Metabolic process engineering applied to cell culture production processes

BIOT 154

Bernhard M. Schilling, bernhard.schilling@bms.com1, Abhinav A. Shukla, abhinav.shukla@bms.com1, and Steven Lee, steven.lee@bms.com2. (1) Biotechnology Development, Bristol-Myers Squibb, P.O. Box 4755, Syracuse, NY 13221-4755, (2) Biotechnology Development & Operations, Bristol-Myers Squibb Co, PO Box 4755, Syracuse, NY 13221-4755
There are increasing demands placed on the understanding of cell culture based production processes for recombinant therapeutic proteins. Drivers include the expectation of a high level of operational robustness, a low level of process variability, and a high level of scientific process knowledge that can be demonstrated to regulatory agencies. The limited time available to develop or improve a cell culture based manufacturing process requires therefore a critical evaluation of the applied strategy. The primary expectation to achieve high productivities may be realized by empirical experimentation. However, such strategy will likely not lead to the generation of process 'know-why' or scientific process knowledge. The here presented approach applies metabolic process engineering to cell culture based manufacturing processes. The understanding behind targeted manipulations to the cell metabolism in the manufacturing process becomes especially critical for the production of complex antibody fusion proteins. Case studies will be presented in this contribution.