Dynamic Simulation and Visualisation of pH-Modulated Fed-batch Fermentation for mAb Production from CHO Cell Cultures

Abstract Monoclonal antibodies (mAbs) are therapeutic proteins used for treating cancer, autoimmune diseases and many other critical ailments, thus constituting essential biopharmaceutical products in global healthcare. The mAb market turnover is predicted to significantly increase, with numerous new products and processes being developed each year. Current mAb processes often rely on Chinese Hamster Ovary (CHO) cell cultures, which are commonly implemented in batch and fed-batch modes, with some demonstrations of continuous/perfusion cultures in pursuit of much leaner manufacturing. Modelling and simulation can allow optimisation of different design and operating parameters towards achieving the most promising process configurations. The dynamic model for mAb fed-batch production from CHO cell cultures employed in this study describes cell growth and death, mAb production and culture volume as a function of time and pH, allowing for systematic simulation in order to elucidate promising dynamic pH modulations. Dynamic pH and state profiles for fed-batch production of mAbs from CHO cells via systematic simulation are presented. Comparisons of attained productivities, resulting concentration profiles and culture volumes are visualised and compared in order to quantitatively elucidate trade-offs in mAb production with a view to manufacturing.