静注人免疫球蛋白新生产工艺病毒灭活/去除效果的验证及评估

Verification and evaluation of virus inactivation/removal efficacy in a novel procedure for production of intravenous human immunoglobulin

目的对静注人免疫球蛋白(intravenous human immunoglobulin,IVIG)新生产工艺的病毒灭活/去除效果进行验证及评估。方法选择4种脂包膜病毒[人免疫缺陷综合征病毒(human immunodeficiency virus,HIV)、伪狂犬病病毒(pseudorabies virus,PRV)、辛德毕斯病毒(Sindbis virus,SV)和水疱性口炎病毒(vesicular stomatitis virus,VSV)]及非脂包膜病毒[猪细小病毒(porcine parvovirus,PPV)]作为验证病毒,在缩小的生产规模条件下考察辛酸钠沉淀/深层过滤、低pH孵放和纳米膜过滤步骤对一种或几种指示病毒的灭活/去除能力。结果辛酸钠沉淀/深层过滤步骤可灭活/去除PPV 1.88 Log;低pH孵放对HIV、PRV、SV和VSV的灭活效果最低分别为≥5.22、≥4.26、≥6.56和≥5.69 Log;Bio EX纳米膜可去除PPV达4 Log以上。结论 IVIG新生产工艺的病毒灭活/去除效果合格,可有效灭活/去除未知的、新出现的病原体。

Objective To verify and evaluate the virus inactivation/removal efficacy in a novel procedure for production of intravenous human immunoglobulin（IVIG）. Methods The virus inactivation/removal efficacy of sodium caprylate precipitation/deep filtration, low pH incubation and nano membrane filtration in a small-scale production procedure was evaluated using human immunodeficiency virus（HIV）, pseudorabies virus（PRV）, Sindbis virus（SV） and vesicular stomatitis virus（VSV） as indicators. Results The titer of PPV after sodium caprylate precipitation/deep filtration decreased by 1. 88 Log. However, the titers of HIV, PRV, SV and VSV after low pH incubation decreased by not less than5. 22, not less than 4. 26, not less than 6. 56 and not less than 5. 69 Log respectively. The PPV titer after Bio EX nano membrane filtration decreased by more than 4 Log. Conclusion The production procedure of IVIG was effective for inactivation/removal of unknown or new viruses.