绝对负压厂房生产的Sabin株脊髓灰质炎灭活疫苗质量研究  

Quality study on Sabin strain inactivated poliomyelitis vaccine produced in absolute negative pressure plant

作　　者：周振歆 易力[1,2] 刘一凡 杨晓蕾 杨净思[1,2,3] Zhou Zhenxin;Yi Li;Liu Yifan;Yang Xiaolei;Yang Jingsi(Institute of Medical Biology,Chinese Academy of Medical Sciences&Peking Union Medical College,Kunming 650031,China;NMPA Key Laboratory for Quality Control and Evaluation of Vaccines and Biological Products,Chengdu 611731,China;National&Local Joint Engineering Research Center for Biological Products for Viral Infectious Diseases,Kunming 650503,China)

机构地区：[1]中国医学科学院&北京协和医学院医学生物学研究所,昆明650031 [2]国家药品监督管理局疫苗及生物制品质量控制与评价重点实验室,成都611731 [3]病毒性传染病生物制品国家地方联合工程研究中心,昆明650503

出　　处：《国际生物制品学杂志》2023年第3期134-140,共7页International Journal of Biologicals

基　　金：国家科技重大专项“重大新药创制”(2018ZX09737-003)。

摘　　要：目的研究绝对负压厂房对Sabin株脊髓灰质炎灭活疫苗(Sabin strain inactivated polio-myelitis vaccine,sIPV)质量的影响.方法按照批准的生产工艺在绝对负压厂房生产sIPVⅠ、Ⅱ和Ⅲ型单价原液各3批,配制3批sIPV三价半成品并分装成3批成品.按照企业注册标准(企标)对原液、半成品和成品进行全项检测,并将有效性指标(D抗原含量、效力试验)检测结果与相对负压厂房生产、检验合格的相对应中间产品和成品检测结果进行对比分析.对绝对负压厂房生产的Ⅰ、Ⅱ和Ⅲ型单价原液及成品进行2~8℃长期稳定性考察和25、37℃加速稳定性考察,以进一步确认该厂房对sIPV质量的影响.结果绝对负压厂房生产的单价原液中Ⅰ、Ⅱ和Ⅲ型D抗原含量分别为≥400、≥200、≥400 D抗原单位(D-antigen unit,DU)/ml,半成品中分别为48~84、54~90、82~128 DU/ml,成品中分别为24~42、27~45、41~64 DU/剂,各项检测结果均符合企标要求;供试品半成品半数有效剂量(50%effective dose,ED50)均高于参考品,且效力试验结果(供试品与参考品ED50比)均在警戒限内波动.相对负压与绝对负压厂房生产的sIPV原液、半成品、成品中Ⅰ、Ⅱ、Ⅲ型D抗原含量及半成品效力试验结果的差异无统计学意义(t值分别为-0.96、-1.69、-1.07、1.61、-0.85、0.07、0.00、-0.66、-1.04,1.93、0.83、1.31,P值均>0.05).稳定性考察结果显示,在疫苗有效期内的各个考察时间点的所有检测结果均符合企标的要求.结论绝对负压厂房生产的sIPV质量稳定、可控,未对疫苗质量造成影响.Objectivee To study the effect of absolute negative pressure plant on the quality of Sabin strain inactivated poliomyelitis vaccine(sIPV).Methods According to the approved production process,3 batches of sIPV types Ⅰ,Ⅱ and Ⅱ monovalent bulks(MVBs)were produced in the absolute negative pressure plant,and MVBs were used to prepare 3 batches of final bulk(FB)and finished product(FP),respectively.The MVBs,FBs and FPs were tested according to the drug registration specifications for sIPV.The test results of efficacy indicators(D-antigen content and potency assay)were compared with those of intermediates and FPs produced in relative negative pressure plant.The 2-8℃long-term stability study and accelerated stability study at 25 and 37℃C were conducted on types Ⅰ,Ⅱ and Ⅱ MVBs and FPs produced in the absolute negative pressure plant in order to further identify the influence of this plant on sIPV quality.Results All test results of MVBs,FBs and FPs produced in absolute negative pressure plant were in compliance with drug registration specification for sIPV.Dantigen contents of types Ⅰ,Ⅱ and Ⅱ in MVBs,FBs and FPs were≥400,≥200,≥400,48-84,54-90,82-128 D-antigen unit(DU)/ml,and 24-42,27-45,41-64 DU/dose,respectively.The 50%effective dose(EDso)values of test vaccines FBs were all higher than reference vaccines FBs,and the potency assay results(EDso of test vaccine/EDso of reference vaccine)fluctuated within the alert limits.There were no statistically significant differences in types Ⅰ,Ⅱ,Ⅱ D-antigen contents of MVBs,FBs and FPs and potency assay results of FB for sIPV produced in relative negative pressure and absolute negative pressure plants(t values were-0.96,-1.69,-1.07,1.61,-0.85,0.07,0.00,-0.66,-1.04,1.93,0.83,1.31,respectively,and all P values were>0.05).Within the validity period of sIPV,the result of each test item at each point during stability study was in compliance with drug registration specification for sIPV.Conclusion The quality of sIPV produced in absolute negative pressure

关 键 词：脊髓灰质炎病毒疫苗 灭活 相对负压厂房 绝对负压厂房 质量研究 

分 类 号：R392-33[医药卫生—免疫学]