Related Experiment Video
Updated: Feb 18, 2026
Cell Culture Techniques and Practices to Avoid Contamination by Fungi and Bacteria in the Research Cell Culture Laboratory
Published on: July 7, 2023
Risk Mitigation in Preventing Adventitious Agent Contamination of Mammalian Cell Cultures
Masaru Shiratori1, Robert Kiss2
1Genentech, Inc. (A Member of the Roche Group), San Francisco, CA, USA. shiratori.masaru@gene.com.
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.
Insights
Viral contamination in mammalian cell cultures poses significant risks. High-temperature, short-time (HTST) heat treatment is a recommended virus barrier to mitigate these risks in biopharmaceutical manufacturing.
Area of Science:
- Biotechnology
- Biopharmaceutical Manufacturing
- Viral Safety
Background:
- Industrial-scale mammalian cell culture is crucial for producing biologics.
- Viral contamination events, though infrequent, can severely impact manufacturing and patient supply chains.
- Assessing and mitigating adventitious agent risks is vital for bioprocess integrity.
Purpose of the Study:
- To identify sources of viral contamination risk in cell culture processes.
- To semiquantitatively assess these contamination risks.
- To describe effective process barriers for risk reduction.
Main Methods:
- Review of adventitious agent contamination sources and risks.
- Semiquantitative risk assessment methodologies.
- Evaluation of process barriers, focusing on High-Temperature, Short-Time (HTST) heat treatment.
- Case study on HTST compatibility with cell culture media.
Main Results:
- Identified key sources and assessed risks of viral contamination.
- Recommended HTST heat treatment as a preferred virus barrier when feasible.
- Demonstrated HTST compatibility with a specific cell culture medium through a case study.
- Shared practical lessons from implementing virus barriers.
Conclusions:
- Proactive risk assessment and implementation of barriers are essential for viral safety in mammalian cell culture.
- HTST heat treatment offers a robust solution for mitigating viral contamination risks.
- Careful compatibility studies are necessary to ensure the efficacy of HTST treatment in specific bioprocesses.
