Moderna and the partnership between Pfizer and the German biotech firm BioNTech are moving neck and neck toward expedited regulatory review of COVID-19 vaccines based on mRNA technology. Their paths will diverge, however, in the next leg of the race, manufacturing.
Unlike some of its peers in the drug industry, Pfizer has retained significant in-house manufacturing assets. It plans to make raw materials, the mRNA active, and finished doses for BNT162b2, the partnership’s vaccine, at its own plants in Andover, Massachusetts; Kalamazoo, Michigan; and St. Louis. It will also use its site in Belgium for the European market.
In contrast, Moderna, a biotech firm with nothing like Pfizer’s manufacturing base, has contracted with Lonza, one of the world’s largest pharmaceutical services firms, to produce much of the mRNA active for its vaccine, mRNA-1273. Lonza will make the active at its complex in Portsmouth, New Hampshire, and at its main site in Visp, Switzerland.
Both vaccine makers have signed on with contract firms for lipid-based excipients used to formulate their vaccines as well as for vial filling and packaging services.
Contract manufacturers say they have been working for months putting capacity in place and are on track to hit targets for full-scale production going into 2021.
“Since we signed the agreement with Moderna in May this year,” says Andre Goerke, Lonza’s global lead for the Moderna project, in an email to C&EN, “the focus has been on getting four manufacturing kits up and running, each capable of producing an estimated 100 million doses of mRNA 1273 per year.”
The company started operations at Portsmouth in July. Lonza has since scaled up the facility and is producing mRNA vaccine for the US market, Goerke says. The company is completing construction of three production lines in Visp to supply markets outside the US. Production is scheduled to begin by the end of the year.
Goerke says Lonza is able to move quickly in Switzerland because of a 2018 investment at the site that added prebuilt “shells” equipped with central services and utilities.
Producing lipids for Moderna’s vaccine is a job that requires a high level of expertise, according to Matthieu Giraud, director of peptides, lipids, and carbohydrates at CordenPharma. The German services firm is supplying the excipients from three facilities in Europe and one in Boulder, Colorado. CordenPharma will supply Moderna with standard lipids, including phospholipids, in addition to custom lipids.
“We anticipated the launch, and we have already done the ramp-up,” Giraud says. “We have almost reached now the maximum capacity that we are going to need, and, in theory, we cover almost three to four times the maximum capacity they ask us to cover.”
CordenPharma says it has had to engineer a greater than tenfold increase in lipid capacity this year. “It hasn’t been easy,” Giraud says. “We had to leverage our whole network.”
CordenPharma performs the final step in the process in Boulder, where it has its largest assets, including manufacturing columns large enough to produce lipids at the level of purification required for the vaccine. “Also, Moderna is in the US,” Giraud adds. He says that CordenPharma has experience managing projects with manufacturing on two continents and is not concerned about shipping delays in the event of a worsening of the pandemic, given the company’s experience in the first severe wave in March and April.
Finally, Moderna has contracted with Catalent to provide vial filling and packaging to support production of an initial 100 million doses of vaccine. Moderna has also contracted with Laboratorios Farmacéuticos Rovi, a Spanish company, to provide similar services for “hundreds of millions” of doses to be supplied outside the US.
Pfizer, for its part, is conducting the different stages of vaccine production at its three-plant network in the US. The linearized DNA template for the vaccine is made in St. Louis, the DNA is incubated to make mRNA in Andover, and mRNA-containing lipid nanoparticles are constructed and sterilized in Kalamazoo. Packaging into vials will occur there as well.
The firm will employ some contractors for services leading to a finished vaccine. For example, Croda, a British specialty chemical firm, will supply Pfizer with lipid-based excipients produced at a site it obtained in its recent acquisition of Avanti Polar Lipids. In an email, Croda says it is investing to deliver on its contract to supply four component excipients for the vaccine for the first 3 years of a 5-year contract.
And the drug services firm Siegfried reports in an email that it will start large-scale filling and packaging of Pfizer’s vaccine in Hameln, Germany, at the beginning of July 2021. Siegfried has invested in a dedicated production line at the site to provide specialized storage capacity.
BioNTech will also produce the vaccine at two sites in Germany.
Industry observers agree that while the pieces are in place, ramping up production to meet demand in the months ahead will prove a challenge. Peter Bigelow, president of xCell Strategic Consulting and a former executive at the contract development and manufacturing organization (CDMO) Patheon, now part of Thermo Fisher Scientific, says the complexity of vaccine manufacturing will inevitably cause some delays, especially at the sterile fill-and-finish step.
“Everyone’s assuming it will all go perfectly, and it’s not going to. There are going to be delays along the way,” Bigelow says.“As for Pfizer, they have such a machine for managing CDMOs, and I know there are a lot of people really focused on it, and they’ll probably stay on top of things.” But a contract firm such as Moderna is in a different position. “They’ve scaled up their organization, but this has got to be totally new to them, managing this, making all the right decisions, and being quick about it,” Bigelow says.
James Bruno, president of the consulting firm Chemical and Pharmaceutical Solutions, is concerned that both vaccine makers will face steep challenges in distribution logistics.
“I don’t think we have all the cold storage that people think we have,” he says, referring to the need to store and ship vaccines at low temperatures. “They’re going to need that in the manufacturing. It’s not just in the shipping of it.”
The COVID-19 vaccine assignment will be a major haul, Lonza’s Goerke acknowledges. “There is no doubt there are challenges scaling a new process to commercial capacity for the first time and on these tight timelines,” he says. Hiring and sourcing equipment and raw materials is more challenging in a pandemic, he says, but “it’s extremely motivating to work on a project like this, and we’re working round the clock to make sure people start receiving a vaccine as soon as possible.”