Expanding access to CAR T cell therapies through local manufacturing.

Abstract

Chimeric antigen receptor (CAR) T cells are changing the therapeutic landscape for hematological malignancies. To date, all six CAR T cell products approved by the US Food and Drug Administration (FDA) are autologous and centrally manufactured. As the numbers of approved products and indications continue to grow, new strategies to increase cell-manufacturing capacity are urgently needed to ensure patient access. Distributed manufacturing at the point of care or at other local manufacturing sites would go a long way toward meeting the rising demand. To ensure successful implementation, it is imperative to harness novel technologies to achieve uniform product quality across geographically dispersed facilities. This includes the use of automated cell-production systems, in-line sensors and process simulation for enhanced quality control and efficient supply chain management. A comprehensive effort to understand the critical quality attributes of CAR T cells would enable better definition of widely attainable release criteria. To supplement oversight by national regulatory agencies, we recommend expansion of the role of accreditation bodies. Moreover, regulatory standards may need to be amended to accommodate the unique characteristics of distributed manufacturing models.