Mouse Minute Virus (MMV) Contamination--A Case Study: Detection, Root Cause Determination, and Corrective Actions.

CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA) The production of biologic drugs using mammalian cell production systems offers the benefits of high yield, proper protein folding, and faithful post-translational modifications. However, mammalian cell culture is vulnerable to contamination with adventitious agents, including mouse minute virus (MMV). The case study presented here demonstrates that MMV is a ubiquitous threat to CHO (Chinese hamster ovary) cell-based production of biologic drugs and that animal-free media components can be a contamination source. Compounding the risk posed by MMV, the contamination may be "silent," with no impact on cell viability and product titers. Furthermore, contamination may not be detected using in vitro virus assays, and assays based on PCR (polymerase chain reaction) are required for reliable detection. The development of effective corrective and preventative action (CAPA) was greatly aided by the identification of the source of the contamination as an animal-free recombinant media additive. The execution of a CAPA that included disposal of contaminated materials, decontamination of the facility, and replacement of the contaminated raw material allowed the resumption of MMV-free production.