药学学报, 2021, 56(2): 565-569
引用本文:
于传飞, 刘春雨, 王兰. 单抗工作参考品的活性赋值研究[J]. 药学学报, 2021, 56(2): 565-569.
YU Chuan-fei, LIU Chun-yu, WANG Lan. Value assignment study on bioactivity of monoclonal antibody working reference standard[J]. Acta Pharmaceutica Sinica, 2021, 56(2): 565-569.

单抗工作参考品的活性赋值研究
于传飞, 刘春雨, 王兰
中国食品药品检定研究院, 北京 102629
摘要:
利用一级参考品对工作参考品的多次标定,对工作参考品进行生物学活性的赋值。本文先理论计算应标定次数,若工作参考品多次标定的均值位于预设相对效价水平内时,则定义工作参考品的效价为100%。结果显示:在活性方法的总中间精密度为11.66%、预设效价水平为95%~105%、置信水平为95%时,应进行至少21次标定。实际22次标定的均值为101.96%,故定义工作参考品与一级参考品效价一致即100%。结果提示采用先计算应标定次数后进行标定的方式,通过判断均值是否位于预设效价水平对工作参考品进行活性赋值,该策略对于生物制药企业具有一定的参考意义。
关键词:    一级参考品      二级参考品      工作参考品      单克隆抗体      生物学活性赋值     
Value assignment study on bioactivity of monoclonal antibody working reference standard
YU Chuan-fei, LIU Chun-yu, WANG Lan
National Institutes for Food and Drug Control, Beijing 102629, China
Abstract:
The bioactivity of a working reference standard was determined by replicate bioassays with calibration against a primary reference standard. In this study the number of bioassay replicates needed for calibration first was calculated theoretically, and if the mean value of the experimental bioassay replicates fell within the predefined bioactivity level the bioactivity of the working reference was defined as 100%. Our results showed that when the total intermediate precision of the bioassay method was at 11.66% and the predefined bioactivity level was set at 95%-105% with a confidence level of 95%, 21 bioassay replicates should be carried out for calibration. The average value of the 22 experimental bioassay replicates was 101.96%, so the bioactivity of the working reference standard was consistent with that of the primary reference standard at 100%. The results suggest that a strategy of first calculating the number of bioassay replicates needed for calibration and then determining whether the resulting experimental mean value is within the predefined bioactivity level will be of value to the biopharmaceutical industry.
Key words:    primary reference standard    secondary reference standard    working reference standard    monoclonal antibody    bioactivity assignment   
收稿日期: 2020-09-03
DOI: 10.16438/j.0513-4870.2020-1437
基金项目: “重大新药创制”国家科技重大专项课题“抗体偶联药物的质量评价方法和质控标准研究平台”(2019ZX09732002-015-001).
通讯作者: 王兰,E-mail:wanglan@nifdc.org.cn
Email: wanglan@nifdc.org.cn
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