Cost-effective bioprocess design for the manufacture of allogeneic CAR-T cell therapies using a decisional tool with multi-attribute decision-making analysis

Reimbursement pressures have resulted in an increased awareness of the importance of estimating and improving manufacturing costs for cell therapy products. This work describes the development and application of a decisional tool capable of computing the manufacturing costs for an allogeneic CAR-T cell bioprocess. The tool was used to facilitate a comparison of the impact on cost of goods (COG) from the use of different process technologies including T-flasks, gas permeable vessels, rocking motion bioreactors, an integrated processing platform, MACS purification and spinning membrane filtration technology. Seven different process flowsheets were compared and the economic drivers of manufacturing costs were analysed. COG per dose values were compared against a specified target selling price (TSP) to understand the feasibility of achieving a target COG as % TSP. Finally, a multi-attribute decision-making (MADM) analysis was conducted in order to allow preference of process design to be determined on the basis of qualitative and quantitative operational attributes, rather than COG alone. The flowsheet containing rocking motion bioreactors, spinning membrane filtration technology and a MACS purification platform was found to result in the lowest COG value. The MADM analysis indicated that this was also the preferred flowsheet when qualitative operational attributes were also considered. Furthermore, process attributes such as viral transduction efficiency and electroporation efficiency were found to be key process economic drivers.