Regulatory Readiness for a Superior Microfluidic CAR-T Therapy Cell Processing System

ABSTRACT The objective of this Commercialization Readiness Program (CRP) project is to advance toward regulatory approval the GPB Scientific Curate™ Cell Processing System to enrich leukocytes for use in chimeric antigen receptor T cell (CAR-T) therapy. In autologous CAR-T therapy, white blood cells are collected from cancer patients, enriched, genetically modified to respond to their cancer, expanded in culture and then infused back into the original patient. With four CAR-T therapies approved by the FDA to date and rt200 more in development, there is a critical unmet need to improve CAR-T manufacturing efficiency as production is scaled up for widespread patient use. The proprietary Curate technology uses deterministic lateral displacement (DLD) microfluidics to separate WBCs based on size in order to simplify and accelerate an early step in the manufacture of CAR-T therapies. This project directly addresses the purpose of the CRP (PAR-20-128) program in that it will advance the transition of a current Phase II STTR project to the market by funding medical device characterization studies that are required to prepare a Type II Drug Master File (DMF) with the FDA as the next step toward commercialization. GPB is completing Phase II of a Fast-Track STTR project to optimize the Curate system to process an entire leukapheresis unit (up to 500 ml) in 1 hr with rt70% WBC and T-cell recovery, rt90% depletion of RBCs, rt80% depletion of PLTs, and rt70% recovery of T-cell expansion capacity. This represents a substantial increase in WBC output and recovery over current methods and will be an important manufacturing advantage. GPB developed a regulatory strategy and is ready to advance the Curate Cell Processing System toward clinical use. Aim 1 is to conduct verification testing to prove that the outputs of the product meet the specified product requirements or design inputs. This will consist of 9 tests required for the Product Requirements (PRD) Document, one of which will be performed to the break point to determine the upper limits of performance. Aim 2 is to perform tests of biocompatibility, leachability/extractability and sterility. These tests are required to confirm the initial safety of the Curate DLD cassettes in processing patient cells for autologous therapy. Completion of these tests with a “pass” will signify that the product is safe and ready for market distribution. Successful completion of this CRP project is a required first step in submitting a Type II DMF with the FDA to advance the Curate Cell Processing System into the market for use in CAR-T therapy manufacture. There will be an immediate market for this device to support clinical ongoing trials of CAR-T therapy and for clinical use.