首批肠道病毒71型人免疫球蛋白国家标准品的研制  

Preparation of National Standard for Enterovirus 71 Immunoglobulin

作　　者：王敏力[1] 赵卉[1] 王威[1] 祝双利[2] 许文波[2] 秦婷婷 刘瑞熙 丁勇 张笑 管利东[1] 孙思才 史新昌[1] 侯继锋[1] 

机构地区：[1]中国食品药品检定研究院,卫生部生物技术产品检定方法及标准化重点实验室,北京100050 [2]中国疾病预防控制中心病毒病预防控制所,北京100050 [3]成都蓉生药业有限责任公司,成都610000 [4]同路生物制药有限公司,合肥230000 [5]江西博雅生物制药股份有限公司,江西抚州344000

出　　处：《中国药学杂志》2015年第5期431-434,共4页Chinese Pharmaceutical Journal

基　　金：国家"863"课题项目(2012AA021903)

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。OBJECTIVE To prepare the first batch of national standard for enterovirus 71 immnnoglobulin for the efficacy test of- EV71 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 mieroneutralization 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 deter- mination, 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 immuno- globulin 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 tempera- tures. 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% , respeetively. 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 

分 类 号：R917[医药卫生—药物分析学] R696[医药卫生—药学]