Coronavirus vaccines are now a reality, making perhaps the most formidable remaining challenge less about scientific research and more about manufacturing might.
The leading vaccine-makers are now aiming to produce hundreds of millions of doses of their shots. The global demand for a COVID-19 vaccine is likely to vastly outstrip supply, turning more attention to the ability of companies to pump out doses.
The manufacturing challenge may be most dramatic for Moderna, a biotech upstart that has never before produced or sold a commercial medicine. Its flagship manufacturing facility in Norwood, Massachusetts, has never been inspected by the US Food and Drug Administration, yet will be depended upon to deliver millions of doses of the company's coronavirus vaccine.
Adding to the challenge, the leading vaccines from both Moderna and Pfizer are based on a new technology called messenger RNA, which has never before been used for a federally approved vaccine or treatment.
"I think the biggest risk is this is new commercial technology," Ian Leavesley, an expert in pharmaceutical manufacturing processes, told Business Insider in an email. "Any new technology, in any field, has a finite risk of unforeseeable risks cropping up. I believe experience is the most valuable tool in rapidly addressing this risk."
A recent spate of manufacturing issues at drug developers show the potential risks. Problems with some raw materials led Pfizer to cut its 2020 vaccine production plans in half in November, the Wall Street Journal reported. And in recent weeks, AstraZeneca, Novavax and Eli Lilly have all faced manufacturing stumbles in COVID-19 vaccine and therapeutic programs. And on Thursday, Bloomberg News reported that Moderna had to disposes of 400,000 of its shot due to a "filtration issue."
Moderna has already notched extraordinary accomplishments in fighting this pandemic, working with the US government to develop a highly effective coronavirus vaccine in less than a year. The US has committed up to $2.48 billion in funding to help develop the shot and buy doses. The shot won emergency use authorization on December 18.
Now, the company is facing an ambitious goal to produce between 500 million and 1 billion doses of its vaccine in 2021.
Moderna is pumping out vaccines from a retooled Polaroid plant
Some of that will come from the company's flagship Norwood facility, a Polaroid plant that it spent $100 million to repurpose.
The 200,000-square-foot plant is custom built for fast-moving, ambitious research projects, not as a major manufacturing facility. Most of the lab equipment is on wheels to allow for quick reconfigurations, lab rooms are paperless to expedite documentation processes, and bins of supplies for disposable equipment like gloves have buttons to automatically trigger an Amazon re-order when supplies run low.
Already, the company has hired hundreds of workers this year to boost manufacturing and started running the plant closer to 24/7.
The FDA will not require a formal inspections of manufacturing plants such as Norwood before issuing an emergency use authorization, top regulators confirmed to Business Insider. Typically, a pre-approval inspection is required to get a full FDA approval for a medicine.
Regulators are confident in the manufacturing process
In interviews with Business Insider, Moderna's CEO and a top FDA leader said they are confident the plant can consistently produce quality medicine without a formal inspection.
Dr. Peter Marks, the man in charge of the vaccine review process who runs the FDA's biologics review center, recently told Business Insider that not requiring inspections before an emergency OK was "very reasonable" given the pandemic.
"I will tell you, right now, that if we had any worry about something, we will do inspections when needed for cause," Marks said. "But to put people in harm's way, unless we have a good reason to do so, is not something I want to do."
Instead of a formal inspection, the FDA leader said reviewers are using an adapted approach that includes informal site visits and audit records.
"The constellation of things we are doing is giving us an amount of confidence that we are not going to have a problem with manufacturing at any sites that we are looking at," he added.
Moderna CEO Stephane Bancel told Business Insider that the company would not compromise to any degree on manufacturing quality, and Americans should trust the process.
"We will fail millions of people if we cut corners on quality," Bancel said.
Not everyone agrees with the FDA decision. Dr. Luigi Notarangelo, a member of an expert panel that evaluated the shots and a National Institutes of Health senior investigator in immunology, said at an October 22 committee meeting that inspections are warranted, Bloomberg's Anna Edney reported.
"This is something that could be done," Notarangelo said. "It would provide some additional trust into the process."
'We cannot cut corners on safety or quality,'
Leavesley, now president of Modern Pharma Consulting, said he has trust in well-established drugmakers, including Pfizer and Lonza, a contract manufacturer that Moderna has tapped to boost supply.
Lonza's facility has been inspected many times in the past, Bloomberg's Edney previously reported.
While Moderna as a company lacks commercial experience, Bancel said the leaders of his manufacturing team come with decades of experience.
For instance, Juan Andres, Moderna's chief technical operations and quality officer, joined the biotech in 2017 after overseeing manufacturing at Novartis, one of the world's largest drugmakers.
Moderna is driven to ensure quality now, because it has a long-term vision for dozens of mRNA medicines in future years, Bancel said.
"We cannot cut corners on safety or quality," he said. "That would fail the mission that we have, which is to make mRNA a new class of medicine."
This article was updated on December 18 with FDA's decision to grant an emergency use authorization for Moderna's vaccine.