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刊物信息

期刊名称:药物分析杂志
主管单位:中国科学技术协会
主办单位:中国药学会
承办:中国食品药品检定研究院
主编:金少鸿
地址:北京天坛西里2号
邮政编码:100050
电话:010-67012819,67058427
电子邮箱:ywfx@nicpbp.org.cn
国际标准刊号:ISSN 0254-1793
国内统一刊号:CN 11-2224/R
邮发代号:2-237
 

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无菌药品生产企业过程污染微生物菌株库的建立及数据分析

Establishment and data analysis of a contaminated microorganisms library for sterile pharmaceutical production processes

分类号:R917
出版年·卷·期(页码):2019,39 (11):1954-1960
DOI: 10.16155/j.0254-1793.2017.01.01
-----摘要:-------------------------------------------------------------------------------------------

目的:建立某无菌药品生产企业过程污染微生物菌株库,为无菌药品生产过程污染微生物有效控制和溯源调查提供指导。方法:对原辅料、包装材料、生产人员、生产环境、制药用水和检验实验室等环节建立污染微生物监控方案,采用基于16S rRNA序列比对等方法鉴定污染微生物,结合微生物种属和来源信息进行分析,建立覆盖药品生产过程的污染微生物菌株库。结果:共分离鉴定292株微生物,其中生产环境污染率最高,占全部污染微生物来源的72.6%;其次是生产用水(13.4%)、原辅料(10.3%)、生产人员(3.77%)。值得关注的是,A级洁净生产区检测到30株微生物。污染微生物主要分布于44个属、95个种,表明药品生产过程污染微生物种类复杂。其中葡萄球菌污染率最高,占全部污染微生物的40.25%,其次是微球菌(11.20%)、芽孢杆菌(8.30%)和不动杆菌(5.81%)。此外,经分析发现,部分污染微生物分布具有空间特异性,如芽孢杆菌主要存在于原辅料活性炭中,而不动杆菌则主要存在于注射用水中。结论:无菌药品生产过程中多个环节都存在微生物污染,且污染微生物种类复杂,建立覆盖整个生产过程的微生物监控和污染微生物数据库,对药品微生物质量控制和溯源调查分析具有非常重要的作用。

-----英文摘要:---------------------------------------------------------------------------------------

Objective: To establish a contaminated microorganisms library for sterile pharmaceutical manufacturing processes, so as to provide guidance for effective microbial control and traceability of contaminated microorganisms. Methods: Microbiological monitoring was conducted for raw materials and products, packaging materials, production personnel, production environment, pharmaceutical water, and microbiology laboratory. 16S rRNA sequencing method was used to identify the contaminating microorganisms. Statistical analysis was performed by combining the information of microbial species and source. A contaminated microorganisms library covering the pharmaceutical production process was established. Results: It was shown that 292 strains were isolated from pharmaceutical manufacturing process. Among them, the production environment showed the highest microbial positive rate, accounting for 72.6%, followed by production water 13.4%, raw materials 10.3% and production personnel 3.77%. Of concern, 30 strains were detected in the Class A clean area. All contaminated microorganisms in this study were distributed in 44 genera and 95 species, demonstrating that the contaminated microorganisms in the pharmaceutical production process are abundant. Staphylococcus (40.25%) and Micrococcus (11.20%) were the dominated microorganisms, followed by Bacillus (8.3%) and Acinetobacter (5.8%). By further analysis, it was found that the distribution of some contaminated microorganisms was spatially specific. For example, Bacillus strains were mainly found in carbon materials, while Acinetobacter strains were mainly present in injection water. Conclusion: Microbial contamination can be found in multiple areas of drug manufacturing process. Therefore, mapping the distribution of contaminated microorganisms in the drug manufacturing process has a very important role in the drugs quality control and microbiological traceability investigation.

-----参考文献:---------------------------------------------------------------------------------------

