(653a) A Hydro-Kinetic Model of Single Use Scale-Down Bioreactor Systems for Mammalian Cell Culture

The development and commercialization of new biologics for therapeutic applications accompany the need to scale up bioprocesses for production capacity. This implies adapting the parameters and procedures for a process that is developed in bench-scale bioreactors (typically 15 mL to 2 L) to industrial scale volumes (of the order of a few thousand liters), which is a critical function to fulfill production demands. Bioprocess scale-up and transfer can be particularly challenging with novel process modalities and reactor design, which can lead to longer and more expensive bioprocess development life cycles. The inherent complexity of the bioprocess, combined with the heterogeneity of the environment in larger vessels across multiple culture zones, can cause significant cell-to-cell variability within the same bioreactor. It is thus imperative that the lab-scale systems in which these bioprocesses are developed are characterized completely and accurately for efficient comparison with the large-scale systems.

Computational fluid dynamics has been widely used to characterize bioprocess containers and relate scale-down models to large-scale operations. Kinetic models provide insights into the impact of bioprocess operating conditions on cell culture performance. In this study, a hybrid hydrodynamic-kinetic model for mammalian cell culture was developed to analyze a bench-scale single-use bioreactor. The hydrodynamic analysis of the vessel using computational fluid dynamics was coupled with a kinetic model of the cell culture to understand the interactions and effects of dissolved oxygen, nutrient concentrations, and hydrodynamic microenvironments on the growth characteristics of the cell culture. The work provides a comprehensive understanding of mammalian cell culture processes and enables the development of a reliable digital twin of single-use bioreactors for rapid process development and biologics manufacturing.