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Tuning metabolic efficiency for increased product yield in high titer fed-batch Chinese hamster ovary cell culture |
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| Authors: | Apolline Helfer Sylvain Gros Dave Kolwyck Daniel J Karst |
| Institution: | 1. Process Sciences, Global Manufacturing Sciences, Biogen International GmbH, Luterbach, Switzerland
Contribution: Formal analysis (equal), ?Investigation (equal), Visualization (lead), Writing - original draft (lead);2. Process Sciences, Global Manufacturing Sciences, Biogen International GmbH, Luterbach, Switzerland;3. Process Sciences, Global Manufacturing Sciences, Biogen International GmbH, Luterbach, Switzerland Contribution: Funding acquisition (equal), Supervision (supporting), Writing - review & editing (equal) |
| Abstract: | High demand in manufactured biologics drives the continued need for increased productivity. In this study elevated lactate metabolization resulted in improved metabolic efficiency and cellular productivity for a readily intensified high titer fed-batch process. Scheduled base or lactate feeds during the stationary growth phase led to increased titers (+9% and +8% respectively) without impacting the overall growth performance. The higher lactate consumption induced by either feed strategy substituted for glutamate catabolism and consequently reduced ammonia build-up. Direct correlation between increased titers and reduced ammonia levels was shown. Product quality attributes were impacted by both feeding strategies but could be matched with the control process by shortening the cell culture duration while maintaining titer constant. |
| Keywords: | CHO cell productivity feed strategy optimization intensified fed-batch cell culture process lactate and base feed |