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

Part of the Advances in Biochemical Engineering/Biotechnology book series (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.

Keywords

  • Viral safety
  • Viral clearance
  • Viral contamination
  • Adventitious agents

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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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Correspondence to Dayue Chen .

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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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