浅析GMP检查发现的风险分级

1、HealthProductsandFoodBranchInspectorate食品与健康类产品检查员Guide-0023指南-0023RiskClassificationofGMPObservations,2003editionGMP检查发现的风险分级，2003版Supersedes:June1st,2000editionDateissued:April4th,2003Dateofimplementation:June1st,2003Cedocumentestaussidisponibleenfraaisn.?本文可提供法语版GuiadaTABLEOFCONTENTS目录TOCo1-5hz1.

2、0PURPOSE目的42.0BACKGROUND背景43.0SCOPE范围44.0DEFINITIONS定义:55.0GUIDE指南正文7Assignmentoftherisktoanobservation针对缺陷界定风险7Assignmentoftheinspectionrating检查评定8Risk1observation:1类风险缺陷8Risk2observation:2类风险缺陷8Risk3observations:3类风险缺陷9Additionalguidanee补充9Appendix1附录110Appendix2附录213Appendix3附录3211.0PURPOSE目的Tocl

3、assifytheobservationsnotedduringestablishmentinspectionsaccordingtotheirrisk.依据风险的程度对企业检查中的发现进行分级。ToensureuniformityamongtheinspectorsoftheHealthProductsandFoodBranchInspectorate(theInspectorate)intheattributionoftheratingfollowingestablishmentinspections.确保食品与健康产品检查员(检查员)在对企业进行评估时采用统一的标准。Toinformth

4、eindustryofthesituationsthattheInspectorateconsidersunacceptableandthatwillgenerateaNonCompliant(NC)ratingfollowinganinspection.将各种不被检察员接受进而导致认证失败的情况明确告知企业。2.0BACKGROUND背景Duringanestablishmentinspection,deviationsfromFothoedandDrugRegulationsandthecurrenteditionoftheGoodManufacturingPractices(GMP)gu

5、idelinesarenotedbytheinspectorandthesedeviationsappearasobservationsintheinspectionexitnotice.Ajudgementbasedontheseobservationsisthenmadebytheinspectorandanoverallrecommendationforthecontinuationorissuanceoftheestablishmentlicence(ratingofCompliance)ornottocontinueorissuethelicence(ratingofNonCompl

6、iance)isgiven.AttributionofaNCratingmayhaveseriousconsequencesforacompany,rangingfromtheimplementationofimportantcorrectivemeasurestothetemporarysuspensionorterminationoftheEstablishmentLicence(EL).Therefore,thesesituationsofnon-conformityhavetobewelldefined,unambiguousanddirectlysupportedbytheappli

7、cableregulations.在工厂检查时，凡违反食品药品法和现行GMP的行为都将被检察员记录下来作为离开时检查通告中的检查缺陷。基于这些缺陷，检查人员将做出判断并对是否应该授予或延续企业许可证(合规评定)或不授予或取消企业许可证(不合规评定)给出综合性意见。得到不合规评定有可能给企业带来严重的后果，包括停业整顿或吊销执照。因此，所有不合规的界定应有清晰明确的定义并有章可循。3.0SCOPE范围ThedefinitionofadruginCanadacoversawidevarietyofproductsrangingfrompharmaceuticalsandbiologicstonat

8、uralhealthproductssuchashomeopathicsandherbalpreparations.ThisguidancedocumentcoversallsuchproductstowhichDivision2ofPartCoFfothoedandDrugRegulationsappliesandisbasedonthecurrenteditionoftheGMPGuidelines.ItisrecognisedthattheevaluationoftheconformitytotheGMPshouldbecommensuratewiththeriskinvolvedtak

9、ingintoaccountthenatureandextentofthedeviationinrelationwiththecategoryofproductsevaluated.Nonetheless,mostofthesituationsinvolvingfraud,misrepresentationorfalsificationofproductsordatawillgenerateaNCrating,irrespectiveofthecategoryofproductsinvolved.在加拿大，药品定义广泛，从生化药物到自然的健康产品如顺势疗法和草药都属于此范畴。本文依照现行GMP

