A distribution-based approach for determining lot sizes in the filling of human-induced pluripotent stem cells

Abstract

Introduction: Toward 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.

Methods: We 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.

Results: A 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.

Conclusions: The 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.

Keywords: Cell manufacturability; Decision-making; Monte Carlo simulation; Optimization; Process design; Process modeling.