（質量認證）加拿大GMP檢查風險分級HealthProductsandFoodBranchInspectorate食品與健康類產品檢查員Guide-0023指南-0023RiskClassificationofGMPObservations,2003editionGMP檢查發現的風險分級，2003版Supersedes:June1st,2000editionDateissued:April4th,2003Dateofimplementation:June1st,2003Cedocumentestaussidisponibleenfran?ais.本文可提供法語版TABLEOFCONTENTS目錄1.0PURPOSE目的32.0BACKGROUND背景33.0SCOPE范圍34.0DEFINITIONS定義:45.0GUIDE指南正文65.1Assignmentoftherisktoanobservation針對缺陷界定風險65.2Assignmentoftheinspectionrating檢查評定75.2.1Risk1observation:1類風險缺陷75.2.2Risk2observation:2類風險缺陷75.2.3Risk3observations:3類風險缺陷85.3Additionalguidance補充8Appendix1附錄19Appendix2附錄212Appendix3附錄3211.0PURPOSE目的Toclassifytheobservationsnotedduringestablishmentinspectionsaccordingtotheirrisk.依據風險的程度對企業檢查中的發現進行分級。ToensureuniformityamongtheinspectorsoftheHealthProductsandFoodBranchInspectorate(theInspectorate)intheattributionoftheratingfollowingestablishmentinspections.確保食品與健康產品檢查員（檢查員）在對企業進行評估時采用統一的標準。ToinformtheindustryofthesituationsthattheInspectorateconsidersunacceptableandthatwillgenerateaNonCompliant(NC)ratingfollowinganinspection.將各種不被檢察員接受進而導致認證失敗的情況明確告知企業。2.0BACKGROUND背景Duringanestablishmentinspection,deviationsfromtheFoodandDrugRegulationsandthecurrenteditionoftheGoodManufacturingPractices(GMP)guidelinesarenotedbytheinspectorandthesedeviationsappearasobservationsintheinspectionexitnotice.Ajudgementbasedontheseobservationsisthenmadebytheinspectorandanoverallrecommendationforthecontinuationorissuanceoftheestablishmentlicence(ratingofCompliance)ornottocontinueorissuethelicence(ratingofNon-Compliance)isgiven.AttributionofaNCratingmayhaveseriousconsequencesforacompany,rangingfromtheimplementationofimportantcorrectivemeasurestothetemporarysuspensionorterminationoftheEstablishmentLicence(EL).Therefore,thesesituationsofnon-conformityhavetobewelldefined,unambiguousanddirectlysupportedbytheapplicableregulations.在工廠檢查時，凡違反食品藥品法和現行GMP的行為都將被檢察員記錄下來作為離開時檢查通告中的檢查缺陷。基于這些缺陷，檢查人員將做出判斷并對是否應該授予或延續企業許可證（合規評定）或不授予或取消企業許可證（不合規評定）給出綜合性意見。得到不合規評定有可能給企業帶來嚴重的后果，包括停業整頓或吊銷執照。因此，所有不合規的界定應有清晰明確的定義并有章可循。3.0SCOPE范圍ThedefinitionofadruginCanadacoversawidevarietyofproductsrangingfrompharmaceuticalsandbiologicstonaturalhealthproductssuchashomeopathicsandherbalpreparations.ThisguidancedocumentcoversallsuchproductstowhichDivision2ofPartCoftheFoodandDrugRegulationsappliesandisbasedonthecurrenteditionoftheGMPGuidelines.ItisrecognisedthattheevaluationoftheconformitytotheGMPshouldbecommensuratewiththeriskinvolvedtakingintoaccountthenatureandextentofthedeviationinrelationwiththecategoryofproductsevaluated.Nonetheless,mostofthesituationsinvolvingfraud,misrepresentationorfalsificationofproductsordatawillgenerateaNCrating,irrespectiveofthecategoryofproductsinvolved.