Roberts Peter L, Feldman Peter, Crombie Debbie, Walker Chris, Lowery Karen
Bio Products Laboratory, Dagger Lane, Elstree, Hertfordshire WD6 3BX, UK.
Biologicals. 2010 Mar;38(2):303-10. doi: 10.1016/j.biologicals.2009.12.006. Epub 2010 Jan 20.
Virus removal from a high purity factor IX, Replenine-VF, by filtration using a Planova 15N filter has been investigated. A wide range of relevant and model enveloped and non-enveloped viruses, of various sizes, were effectively removed by this procedure. Virus removal was confirmed to be effective when different batches of filter were challenged with poliovirus-1. It was confirmed that intentionally modified filters that failed the leakage test had completely lost the ability to remove virus, thus confirming that this test demonstrates gross filter failure. In the case of the more sensitive integrity test based on gold particle removal, it was found that a pre-wash step was not essential. Planova filters that had been modified by sodium hydroxide treatment to make them more permeable, and filters manufactured with varying pore-sizes over the range of 15-35 nm, were tested. The integrity test value that resulted in the removal of >4 log(10) of poliovirus-1 from the product correlated with that recommended by the filter manufacturer. Virus removal from the product was not influenced by filter load mass, flow-rate or pressure. These studies confirm the robustness of this filtration procedure and allow suitable process limits to be set for this manufacturing step.
已对使用Planova 15N过滤器过滤从高纯度凝血因子IX（Replenine-VF）中去除病毒进行了研究。通过该程序可有效去除各种大小的多种相关及模型包膜病毒和非包膜病毒。当用1型脊髓灰质炎病毒对不同批次的过滤器进行挑战时，证实病毒去除是有效的。已证实故意修改且泄漏测试不合格的过滤器完全丧失了去除病毒的能力，从而证实该测试表明过滤器严重失效。在基于金颗粒去除的更灵敏完整性测试中，发现预洗步骤并非必不可少。测试了用氢氧化钠处理使其更具渗透性的Planova过滤器，以及制造的孔径在15 - 35纳米范围内变化的过滤器。从产品中去除>4 log(10)的1型脊髓灰质炎病毒的完整性测试值与过滤器制造商推荐的值相关。从产品中去除病毒不受过滤器负载质量、流速或压力的影响。这些研究证实了该过滤程序的稳健性，并可为该制造步骤设定合适的工艺限度。
