Schleh Marc, Romanowski Peter, Bhebe Prince, Zhang Li, Chinniah Shivanthi, Lawrence Bill, Bashiri Houman, Gaduh Asri, Rajurs Viveka, Rasmussen Brian, Chuck Alice, Dehghani Houman
Biosafety Development Laboratory, Amgen, Seattle, WA 98119, USA.
Biotechnol Prog. 2009 May-Jun;25(3):854-60. doi: 10.1002/btpr.181.
Viral contaminations of biopharmaceutical manufacturing cell culture facilities are a significant threat and one for which having a risk mitigation strategy is highly desirable. High temperature, short time (HTST) mammalian cell media treatment may potentially safeguard manufacturing facilities from such contaminations. HTST is thought to inactivate virions by denaturing proteins of the viral capsid, and there is evidence that HTST provides ample virucidal efficacy against nonenveloped or naked viruses such as mouse minute virus (MMV), a parvovirus. The aim of the studies presented herein was to further delineate the susceptibility of MMV, known to have contaminated mammalian cell manufacturing facilities, to heat by exposing virus-spiked cell culture media to a broad range of temperatures and for various times of exposure. The results of these studies show that HTST is capable of inactivating MMV by three orders of magnitude or more. Thus, we believe that HTST is a useful technology for the purposes of providing a barrier to adventitious contamination of mammalian cell culture processes in the biopharmaceutical industry.
生物制药生产细胞培养设施中的病毒污染是一个重大威胁,因此制定风险缓解策略非常必要。高温短时(HTST)哺乳动物细胞培养基处理可能会保护生产设施免受此类污染。HTST被认为是通过使病毒衣壳蛋白变性来使病毒粒子失活,并且有证据表明HTST对诸如细小病毒小鼠微小病毒(MMV)等无包膜或裸露病毒具有足够的杀病毒效力。本文所述研究的目的是通过将接种病毒的细胞培养基暴露于广泛的温度范围和不同的暴露时间,进一步描述已知污染哺乳动物细胞生产设施的MMV对热的敏感性。这些研究结果表明,HTST能够使MMV失活三个数量级或更多。因此,我们认为HTST是一种有用的技术,可为生物制药行业中哺乳动物细胞培养过程的偶然污染提供屏障。