10、制定，适用于所有食品药品法C部第2章节所规定的产品。GMP合规评估和风险评估是同时进行的，而风险评估需要根据缺陷的性质与程度同时与评估产品的类别联系起来，这些都已得到业界的认同。但是，大多数导致认证失败的发现如产品或数据存在虚假，歪曲或蓄意伪造都没有考虑产品的类别。Theappendicesattachedtothepresentdocumentdescribetheobservationsrelatedtoeachcategoryofrisk.Pleasenotethatthelistofobservationsineachappendixisnotexhaustiveandthataddi

11、tionalobservationsmaybeaddedwhereappropriate.本文附录描述了检查发现相应的风险级别。请注意附录中并未完全列举所有的检查发现，需要之处可以补充。ThenumberingsystemassignedtoeachsectionintheappendicesisareferencetotheapplicableregulationsinthecurrenteditionoftheGMPguidelines.附件各章节中的数字代表现行GMP法规中相关章节，以备参考。4.0DEFINITIONS定义:Thefollowingdefinitionsareprovi

12、dedtocomplementthosealreadyavailableundertheglossaryoftermsinthecurrenteditionoftheGMPGuidelinesorotherrelateddocumentsreferencedintheGMPGuidelines.以下定义是对现行GMP法规或其相关文件释义部分的补充Observation缺陷:AdeviationordeficiencytoGMPnotedbyaninspectorduringtheinspectionofadrugestablishmentthatisconfirmedinwritingtoth

13、ecompanyintheexitnoticTeh.eobservationsareclassifiedas“Critica,l“M”ajora”nd“Othera”ndareassignedariskclassification,rangingfrom“1crfiotircal”to2for“majorto”3for“other”.药品企业检查过程中，所有被检查人员写入报告的偏差或不足。缺陷分为严重，主要和一般，分别用1（代表严重），2（代表主要），3（代表一般）表示其风险级别。Criticalobservation严重缺陷：Observationdescribingasituationth

14、atislikelytoresultinanon-compliantproductorasituationthatmayresultinanimmediateorlatenthealthriskandanyobservationthatinvolvesfraud,misrepresentationorfalsificationofproductsords严重缺陷包括可能导致产品不合格的缺陷，可能对健康造成立即的或延后的危害的缺陷以及涉及产品或数据存在虚假，歪曲或蓄意伪造的缺陷。AppendixIlistsobservationsthattheInspectorateconsiderscriti

15、calwhichwillbeassignedaRisk1.附录1列出了检察员认为属于1类风险的严重缺陷。Majorobservation主要缺陷：Observationthatmayresultintheproductionofadrugnotconsistentlymeetingitsmarketingauthorization.主要缺陷是指导致产品不能持续达到既定标准的缺陷。Appendix2listsobservationsthatareconsideredmajorandwhichwillbeassignedaRCkiiainRisk2observationsmaybeupgraded

16、toRisk1.Theyareindicatedwithanari)ow附录2列出了检察员认为属于2类风险的主要缺陷。一部分可以上升为1类风险的2类风险已用箭头标明。Otherobservation般缺陷：ObservationthatisneithercriticalnormajorbutisadeparturefromtheGMP.一般缺陷指不属于严重或主要缺陷但偏离GMP要求的缺陷。“Otherobservationsarenotlistedassuch(Observationsthatareneithercriticalnormajorareconsideredas“otherandw

17、illbeassignedaRisk3)Appendix3listsRisk3observationsthatmaybeupgradedtoRisk2.般风险没有像1，2类风险一样被全部列举出来(所有不属于严重或主要的缺陷都归于一般缺陷，属3类风险。)附录3列举了可以上升为2类风险的3类风险。Criticalproduc最高风险产品:Acriticalproductisoneforwhichanyofthefollowingcriteriamayapply:下列情况有任何一条成立，则该产品属于最高风险产品。Inarrowtherapeuticwindo具有窄治疗窗的药物Ihightoxicit

