A Dynamic and Probabilistic Design Space Determination Method for Mesenchymal Stem Cell Cultivation Processes

A five-step method is proposed for determining the design space of mesenchymal stem cell (MSC) cultivation processes incorporating system dynamics and variabilities. The uses mechanistic models to capture MSC while performing stochastic simulation consider influences variabilities at raw material, cell, process specification, operation levels. Simulated time-dependent changes in critical quality attributes (CQAs) are used determine a dynamic probabilistic followed by global sensitivity analysis. was applied an case study where could be obtained given set CQAs parameters. Sensitivity analysis revealed maximum density dominant parameter interest. input probability distributions were re-evaluated on basis scenario change substrate material which affect density. updated calculation yielded broader viable space.