Current status and issues with CAR-T cell products in Japan: a regulatory perspective.

The development of chimeric antigen receptor (CAR)-T cell products is accelerating worldwide. CAR-T cell therapy represents one of the most significant therapeutic advances, as it elicits remarkably effective and durable clinical responses. Approved CAR-T cell products target one of two antigens on B cells: CD19 or B cell maturation antigen (BCMA). In Japan, all CAR-T cell products are approved for the treatment of relapsed or refractory hematologic malignancies, including acute lymphoblastic leukemia, B cell lymphomas, and multiple myeloma. Although CAR-T cell therapy is indisputably one of the most recommended therapies, it has faced scrutiny for its high cost and several unresolved issues. This article outlines issues with and important considerations for CAR-T cell products reviewed by the Pharmaceuticals and Medical Devices Agency. We describe the approval process for CAR-T cell products; differences in indications for their use, including optimal clinical use guidelines; and manufacture of CAR-T cells, especially out-of-specification products. We also describe key considerations in the regulatory review of CAR-T cell products, with a focus on clinical evaluation.