(204b) Depth Filter Train Optimization of a High Cell Density Product Stream

Authors: 
Molek, J. R., GlaxoSmithKline
Deiner, A. S., GlaxoSmithKline
Ardeshna, H. D., GlaxoSmithKline
Weber, A. D., GlaxoSmithKline
Goklen, K. E., GlaxoSmithKline


Removal of cells and cell debris with centrifugation followed by depth filtration are often the first steps in primary recovery of expressed proteins from a microbial fermentation broth. In expression systems containing high volumes of solids, the depth filtration step is a challenging task. The case study presented here focuses on optimizing the filter train containing high levels of cell debris. By understanding the effects of the centrifuge processing steps that affect broth characteristics, as well as characteristics of the cell broth itself, the filter train can be designed to be both effective and robust. By taking a build approach in which the final membrane filter is defined and the depth filters are ?built? onto the train, the overall filter train capacity as well as the clarification is increased. Resistance curves generated as a function of throughput are compared to basic filter fouling models to provide insight into the filtration process. Factors such as the effect of filter ratio and feed flow rate on the overall capacity of the filter train are also analyzed to better understand the filter system. Using the results of the bench scale experiments along with appropriate scaling factors, a successful large scale clarification was performed, in agreement with our small scale models.