纳米膜过滤和低pH孵放法去除/灭活静注人免疫球蛋白中病毒效果的验证

Validation of virus removal/inactivation by nanofilm filtration and low pH incubation in human immunoglobulin for intravenous injection

目的验证纳米膜过滤法和低pH孵放法去除/灭活静注人免疫球蛋白中病毒的效果。方法纳米膜过滤法选用猪细小病毒为指示病毒,低pH孵放法选用水疱性口炎病毒、辛德比斯病毒、HIV和伪狂犬病毒为指示病毒,高浓度静注人免疫球蛋白在pH4.6~5.0、30~32 ℃条件下作用不同时间后,取样检测样品中残余病毒滴度以评价病毒灭活效果。结果纳米膜过滤可降低猪细小病毒滴度达4.50~4.68 lg,低pH孵放法对伪狂犬病毒、辛德比斯病毒、水疱性口炎病毒、HIV等指示病毒的滴度降低量均大于4 lg。结论纳米膜过滤法和低pH孵放法均能有效去除/灭活指示病毒,提高静注人免疫球蛋白产品的安全性。

Objective To verify the efficacy of nanofiltration and incubation with low pH to remove/inactivate the viruses in human immunoglobulin intravenous injection.Method Porcine parvovirus(PPV)was used as the indicator virus for nanofilm filtration virus removal.Low pH incubation method used vesicular stomatitis virus(VSV),Sindbis virus(Sindbis),HIV and pseudorabies virus(PRV)as the indicator viruses.High concentration human immunoglobulin for intravenous injection was incubated under pH4.6-5.0,30-32℃conditions for different time,then sampled and tested for the residual virus titer to evaluate the effect of virus inactivation.Results The removal of PPV by nanofilm filtration was 4.50-4.68 lg,and the titer reductions of PRV,Sindbis,VSV and HIV were all>4 lg.Conclusion Both nanofiltration and incubation with low pH can effectively remove/inactivate the indicator viruses and improve the safety of human immunoglobulin for intravenous injection.