18、y毒性药物Isterileproduc无菌产品工biologicaldru生物药品工complexmanufacturingproce生产工艺复杂的产品Processforwhichslightdeviationsinthecontrolofparanceteld5resultinanon-uniformproductoraproductnotmeetingitsspecifications.Asexample,powdermixingorgranulationforlowdosagesolidforms,longacting/delayedactionproducts,sterileprod

19、i工艺参数控制上一点小的偏差便能引发产品不均一或不合格的情况。如小剂量固体制剂中的混合与制粒，长效或缓释药品，无菌药品。Note注意：OTClowdosagevitaminsandmineralspreparationsandCategory4products(aslistedinInterpretation2.3undersectionC.02.028)shouldnotbeconsideredascriticalproductsevenwhenthemanufacturingprocessesinvoIvedarecomplex.非处方低剂量药物如维生素，微量元素类制剂以及4类产品(参见章

20、节下2.3的解释)尽管制造工艺非常复杂但仍不被认作为最高风险产品。Highriskproduc高风险产品:Anyproductthatmaytriggerahealthriskevenatlowlevels,followingcross-contamination.Thoseincludebutarenotlimitedtopenicillins,certaincytotoxicandbiologicalproducts.任何只需小剂量便能危害健康，引起交叉污染的产品，包括但不仅限于：盘尼西林，部分细胞毒素和生物制品。LowRiskproduct风险产品:ProductssuchasCateg

21、ory4product（aslistedinInterpretation2.3undersectionC.02.028）,naturalhealthproductsincludingvitaminsandmineralspreparationsthatarenotascheduledrugorasteriledrug,andcertaintopicalnonprescriptionveterinaryformulationsregistereoideugs”.4类产品（参见节下2.3的解释），自然健康产品包括维生素，微量元素类非周期性，非无菌性制剂，还有部分注册为“老药”的非处方类兽药。Acr

22、onymS缩写:C:Complian合规CIP:Clean-ln-Placet线清洁COA:EL:CertificateofAnalys检验报告EstablishmentLicen企业许可证GMP:HVAC:GoodManufacturingPractices品生产质量管理规范Heat,Ventilation,AirConditionin空调系统IRS:InspectionReportingSyste检查报告MRA:MutualRecognitionAgreeme互认协议NC:Non-compliant不合规OTC:Over-The-Counter非处方药PM:PackagingMateria

23、包材PW:PurifiedWater纯化水QC:QualityControl质量管理部门（QA+QC）RM:RawMaterial原料WFI:WaterForInjection注射用水5.0GUIDE指南正文Assignmentoftherisktoanobservation对缺陷界定风险Whereasitisrecognizedthatitisimpossibletoencompasseverysituationthatmaygeneratearisk,thefollowingprinciplesshouldbeconsidered:鉴于我们都认识到不可能将所有可能导致危险的情况都罗列出来，

24、因此在界定风险时请考虑以下准则：-Theriskassignedwillbeinrelationtothenatureofthedeviationaswellasthenumberofoccurrences.风险的界定应与缺陷的性质与发生次数关联起来。Generally,whenonlylowriskproductsareinvoIved,arisk1willnotbeassignedtoobservationsdescribedinAppendix1,exceptforextremesituationssuchasfraudorwidespreadcross-contamination,in

25、festationorunsanitaryconditions.般而言，当涉及的产品为低风险产品时，附录1中所描述的缺陷不应被界定为1类风险，除非极端情况发生，如：虚假，大范围交叉污染，感染或不卫生情形。Wherearisk2observationisre-evaluatedasarisk1(risk2observationwithanarrtohwis),situationisimmediatelybroughttotheattentionofcothmepanysofficials,properexplanationwillbeprovidedtotheestablishmentandth

26、isexplanationshouldbecaptured“inIntshpeectorsComments”fieldofthe“InspecntioSummary”intheIRS.当2类风险被重新评估为一类风险时(2类风险中标有箭头的缺陷)，应立即告知企业的管理层并进行合理的解释，解释内容应记录在检查报告总结部分的检察员意见栏中。Assignmentoftheinspectionratin检查评定Theoverallinspectionratingassignedisbasedontheriskinvolvedtakingintoaccountthenatureandextentofthe

