437476 An in-House Medium Development Platform: Development of a Chemically Defined Feed Medium for Monoclonal Antibody Production

Wednesday, November 11, 2015: 1:30 PM
150D/E (Salt Palace Convention Center)
Zhongqiang Wang1, Yunling Bai2, Peter Zhang2, Jennifer Autsen2, Rose Malinow2 and Rajesh Krishnan3, (1)Upstream Process Development, Gilead Sciences, Oceanside, CA, (2)Gilead Sciences, Oceanside, CA, (3)Oceanside Biologics Development, Gilead Sciences, Oceanside, CA

An in-house medium development platform was developed and tested across different culture scales, ranging from shake flasks, automated microscale bioreactors (AMBR15TM) and 2-L bioreactors integrated with high-throughput bioprocess analyzers. The platform was used to develop a prototype version of a chemically defined (CD) feed medium for fed-batch production of a recombinant monoclonal antibody in Chinese hamster ovary (CHO) cells.  The medium design was conducted in two stages.  First, studies were performed using a Plackett-Burman design to evaluate the statistical impact of grouped nutrient components on cell growth, productivity and viability. After two rounds of screening, elevated cell growth and viability were achieved with the prototype feed medium relative to a commercial feed medium control.  Next, various titer enhancers were screened to improve culture productivity and process robustness.  Feed formulation and feeding schedules were also optimized through a combination of multivariate DOE strategies in both shake flask and high throughput AMBR15TM. After three rounds of optimization, a ~2.5 fold increase in titer was achieved with the feed medium, which slightly exceeded performance of the commercial feed medium.  The results were confirmed in 2-L fed-batch bioreactors, showing comparable cell growth, viability and titer with the commercially available medium. The platform strategy will be leveraged for long-term media component screening and optimization.

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