plotkin, a vaccine industry consultant, told Kaiser Health News. “We are expecting other vaccines in a matter of weeks, so it might be faster to bring them into use.”

What to watch: Johnson & Johnson has requested emergency use authorization from the FDA for its single-dose vaccine, but is reportedly lagging in production, the NYT first reported last month.