27、deviationswiththecategoryofproductsevaluated.综合评定基于存在的风险，缺陷的性质与程度以及评估产品的类别。5.2.1Risk1observation类风险缺陷Generally,aNCratingisassignedwhenaRisk1observationisnotedduringaninspection.一般而言，出现1类风险缺陷，企业将被评定为不合规。Suchsituationisimmediatelybroughttotheattentionmanagementistobenotifiedinatimelymanner.这类情况应被立即告知企

28、业管理层并及时报告给检查机构管理层Whereintheopinionoftheinspectortheresultingproductspresentasignificanthealthhazard,appropriateenforcementactionsmaybeinitiated.如果检察员认为相关产品存在对健康的严重威胁，将会对其启动适当的强制手段。Risk2observation:2类风险缺陷Generally,aCratingisassignedwhenRisk2observationsarenotedduringaninspeHcotiowne.ver,aNCratingmayb

29、eassignedinthefollowingsituations:一般而言，出现2类风险缺陷，企业仍将被评定为合规，但在以下情况出现时，企业将被评定为不合规：-WhennumerousRisk2observationsarenotedduringaninspectionindicatingthatthecompanydoesnotcontrolitsprocessesandoperationssufficiently.当2类风险缺陷显示出企业在工艺和运作方面没能加以足够的控制时。-RepetitionofmanyRisk2observationsnotedduringpreviousinsp

30、ectionsindicatingthatthecompanydidnot:当许多前次检查发现的2类风险缺陷重复出现，显示出企业没有能够-implementthecorrectiveactionssubmittedfollowingthepreviousinspectionor按照递交的计划执行前一次检查缺陷的纠正工作或-didnotputinplaceadequatepreventiveactionsinatimelymannertoavoidrecurrenceofsuchdeviations.没有及时采取足够的预防措施来防止偏差的再次发生。523Risk3observations：3类风

31、险缺陷ACratingwillbeassignedinallsituationswhereonlyRisk3observationsarenoted.如果仅发现3类风险缺陷，企业将被评定为合规的。5.3Additionalguidance卜充WhenaNCratingisassigned,theinspectorwillissueadraftInspectionExitNoticeduringtheexitmeeting.Thedraftinspectionexitnoticewillbereviewedforqualityassurancepurposesbeforethefinalrepo

32、rtisissuedtoanestablishment.当企业被评定为不合规时，检查员将在检查结束的总结会上递交检查通告草稿。在最终报告发至企业之前，草稿可以用于质量保证目的的阅读。Whenobservation(s)leadingtoaNCratingaremade,theInspectionExitNoticecouldbeissuedwithaCratingif,duringtheinspection:当出现导致企业被评定为不合规的缺陷时，如果企业能够在检查其间完成下列工作，检查通告仍会给出企业合规的结论：-theestablishmentimmediatelyimplementsall

33、necessaryactionstoresolvethecause(s)oftheobservation(s)leadingtotheNCratingand,企业立即采取必要措施根除导致缺陷发生的原因并且sufficientassurancecanbeprovidedtopreventarecurrence.-采取足够的预防措施防止缺陷再度发生。Insuchinstances,theriskassignedtotheobservationwillremainthesame.这种情况下，原来对缺陷所作的风险评估等级仍保持不变。Ifthemanagementofthecompanywishesto

34、disputetheresultsoftheinspectionre“poDrt,istphueteresolutionandappea”lsmechanismdescribedintheGMPandELEnforcementPolicyPOL-0004shouldbefollowed.如果企业希望对检查结果进行申辩，GMP与企业强制认证政策POL-0004中的“争议解决与上诉”机制将被启动。Appendix1附录1Risk1(Critical)Observations类风险(严重)缺陷厂房-Noairfiltrationsystemtoeliminateairbornecontaminant

