(68b) Gas Transfer Based Methodology to Scale Single Use Bioreactor Processes

Single-use bioreactor (SUB) systems are widely applied in biopharmaceutical industry for cell culture process development and clinical manufacturing due to reduction in unit operation time and costs. However, due to different bioreactor design, SUBs may have different physical characteristics from traditional stainless steel bioreactors (SSBs) such as energy dissipation, oxygen transfer, shear stress and mixing behaviors. These parameters have been demonstrated critical for scaling-up/-down an upstream bioprocess. Currently, most of our scale up experience is accumulated in SSBs. To successfully scale upstream bioprocesses in SUB systems, we have developed a comprehensive mathematical method to estimate the oxygen transfer rate (OTR) across the different GE Xcellerex^TM (XDR) SUB scales. The method uses a mass balance-based approach to characterizing the oxygen gas transfer coefficients (k_La) in bench-, in pilot- and in GMP- scale XDR bioreactors that considers contribution from sparged bubbles and from surface exchange. This method enables us to estimate oxygen transfer rate (OTR) and dissolved carbon dioxide concentration dynamic profiles. Using this ability to simulate OTR, one can make rational decisions on how to operate the bioreactors with similar cellular micro-environment across various scales and between different bioreactors. The results from scale-up and transfer of processes based on matching OTRs and verification of estimated OTR will be presented.