A Case Study in Clone Screening: A Comprehensive Approach for a Product With High Projected Market Demand
The cell line used for production of recombinant proteins typically has the most significant impact on the overall productivity of a cell culture process. Therefore, a carefully designed cell line selection process is crucial to achieve high titers while maintaining consistent product quality. Because of projected high market demand for the product being discussed, achieving high productivity within relatively short cell culture fed-batch process duration is critical. By meeting the productivity and culture duration goals, available capacity across the Genentech manufacturing network is most efficiently utilized, and the cost of goods target can be met (Kelly, MAbs, 1(5):443–52, 2009). Therefore, a carefully designed, comprehensive cell line selection effort using a phased approach was undertaken. Clone screening experiments were conducted using a variety of cell culture platforms, including a low volume, high-throughput system (Cheung et al., International Bioprocessing Conference, 2008, Anaheim, CA) as well as 2-L bioreactors. Use of high-throughput technologies allowed for multiple process conditions to be evaluated for each clone, ensuring that each cell line was evaluated for robustness under different process conditions, and that cell line decisions were made based on multiple results. Bioreactor studies were conducted to confirm high-throughput results, and to ensure that the cell lines selected will perform as expected at pilot and manufacturing scale.
KeywordsBioreactor Experiment Full Factorial Experimental Design Cell Line Selection Cell Culture Platform Clone Screening
The authors would like to thank Domingos Ng, Christine Shields, Lisa Zheng, Amy Shen, Robert Shawley, Louis Cheung, Peter Harms, Robert Kiss, and John Joly at Genentech.
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