35、sthatarelikelytobegeneratedduringfabricationorpackaging.-没有空气过滤系统以消除生产和包装时可能产生的沉降污染。-Generalizedmalfunctioningoftheventilationsystem(s)withevidenceofwidespreadcrosscontamination.大范围交叉污染的事实表明通风系统存在故障。Inadequatesegregationofmanufacturingortestingareasfromothermanufacturinghairgehasforriskproducts.高风险产

36、品之间的生产区域或测试区域没能有效地隔开。设备Equipmentusedforcomplexmanufacturingoperationsofcriticalproductsnotqualifiedandwithevidenceofmalfunctioning.用于最高风险产品复杂生产过程的设备不合规定同时也存在故障。人员IndividualinchargeofQualityControl(QC)orproductionforafabricatocrroitfical/highriskproductsdoesnotholdauniversitydegreeinasciencerelatedto

37、theworkbeingconadnucdteddoesnothavesufficientpracticalexperienceintheirresponsibilityarea.管理最高风险，高风险产品质量管理或生产的人员没有相关领域的大学文凭同时缺乏足够的实践经验。卫生-Evidenceofwidespreadaccumulationofresidues/extraneousmatterindicativeofinadequatecleaning.-清洁的不够充分，存在大范围残留/异物积聚。-Evidenceofgrossinfestation.-明显的虫害或污染原料检验Evidenceo

38、ffalsificationormisrepresentationofanalyticalresults.分析结果造假或歪曲Noevidenceoftesting(COA)availablefromthesupplier/syntheatnizdernotestingdonebytheCanadianfabricator.缺少供应商的检验报告同时企业也没做相关的测试。生产控制-NowrittenMasterFormula.-没有书面的主处方-MasterFormulaormanufacturingbatchdocumentshowinggrossdeviationsorsignificantc

39、alculationerrors.-主处方或生产批记录存在明显的偏差或严重的计算错误。-Evidenceoffalsificationormisrepresentationofmanufacturingandpackagingorders.-生产和包装订单的造假或错误质控部门-NopersoninchargeofQCavailableonpremisesinCanada.-加拿大工厂内没有质量管理负责人-QCdepartmentnotadistinctandindependentunit,lackingrealdecisionalpoweer,viwdiethncethatQCdecision

40、sareoftenoverruledbyproductiondepartmentormanagement.-质量管理部门不是独立的机构，缺乏真正的决定权，有证据表明质量管理部门的决定常被生产或管理层否定。成品检验-Finishedproductnottestedforcompliancewithapplicablespecificationsbytheimporter/distributorbeforereleaseforsaleandnoevidenceisavailablethattheproductshavebeentestedbythefabricator.-销售前，进口商/分销商没有

41、按照合适的标准对成品进行检验同时没有证据显示生产商做过相关测试。-Evidenceoffalsificationormisrepresentationoftestingresults/forgeryofCOA.-检验结果造假或歪曲/伪造检验报告记录-Evidenceoffalsificationormisrepresentationofrecords.-记录造假或歪曲事实稳定性-Nodataavailabletoestablishtheshelf-lifeofproducts.-缺少建立产品效期的数据-Evidenceoffalsificationormisrepresentationofst

42、abilitydata/forgeryofCOA.-稳定性数据的造假或歪曲/伪造检验报告无菌产品-CriticalsterilizationcyclesbasedonProbabilityofSurvivalnotvalidated.-关键灭菌过程没有基于细菌存活率的进行验证。-WaterforInjection(WFI)systemsnotvalidatedwithevidenceofproblemssuchasmicrobial/endotoxincountsnotwithinspecifications.-注射用水系统未作验证，存在微生物/内毒素超标的情况。-Nomediafillspe

43、rformedtodemonstratethevalidityofasepticfillingoperations.-无菌灌装工艺未做培养基灌装验证。-Noenvironmentalcontrols/Nomonitoringforviablemicroorganismsduringfillingforasepticallyfilledproducts.-无菌灌装产品在灌装期间缺少环境监控/微生物监控。-Asepticfillingoperationsmaintainedfollowingunsatisfactoryresultsobtainedformediafills.-培养基灌装验证失败后

