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A Case Study in Clone Screening: A Comprehensive Approach for a Product With High Projected Market Demand

  • Kirin M. Jamison
  • Dacia R. Brooks
  • Szu-Han Wang
  • Martin Gawlitzek
Conference paper
Part of the ESACT Proceedings book series (ESACT, volume 5)

Abstract

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.

Keywords

Bioreactor Experiment Full Factorial Experimental Design Cell Line Selection Cell Culture Platform Clone Screening 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

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.

References

  1. Cheung, L., et al., Poster Presentation: Developing an Automated High-Throughput System for Cell Culture Process Development. International Bioprocessing Conference, 2008. Anaheim, CA.Google Scholar
  2. Gawlitzek, M., et al., Identification of cell culture conditions to control N-glycosylation site-occupancy of recombinant glycoproteins expressed in CHO cells. Biotechnol Bioeng, 2009. 103(6): 1164–75.PubMedCrossRefGoogle Scholar
  3. Kaufmann, H., et al., Influence of low temperature on productivity, proteome and protein phosphorylation of CHO cells. Biotechnol Bioeng, 1999. 63(5): 573–82.PubMedCrossRefGoogle Scholar
  4. Kelley, B., Industrialization of mAb production technology: the bioprocessing industry at a crossroads. MAbs, 2009. 1(5): 443–52.PubMedCrossRefGoogle Scholar
  5. Vijayasankaran, N., et al., Animal Cell Culture Media. In: Encyclopedia of Industrial Biotechnology (Flickinger, M. ed.). Wiley, London, 2010. 1–15.Google Scholar

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Kirin M. Jamison
    • 1
  • Dacia R. Brooks
    • 1
  • Szu-Han Wang
    • 1
  • Martin Gawlitzek
    • 1
  1. 1.Late Stage Cell Culture, Pharma Technical DevelopmentGenentech, A Member of the Roche GroupSouth San FranciscoUSA

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