Abstract
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.
Highlights
Many chimeric antigen receptor (CAR) T cell therapies currently in development are autologous
This paper evaluates the use of different types of cell culture vessels when used in conjunction with a variety of different devices for media removal
A case study has been presented whereby a decisional tool, consisting of a bioprocess economics model, information database and multi-attribute decision making (MADM) analysis has been developed in order to facilitate decision making with regards to process design for an allogeneic CAR-T cell manufacturing process
Summary
Many chimeric antigen receptor (CAR) T cell therapies currently in development are autologous. Spinning filter membrane technologies [9] (e.g. Lovo Cell Processing System (Fresenius Kabi, Lake Zurich, IL, USA)) and fluidised bed centrifuge systems (e.g. kSep (Sartorius, Göttingen, Germany)) [10], along with integrated systems mentioned above where the cell culture chamber acts as a centrifuge, offer efficient means of cell concentration in a closed environment This represents a welcome shift from more conventional, planar technologies that do not offer the process control, flexibility, or potential for scale-up associated with modern technologies. This study describes the development and application of a decisional tool that has been designed to capture the resource requirements and COG associated with different bioprocess flowsheets put forward for the production of an allogeneic CAR-T cell therapy for the treatment of haematological malignancies. This is the first time such an analysis has been applied to the production of an allogeneic CAR-T cell therapy
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