Mouse Minute Virus (MMV) Contamination--A Case Study: Detection, Root Cause Determination, and Corrective Actions.
Mouse Minute Virus (MMV) Contamination--A Case Study: Detection, Root Cause Determination, and Corrective Actions.
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DOI：
10.5731/pdajpst.2011.00824
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发表时间：
2011-11-01
影响因子：
--
通讯作者：
Khan, Fazal
中科院分区：
文献类型：
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作者：
Moody, Mark;Alves, Washington;Khan, Fazal
生物制品中的PDA/FDA外源病毒会议记录：检测和缓解策略研讨会，美国马里兰州贝塞斯达; 2010年12月1日至3日，客座编辑：阿里法·汗（贝塞斯达，医学博士），帕特里夏休斯（Bethesda，MD）和Michael Wiebe（San弗朗西斯科，CA）使用哺乳动物细胞生产系统生产生物药物提供了高产率，适当的蛋白质折叠，和忠实的翻译后修饰。然而，哺乳动物细胞培养物易受外源因子（包括小鼠微小病毒（MMV））污染。这里介绍的案例研究表明，MMV是一个无处不在的威胁CHO（中国仓鼠卵巢）细胞为基础的生物药物的生产和无动物的培养基成分可能是一个污染源。除了MMV造成的风险外，污染可能是“沉默的”，对细胞活力和产品滴度没有影响。此外，使用体外病毒检测可能无法检测到污染，需要基于PCR（聚合酶链反应）的检测来进行可靠的检测。通过将污染源确定为无动物重组培养基添加剂，极大地帮助了有效纠正和预防措施（CAPA）的制定。执行CAPA（包括受污染材料的处置、设施的去污和受污染原材料的更换）允许恢复无MMV的生产。
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.