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Safety Assurance for Biologics Manufactured in Mammalian Cell Cultures: A Multitiered Strategy

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Mammalian Cell Cultures for Biologics Manufacturing

Part of the book series: Advances in Biochemical Engineering/Biotechnology ((ABE,volume 139))

Abstract

Contamination by viral and microbial agents is a serious risk for biopharmaceuticals produced by mammalian cell culture processes. In order to effectively mitigate the risk and minimize the occurrence of such contamination events, a multi-tiered approach has been adopted to safeguard the manufacturing processes from A to Z. The multi-tiered approach consists of three separate, yet complementary, elements: (1) control and testing of raw materials in general, and animal sourced materials (ASM) in particular; (2) in-process and release testing for adventitious agents with emphasis on viruses based on risk assessment; and (3) demonstration of an adequate, robust, and consistent viral clearance capability by the downstream purification process. The implementations of these measures will be described in the context of regulatory compliance and GMP manufacturing.

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Acknowledgments

The author wants to thank Ms. Michelle Quertinmont, Dr. Sean O’Donnell, and Dr. Marie Murphy for carefully reviewing the draft manuscript and providing helpful comments and suggestions. Drs. Qi Chen, Ray Nims, and Thomas Kreil provided their invaluable and expert critiques during the preparation of this chapter, for which the author is deeply in debt to each one of them. Finally, the author would like to express his gratitude to Drs. Morrey Atkinson, Uma Kuchibhotla, Catherine Srebalus Barnes, Jerome Kinzel, Victor Vinci, Jace Fogle, Allison Kennington, Tongtong Wang, Michael De Felippis, and Terri Vicenzi for their support and encouragement.

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Authors and Affiliations

  1. Bioproduct Research and Development, Lilly Research Laboratories, Eli Lilly and Company, DC3941, Lilly Corporate Center, Indianapolis, IN, 46285, USA

    Dayue Chen

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  1. Dayue Chen
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Correspondence to Dayue Chen .

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Editors and Affiliations

  1. WuXi AppTec Co., Ltd, Shanghai, People's Republic of China

    Weichang Zhou

  2. Alexion Pharmaceuticals, Cheshire, USA

    Anne Kantardjieff

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Chen, D. (2013). Safety Assurance for Biologics Manufactured in Mammalian Cell Cultures: A Multitiered Strategy. In: Zhou, W., Kantardjieff, A. (eds) Mammalian Cell Cultures for Biologics Manufacturing. Advances in Biochemical Engineering/Biotechnology, vol 139. Springer, Berlin, Heidelberg. https://doi.org/10.1007/10_2013_213

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