Use of computational fluid dynamics as a tool for establishing process design space for mixing in a bioreactor

The concept of design space plays an integral part in implementation of quality by design for pharmaceutical products. ICH Q8 defines design space as the multidimensional combination and interaction of input variables (e.g., material attributes) and process parameters that have been demonstrated to provide assurance of quality. Working within the design space is not considered as a change. Movement out of the design space is considered to be a change and would normally initiate a regulatory post-approval change process. Design space is proposed by the applicant and is subject to regulatory assessment and approval. Computational fluid dynamics (CFD) is increasingly being used as a tool for modeling of hydrodynamics and mass transfer. In this study, a laboratory-scale aerated bioreactor is modeled using CFD. Eulerian-Eulerian multiphase model is used along with dispersed ke turbulent model. Population balance model is incorporated to account for bubble breakage and coalescence. Multiple reference frame model is used for the rotating region. We demonstrate the usefulness of CFD modeling for evaluating the effects of typical process parameters like impeller speed, gas flow rate, and liquid height on the mass transfer coefficient (kLa). Design of experiments is utilized to establish a design space for the above mentioned parameters for a given permissible range of kLa. (c) 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2012