FREDERICK, Md. -- It has been used in clinical studies on four continents and has been tested in thousands of volunteers. It was produced at the Frederick National Laboratory for Cancer Research over a five-year span to meet increasing clinical demand, and it may play an ongoing role in the future of HIV research.
The investigational product, known as VRC01, is a type of monoclonal antibody, which is made by identical immune cells that are clones of a unique parent cell. VRC01 is broadly neutralizing, meaning it has been shown in a laboratory setting to stop multiple HIV strains from infecting human cells. It’s the first in a class of broadly neutralizing monoclonal antibodies to prevent HIV infection.
The Vaccine Clinical Materials Program (VCMP) Pilot Plant at the Frederick National Laboratory, operated by Leidos Biomedical Research, was tasked by the Vaccine Research Center (VRC), part of the National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health, with producing VRC01 starting in 2013. Late this summer 2018, the VCMP received an award from the VRC leadership commending the group for its five-year campaign to manufacture VRC01.
VCR01 is being tested in the NIAID-funded Antibody-Mediated Prevention (AMP) Studies, two global Phase 2b trials that are investigating whether VRC01 can prevent HIV infection in humans.
Though the award recognizes a job well done, Barbara Brooks, Director of Manufacturing Operations at the VCMP, said that VCMP staff at the 12-year-old Pilot Plant see it as much more. In a way, the award indicates that the Pilot Plant has “come of age” and that the VCMP has proven itself capable of completing complex and demanding tasks, she explained.
Manufacturing the antibody monopolized the Pilot Plant’s 2,000-liter scale manufacturing train, the largest of its four production lines, for the entire duration of the project. Even so, VCMP staff continued to manufacture separate products on the remaining lines while meeting VRC01’s demanding schedule.
“Expansion activities at the Pilot Plant in 2016–2018 enabled uninterrupted production of VRC01 in Train 4 while ensuring the production of competing products in the VRC pipeline,” said David Lindsay, Ph.D., Director of the VCMP.
The production of VRC01 also required rigorous coordination among the VCMP’s departments. The Pilot Plant is equipped with all functions necessary to produce VRC01 under the same roof. The VCMP is able to create the drug substance (the “raw” form of the medicine) and the drug product (the finished medicine), test it, store it, and prepare it for shipment, all within the same facility, which creates the advantage of being able to produce VRC01 on a large scale.
“This provides the opportunity to expedite or run some processes in parallel for more rapid completion and availability to the clinic for trials,” Brooks said.
The VCMP staff manufactured 38 batches of VRC01 without experiencing a single production failure or falling behind the high demand of the AMP Study’s rapid participant enrollment. Together, the batches yielded 82.6 kilograms of purified VRC01, roughly as much as an adult human. Each batch took just six weeks to complete. The batches were then filled into glass vials for clinic use, with record levels of production totaling 153,721 vials to date.
The AMP Study was active at 47 sites in 11 countries, and completed enrollment in October 2018 with 4,625 volunteers—healthy adults who have a high risk of becoming infected with HIV during their daily lives. Researchers will monitor these individuals for two years to determine VRC01’s effectiveness.
On her involvement with the project, Brooks said, “I may not speak for everyone, but working on VRC01 and knowing the significance of this antibody in the challenge to find a vaccine or therapeutic to combat HIV/AIDS makes my job very rewarding.”
By Samuel Lopez, staff writer; contributed image
Image: VCMP staff receive the award from Vaccine Research Center leaders during the retreat. From left: John Mascola (VRC), Barney Graham (VRC), Frank Arnold (VRC), Richard Koup (VRC), Barbara Brooks (VCMP), Scott Emerick (VCMP), Matt Westerman (VCMP), Adriel Ramkissoon (VCMP), Christopher Case (VCMP), and Judy Stein (VRC).Tagged: