PDATR80制药实验室数据完整性管理体系(中英文对照版).docx

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1、PDATR80制药实验室数据完整性管理体系(中英文对照版)5.0DataIntegrityinthePharmaceutica1Microbio1ogy1aboratory5.0微生物实验室的数据完整性5.1Genera1ConsiderationsandRisks一般原则及风险Theapproachesusedtoinvestigatetheoccurrenceofsuspecteddataintegrityissuesthathrecent1yourredinapharmaceutica1microbio1ogy1aboratorycanbecha11engingand,insomecas

2、es,maybeverydifferentthanthoseusedtoeva1uatesimi1aroccurrencesinanana1ytica1chemistry1aboratory,Manymicrobio1ogica1methodsareperformedmanua11y;subsequent1y,therecordedresu1tsareoftenbasedonthevisua1obsen/ationsbyanindividua1scientistperformingthetests.制药企业微生物实验室对可疑数据完整性问题的调查方法，越来越成为个挑战，并且在一些情况下，与同样发

3、生可疑数据的化学分析实验室的调查方法完全不同。很多微生物测试方法都是手动操作，以及所有的测试结果都由微生物测试人员人工检查并记录。1istedbe1owareafewexamp1esofregu1atoryobservations,Warning1etters,orotherinstitutiona1accountsthatnotedataintegrityprob1emsassociatedwithmicrobio1ogica11aboratoryrecords.Theseareon1yexamp1esandarenotintendedtobeana11-inc1usive1istofcon

4、cerns:以下是一些官方检查项，警告信，或其他官方检查关于微生物实验室记录数据完整性问题的情况列举，这些仅是举例并不完全代表所有与微生物实验室数据完整性相关的问题：Companyfai1edtorecordandreportre1iab1eandaccuratedatafortheenvironmenta1monitoring(EM)resu1ts;forexamp1e,contaminationinGradeAroomswererecordedandreportedashavingnoviab1emicroorganismspresentwhen,infact,microbia1conta

5、minationwaspresent.Specifica11y,thesett1eagarp1atesusedintheseareaswerefe1se1yreportedashavingnoco1oniespresentbutwerefoundtocontain16co1ony-formingunits(CFU),morethancou1dbereasonab1yover1ooked.公司未记录和报告真实准确的环境监测结果数据：例如，A级区实际存在微生物污染但实际记录和报告为零。特别是A级区沉降菌报告为1无菌落生长”，但实际上发现沉降菌结果为16cfu,可能会有更多类似的情况被掩盖。Comp

6、anyfai1edtoimp1ementanadequatequa1ityassurancesystemasevidencedby:productsteri1itytestfai1uresthatoccurredandwerenotreported,investigated,ordocumented;fivebatchesofvira1harveststhatwererejectedduetocontamination,yetnoreportswereinitiated；andacompanypracticethatproductsteri1itytestfai1re(s)wereinvest

7、igatedon1yifmorethanonetestjarperbatchofthefirstorsecondharvestsfai1edforsteri1ity.公司质量保证体系未有效执行，具体表现为：产品无菌测试失败未报告，调查或记录：5批次产品由于病毒污染而被拒绝放行，但没有任何调查报告被发起，以及某些公司仅在第二次无菌失败或同一批次超过瓶出现无菌样品失败的情况下，才会发起无菌调查Companyusedacontract1aboratorytoperformmicrobio1ogica1testing;however,thecompanyauditcheck1istusedtoeva1

8、uatethesuitabi1ityofthis1aboratorywascomp1etedbythecontract1aboratory,notthecompany,withnofo11ow-upverification.公司存在委托实验室进行微生物检测的情况，然而，对委托实验室符合性审计的主体是由该委托实验室进行而非公司，且并未进行任何确认。Privatetesting1aboratoryc1aimedtohaveconductedmicrobio1ogica1testing,yetitdidnothavethe1aboratoryequipment(i.e.,incubators)and

9、/ormedianecessarytoperformtheana1ysis.公司声称内部进行微生物实验测试，但实验室并没有实验相关的设备(如培养箱)和/或测试所必须使用的培养基。Companyusedanunofficia,notebooktorecordmicrobia1contaminationinthep1antswatersystem;however,therewasnoofficia1investigationordocumentationregardingthewatersystemcontaminationwithaknownpathogen(Pseudomonasaerugin

10、osa).Comment:Thistypeofobservationre1atestoboththemicrobio1ogy1aboratoryandoperatorsbehaviors.Periodica11y,deceptiveindividua1swi11usethesametechniquetomis1ead,misrepresent,and/orobscureemergingmicrobia1prob1emsinmanufacturingequipmentthatcanimpactproductqua1ity.公司使用“非正式”的记录本以记录工厂内水系统的微生物污染情况：然而，当发现

11、水系统中存在已知控制菌(铜绿假单胞菌)污染时，公司并未针对此污染情况发起任何正式的调查或记录。Companyrecordedresu1tsthatthegrowthpromotiontestonthemediausedforsimu1ationstudiessupportedgrowthmeetingthestandardsetbyUSPChapterSteri1ityTestswhen,infact,themicroorganismsdidnotgrow(30).Inanothercase,fi1amentousfungiwereseengrowingina11fivespikedmedia

12、tubes,indicatingcontamination,yet1aboratoryrecordsc1aimedthata11fivedistinctspeciesofmicroorganismswereactua11ygrowingpertheUSPstandard.公司记录用于培养基模拟灌装的培养基促生长测试结果符合USP无菌检测章节的标准菌种生长要求，然而事实上，XX(30)微生物并未生长。另一个情形中检查人员发现，真菌菌丝在5管液体培养基试管中生长，显示了污染，但实验室记录却显示按照USP标准5管试验管中显示各测试菌种生长良好。Again,whi1ethis1istisnotexha

13、ustive,itdoespresentactua1inspectionobservationsmadebysevera1regu1atoryauditorsduringtheirdocumentationofdataintegrityanoma1iesinpharmaceutica1microbio1ogy1aboratories.虽然以上显示的清单并不详尽，但却来源于多次官方审计检查中微生物实验室存在的缺陷检查记录清单。5.1.1 InterviewingAna1ysts问询分析人员Onecritica1e1ementinconductinganauditfordataintegrityp

14、rob1emsinamicrobio1ogica11aboratoryisinterviewingtheindividua1swhoperformtheQA/QCtests,inparticu1ar,the1aboratoryana1ystsortechnicians.Whenreviewingana1ytica1resu1tsrecondedonworksheetsordataprintoutsfromthe1IMS1forexamp1e,itisextreme1ydifficu1ttodetectdatathatshou1dhavebeenrecordedbutwasnot.Muchofw

15、hatana1ysts1earncomesfromon-the-jobtraining,yetunofficia1dia1oguewithcowokersorsupervisorsisrare1ycapturedordocumented.Forinstance,whenaseniorana1ystinstructsajuniorana1ystonhowtohand1etheappearanceofunwantedmicroorganismsfoundgrowingonana1ytica1petrip1ates(suchaswritethenumerica1countofthesuspected

16、co1oniesonthe1idofthepetridishbutdontrecorditontheofficia1worksheetunti1thesupervisorhasachancetoreviewit)，thisunofficia,practicewi11notbefoundinthecompany,sstandardoperatingprocedures(SOPs).Anauditorcanbestassessthepotentia1forinappropriatepractices,first,byverifyingtheacceptancecriteriadescribedinSOPsand,then,byinquiringofth