Data-driven parameterization and development of mechanistic cell cultivation models in monoclonal antibody production processes: Shifts in cell metabolic behavior

Representative kinetic models to describe monoclonal antibody (mAb) production processes are needed for effective process design. The development of mechanistic models can be impeded by the lack of complete understanding of changes in cell metabolism, e.g., lactate metabolic shifts. State-estimation-based methods were applied to assess the fit of available kinetic models over experimental runs. The results indicated the regions where model parameter updates were required. Different clustering strategies were applied to isolate the variations in the culture environment and correlate them to the lactate shifts. Alternative formulations for the specific lactate consumption/production term were provided for each identified phase. Two case studies are presented for pilot-scale data in different reactor types. The results show the improvement in modeling accuracy and highlight the role of oxygen and nutrient levels on the shifts. The approach showcases the use of data-driven insights to effectively utilize limited experimental data to develop robust mechanistic models.