Effects of Lowering Culture Temperature in a Continuous Perfusion Platform When Optimizing Upstream Bioprocessing


Upstream bioprocess development generally involves the study and characterization of a number of parameters as they relate to their impact on cell growth, and volumetric productivity among others.  These process variables are many, and their corresponding effects and ideal parameters will vary based on the nature of the cell line and molecule under study, as well as the cell culture platform utilized.  While fed-batch culture has become quite popular, continuous perfusion systems continue to offer strategically advantageous benefits for the production of unstable or complex recombinant proteins. It is, however, necessary to recognize the fundamentally different effects that varying process parameters can have based on the cell culture platform used.  Reduced temperature, for example, has been shown to stimulate increased productivity in batch and fed-batch culture and, while this phenomenon is frequently exploited in current bioprocesses, the implementation of a temperature reduction strategy has the potential to upset the somewhat delicate process of continuous perfusion.