Biopharmaceutical manufacturing processes may include a low pH treatment step as a means of inactivating enveloped viruses. Small scale virus clearance studies are routinely performed using model enveloped viruses such as murine leukemia virus to assess inactivation at the pH range used in the downstream manufacturing process. Further, as a means of bioburden reduction, chromatography resins may be cleaned and stored using sodium hydroxide and this can also inactivate viruses. The susceptibility of SARS-CoV-2 and SARS-CoV to low pH conditions using protein A eluate derived material from a monoclonal antibody production process as well as high pH cleaning conditions was addressed. SARS-CoV-2 was effectively inactivated at pH 3.0, moderately inactivated at pH 3.4, but not inactivated at pH 3.8. Low pH was less effective at inactivating SARS-CoV. Both viruses were inactivated at a high pH of ca.13.4. These studies provide important information regarding the effectiveness of viral clearance and inactivation steps of novel coronaviruses when compared to other enveloped viruses.

中文翻译：

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mAb 纯化过程中洗脱的病毒掺入蛋白 A 中 SARS-CoV-2 和 SARS-CoV 的 pH 失活

生物制药生产过程可能包括低 pH 值处理步骤，作为灭活包膜病毒的手段。通常使用模型包膜病毒（例如鼠白血病病毒）进行小规模病毒清除研究，以评估下游制造过程中使用的 pH 范围内的灭活情况。此外，作为减少生物负荷的一种手段，可以使用氢氧化钠清洁和储存层析树脂，这也可以灭活病毒。使用来自单克隆抗体生产过程的蛋白 A 洗脱液衍生材料以及高 pH 清洁条件解决了 SARS-CoV-2 和 SARS-CoV 对低 pH 条件的敏感性。 SARS-CoV-2 在 pH 3.0 时被有效灭活，在 pH 3.4 时中度灭活，但在 pH 3.8 时未灭活。低 pH 值对 SARS-CoV 的灭活效果较差。两种病毒在约 13.4 的高 pH 值下均被灭活。这些研究提供了有关新型冠状病毒与其他包膜病毒相比的病毒清除和灭活步骤有效性的重要信息。