在加拿大，藥品定義廣泛，從生化藥物到自然的健康產品如順勢療法和草藥都屬于此范疇。本文依照現行GMP制定，適用于所有食品藥品法C部第2章節所規定的產品。GMP合規評估和風險評估是同時進行的，而風險評估需要根據缺陷的性質與程度同時與評估產品的類別聯系起來，這些都已得到業界的認同。但是，大多數導致認證失敗的發現如產品或數據存在虛假，歪曲或蓄意偽造都沒有考慮產品的類別。Theappendicesattachedtothepresentdocumentdescribetheobservationsrelatedtoeachcategoryofrisk.Pleasenotethatthelistofobservationsineachappendixisnotexhaustiveandthatadditionalobservationsmaybeaddedwhereappropriate.本文附錄描述了檢查發現相應的風險級別。請注意附錄中并未完全列舉所有的檢查發現，需要之處可以補充。ThenumberingsystemassignedtoeachsectionintheappendicesisareferencetotheapplicableregulationsinthecurrenteditionoftheGMPguidelines.附件各章節中的數字代表現行GMP法規中相關章節，以備參考。4.0DEFINITIONS定義:ThefollowingdefinitionsareprovidedtocomplementthosealreadyavailableundertheglossaryoftermsinthecurrenteditionoftheGMPGuidelinesorotherrelateddocumentsreferencedintheGMPGuidelines.以下定義是對現行GMP法規或其相關文件釋義部分的補充Observation缺陷:AdeviationordeficiencytoGMPnotedbyaninspectorduringtheinspectionofadrugestablishmentthatisconfirmedinwritingtothecompanyintheexitnotice.Theobservationsareclassifiedas“Critical”,“Major”and“Other”andareassignedariskclassification,rangingfrom1for“critical”to2for“major”to3for“other”.藥品企業檢查過程中，所有被檢查人員寫入報告的偏差或不足。缺陷分為嚴重，主要和一般，分別用1（代表嚴重），2（代表主要），3（代表一般）表示其風險級別。Criticalobservation嚴重缺陷:Observationdescribingasituationthatislikelytoresultinanon-compliantproductorasituationthatmayresultinanimmediateorlatenthealthriskandanyobservationthatinvolvesfraud,misrepresentationorfalsificationofproductsordata.嚴重缺陷包括可能導致產品不合格的缺陷，可能對健康造成立即的或延后的危害的缺陷以及涉及產品或數據存在虛假，歪曲或蓄意偽造的缺陷。AppendixIlistsobservationsthattheInspectorateconsiderscriticalwhichwillbeassignedaRisk1.附錄1列出了檢察員認為屬于1類風險的嚴重缺陷。Majorobservation主要缺陷:Observationthatmayresultintheproductionofadrugnotconsistentlymeetingitsmarketingauthorization.主要缺陷是指導致產品不能持續達到既定標準的缺陷。Appendix2listsobservationsthatareconsideredmajorandwhichwillbeassignedaRisk2CertainRisk2observationsmaybeupgradedtoRisk1.Theyareindicatedwithanarrow(↑).附錄2列出了檢察員認為屬于2類風險的主要缺陷。一部分可以上升為1類風險的2類風險已用箭頭標明。Otherobservation一般缺陷:ObservationthatisneithercriticalnormajorbutisadeparturefromtheGMP.一般缺陷指不屬于嚴重或主要缺陷但偏離GMP要求的缺陷。“Other”observationsarenotlistedassuch(Observationsthatareneithercriticalnormajorareconsideredas“other”andwillbeassignedaRisk3).Appendix3listsRisk3observationsthatmaybeupgradedtoRisk2.一般風險沒有像1，2類風險一樣被全部列舉出來（所有不屬于嚴重或主要的缺陷都歸于一般缺陷，屬3類風險。）附錄3列舉了可以上升為2類風險的3類風險。Criticalproduct最高風險產品:Acriticalproductisoneforwhichanyofthefollowingcriteriamayapply:下列情況有任何一條成立，則該產品屬于最高風險產品。