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Industrialization of bioreactors has been achieved by applying several core concepts of science and engineering. Modeling has deepened the understanding of biological and physical phenomena. In this paper, the state of existing cell culture models is summarized. A framework for development of dynamic and computationally feasible models that capture the interactions of hydrodynamics and cellular activities is proposed. Operating conditions are described by impeller rotation speed, gas sparging flowrate, and liquid fill level. A set of admissible operating states is defined over discretized process parameters. The burden on a dynamic solver is reduced by assuming hydrodynamics at its fully developed state and implementation of compartmental modeling. A change in the conditions of operation is followed by hydrodynamics switching instantaneously to the steady state that would be reached under new conditions. Finally, coupling the model with optimization solvers leads to improvements in operation.

A Framework for the Development of Integrated and Computationally Feasible Models of Large-Scale Mammalian Cell Bioreactors