“I’ve been like a ghost,” says Mike Smith from Moderna’s production facility in Norwood, MA, the building he’s haunted for the past ten months. He’s in a conference room, clean shaven and surprisingly energetic as he tries to describe just how extraordinary the year has been. As an associate director of production at Moderna, one of the companies currently seeking regulatory approval for a promising COVID-19 vaccine (Pfizer and its partner BioNTech and AstraZeneca and its partner Oxford University are the others), Smith oversees about 65 people, working in three shifts around the clock to manufacture Moderna’s vaccine. Occasionally, he finds himself working 32 hours straight.
“My phone is pinging all hours of the day and night. I hear it in my dreams,” Smith, 35 years old, says. He has three young children, including a one-year-old girl who was born around the time COVID-19 first emerged in China in 2019. Smith had planned to take paternity leave earlier this year, but that went out the window in January. “Just last night my wife said, ‘I haven’t seen you in a year,’” Smith adds.
The biggest challenges were problems of engineering, scale, and speed. How do you increase batches of vaccine from milliliters to thousands of liters and transport them around the world without compromising their delicate chemistry? That challenge is why Smith, a self-described nano-particle geek who has spent his career focusing on units in the order of one-billionth of a meter, has spent much of the past year thinking on a much larger scale, figuring out how to produce enough vaccine for about one-seventh of the world’s population by the end of 2021. The solution has required some flexibility. In recent months Smith has alternated between roles as a scientist, a process engineer, and a production manager. For others at Moderna, the solution has required brute force. When Smith’s colleagues couldn’t fit a massive piece of equipment through a door at the company’s headquarters one summer weekend, rather than wait until Monday to submit a work order to facilities, they found a sledgehammer and knocked down the wall themselves.
“There’s a lot of worry about speed and development,” Smith says, referring to the alarming number of Americans who say they won’t take a COVID-19 vaccine when one is available. “That’s when you rush, when there’s something in the way you can literally knock down. What wasn’t rushed, was this thing that I care so much about — the technology involved.”
The technology, in this case, is both the hardware and chemistry that went into producing the formula Moderna employees call “mRNA-1273.” For the better part of the last decade, Moderna and other biotech companies have been developing mRNA — short for “messenger RNA” — vaccines. (Pfizer’s COVID-19 vaccine also uses mRNA.) Rather than injecting patients with the antigen protein itself, mRNA vaccines train cells to make their own protein, setting off the body’s immune responses. Before the pandemic, Smith worked primarily on fine-tuning the mechanism, called the lipid nanoparticle or LNP, used to deliver mRNA to cells without damaging the payload. Moderna’s technology was unique because its “platform,” as Smith calls it, could swap out genetic sequences so that it could be used to vaccinate against all manner of ailments, like a miracle gadget you might buy on QVC.
The mRNA application that most excited Smith was its use to create personalized “therapeutic vaccines” for cancer patients. Using the genome sequences of both the patient and the cancer, Moderna could design a customized dose for one person that would stop the cancer from spreading. Smith worked to get the entire process down to a little over a month. The lessons Smith learned refining that process and increasing production speed would come in handy when Moderna enlisted its platform in the fight against COVID-19.
“It’s like the stars were aligned and the science was ready. The scientific concepts and the physics were established, we had all of the pieces and components,” says Smith. “If this had happened five years ago, I don’t think we would have been ready to respond at the speed we did. This is a weird thought, but I feel like we — all of us — got really lucky.”
By late January, scientists in China had sequenced the SARS-CoV-2 genome. Soon after that, Moderna scientists in Cambridge fed that code into mRNA which was shuttled to cells via the LNP and, sure enough, the cells began to produce the protein necessary to trigger the body’s immune response. “It all just clicked. It was working just as designed,” says Smith. It took only 42 days to develop the vaccine. (The previous record was four years.) By late March, Moderna’s mRNA-1273 was being administered to subjects in its first human trial, an experience Smith describes as surreal.
“You don’t normally have so much press coverage of clinical trials,” he says. “I was sharing a photo of a patient getting injected in her arm and I zoomed in on the syringe and my colleagues were huddled around staring at it saying, ‘Oh, man it looks good.’ It was heavy though, because you look over at the patient sitting there and she is a person receiving that product. It was emotional for me as a scientist.”
Last month, the vaccine showed 94-percent efficacy in phase three trials, far surpassing even the most optimistic predictions being made in the fall. The good news didn’t end there, Moderna’s vaccine was 100 percent effective against severe disease — not a single trial participant who received mRNA-1273 was sent to the hospital. Moderna has had plenty of help along the way. The company took close to $1 billion in federal funding as part of Operation Warp Speed, all of which the company says went toward the clinical trials. On Monday, Moderna filed an application for an Emergency Use Authorization with the FDA, meaning the first doses of the vaccine could be injected in patients as soon as December 21. While Pfizer’s vaccine is likely to be available a few days before Moderna’s, one distinct advantage Moderna’s mRNA-1273 has over Pfizer’s mRNA vaccine is that it doesn’t require ultra-cold storage conditions. (When I ask him to explain why, he says he needs to choose his words carefully in order to protect Moderna’s intellectual property.) Moderna CEO Stéphane Bancel has said his company is ready to ship 20 million doses of the vaccine — enough for 10 million people, as it requires two shots administered a month apart — before the end of 2020, 100 to 125 million doses in the first quarter of next year, and a total of 500 million to a billion doses by the end of 2021. It’s a previously unimaginable timeline that is possible in large part because the vaccine, even before it has been approved, is being produced by Smith’s team at all hours of the day.
Since January, Moderna has hired hundreds of people and built the new, state-of-the-art manufacturing facility in Norwood. It contracted with Lonza, a manufacturer that had facilities in New Hampshire and Switzerland. Smith was tasked with figuring out how to scale up the production technology. Normally, Smith would produce batches of vaccine no larger than a small milk carton. Now, Smith’s team needed to consistently produce batches that could fill a hot tub, a difficult job given the delicate chemistry and physics at work and a treacherous one considering the margin for error. Very quickly, Smith ran into supply-chain bottlenecks. Would there be enough high-quality water? What about single-use sterile bags? And glass for vials? The manufacturers who produced these specialized raw materials hadn’t anticipated suddenly getting an order for the largest-scale vaccine during a pandemic. Once he’d figured out how to scale up the technology, Smith switched to his current role overseeing the manufacturing team that set to work making batches of the vaccine, all day, every day.
Smith says Moderna is on track to hit the production goals Bancel has laid out. Still, he hasn’t made vacation plans. Anytime he is away from the office, Smith says he is surrounded by reminders of why he needs to get back to work. “I want my kids to see their grandparents again. I have a one-year-old who hasn’t really interacted with any family this whole time,” he says, quick to add that he thinks he’s one of the lucky ones. “It just feels like a crushing responsibility.”