A production scheduling and control system for CAR T cell manufacturing

This paper addresses some of the new challenges posed by scheduling and controlling the production of chimeric antigen receptor (CAR) T cells for personalized therapies. In this therapy, the patient’s T cells are genetically modified by adding a gene for a receptor to help T cells attach to the cancer cell antigens. Then, the modified cells are grown and multiplied (called cell expansion) and finally returned to the patient. The production takes place in a manufacturing system that comprises several devices, which are capable of processing cells from multiple patients at the same time. The efficient operation of such a complex system requires a sophisticated control system accompanied by a scheduler to optimize the production of CAR T cells for several patients simultaneously. We propose a scheduling algorithm, which can handle the uncertain duration of cell expansion, and the maximum time lags between consecutive processes simultaneously, a combination hardly studied in the literature. We also describe the main features of an adaptive control system including service-oriented device connections as well as centralized control and monitoring. Finally, we describe how the overall system works, including a JSON based communication between scheduler and control system.