Development and Production of Anti-Malarial Biologicals

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications, trials & patents

Abstract

Malaria mAb CIS43LS was discovered at the VRC and provided to the Vaccine Production Program Laboratory (VPP). The VPP is responsible for cGMP production and the manufacturing documentation needed for regulatory submission of VRC mAbs for clinical trials. To expeditiously meet the critical program needs of its Clinical Trials Program, the VRC developed a vaccine pilot plant, known as the VCMP (Vaccine Clinical Materials Program) for the manufacture of clinical materials for Phase I/II/III trials. The VPP expanded the capability of the VCMP to include the manufacture of monoclonal antibodies. The VPP also engages in partnerships and contracts with companies in the vaccine/biotech industry for additional capacity and capability in biologicals manufacturing. The VPP developed the manufacturing process, final formulation buffer, and analytical methods needed for manufacturing the CIS43LS, transferred the process to the VCMP for cGMP production and product release/stability testing. The VRC received safe-to-proceed in November 2019 and initiated Phase I clinical trials. Due to the COVID-19 pandemic, the controlled-human malaria infection part of the Phase I was delayed until October 2020. Additionally, in May of 2021 a Phase II clinical trial was initiated for CIS43LS in Mali for the prevention of malaria infection. Enrollment completed in August of 2021 with results from the trial expected in early 2022. The demand for these biologicals has increased, requiring the development groups to further improve the manufacturing process and test methods to keep up with demand. The VPP developed a second anti-malaria mAb, L9LS, leading to the production of a master cell bank, drug substance, drug product and the filing of an IND in August 2021. During development, The VPP discovered that the mAb was highly stable in certain buffer formulations, allowing for the VPP to concentrate L9LS to 50% higher than most mAbs. This allows for clinical dosing and routes of administration that would not have been possible at lower mAb Drug Product concentrations. FDA review of the IND is in-progress, to enable a clinical trial start in September 2021.