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Risk Mitigation in Preventing Adventitious Agent Contamination of Mammalian Cell Cultures

  • Masaru Shiratori
  • Robert Kiss
Chapter
Part of the Advances in Biochemical Engineering/Biotechnology book series (ABE, volume 165)

Abstract

Industrial-scale mammalian cell culture processes have been contaminated by viruses during the culturing phase. Although the historical frequency of such events has been quite low, the impact of contamination can be significant for the manufacturing company and for the supply of the product to patients. This chapter discusses sources of adventitious agent contamination risk in a cell culture process, provides a semiquantitative assessment of such risks, and describes potential process barriers that can be used to reduce contamination risk. High-temperature, short-time (HTST) heat treatment is recommended as the process barrier of choice, when compatible with the process. A case study assessing the compatibility of HTST heat treatment with a cell culture medium is presented, and lessons learned are shared from our experiences over many years of developing and implementing virus barriers in mammalian cell culture processes.

Graphical Abstract

Keywords

Contamination risk assessment HTST heat treatment Nanofiltration UV radiation Virus barriers Virus contamination 

Notes

Acknowledgments

We acknowledge many individuals too numerous to specifically name who, over the course of many years since the initial decision to develop and implement additional virus barriers, have contributed significant time and effort to ensuring success. It has truly taken a village.

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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Genentech, Inc. (A Member of the Roche Group)San FranciscoUSA

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