Djemal Leïla, Fournier Clemence, von Hagen Joerg, Kolmar Harald, Deparis Véronique
Manufacturing Science and Technology, Merck KGaA, Corsier-sur-Vevey, Switzerland.
Department of Applied Biochemistry, Technical University of Darmstadt, Darmstadt, Germany.
Biotechnol Prog. 2021 May;37(3):e3117. doi: 10.1002/btpr.3117. Epub 2021 Jan 9.
Events of viral contaminations occurring during the production of biopharmaceuticals have been publicly reported by the biopharmaceutical industry. Upstream raw materials were often identified as the potential source of contamination. Viral contamination risk can be mitigated by inactivating or eliminating potential viruses of cell culture media and feed solutions. Different methods can be used alone or in combination on raw materials, cell culture media, or feed solutions such as viral inactivation technologies consisting mainly of high temperature short time, ultraviolet irradiation, and gamma radiation technologies or such as viral removal technology for instance nanofiltration. The aim of this review is to present the principle, the advantages, and the challenges of high temperature short time (HTST) technology. Here, we reviewed effectiveness of HTST treatment and its impact on media (filterability of media, degradation of components), on process performance (cell growth, cell metabolism, productivity), and product quality based on knowledge shared in the literature.
生物制药行业已公开报道了生物制药生产过程中发生的病毒污染事件。上游原材料常被确定为潜在污染源。通过灭活或消除细胞培养基和补料溶液中的潜在病毒,可以降低病毒污染风险。不同的方法可以单独使用,也可以组合用于原材料、细胞培养基或补料溶液,例如主要由高温短时、紫外线照射和伽马辐射技术组成的病毒灭活技术,或例如纳滤等病毒去除技术。本综述的目的是介绍高温短时(HTST)技术的原理、优点和挑战。在此,我们根据文献中分享的知识,综述了HTST处理的有效性及其对培养基(培养基的过滤性、成分降解)、工艺性能(细胞生长、细胞代谢、生产力)和产品质量的影响。