首批肠道病毒71型人免疫球蛋白国家标准品的研制

王敏力,赵卉,王威,祝双利,许文波,秦婷婷,刘瑞熙,丁勇,张笑,管利东,孙思才,史新昌,侯继锋*

中国药学杂志 ›› 2015, Vol. 50 ›› Issue (5) : 431-434.

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中国药学杂志 ›› 2015, Vol. 50 ›› Issue (5) : 431-434. DOI: 10.11669/cpj.2015.05.013
论著

首批肠道病毒71型人免疫球蛋白国家标准品的研制

  • 王敏力1,赵卉1,王威1,祝双利2,许文波2,秦婷婷3,刘瑞熙3,丁勇4,张笑4,管利东1,孙思才5,史新昌1,侯继锋1*
作者信息 +

Preparation of National Standard for Enterovirus 71 Immunoglobulin

  • WANG Min-li1,ZHAO Hui1,WANG Wei1,ZHU Shuang-li2,XU Wen-bo2,QIN Ting-ting3,LIU Rui-xi3,DING Yong4,ZHANG Xiao4,GUAN Li-dong1,SUN Si-cai5, SHI Xin-chang1, HOU Ji-feng1*
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摘要

目的 制备首批肠道病毒71型免疫球蛋白国家标准品,用于肠道病毒71型特异性免疫球蛋白产品效价测定。方法 选择国内经批签发检验合格的静注人免疫球蛋白产品以及高效价肠道病毒71型人免疫球蛋白作为原料进行合并,分装冻干后并按规定对标准品的水分含量、分装精度、无菌检查和稳定性进行考察。在5家实验室按微量细胞病变法进行协作标定,以肠道病毒71型中和抗体滴度的倒数作为中和效价,单位定义为u。结果 5家实验室共进行了63次协作标定,结果均经LOG转换后进行计算,实验室内几何变异系数GCV范围为1.5%~4.1%,实验室间几何变异系数GCV平均值为3.1%,效价几何平均值为327 U。为以后使用和计算方便,该批次标准品赋值为330 U。该标准品160 d加速破坏实验和22 m长期稳定性考察显示效价稳定无下降趋势,12 m测定不同温度点的单体加二聚体(HPLC-SEC法)含量大于98.0%,有效成分稳定。该标准品的水分含量为0.6%,分装精度为0.56%,无菌检查合格。结论 该批肠道病毒71型人免疫球蛋白标准品各项检测指标符合要求,可以作为国家标准品发放用于肠道病毒71型特异性免疫球蛋白的效价测定。

Abstract

OBJECTIVE To prepare the first batch of national standard for enterovirus 71 immunoglobulin for the efficacy test ofEV71 human immunology products.METHODS The domestic intravenous immunoglobulin products with batch release certification and high efficacy EV71 immunoglobulin products were mixed, filled, and lyophilized under aseptic conditions to get the first batch of national standard for enterovirus 71 immunoglobulin. The standards were distributed to five laboratories for cooperative calibration according to the unified SOP for microneutralization test. Neutralizing titer which corresponded to the reciprocal of the highest serum dilution that neutralized enterovirus 71 was defined as the efficacy (reported as unit) of the national standard. Sterility test, moisture determination,precision for filling test, and stability of potency were verified.RESULTS A total of 63 calibration tests were carried out by the five collaboration laboratories,and the results were statistically analyzed after logistic convertion.The inter-laboratories variations varied from 1.5%-4.1% and the intra-laboratories variation was 3.1%. The geometric mean of the prepared national EV71 immunoglobulin standard was 327 U and defined as 330 U for convenience of use. The potency of the prepared standard was stable after 22m and the contents of monomer plus dimer determined by HPLC-SEC were more than 98.0% during storage at a wide range of temperatures. The prepared national EV71 immunoglobulin standard was qualified in the sterility test, and the moisture content and precision for filling were 0.6% and 0.56%, respectively.CONCLUSION The prepared national EV71 immunoglobulin standard met all the relevant requirements and may be served as the first generation of national standard for the potency test of EV71 immunoglobulin products.

关键词

国家标准品 / 肠道病毒71型 / 人免疫球蛋白 / 血液制品 / 中和效价 / 微量细胞病变法

Key words

national standard / enterovirus 71 / immunoglobulin / blood product / neutralizing efficacy test / microneutralization test

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导出引用
王敏力,赵卉,王威,祝双利,许文波,秦婷婷,刘瑞熙,丁勇,张笑,管利东,孙思才,史新昌,侯继锋*. 首批肠道病毒71型人免疫球蛋白国家标准品的研制[J]. 中国药学杂志, 2015, 50(5): 431-434 https://doi.org/10.11669/cpj.2015.05.013
WANG Min-li,ZHAO Hui,WANG Wei,ZHU Shuang-li,XU Wen-bo,QIN Ting-ting,LIU Rui-xi,DING Yong,ZHANG Xiao,GUAN Li-dong,SUN Si-cai, SHI Xin-chang, HOU Ji-feng*. Preparation of National Standard for Enterovirus 71 Immunoglobulin[J]. Chinese Pharmaceutical Journal, 2015, 50(5): 431-434 https://doi.org/10.11669/cpj.2015.05.013
中图分类号: R917    R696   

参考文献

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国家“863”课题项目(2012AA021903)
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