narrowtherapeuticwindow具有窄治療窗的藥物hightoxicity劇毒性藥物sterileproduct無菌產品biologicaldrug生物藥品complexmanufacturingprocess:生產工藝復雜的產品Processforwhichslightdeviationsinthecontrolofparameterscouldresultinanon-uniformproductoraproductnotmeetingitsspecifications.Asexample,powdermixingorgranulationforlowdosagesolidforms,longacting/delayedactionproducts,sterileproducts.工藝參數控制上一點小的偏差便能引發產品不均一或不合格的情況。如小劑量固體制劑中的混合與制粒，長效或緩釋藥品，無菌藥品。Note注意:OTClowdosagevitaminsandmineralspreparationsandCategory4products(aslistedinInterpretation2.3undersectionC.02.028)shouldnotbeconsideredascriticalproductsevenwhenthemanufacturingprocessesinvolvedarecomplex.非處方低劑量藥物如維生素，微量元素類制劑以及4類產品（參見C.02.028章節下2.3的解釋）盡管制造工藝非常復雜但仍不被認作為最高風險產品。Highriskproduct高風險產品:Anyproductthatmaytriggerahealthriskevenatlowlevels,followingcross-contamination.Thoseincludebutarenotlimitedtopenicillins,certaincytotoxicandbiologicalproducts.任何只需小劑量便能危害健康，引起交叉污染的產品，包括但不僅限于：盤尼西林，部分細胞毒素和生物制品。LowRiskproduct低風險產品:ProductssuchasCategory4product(aslistedinInterpretation2.3undersectionC.02.028),naturalhealthproductsincludingvitaminsandmineralspreparationsthatarenotascheduledrugorasteriledrug,andcertaintopicalnonprescriptionveterinaryformulationsregisteredas“olddrugs”.4類產品（參見C.02.028章節下2.3的解釋），自然健康產品包括維生素，微量元素類非周期性，非無菌性制劑，還有部分注冊為“老藥”的非處方類獸藥。Acronyms縮寫:Compliant合規CIP: Clean-In-Place在線清潔COA: CertificateofAnalysis檢驗報告EL: EstablishmentLicence企業許可證GMP: GoodManufacturingPractices藥品生產質量管理規范HVAC: Heat,Ventilation,AirConditioning空調系統IRS: InspectionReportingSystem檢查報告MRA: MutualRecognitionAgreement互認協議NC: Non-compliant不合規OTC: Over-The-Counter非處方藥PM: PackagingMaterial包材PW: PurifiedWater純化水QC: QualityControl質量管理部門(QA+QC)RM: RawMaterial原料WFI: WaterForInjection注射用水GUIDE指南正文Assignmentoftherisktoanobservation針對缺陷界定風險Whereasitisrecognizedthatitisimpossibletoencompasseverysituationthatmaygeneratearisk,thefollowingprinciplesshouldbeconsidered:鑒于我們都認識到不可能將所有可能導致危險的情況都羅列出來，因此在界定風險時請考慮以下準則：Theriskassignedwillbeinrelationtothenatureofthedeviationaswellasthenumberofoccurrences.風險的界定應與缺陷的性質與發生次數關聯起來。Generally,whenonlylowriskproductsareinvolved,arisk1willnotbeassignedtoobservationsdescribedinAppendix1,exceptforextremesituationssuchasfraudorwidespreadcross-contamination,infestationorunsanitaryconditions.一般而言，當涉及的產品為低風險產品時，附錄1中所描述的缺陷不應被界定為1類風險，除非極端情況發生，如：虛假，大范圍交叉污染，感染或不衛生情形。Wherearisk2observationisre-evaluatedasarisk1(risk2observationwithanarrow),thissituationisimmediatelybroughttotheattentionofthecompany’sofficials,properexplanationwillbeprovidedtotheestablishmentandthisexplanationshouldbecapturedinthe“Inspector’sComments”fieldofthe“InspectionSummary”intheIRS.當2類風險被重新評估為一類風險時（2類風險中標有箭頭的缺陷），應立即告知企業的管理層并進行合理的解釋，解釋內容應記錄在檢查報告總結部分的檢察員意見欄中。