重组人粒细胞刺激因子生物学活性国家标准品的制备及协作标定  

Preparation and collaborative calibration of national standard material for biological activity of recombinant human granulocyte stimulating factor

作　　者：刘兰[1] 于雷[1] 丁有学[1] 郭莹[1] 史新昌[1] 饶春明[1] LIU Lan;YU Lei;DING You-xue;GUO Ying;SHI Xin-chang;RAO Chun-ming(Key Laboratory of the Ministry of health for Research on Quality and standardization of Biotech Products,National Institute of Food and Drug Control,Beijing 100050,China)

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其标准化重点实验室,北京100050

出　　处：《中国生物制品学杂志》2021年第3期290-293,共4页Chinese Journal of Biologicals

基　　金：国家重大新药创制(2018ZX09101-001)。

摘　　要：目的制备重组人粒细胞刺激因子(recombinant humna granulocyte colony-stimulating factor,rhG-CSF)生物学活性国家标准品,并进行协作标定。方法 rhG-CSF原液中加入冻干保护剂制备待标品,进行外观、无菌检查及水分、生物学活性检测。将待标品置-20、4、25、37℃分别保存1、2和3个月,取样,检测相对生物学活性,评价热加速稳定性。组织国内5家实验室对待标品进行协作标定。结果制备的待标品灌装变异度<1%,其外观、水分、无菌、生物学活性检查结果均符合相关要求;热加速稳定性试验结果拟合Eyring方程为:ln{k(t)}=18.49-7 853/T+ln(T),R^(2)=0.880,预测待标品于-20℃贮存时,生物学活性衰减10%约需111个月;于-30℃贮存时,生物学活性衰减10%约需417个月。5家实验室协作标定制备的待标品赋值为4.2×10^(6) IU/支。结论制备的rhG-CSF生物学活性国家标准品具有良好的稳定性,可用于rhG-CSF制品的质量评价。Objective To prepare and collaboratively calibrate the national standard material for biological activity of recombinant human granulocyte stimulating factor(rhG-CSF). Methods The candidate for national standard material for biological activity of rhG-CSF was prepared by addition of stabilizer into bulk of rhG-CSF,observed for appearance,tested for sterility,and determined for moisture and biological activity,then stored at-20,4,25 and 37 ℃ for 1,2 and 3 months separately, followed by determintion for relatively biological activity to evaluate the accelerated thermal stability,and collaboratively calibrated by five laboratories. Results The filling variation of prepared samples to be calibrated was l ess than 1%,while the appearance,moisture,sterility,biological activity met the relevant requirements. The experimental results of accelerated thermal stability was fitted as an Eyring equation as follows:ln{k(t)} = 18. 49-7 853/T + ln(T)(R^(2) = 0. 880). It was predicted that the time for decrease of biological activity of the samples to be calibrated by 10% was about 111 months at -20 ℃ and about 417 months at-30 ℃. The biological activity of prepared national standard material collaboratively calibrated by five laboratories was defined as 4. 2 × 10^(6) IU per container. Conclusion The national standard material for biological activity of rhG-CSF was prepared,which showed high stability and might be used for the quality evaluation of rhC-CSF.

关 键 词：重组人粒细胞刺激因子 生物学活性 国家标准品 协作标定 

分 类 号：R917[医药卫生—药物分析学]