总有机碳(TOC)测定方法在疫苗生产企业清洁验证中的初步应用研究

目的：对疫苗生产企业的目标清洁产物的检测方法进行验证，以找到适合于疫苗生产企业制药设备清洁样品的检测方法。方法：规定残留限度10^-5作为清洁验证的标准，对目标清洁产物稀释至10^-5进行鉴别试验、总蛋白检测和总有机碳（total organic carbon, TOC）检测，对比分析选择适宜的清洁验证分析方法。结果：TOC分析方法精密度可达到要求。建立的清洁验证规程可行，对实际的清洁淋洗水样品进行检测，TOC数据重现性良好，RSD小于10%，低于设立的允许残留限值。结论：TOC分析方法适用于含有混合有机物清洁样品的检测，该方法非常适用于疫苗生产企业制药设备的清洁验证。

Objective: To validate the detection method of target cleaning products in vaccine production enterprises, so as to find a method for cleaning the sample of the pharmaceutical equipment in the vaccine production enterprise. Methods: The residue limits of 10^-5 was defined as cleaning.The target cleaning products were diluted to 10^-5 for standard and experimental identification and validation,total protein and total organic carbon(TOC) detection.Finally, comparative analysis was performed to select suitable cleaning validation analysis method.Results: The TOC analysis method could meet the requirements of precision.The establishment of a clean verification procedure was feasible for the actual cleaning rinse water samples detection.The TOC data reproducibility was good with RSD less than 10%,which was lower than the set of allowable residue limits.Conclusion: The total organic carbon analysis method is suitable for the detection of clean samples containing mixed organic compounds.The TOC method is very suitable for the cleaning validation of pharmaceutical equipment in vaccine manufacturing enterprises.

[1] 中华人民共和国卫生部.药品生产质量管理规范(2010修订)[S].2010:16 Ministry of Health of the People's Republic of China.Good Manufacturing Practice(2010 Revision)[S].2010:16
[2] FDA Guide For Inspections:Cleaning Validation[EB/OL].[2016-01-08].http://www.fda.gov/ICECI/Inspections/InspectionGuides/ucm074922.htm
[3] 辽宁成大生物股份有限公司.人用狂犬病疫苗(Vero细胞)鉴别试验(SOP-QC-05-028)[K].2013 Liaoning Cheng Da Biotechnology Co.,Ltd.Rabies Vaccine(Vero Cell)for Human Use Identification Test(SOP-QC-05-028)[K]. 2013
[4] 辽宁成大生物股份有限公司.乙型脑炎灭活疫苗鉴别试验(SOPQC-03-022)[K].2013 Liaoning Cheng Da Biotechnology Co.,Ltd.Japanese Encephalitis Vaccine(Vero Cell),Inactivated Identification Test(SOP-QC-03-022)[K].2013
[5] 辽宁成大生物股份有限公司.蛋白质含量测定(Lowry法)(SOPQC-05-019)[K].2015 Liaoning Cheng Da Biotechnology Co.,Ltd.Determination of Protein Content(Lowry Method)[K].2015
[6] 辽宁成大生物股份有限公司.总有机碳测定法(SOP-QC-01-219)[K].2014 Liaoning Cheng Da Biotechnology Co.,Ltd.Determination of Total Organic Carbon(SOP-QC-01-219)[K].2014
[7] 廖锐仑.浅谈总有机碳(TOC)分析法在制药设备清洁验证中的应用价值[J].当代医药论丛,2015,13(10):16 LIAO RL.Discussion on the application value of total organic carbon (TOC)analysis in cleaning validation of pharmaceutical equipment[J].Contemp Med Forum,2015,13(10):16
[8] 王燕,梁毅.在线总有机碳分析应用于清洁验证的可行性研究[J].机电信息,2010(23):25 WANG Y,LIANG Y.Feasibility study on the application of total organic carbon analysis in cleaning validation[J].Mech Elect Inf, 2010(23):25
[9] 陶雪筠,李伟举.总有机碳(TOC)分析在制药设备清洁验证中的应用[J].药物分析杂志,2013,33(3):478 TAO XJ,LIWJ.Total organic carbon(TOC)analysis application in cleaning validation of pharmaceutical equipments[J].Chin J Pharm Anal,2013,33(3):478