In February, engineer-procure-construct contractor CRB was in the final stages of construction on a new production facility for Grand River Aseptic Manufacturing (GRAM) in Grand Rapids, Mich.
Process qualification—in which federal and pharmaceutical industry authorities inspect and approve a manufacturing facility, steps that can take up to a year—loomed. The plant was designed and built by CRB to formulate and produce drugs prescribed by doctors that are developed and owned by companies such as Johnson & Johnson, AstraZeneca and Pfizer. Then COVID-19 happened.
"Toward the tail end of the project is really when COVID hit," says Jesse Adams, CRB's senior project manager. "Some of those [qualification] elements really had to be expedited and focused. In terms of the brick-and-mortar elements, we were near completion."
The 61,500-sq-ft facility was ready to begin production of a COVID-19 vaccine by July and is contracted for a full year of production with a division of Johnson & Johnson as part of the federal Operation Warp Speed effort to expedite vaccines to market. It was one project exempted from Michigan Gov. Gretchen Whitmer's original stay-at-home order for construction because it would make life-saving medicine.
Trade contractors were even less available than usual to Adams' team as the pandemic hit, however, and site equipment availability was also affected by the slowdown in global supply chains.
It was "equipment production-related issues more than anything," Adams said. "Everybody was booked up, and capacity really wasn't there from a manufacturing perspective. Our trade contractors were overbooked. It was a very busy time and a very critical time."
Qualified on Time
The new facility was completed and qualified on time despite the obstacles of early 2020. One of three GRAM pharmaceutical manufacturing facilities in the U.S. it was designed to increase the company's large-scale fill and finish capacity. The process of filling vials with medicine—usually vaccines—and finishing them is the last step before packaging for distribution.
The pandemic will test the capacity of contract and development manufacturing firms such as GRAM in the coming months. No pandemic vaccine has ever needed to be this widely distributed in the U.S. The groundbreaking polio vaccine developed by Dr. Jonas Salk and distributed in the 1960s is the only comparable rollout with an even closely comparable pharmaceutical industry response—and that was only given to children.
"It's been interesting because you're working on getting a facility up and running and getting it qualified," says John Wichelt, GRAM vice president of client pharmaceutical services. "At the same time, we were also working on getting our manufacturing process in place as soon as the government and Johnson & Johnson say, 'go ... start making it a vaccine.'"
Manufacturers such as GRAM have the ability to change their fill-and-finish and other production lines for whatever products are being produced in them.
"Some of our clients want pharmaceutical lines that will be dedicated to a single product," Wichelt says. "GRAM is set up to have a little more flexibility. Since we're a CDMO—a contract development manufacturing organization—we make products for numerous customers. We have to have that flexibility, not just in the design of the filling line, but in the design of the facility as well to be able to manufacture lots of different types of products. That was critical in the design for CRB."
While GRAM's capacity is committed to its COVID-19 vaccine for next year, the flexible building design will allow it to pivot to produce other drugs in the future. GRAM is one of many CDMOs that have been manufacturing millions of doses of COVID-19 vaccines in anticipation of federal approval. Much of its production is already completed and awaiting rollout in refrigerated warehouses.
Pfizer, the company that was first to ask the federal Food and Drug Administration for emergency approval of its vaccine, has already planned its manufacturer-to-provider supply chain. One complication is that its vaccine must be stored at temperatures below -94° F.
"We have developed detailed logistical plans and tools to support effective vaccine transport, storage and continuous temperature monitoring," says Francesca Marzullo, manager of Pfizer global supply communications. "Our distribution is built on a flexible just-in-time system, which will ship the frozen vials to the point of vaccination."
That system includes distributing up to 50 million vaccine doses in the first year, Marzullo says.
Because there are so few cold storage facilities that are cold enough to store vaccine [the average temperature on Mars is only -81° F comparatively, according to NASA], the dry-ice-reinforced packaging is being designed to hold it at pharmacies, hospitals and doctors' offices for up to 10 days.
Some pharmacies and hospitals have medical freezers designed to hold medicines that need to be kept in extreme cold, but Pfizer and its German vaccine partner BioNTech are preparing the packaging for long-term use since most of those freezers are too small to store bulk shipments of the vaccine.
Marzullo said the distribution approach will primarily be to ship from Pfizer's Kalamazoo, Mich., fill-and-finish facility directly to point of use, generally a hospital, doctor's office or pharmacy. She said the company may also use its existing distribution center in Pleasant Prairie, Wis., for COVID-19 shipments.
"This distribution center will have a dedicated area designated to store product that is not going direct from our Kalamazoo site to point of use," she explained.
Both the manufacturing investments of companies like GRAM and the logistics investments of pharmaceutical companies will be tested by the manufacturing and delivery of the largest vaccine rollout in American history, experts report.