Impact of allogeneic stem cell manufacturing decisions on cost of goods, process robustness and reimbursement

This article presents a framework to evaluate holistically the operational and economic performance of different manufacturing platforms for the expansion of allogeneic mesenchymal stromal cells (MSCs) across different commercialisation scenarios. The tool comprised models for whole bioprocess economics linked to uncertainty analysis, dynamic scheduling, brute-force optimisation and multi-attribute decision-making. The tool was used to determine the cost of goods (COG), robustness, operational ease and business feasibility of competing cell culture technologies under different scale, demand, reimbursement and dose size scenarios, and to determine the performance improvements required for commercial success. The results revealed that in low annual demand (10 billion cells/year) scenarios, multi-plate bioreactors have superior operational and economic characteristics. At larger annual demands (10 trillion cells/year), however, the tool predicts that microcarrier-based bioreactors are optimal due to their relative cost-effectiveness and operational benefits conferred by their closed and controlled characteristics that outweigh the uncertainties associated with their use. Moreover, whilst further analysis of high dose, high demand (1 billion cells/dose, 10,000 doses/year) scenarios has shown that significant improvement in the performance of cell culture processes may result in satisfactory COG, current limitations in the capacity of downstream processing (DSP) technologies may not allow full market capture. (C) 2018 The Authors. Published by Elsevier B.V.