44、仍继续进行无菌灌装生产。-Batchesfailinginitialsterilitytestreleasedforsaleonthebasisofasecondtestwithoutproperinvestigation.-产品基于第二次无菌检测结果放行，而对首次的菌检失败未作调查。Appendix2附录2Risk2(Major)Observations2类风险(主要)缺陷厂房-Malfunctioningoftheventilationsystemthatcouldresultinpossiblelocalizedorocccarosisosn-alcontamination.-通风系统的

45、故障导致固定的或间歇性的交叉污染。-Maintenance/periodicverificationsuchasairfilterreplacement,monitoringofpdreiffsesruernetialsnotperformed(T)-没有做维护/周期性的性能确认如：空气过滤器的更换，检测压差。Accessorysupplies(steam,air,nitrogen,dustcollection,etc.)notqualified.辅助系统(蒸气，空气，氮气，灰尘收集)不符合要求HeatVentilationAirConditioning(HVAC)andpurifiedwat

46、er(PW)systemnotqualified.空调系统和纯化水系统不符合要求Temperatureandhumiditynotcontrolledormonitoredwhennecess(ea.ryg.storagenotinaccordancewithlabellingrequirements).在需要监控温湿度的环节没能监控温湿度(如未按温湿度要求存放标签)Damages(holes,cracksorpeelingpaint)towalls/ceilingsimmediatelyadjacentorabovemanufacturingareasorequipmentwherethep

47、roductisexposed.与产品暴露区域直接相邻或在其上方的墙面，天花板损坏(破洞，裂缝或油漆剥落)Un-cleanablesurfacescreatedbypipes,fixturesorductsdirectlyaboveproductsormanufacturingequipment.无法进行表面清洁的管道经过产品或生产设备的上方。Surfacesfinish(floors,wallsandceilings)thatdonotpermiteffectivecleaning.地板，墙体和天花板表面的外层涂料或覆盖无法有效清洁。Unsealedporousfinishinmanufac

48、turingareaswithevidenceofcontamination(mildew,mould,powderfrompreviousproductions,etc(.T.)生产区域未封闭的孔状表面内在污染(霉菌，前批生产的药粉等等)Insufficientmanufacturingspacethatcouldleadtomix(-uTp)s.生产区域空间太小易造成差错Physicalandelectronicquarantineaccessibletounauthorizedpersonnel/Physicalqauraerantinenotwellmarkedand/ornotres

49、pectedwhenus(eTd).未经授权的人员可以通过机械和电子门禁/机械隔离的区域缺少标示而且/或没有按规程使用。Noseparatearea/Insufficientprecautionstopreventcontaminationorcross-contamdiunraintigonRMsampling.原料抽样缺少独立区域/没有足够的预防措施来防止污染或交叉污染。设备Equipmentdoesnotoperatewithinitsspecificatio(Tn)s.不在其额定范围内操作设备。Equipmentusedforcomplexmanufacturingoperations

50、notqua(lTif)ied.-用于复杂生产的设备不合要求。-CleaninPlace(CIP)equipmentnotvalidated.-在线清洁设备没有验证。-Tanksformanufacturingofliquidsandointmentsnotequippedwithsanitaryclamps.-液体制剂或油膏剂的生产罐没有采用清洁卡箍。Storedequipmentnotprotectedfromcontamina(iOn.设备存放时未作保护以防止污染。Inappropriateequipmentforproduction:surfacesporousandnon-clean

51、able/materialtoshedparticles(T)设备不适于生产：表面多孔无法清洁/材料自身易产生颗粒。Evidenceofcontaminationofproductsbyforeignmaterialssuchasgrease,oil,rustandfproamrticlestheequipmen(tT.)产品被设备上的物质污染如油脂，锈迹和颗粒。Nocoversfortanks,hoppersorsimilarmanufacturingequipment.罐体，料斗或类似的生产设备没有盖子。No/inadequateprecautionstakenwhenequipments

