Abstract：
The use of detergents or low pH hold are commonly employed techniques in biologics downstream processing to inactivate enveloped viruses. These approaches have been demonstrated to be robust and are detailed in ASTM E2888 (low pH) and ASTM E3042-16 (Triton X-100), accordingly. One of the recent challenges is the need for a replacement of Triton X-100 with a more environmentally friendly detergent with similar log10 reduction value (LRV) achieved. The presentations in this session focused on a detailed assessment of a range of detergents. The most well characterized and potentially robust detergents identified were TDAO (n-Tetradecyl-N,N-dimethylamine-N-oxide) and Simulsol SL 11 W. Key performance factors assessed (in direct comparison with the industry standard Triton X-100) were viral inactivation kinetics (total elapsed time to achieve equilibrium), LRV achieved of enveloped viruses, toxicity, potential impact on product quality and process performance, clearance of residual detergent in subsequent downstream steps, assays to support assessment with appropriate limit of quantification, and commercial supply of detergent of the appropriate quality standard. Both TDAO and Simulsol SL11 had similar overall LRV as Triton-100. In addition, for the low pH viral inactivation, reduced LRV was observed at pH > 3.70 and low salt concentration (outside of the ASTM range), which is a cautionary note when applying low pH inactivation to labile proteins.
摘要：
使用洗涤剂或低pH保持是生物制品下游加工中常用的技术,以灭活包膜病毒。这些方法已被证明是强大的，并在ASTME2888（低pH）和ASTME3042-16（TritonX-100）中有详细说明，因此。最近的挑战之一是需要用更环保的洗涤剂代替TritonX-100,实现类似的log10降低值(LRV)。本次会议的演讲重点是对一系列洗涤剂的详细评估。鉴定的最充分表征和潜在稳健的洗涤剂是TDAO(n-十四烷基-N，N-二甲胺-N-氧化物）和SimulsolSL11W.评估的关键性能因素（与行业标准TritonX-100直接比较）是病毒灭活动力学（达到平衡的总经过时间），包膜病毒获得的LRV，毒性,对产品质量和工艺性能的潜在影响，清除后续下游步骤中的残留洗涤剂，以适当的定量极限支持评估的测定，和商业供应的洗涤剂的适当的质量标准。TDAO和SimulsolSL11都具有与Triton-100相似的总体LRV。此外,对于低pH病毒灭活，在pH>3.70和低盐浓度（在ASTM范围之外）下观察到LRV降低，这是对不稳定蛋白质应用低pH失活时的注意事项。
