Dynamic Modelling and Simulation of Chinese Hamster Ovary (CHO) Cell Fermentation for Advanced Biopharmaceutical Manufacturing

Chinese hamster ovary (CHO) cells are widely used in fermentation processes towards biopharmaceutical manufacturing of monoclonal antibodies (mAbs). This work presents dynamic models of two different fermentation modes: batch mode to produce interferon (IFN)-gamma and perfusion mode to produce mAbs. The models predict concentration profiles of cells, substrate, by-product and product, which are validated versus experimental results from the literature. Sensitivity analyses were conducted to establish important parameters for dynamic states that can be investigated in process design. Time and operating costs were evaluated using dynamic models for batch and perfusion modes. Varying initial cell concentration shows a trade-off between production time and cost towards modelling and optimisation of advanced biopharmaceutical manufacturing.