IMPACT OF MIXING AND AERATION ON CELL CULTURE PERFORMANCE AND QUALITY

摘要

In order to support large-scale biologics manufacturing, it is important to establish scale-down models which can match the process performance and product quality of large scale bioreactors. This can potentially be achieved by mimicking the microenvironment that the cells experience in large scale by maintaining same set points for scale independent parameters and scaling down other scale dependent parameters such as agitation and aeration. In order to understand the impact of agitation and aeration on cell culture performance and product quality, we studied different impellers and sparger configurations in a 3L scale down model using CHO cells. The experiments showed significant impacts of impeller types, impeller orientation, and sparger types on cell culture performance and product quality. This data along with additional bioreactor characterization data for kLa, mixing times and shear stress will be presented. These studies demonstrate the importance of microenvironment as cell culture processes are scaled up or down and help establish a successful scale down model for a product manufactured at multiple manufacturing sites.