重组人生长激素-Fc融合蛋白中试工艺病毒灭活/去除效果验证  

Verification of virus inactivation/removal efficacy in pilot-scale procedure of recombinant human growth hormone-Fc

作　　者：高启航 刘玉林 尉建 赵磊 孙中涛 张凯宁 赵竟男 刘涵 GAO Qihang;LIU Yulin;YU Jian;ZHAO Lei;SUN Zhongtao;ZHANG Kaining;ZHAO Jingnan;LIU Han(Changchun Institute of Biological Products Co.,Ltd.,Changchun 130012,Jilin Province,China)

机构地区：[1]长春生物制品研究所有限责任公司,吉林长春130012

出　　处：《中国生物制品学杂志》2025年第2期185-189,共5页Chinese Journal of Biologicals

基　　金：吉林省重点科技攻关项目(20160204034YY)。

摘　　要：目的对重组人生长激素-Fc(recombinant human growth hormone-Fc,rhGH-Fc)融合蛋白中试工艺的病毒灭活/去除效果进行验证,以期保证制品质量及患者安全。方法选择伪狂犬病病毒(pseudorabies virus,PRV)、异嗜性小鼠白血病病毒(xenotropic murine leukemia virus,X-MuLV)、小鼠微小病毒(minute virus of mice,MVM)、呼肠孤病毒Ⅲ型(reovirus-3,Reo-3)4种病毒作为指示病毒,在缩小规模的条件下考察有机溶剂/表面活性剂(solvent and detergent,S/D)法对PRV、X-MuLV的灭活能力;亲和层析法对X-MuLV、MVM的去除能力;膜过滤法对MVM、Reo-3的去除能力。结果S/D法对PRV和X-MuLV的灭活能力分别≥4.95、>5.15 Log;亲和层析法对X-MuLV和MVM的去除能力分别≥4.36、1.68 Log;膜过滤法对MVM和Reo-3的去除能力分别>5.36、5.40 Log。结论建立的rhGH-Fc融合蛋白灭活/去除工艺可有效灭活/去除未知的、新出现的病毒。Objective To verify the virus inactivation/removal efficacy in pilot-scale procedure of recombinant human growth hormone-Fc(rhGH-Fc)fusion protein in order to ensure the product quality and patient safety.Methods Four viruses,pseudorabies virus(PRV),xenotropic murine leukemia virus(X-MuLV),minute virus of mice(MVM),and reovirus-3(Reo-3),were used as indicator viruses.Under the condition of scaling down,the inactivation ability of solvent and detergent(S/D)method on PRV and X-MuLV,the removal ability of X-MuLV and MVM by affinity chromatography,and the removal ability of MVM and Reo-3 by nanofilm filtration,were investigated.Results The inactivation ability of PRV and X-MuLV by S/D method was≥4.95 and>5.15 Log,respectively.The removal ability of X-MuLV and MVM by affinity chromatography was≥4.36 and 1.68 Log,respectively.The removal capacity of MVM and Reo-3 by nanofilm filtration was>5.36 and>5.40 Log,respectively.Conclusion The established rhGH-Fc fusion protein inactivation/removal process can effectively inactivate/remove the unknown and emerging viruses.

关 键 词：重组人生长激素-Fc融合蛋白 病毒灭活 病毒去除 S/D法 亲和层析法 膜过滤法 

分 类 号：R392-33[医药卫生—免疫学]