5.2Assignmentoftheinspectionrating檢查評定Theoverallinspectionratingassignedisbasedontheriskinvolvedtakingintoaccountthenatureandextentofthedeviationswiththecategoryofproductsevaluated.綜合評定基于存在的風險，缺陷的性質與程度以及評估產品的類別。5.2.1Risk1observation:1類風險缺陷Generally,aNCratingisassignedwhenaRisk1observationisnotedduringaninspection.一般而言，出現1類風險缺陷，企業將被評定為不合規。Suchsituationisimmediatelybroughttotheattentionofthecompany’sofficials.TheInspectoratemanagementistobenotifiedinatimelymanner.這類情況應被立即告知企業管理層并及時報告給檢查機構管理層。Whereintheopinionoftheinspectortheresultingproductspresentasignificanthealthhazard,appropriateenforcementactionsmaybeinitiated.如果檢察員認為相關產品存在對健康的嚴重威脅，將會對其啟動適當的強制手段。5.2.2Risk2observation:2類風險缺陷Generally,aCratingisassignedwhenRisk2observationsarenotedduringaninspection.However,aNCratingmaybeassignedinthefollowingsituations:一般而言，出現2類風險缺陷，企業仍將被評定為合規，但在以下情況出現時，企業將被評定為不合規：WhennumerousRisk2observationsarenotedduringaninspectionindicatingthatthecompanydoesnotcontrolitsprocessesandoperationssufficiently.當2類風險缺陷顯示出企業在工藝和運作方面沒能加以足夠的控制時。RepetitionofmanyRisk2observationsnotedduringpreviousinspectionsindicatingthatthecompanydidnot:當許多前次檢查發現的2類風險缺陷重復出現，顯示出企業沒有能夠implementthecorrectiveactionssubmittedfollowingthepreviousinspectionor按照遞交的計劃執行前一次檢查缺陷的糾正工作或didnotputinplaceadequatepreventiveactionsinatimelymannertoavoidrecurrenceofsuchdeviations.沒有及時采取足夠的預防措施來防止偏差的再次發生。5.2.3Risk3observations:3類風險缺陷ACratingwillbeassignedinallsituationswhereonlyRisk3observationsarenoted.如果僅發現3類風險缺陷，企業將被評定為合規的。5.3Additionalguidance補充WhenaNCratingisassigned,theinspectorwillissueadraftInspectionExitNoticeduringtheexitmeeting.Thedraftinspectionexitnoticewillbereviewedforqualityassurancepurposesbeforethefinalreportisissuedtoanestablishment.當企業被評定為不合規時，檢查員將在檢查結束的總結會上遞交檢查通告草稿。在最終報告發至企業之前，草稿可以用于質量保證目的的閱讀。Whenobservation(s)leadingtoaNCratingaremade,theInspectionExitNoticecouldbeissuedwithaCratingif,duringtheinspection:當出現導致企業被評定為不合規的缺陷時，如果企業能夠在檢查其間完成下列工作，檢查通告仍會給出企業合規的結論：theestablishmentimmediatelyimplementsallnecessaryactionstoresolvethecause(s)oftheobservation(s)leadingtotheNCratingand,企業立即采取必要措施根除導致缺陷發生的原因并且sufficientassurancecanbeprovidedtopreventarecurrence.采取足夠的預防措施防止缺陷再度發生。Insuchinstances,theriskassignedtotheobservationwillremainthesame.這種情況下，原來對缺陷所作的風險評估等級仍保持不變。Ifthemanagementofthecompanywishestodisputetheresultsoftheinspectionreport,the“Disputeresolutionandappeals”mechanismdescribedintheGMPandELEnforcementPolicyPOL-0004shouldbefollowed.如果企業希望對檢查結果進行申辯，GMP與企業強制認證政策POL-0004中的“爭議解決與上訴”機制將被啟動。Appendix1附錄1Risk1(Critical)Observations1類風險（嚴重）缺陷PremisesC.02.004廠房Noairfiltrationsystemtoeliminateairbornecontaminantsthatarelikelytobegeneratedduringfabricationorpackaging.