Monday, July 30, 2007
P48

Achieving Significant Improvement in Protein Production Through Process Optimization: A Case Study

Stacy Holdread, Tammy Hill, Cindy Hunt, and James W. Brooks. Research and Development, BD Advanced Bioprocessing, 54 Loveton Circle, Sparks, MD 21152

Increased production goals continue to drive the need to optimize key production factors directly affecting mammalian cell performance.  Media optimized specifically for the cell line can greatly improve protein production.  The addition of an animal free peptone or peptones can further increase the protein yield.  However, most significant production improvements are achieved when the optimized medium and peptone supplementation scheme are coupled with a thorough, methodical process optimization study.  Optimal cell performance is achieved when the media, peptone supplementation, and production process are all optimized to work together.    

 This optimization strategy was successfully utilized to increase protein production of a CHO line producing IgG1.  The cell line was first screened through a library of chemically defined media in order to identify a new base medium.  Key components in the selected formulation were further optimized to meet the specific nutritional requirements of the cell line.  Utilizing the optimized base medium, the cells were screened against a diverse panel of animal free peptones and an individual peptone was identified.  Several rounds of process optimization were then performed to identify the optimal production parameters.  Using the optimized media and process identified in this study, a 7-fold increase in protein production was achieved in less than a year.