[1] EISSA ME.Quantitative microbial risk assessment of pharmaceutical products[J].PDA J Pharm Sci Technol,2017,71(3):245
[2] 姚瑜嫔,陈永法,邵蓉.药害事件频发原因分析及防范对策[J].上海医药,2008,29(4):160 YAO YB,CHEN YF,SHAO R.Analysis on the causes of frequent drug injurg events and prevention methods[J].Shanghai Med Pharm J,2008,29(4):160
[3] 高志峰,姚蕾.浅谈药害事件发生的原因与防范[J].药品评价,2012,9(17):42 GAO ZF,YAO L.Discussion on the causes and prevention of drug emergency[J].Drug Eval,2012,9(17):42
[4] 李琼琼,宋明辉,秦峰,等.制药企业生产环境中污染葡萄球菌菌种鉴定方法的比较评价及毒素基因调查分析[J].中国医药工业杂志,2019,50(4):416 LI QQ,SONG MH,QIN F,et al.Species identification analysis by different methods and toxin genes detection of Staphylococcus strains isolated from drug manufacturing enterprises[J].Chin J Pharm,2019,50(4):416
[5] 胡昌勤.药品微生物控制现状与展望[J].中国药学杂志,2015,50(20):1747 HU CQ.Current situation and trend in pharmaceutical microbial control[J].Chin Pharm J,2015,50(20):1747
[6] 户美玲,陈佩,严东珍,等.建立洁净区微生物数据库与无菌药品GMP生产过程控制的探讨[J].微生物学免疫学进展,2013,41(3):33 HU ML,CHEN P,YAN DZ,et al.Study on establishing a microorganism database of clean oreas and GMP manufacturing process-control for sterile medicinal products[J].Prog Microbiol Immunol,2013,41(3):33
[7] 宋明辉,李琼琼,冯震,等.葡萄球菌属不同靶基因序列种水平鉴定能力的比较评价研究[J].药物分析杂志,2018,38(4):672 SONG MH,LI QQ,FENG Z,et al.Evaluation on molecular identification capacity of different target gene sequences for Staphylococcus species[J].Chin J Pharm Anal,2018,38(4):672
[8] KIM M,OH HS,PARK SC,et al.Towards a taxonomic coherence between average nucleotide identity and 16S rRNA gene sequence similarity for species demarcation of prokaryotes[J].Int J Syst Evol Microbiol,2014,64(2):346
[9] 丁勃,刘艳,孙铜,等.中药口服液微生物污染溯源分析及污染风险的评价与控制[J].中国医药工业杂志,2016,47(10):1311 DING B,LIU Y,SUN T,et al.Traceable analysis of microbial contamination to traditional chinese medicine oral liquid and its evaluation and control[J].Chin J Pharm,2016,47(10):1311
[10] 刘鹏,战宏利,严倩倩,等.中成药口服给药制剂及其原料药微生物污染相关性分析[J].药物分析杂志,2014,34(6):1068 LIU P,ZHAN HL,YAN QQ,et al.Analysis of the correlation of microbial contamination of oral preparations of Chinese patent medicine and crude drugs[J].Chin J Pharm Anal,2014(6):1068
[11] 范一灵,房蕊,蒋波,等.微生物鉴定分型技术应用于医药企业微生物污染调查[J].中国医药工业杂志,2010,41(11):810 FAN YL,FANG R,JIANG B,et al.Application of identification and characterization methods for microbial contamination survey in pharmaceutical industry[J].Chin J Pharm,2010,41(11):810
[12] 陈伟盛,关倩明,朱荣峰,等.药品微生物限度检查中微生物污染的鉴定和溯源分析[J].药物分析杂志,2014,34(1):58 CHEN WS,GUAN QM,ZHU RF,et al.Identification and characterization of bacterial contaminations isolated by microbial limit test[J].Chin J Pharm Anal,2014,34(1):58
[13] STAMATOSKI B,ILIEVSKA M,BABUNOVSKA H,et al.Optimized genotyping method for identification of bacterial contaminants in pharmaceutical industry[J].Acta Pharm,2016,66(2):89
[14] 张国林,苏远科,沈海英,等.16S rRNA/ITS基因序列分析与微生物分类鉴定及其在药品微生物质量控制中的应用[J].中国现代应用药学,2017,34(10):129 ZHANG GL,SHU YK,SHEN HY,et al.Application of 16S rRNA/ITS sequencing and analysis in the identification,classification of microbial and drug quality control[J].Chin J Mod Appl Pharm,2017,34(10):129
[15] 朱诗应,戚中田.16S rDNA扩增及测序在细菌鉴定与分类中的应用[J].微生物与感染,2013,8(2):104 ZHU SY,QI ZT.Application of bacterial 16S rDNA amplication and sequencing in the classification and identification of bacteria[J].J Microb Infect,2013,8(2):104
[16] SHAH MM,IIHARA H,NODA M,et al.dnaJ gene sequence-based assay for species identification and phylogenetic grouping in the genus Staphylococcus[J].Int J Syst Evol Microbiol,2007,57(Pt 1):25
[17] 范一灵,冯震,钟玮,等.无菌药品生产企业核心区微生物污染调查与分析[J].中国药事,2014,28(6):586 FANG YL,FENG Z,ZHONG W,et al.Investigation and analysis of microbiological contamination in core area of sterile drug manufacturing enterprises[J].Chin Pharm Aff,2014,28(6):586
[18] 胡立荣,欧阳波,晓柯.中药制剂生产中的微生物污染途径及控制[J].中国药事,2015,29(6):613 HU LR,OUYANG B,XIAO K.Microbial contamination routes in production of traditional Chinese medicine preparations and its controls[J].Chin Pharm Aff,2015,29(6):613

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