Objective: To evaluate feasibility of the BacT/ALERT 3D Dual-T rapid microbial detection system based on carbon dioxide signal detection technology as an alternative to the pharmacopoeia sterility test for innovative biologics. Methods: Taking cell products as the application object and referring to pharmacopoeia and foreign guidelines, whether the pharmacopoeia method could be replaced with the rapid method in terms of specificity, LOD and non-inferiority. Results: The evaluation results show that the rapid method was equivalent to the pharmacopoeia method in terms of specificity and detection limit parameters; in most cases, it could report positive results faster than the pharmacopoeia method. The rapid method was not inferior to the compendial method in product quality decision-making, and had advantages in terms of data integrity. Conclusion: Under the premise of risk management, the proven rapid microbiological method can be used as an alternative method to pharmacopoeia sterility testing for rapid release of innovative biologics..
LI Gao-min, PAN Wei-jing, WANG Can, CHEN Gang, SHAO Hong
. Evaluation of carbon dioxide signal based rapid microbiological method for sterility testing of cell preparations*[J]. Chinese Journal of Pharmaceutical Analysis, 2022
, 42(1)
: 147
-155
.
DOI: 10.16155/j.0254-1793.2022.01.17
[1] 中华人民共和国药典2020年版. 三部[S].2020: 13, 520, 542
ChP 2020. Vol Ⅲ[S].2020: 13, 520, 542
[2] USP 43-NF 38[S].2020: 6472, 6481, 8144
[3] EP 10.0. Vol Ⅰ[S].2019: 191, 194, 231, 628
[4] 孟淑芳, 王佑春, 吴雪伶, 等. CAR-T细胞治疗产品质量控制检测研究及非临床研究考虑要点[J].中国药事, 2018, 32(6): 831
MENG SF, WANG YC, WU XL, et al. Technical considerations on the quality control and nonclinical research for CAR-T cell therapy products[J].Chin Pharm Aff, 2018, 32(6): 831
[5] 国家药品监督管理局药品审评中心. 细胞治疗产品研究与评价技术指导原则[EB/OL].[2019-07-01].http://www.cde.org.cn/zdyz.do?method=largePage&id=eae71557b 900d210
Center for Drug Evaluation, NMPA. Guidelines for Research and Evaluation of Cell Therapy Products[EB/OL].[2019-07-01].http://www.cde.org.cn/zdyz.do?method=largePage&id=eae71557b900d210
[6] 郑小玲, 王银环, 陈君豪, 等. 药品微生物检验替代方法国内外研究进展[J].药物分析杂志, 2020, 40(4): 577
ZHENG XL, WANG YH, CHEN JH, et al. Progress on alternative microbiological methods for pharmaceuticals[J].Chin J Pharm Anal, 2020, 40(4): 577
[7] USP 42-NF 37 Second Supplement[S].2019: 9585
[8] 中华人民共和国药典2020年版. 四部[S].2020: 494
ChP 2020 Vol Ⅳ[S].2020: 494
[9] MILLER MJ, JONES D, ALBRIGHT J, et al. Evaluation, Validation and Implementation of Alternative and Rapid Microbiological Methods[M].Revised Ed. Bethesda: Parenteral Drug Association, 2013
[10] PARVEEN S, KAUR S, DAVID SA, et al. Evaluation of growth based rapid microbiological methods for sterility testing of vaccine and other biological products[J].Vaccine, 2011, 29(45): 8012
[11] LUIS J, NARENDRA R, JOSEPH A, et al. Validation of the BacT/alert3D system for rapid sterility testing of biopharmaceutical samples[J].PDA J Pharm Sci Technol, 2012, 66(1): 38
[12] KAISER SJ, MUTTERS NT, BACKHAUS J, et al. Sterility testing of injectable products: evaluation of the growth based BacT/ALERT3DTMDual T culture system[J].PDA J Pharm Sci Technol, 2016, 70(6): 568
[13] GORDON O, GOVERDE M, STAERK A, et al. Validation of Milliflex Quantum for bioburden testing of pharmaceutical products[J].PDA J Pharm Sci Technol, 2017, 71(3): 206
[14] ENGLAND MR, STOCK F, GEBO JET, et al. Comprehensive Evaluation of Compendial USP<71>, BacT/Alert Dual-T, and Bactec FX for Detection of Product Sterility Testing Contaminants[J].J Clin Microbiol, 2019, 57(2): e01548
[15] 魏树源, 杨京生, 陈晓琦, 等. 三磷酸腺苷生物发光快速微生物检测法在疫苗中间品无菌试验中的应用[J].中国生物制品学杂志, 2010, 23(10): 1120
WEI SY, YANG JS, CHEN XQ, et al. Application of rapid determination of microorganisms by ATP bioluminescence assay to sterility test of intermediate product of vaccine[J].Chin J Biol, 2010, 23(10):1120
[16] 李珏, 王知坚, 郑小玲, 等. BacTALERT3D 微生物检测系统作为无菌检查替代方法可行性的探讨[J].中国现代应用药学, 2015, 32(4): 474
LI J, WANG ZJ, ZHENG XL, et al. Discussion on feasibility of alternative sterility test of BacTALERT 3D Microbial Detection System[J].Chin J Mod Appl Pharm, 2015, 32(4): 474
[17] CUNDELL T, DRUMMOND S, FORD I, et al. Risk assessment approach to microbiological controls of cell therapies[J].PDA J Pharm Sci Technol, 2020, 74(2): 229
[18] 国家药监局关于发布《药品生产质量管理规范(2010年修订)》生物制品附录修订稿的公告(2020年第58号) [EB/OL].[2020-07-01].https://www.nmpa.gov.cn/yaopin/ypggtg/20200426172601351.html
Announcement of NMPA (No. 58 of 2020) on the Issuance of the Revised Draft of Biologics Appendix to the <Good Manufacturing Practices for Pharmaceutical Products (Amended in 2010)> [EB/OL].[2020-07-01].https://www.nmpa.gov.cn/yaopin/ypggtg/20200426172601351.html