沒有空氣過濾系統以消除生產和包裝時可能產生的沉降污染。Generalizedmalfunctioningoftheventilationsystem(s)withevidenceofwidespreadcross-contamination.大范圍交叉污染的事實表明通風系統存在故障。Inadequatesegregationofmanufacturingortestingareasfromothermanufacturingareasforhighriskproducts.高風險產品之間的生產區域或測試區域沒能有效地隔開。EquipmentC.02.005設備Equipmentusedforcomplexmanufacturingoperationsofcriticalproductsnotqualifiedandwithevidenceofmalfunctioning.用于最高風險產品復雜生產過程的設備不合規定同時也存在故障。PersonnelC.02.006人員IndividualinchargeofQualityControl(QC)orproductionforafabricatorofcritical/highriskproductsdoesnotholdauniversitydegreeinasciencerelatedtotheworkbeingconductedanddoesnothavesufficientpracticalexperienceintheirresponsibilityarea.管理最高風險，高風險產品質量管理或生產的人員沒有相關領域的大學文憑同時缺乏足夠的實踐經驗。SanitationC.02.007C.02.008衛生- Evidenceofwidespreadaccumulationofresidues/extraneousmatterindicativeofinadequatecleaning.清潔的不夠充分，存在大范圍殘留/異物積聚。Evidenceofgrossinfestation.明顯的蟲害或污染RawMaterialTesting C.02.009 C.02.010原料檢驗Evidenceoffalsificationormisrepresentationofanalyticalresults.分析結果造假或歪曲Noevidenceoftesting(COA)availablefromthesupplier/synthetizerandnotestingdonebytheCanadianfabricator.缺少供應商的檢驗報告同時企業也沒做相關的測試。ManufacturingControl C.02.011 C.02.012生產控制NowrittenMasterFormula.沒有書面的主處方MasterFormulaormanufacturingbatchdocumentshowinggrossdeviationsorsignificantcalculationerrors.主處方或生產批記錄存在明顯的偏差或嚴重的計算錯誤。Evidenceoffalsificationormisrepresentationofmanufacturingandpackagingorders.生產和包裝訂單的造假或錯誤QualityControlDepartment C.02.013 C.02.014 C.02.015質控部門NopersoninchargeofQCavailableonpremisesinCanada.加拿大工廠內沒有質量管理負責人QCdepartmentnotadistinctandindependentunit,lackingrealdecisionalpower,withevidencethatQCdecisionsareoftenoverruledbyproductiondepartmentormanagement.質量管理部門不是獨立的機構，缺乏真正的決定權，有證據表明質量管理部門的決定常被生產或管理層否定。FinishedProductsTesting C.02.018 C.02.019成品檢驗-Finishedproductnottestedforcompliancewithapplicablespecificationsbytheimporter/distributorbeforereleaseforsaleandnoevidenceisavailablethattheproductshavebeentestedbythefabricator.銷售前，進口商/分銷商沒有按照合適的標準對成品進行檢驗同時沒有證據顯示生產商做過相關測試。Evidenceoffalsificationormisrepresentationoftestingresults/forgeryofCOA.檢驗結果造假或歪曲/偽造檢驗報告Records C.02.020toC.02.024記錄Evidenceoffalsificationormisrepresentationofrecords.記錄造假或歪曲事實Stability C.02.027 C.02.028穩定性Nodataavailabletoestablishtheshelf-lifeofproducts.缺少建立產品效期的數據Evidenceoffalsificationormisrepresentationofstabilitydata/forgeryofCOA.穩定性數據的造假或歪曲/偽造檢驗報告SterileProducts C.02.029無菌產品CriticalsterilizationcyclesbasedonProbabilityofSurvivalnotvalidated.關鍵滅菌過程沒有基于細菌存活率的進行驗證。WaterforInjection(WFI)systemsnotvalidatedwithevidenceofproblemssuchasmicrobial/endotoxincountsnotwithinspecifications.注射用水系統未作驗證，存在微生物/內毒素超標的情況。