Patient-specific hiPSC bioprocessing for drug screening: Bioprocess economics and optimisation

This paper describes a decisional tool that is designed to identify cost-effective process designs for drug screening products derived from human induced pluripotent stem cells (hiPSC). The decisional tool comprises a bioprocess economics model linked to a search algorithm to assess the financial impact of manual and automated bioprocessing strategies that use 2D-planar tissue culture technologies. The tool was applied to a case study that examines the production of patient-specific iPSC-derived neurons for drug screening. The production strategies were compared across three analytical drug screening methods, each requiring cell production at a distinct scale (manual patch-clamp analysis, high throughput screening and plate-based pharmacology), as well as different annual cell line utilization requirements ('throughputs') (between 10 and 100 lines) so as to represent different industry scenarios. The tool determined the critical cell line throughput where the most cost-effective production strategy switched from the manual to automated workflow. The key process economics driver was the number of iPSC expansion stages required. Stochastic modelling of the bioprocess illustrated that the automated was more robust than the manual workflow in the scenarios investigated. The tool predicted the level of performance improvements required in iPSC expansion and differentiation as well as reductions in indirect costs and media costs so as to achieve an acceptable cost of goods (COG).