52、uchasovenorautoclavecontaitnhsanmoreoneproduct(possibilityofcross-contaminationormix-u(pTs).同时存放有多个产品的生产设备如烘箱或灭菌柜没有预防交叉污染或混淆的措施或措施不充分。Equipmentlocationdoesnotpreventcross-contaminationorpossiblemix-upsforoperationsperformedincommonare(aT.)共用区域内设备的摆放位置不能防止交叉污染或混淆。PWsystemnotmaintainedoroperatedtoprov

53、idewaterofadequatequ(aTl)ity.纯化水系统未很好地维护与操作，导致不能提供合格的水。Leakinggaskets.垫圈破漏Nocalibrationprogramforautomatic,mechanical,electronicormeasuringequipment/norecordsmaintained.自动化设备，机械设备，电子设备或测量设备没有校验计划/没有校验记录。Noequipmentusagelogs.没有设备使用记录。人员IndividualinchargeofQCorProductionforafabricator,packager/labelle

54、rortesterdoehsolndotauniversitydegreeinasciencerelatedtotheworkbeingcondourctdeodesnothavesufficientpracticalexperienceintheirresponsibilityarea.-负责生产，包装/贴签或测试的质量管理或生产人员没有相关领域的大学文凭同时缺少足够的实践经验。IndividualinchargeofQCforadistributor,importerorwholesalerisnotqualifiedbyacademictrainingandexperience.负责分销

55、商，进口商或批发商的质量管理人员没有达到应有的教育与工作经验要求。DelegationofresponsibilitiesforQCorProductiontoinsufficientlyqualifiedpersons.质量管理与生产没有足够的合格人员以履行其职责。InsufficientpersonnelforQCorProductionoperationsresultinginahighprobabilityoferror.质量管理与生产人手不足导致错误率很高。-InsufficienttrainingforpersonnelinvolvedinproductionandQCresult

56、inginrelatedeGvMiaPtions.-生产与质量管理人员培训不足导致了相应的GMP偏差发生。清洁-Sanitationprogramnotinwritingbutpremisesinacceptablestateofcleanliness.厂房虽然洁净但缺少书面的清洁计划。NoStandardOperatingProcedure(SOP)formicrobial/environmentalmonitoring,nolaimctitiosnforareaswheresusceptiblenon-sterileproductsaremanufactured.没有微生物/环境监控的标准

57、操作流程，在易受污染的非无菌产品生产区域没有设立监控措施限。Cleaningprocedureforproductionequipmentnotvalidated(includinganalyticalmethods).生产设备清洁方法没做验证(包括分析方法)Cleaningprocedureforproductionequipmentnotvalidatedwhennon-dedicatedequipumsedntisforhighriskproductst).在非专用设备用于高风险类产品生产的情况下，设备清洁方法没做验证。Incompletehealthrequirements.不完整的健

58、康要求。原料检验Reducetestingprograminplacewithoutadequatecertificationofthevendors/suppliers.在未对销售商/供应商进行足够资质认证的情况下减少测试项目。Waterusedintheformulationisnotofacceptablequality.配方用水质量达不到要求。Noidentitytestperformedbythemanufacturerafterreceiptonitspremises/TestingforidentitynotdoneoneachcontainerforAPIsorafterman

59、ipulationorrepackagingbythirdparty.收料后没做鉴别/未对每桶原料做鉴别/经第三方处理或重包装后未做鉴别。COAshowingincompletetesting.检验报告上的测试不完全。Incompletespecifications.标准不全。SpecificationsnotapprovedbyQC.标准未被质量管理部门批准。Testmethodsnotvalidated.检验方法没有验证。UseofAPIaftertheretestdatewithoutproperretesting.过再验期的活性成分原料没做再检验而直接使用。UseofinactiveR

60、Maftertheexpirationdatewithoutproperretesting.未做检验而使用过期的非主成分原料。Multiplelotscomprisingonereceptionnotconsideredasseparateforsampling,testingandrelease.将多批物料做为一次收料而未分开采样，测试与放行。NoSOPforconditionsoftransportationandstorage.-没有规定运输储藏条件的SOP。-Certificationofbrokersorwholesalersallowedwithoutproperdocumenta