Identification and characterization of a Triton X-100 replacement for virus inactivation
Identification and characterization of a Triton X-100 replacement for virus inactivation
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DOI：
10.1002/btpr.3036
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发表时间：
2020-07-06
影响因子：
2.9
通讯作者：
O'Donnell, Sean
中科院分区：
文献类型：
--
作者：
Luo, Wen;Hickman, Danielle;O'Donnell, Sean
Triton X-100 洗涤剂处理是生物制药制造过程中包含的强大的包膜病毒灭活单元操作。然而，欧盟委员会于2017年正式将Triton X-100列入附件XIV授权清单，因为Triton X-100的降解产物4-(1,1,3,3-四甲基丁基)苯酚（也称为4-叔辛基苯酚）被认为具有有害的内分泌干扰活性。因此，除非在 2021 年 1 月 4 日日落日期之后获得 ECHA 授权，否则 Triton X-100 将不允许在欧洲经济区 (EEA) 使用。这促使生物制药制造商寻找新型、环保的替代去污剂来灭活包膜病毒。在这项研究中，我们报告了这种新型洗涤剂 Simulsol SL 11W 的鉴定。 Simulsol SL 11W 是一种由葡萄糖和 C11 脂肪醇生产的十一烷基糖苷表面活性剂。我们在此报告，Simulsol SL 11W 能够有效灭活有包膜病毒，例如异嗜性鼠白血病病毒 (XMuLV) 和伪狂犬病病毒 (PRV)。以XMuLV为代表的包膜病毒，评估了各种参数对病毒灭活效果的影响。 Simulsol SL 11W 在广泛的浓度、pH 和温度范围内对不同的澄清生物反应器收获物进行病毒灭活。 Simulsol SL 11W 浓度、灭活温度和处理时间被确定为病毒灭活的关键工艺参数。通过 Protein A 色谱法可以轻松去除 Simulsol SL 11W，并且产品质量不受洗涤剂处理的影响。总而言之，这些结果表明 Simulsol SL 11W 作为 Triton X-100 理想的包膜病毒灭活替代品的潜力，可以轻松应用于生物制药制造工艺。
Triton X-100 detergent treatment is a robust enveloped virus inactivation unit operation included in biopharmaceutical manufacturing processes. However, the European Commission officially placed Triton X-100 on the Annex XIV authorization list in 2017 because a degradation product of Triton X-100, 4-(1,1,3,3-tetramethylbutyl) phenol (also known as 4-tert-octylphenol), is considered to have harmful endocrine disrupting activities. As a result, the use of Triton X-100 in the European Economic Area (EEA) would not be allowed unless an ECHA issued authorization was granted after the sunset date of January 4, 2021. This has prompted biopharmaceutical manufacturers to search for novel, environment-friendly alternative detergents for enveloped virus inactivation. In this study, we report the identification of such a novel detergent, Simulsol SL 11W. Simulsol SL 11W is an undecyl glycoside surfactant produced from glucose and C11 fatty alcohol. We report here that Simulsol SL 11W was able to effectively inactive enveloped viruses, such as xenotropic murine leukemia virus (XMuLV) and pseudorabies virus (PRV). By using XMuLV as a representative enveloped virus, the influence of various parameters on the effectiveness of virus inactivation was evaluated. Virus inactivation by Simulsol SL 11W was effective across different clarified bioreactor harvests at broad concentrations, pH, and temperature ranges. Simulsol SL 11W concentration, temperature of inactivation, and treatment time were identified as critical process parameters for virus inactivation. Removal of Simulsol SL 11W was readily achieved by Protein A chromatography and product quality was not affected by detergent treatment. Taken together, these results have shown the potential of Simulsol SL 11W as a desirable alternative to Triton X-100 for enveloped virus inactivation that could be readily implemented into biopharmaceutical manufacturing processes.