安佰诺工艺变更前后生物学活性可比性统计方法探讨  

Statistical methods study for comparability assessment of biological activity in pre-and post-manufacturing change of Anbainuo

作　　者：聂磊 张胜 阎续 李镭 林群海 郭婷婷 王海彬 瞿海斌[1] NIE Lei;ZHANG Sheng;YAN Xu;LI Lei;LIN Qun-hai;GUO Ting-ting;WANG Hai-bin;QU Hai-bin(College of Pharmaceutical Sciences,Zhejiang University,Hangzhou 310058,China;Zhejiang Hisun Pharmaceutical Co.,Ltd.,Taizhou 318000,China)

机构地区：[1]浙江大学药学院,杭州310058 [2]浙江海正药业股份有限公司,台州318000

出　　处：《中国新药杂志》2019年第1期17-21,共5页Chinese Journal of New Drugs

基　　金：国家"重大新药创制"科技重大专项资助项目(2018ZX09737018)

摘　　要：目的:评估安佰诺生产工艺变更前后生物学活性的可比性,并对不同的可比性统计方法进行探讨。方法:采集工艺变更前61批生物学活性数据(含40批商业化生产批次)和工艺变更后11批生物学活性数据,用统计容忍区间法和等效性检验法对工艺变更前后的生物学活性进行对比研究,其中在等效性检验时,考虑到样本量不平衡,采用数据分割法和标准误调整法进行对比分析。结果:统计容忍区间法和等效性检验法的分析结果均表明,安佰诺工艺变更前后的生物学活性等效一致,生产工艺变更对安佰诺生物学活性无显著影响。结论:统计容忍区间法和等效性检验法均适用于工艺变更前后的可比性研究,但适用范围不同,需根据质量属性特点、样本量及数据类型等进行具体分析和充分评估。Objective: To evaluate the comparability of biological activity in pre-and post-manufacturing change of Anbainuo and to discuss different statistical methods for comparability study. Methods: Biological activity data of 61 pre-change batches including 40 commercial batches and 11 post-change batches were collected. Statistical tolerance interval and equivalence test were used for comparability study of biological activity. Considering the unbalance of sample size,data splitting and standard error adjustment were further applied and analyzed in the equivalence test. Results: The results show that the post-change biological activity of Anbainuo is comparable with that of pre-change,indicating the changes of manufacturing process have no significant effect on biological activity of the product. Conclusion: Both statistical tolerance interval and equivalence test can be used for comparability study before and after manufacturing change,but with different application limits. Specific analysis and full evaluation of statistical methods for comparability study should be performed based on quality attribute characteristics,sample size and data type.

关 键 词：可比性研究 工艺变更 等效性检验 统计容忍区间 安佰诺 

分 类 号：R963[医药卫生—微生物与生化药学]