Abstract：
A continuous viral inactivation (CVI) tubular reactor was designed for low pH viral inactivation within a continuous downstream system across multiple scales of operation. The reactors were designed to provide a minimum residence time of >60 min. The efficacy of this tubular reactor was tested with xenotropic murine leukemia virus (X-MuLV) through pulse injection experiments. It was determined that the minimum residence time of the small-scale reactor design, when operated at the target process flow rate, occurred between 63 and 67 min. Inactivation kinetics were compared between continuous operation and standard batch practices using three monoclonal antibodies. The quantification of the virus log reduction values (LRV) was similar between the two modes of operation and most of the acid-treated samples had virus concentrations below the limit of detection. However, residual infectivity was still present in the endpoint batch samples of two experiments while the continuous samples always remained below the limit of detection. This provides the foundation for leveraging a standard batch-based model to quantify the LRV for a CVI unit operation.
摘要：
连续病毒灭活(CVI)管式反应器被设计用于在多个操作规模的连续下游系统内的低pH病毒灭活。设计反应器以提供>60min的最小停留时间。通过脉冲注射实验，用异型鼠白血病病毒（X-MuLV）测试了该管状反应器的功效。确定了小型反应器设计的最小停留时间，当在目标过程流量下运行时，发生在63到67分钟之间。使用三种单克隆抗体在连续操作和标准分批实践之间比较失活动力学。两种操作模式之间的病毒对数减少值（LRV）的定量相似，并且大多数酸处理样品的病毒浓度低于检测限。然而,两个实验的终点批次样品中仍然存在残留感染性,而连续样品始终保持在检测限以下.这为利用标准的基于批次的模型来量化CVI单元操作的LRV提供了基础。
