(67d) Energy-Based Medium Design for Mammalian Cell Fed-Batch Cultures
Herein, a novel predictive model for GS-NS0 cells producing cB72.3 mAb has been developed considering cell and product composition as well as cellular energy requirements for maintenance, proliferation, and mAb production. The development of this model follows the framework described in  and describes growth kinetics, metabolism, mAb secretion and the production/consumption of ATP based on glucose and 15 amino acid energy metabolic pathways. The full range of the model parameters was subjected to Global Sensitivity Analysis (GSA) to identify the significant parameters that were then estimated from specifically-designed batch experiments. Subsequently, the validated model was utilised to design a low cost supplemental medium for the implementation of an optimized fed-batch strategy which increased production by 60% and extended viability and culture longevity by 24 hrs. As a result of this feeding strategy, nutrient and ATP concentrations were controlled in a tight range without accumulation. The successful coupling of cell and product composition with energy requirements has enabled the development of a tailored medium composition reducing operational costs whilst maximising production. This integrated model-based platform, which is experimentally validated, presents a cost-effective and efficient approach for media development and upstream optimisation of a wide range of biopharmaceutical products.
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