BEMSCA: A novel decision support tool applied to the optimal design of a large-scale human induced pluripotent stem cell expansion bioprocess

Human induced pluripotent stem cells (hiPSCs) are set to play a predominant role in the up-and-coming field of cell and gene therapy. However, if this is to become reality, hiPSCs must be made available in sufficiently large numbers, usually in the magnitude of billions of cells per patient. This can only be achieved by establishing economically viable and robust large-scale expansion bioprocesses. The design of such bioprocesses is a complex and costly affair, making any tool capable of aiding aspiring manufacturers in this endeavor extremely valuable. In this work, an economic modeling approach to the design of a large-scale hiPSC expansion bioprocess is presented. A computational decision support tool, named Bioprocess Economic Model for Stem Cell Applications (BEMSCA), was developed to determine the optimal workflow of the bioprocess and evaluate how it might be affected by different process parameters. BEMSCA was used to evaluate three promising strategies identified from the literature, namely dextran sulfate supplementation, low-density inoculation and the use of B8 culture medium. BEMSCA estimated that these strategies could lower the batch costs of the bioprocess by 44%, 30% and up to 58%, respectively, corroborating their expected benefits. The results here presented show the applicability and importance of bioprocess economic models such as BEMSCA in the development of novel hiPSC-based therapies.