IntroductionToward the commercial production of human-induced pluripotent stem (hiPS) cells, the process design and operation have to be standardized. Considering the change in cell quality during filling of the hiPS cells into containers, lot sizing during filling also needs to be standardized.MethodsWe present a distribution-based approach that can be used for determining the lot sizes in the filling of hiPS cells by considering change in cell quality during filling. The approach describes the “survival capability” of the cells as a continuous probability distribution, and expresses the change in quality during filling by “trimming” the distribution.ResultsA lognormal distribution was assumed as the survival capability distribution of the cells that were to be filled. The distributions after different filling times were calculated, which were compared with the distribution of the initial filling time regarding the yield of the cells and the similarity. These conditions served as strong quality constraints in determining an economically optimal lot size.ConclusionsThe presented conceptual approach would be effective in determining the lot size considering the change in cell quality during filling. For actual application, measuring the distribution information on the survival capability of hiPS cells is encouraged.
Standardization in process design and operation is needed in the commercial production of human-induced pluripotent stem (hiPS) cells. Lot sizing in the filling of hiPS cells into containers, a part of the preservation process, also needs to be standardized because of the temporal changes in cell quality during the process. Here, we present an apoptosis-based method that can determine lot sizes in the filling of hiPS cells considering temporal changes in cell quality. Two indicators were developed for (i) the cell quality change using reactive oxygen species (ROS) measurement and (ii) the cell survival and probability of filling success, which are parts of the lot-sizing problem. Using computational simulation, a map out of the optimal lot size was produced that minimized the expected production costs at a given cell demand and an acceptable change in cell quality. At a filling temperature of 4 C, the largest possible lot size was calculated as 6 L (corresponding to a filling time of 125 min). The results of a sensitivity analysis recommended cold filling or the addition of an antioxidant. The presented method is effective to determine the lot size considering the change in cell quality during filling. The study uniquely combines the experimental results with mathematical modeling and computational simulation techniques. The map out of the optimal lot size could guide the development of industrial filling processes of hiPS cells.
The cover image is based on the Original Article Apoptosis‐based method for determining lot sizes in the filling of human‐induced pluripotent stem cells by Hirokazu Sugiyama et al., https://doi.org/10.1002/term.3127.
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