安佰诺工艺变更前后生物学活性可比性统计方法探讨
|
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.
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.
引文
[1]李敏,常卫红,高恩明.治疗用生物制品上市后变更的药学可比性研究[J].中国生物制品学杂志,2012,25(10):1399-1401.
[2] ICH. Guidance for industry:Q5E comparability of biotechnological/biological products subject to changes in their manufacturing process[M]. Geneva:ICH,2004.
[3] FDA. FDA guidance concerning demonstration of comparability of human biological products including therapeutic biotechnologyderived products[M]. Rockville:MD,1996.
[4] EMA. Guideline on comparability of biotechnology-derived medicinal products after a change in the manufacturing process[M].London:UK,2007.
[5] WHO. Guidelines on procedures and data requirements for changes to approved biotherapeutic products[M]. Geneva:WHO,2017.
[6]国家食品药品监督管理总局药品审评中心.生物制品生产工艺过程变更管理技术指导原则[S]. 2005.
[7]国家食品药品监督管理总局药品审评中心.疫苗生产场地变更质量可比性研究技术指导原则[S]. 2014.
[8]国家食品药品监督管理总局药品审评中心.生物制品上市后变更研究的技术指导原则[S]. 2017.
[9]安胜利,陈平雁.等效性检验与差异性检验的区别及其模拟验证[J].中国卫生统计,2007,24(3):226-228.
[10] EMA. Reflection paper on statistical methodology for the comparative assessment of quality attributes in drug development(Draft)[M]. London:UK,2017.
[11] CHATFIELD MJ,BORMAN PJ,DAMJANOV I. Evaluating change during pharmaceutical product development and manufacture comparability and equivalence[J]. Qual Reliab Eng Int,2011,27(5):629-640.
[12] BURDICK RK,LEBLOND DJ,PFAHLER LB,et al. Analytical comparability and similarity. Statistical applications for chemistry,manufacturing and controls(CMC)in the pharmaceutical industry[M]. Cham:Springer International Publishing,2017:329-369.
[13] CHOW SC. On assessment of analytical similarity in biosimilar studies[J]. Drug Des,2014,3(119):2169-2183.
[14]中华人民共和国国家质量监督检验检疫总局和中国国家标准化管理委员会.数据的统计处理和解释-统计容忍区间的确定(GB-T_3359-2009)[S]. 2009.
[15] DONG X,WENG YT,TSONG Y. Adjustment for unbalanced sample size for analytical biosimilar equivalence assessment[J].J Biopharm Stat,2017,27(2):220-232.
[16] YOUNG DS,GORDON CM,ZHU S,et al. Sample size determination strategies for normal tolerance intervals using historical data[J]. Qual Eng,2016,28(3):337-351.
[17] LIMENTANI GB,RINGO MC,YE F,et al. Beyond the t-test:statistical equivalence testing[J]. Anal Chem,2005,77(11):221-226.
[18] TSONG Y,DONG X,SHEN M. Development of statistical methods for analytical similarity assessment[J]. J Biopharm Stat,2017,27(2):197-205.
[19] FDA. Statistical approaches to evaluate analytical similarity(Draft)[M]. Rockville:MD,2017.
[2] ICH. Guidance for industry:Q5E comparability of biotechnological/biological products subject to changes in their manufacturing process[M]. Geneva:ICH,2004.
[3] FDA. FDA guidance concerning demonstration of comparability of human biological products including therapeutic biotechnologyderived products[M]. Rockville:MD,1996.
[4] EMA. Guideline on comparability of biotechnology-derived medicinal products after a change in the manufacturing process[M].London:UK,2007.
[5] WHO. Guidelines on procedures and data requirements for changes to approved biotherapeutic products[M]. Geneva:WHO,2017.
[6]国家食品药品监督管理总局药品审评中心.生物制品生产工艺过程变更管理技术指导原则[S]. 2005.
[7]国家食品药品监督管理总局药品审评中心.疫苗生产场地变更质量可比性研究技术指导原则[S]. 2014.
[8]国家食品药品监督管理总局药品审评中心.生物制品上市后变更研究的技术指导原则[S]. 2017.
[9]安胜利,陈平雁.等效性检验与差异性检验的区别及其模拟验证[J].中国卫生统计,2007,24(3):226-228.
[10] EMA. Reflection paper on statistical methodology for the comparative assessment of quality attributes in drug development(Draft)[M]. London:UK,2017.
[11] CHATFIELD MJ,BORMAN PJ,DAMJANOV I. Evaluating change during pharmaceutical product development and manufacture comparability and equivalence[J]. Qual Reliab Eng Int,2011,27(5):629-640.
[12] BURDICK RK,LEBLOND DJ,PFAHLER LB,et al. Analytical comparability and similarity. Statistical applications for chemistry,manufacturing and controls(CMC)in the pharmaceutical industry[M]. Cham:Springer International Publishing,2017:329-369.
[13] CHOW SC. On assessment of analytical similarity in biosimilar studies[J]. Drug Des,2014,3(119):2169-2183.
[14]中华人民共和国国家质量监督检验检疫总局和中国国家标准化管理委员会.数据的统计处理和解释-统计容忍区间的确定(GB-T_3359-2009)[S]. 2009.
[15] DONG X,WENG YT,TSONG Y. Adjustment for unbalanced sample size for analytical biosimilar equivalence assessment[J].J Biopharm Stat,2017,27(2):220-232.
[16] YOUNG DS,GORDON CM,ZHU S,et al. Sample size determination strategies for normal tolerance intervals using historical data[J]. Qual Eng,2016,28(3):337-351.
[17] LIMENTANI GB,RINGO MC,YE F,et al. Beyond the t-test:statistical equivalence testing[J]. Anal Chem,2005,77(11):221-226.
[18] TSONG Y,DONG X,SHEN M. Development of statistical methods for analytical similarity assessment[J]. J Biopharm Stat,2017,27(2):197-205.
[19] FDA. Statistical approaches to evaluate analytical similarity(Draft)[M]. Rockville:MD,2017.