Nomediafillsperformedtodemonstratethevalidityofasepticfillingoperations.無菌灌裝工藝未做培養基灌裝驗證。Noenvironmentalcontrols/Nomonitoringforviablemicroorganismsduringfillingforasepticallyfilledproducts.無菌灌裝產品在灌裝期間缺少環境監控/微生物監控。Asepticfillingoperationsmaintainedfollowingunsatisfactoryresultsobtainedformediafills.培養基灌裝驗證失敗后仍繼續進行無菌灌裝生產。Batchesfailinginitialsterilitytestreleasedforsaleonthebasisofasecondtestwithoutproperinvestigation.產品基于第二次無菌檢測結果放行，而對首次的菌檢失敗未作調查。Appendix2附錄2Risk2(Major)Observations2類風險（主要）缺陷PremisesC.02.004廠房Malfunctioningoftheventilationsystemthatcouldresultinpossiblelocalizedoroccasionalcross-contamination.通風系統的故障導致固定的或間歇性的交叉污染。Maintenance/periodicverificationsuchasairfilterreplacement,monitoringofpressuredifferentialsnotperformed.(↑)沒有做維護/周期性的性能確認如：空氣過濾器的更換，檢測壓差。Accessorysupplies(steam,air,nitrogen,dustcollection,etc...)notqualified.輔助系統（蒸氣，空氣，氮氣，灰塵收集）不符合要求HeatVentilationAirConditioning(HVAC)andpurifiedwater(PW)systemnotqualified.空調系統和純化水系統不符合要求Temperatureandhumiditynotcontrolledormonitoredwhennecessary(e.g.storagenotinaccordancewithlabellingrequirements).在需要監控溫濕度的環節沒能監控溫濕度（如未按溫濕度要求存放標簽）Damages(holes,cracksorpeelingpaint)towalls/ceilingsimmediatelyadjacentorabovemanufacturingareasorequipmentwheretheproductisexposed.與產品暴露區域直接相鄰或在其上方的墻面，天花板損壞（破洞，裂縫或油漆剝落）Un-cleanablesurfacescreatedbypipes,fixturesorductsdirectlyaboveproductsormanufacturingequipment.無法進行表面清潔的管道經過產品或生產設備的上方。Surfacesfinish(floors,wallsandceilings)thatdonotpermiteffectivecleaning.地板，墻體和天花板表面的外層涂料或覆蓋無法有效清潔。Unsealedporousfinishinmanufacturingareaswithevidenceofcontamination(mildew,mould,powderfrompreviousproductions,etc..)(↑)生產區域未封閉的孔狀表面內在污染（霉菌，前批生產的藥粉等等）Insufficientmanufacturingspacethatcouldleadtomix-ups.(↑)生產區域空間太小易造成差錯Physicalandelectronicquarantineaccessibletounauthorizedpersonnel/Physicalquarantineareanotwellmarkedand/ornotrespectedwhenused.(↑)未經授權的人員可以通過機械和電子門禁/機械隔離的區域缺少標示而且/或沒有按規程使用。- Noseparatearea/Insufficientprecautionstopreventcontaminationorcross-contaminationduringRMsampling.原料抽樣缺少獨立區域/沒有足夠的預防措施來防止污染或交叉污染。EquipmentC.02.005設備Equipmentdoesnotoperatewithinitsspecifications.(↑)不在其額定范圍內操作設備。Equipmentusedforcomplexmanufacturingoperationsnotqualified.(↑)用于復雜生產的設備不合要求。CleaninPlace(CIP)equipmentnotvalidated.在線清潔設備沒有驗證。Tanksformanufacturingofliquidsandointmentsnotequippedwithsanitaryclamps.液體制劑或油膏劑的生產罐沒有采用清潔卡箍。Storedequipmentnotprotectedfromcontamination.(↑)設備存放時未作保護以防止污染。Inappropriateequipmentforproduction:surfacesporousandnon-cleanable/materialtoshedparticles.(↑)設備不適于生產：表面多孔無法清潔/材料自身易產生顆粒。Evidenceofcontaminationofproductsbyforeignmaterialssuchasgrease,oil,rustandparticlesfromtheequipment.(↑)產品被設備上的物質污染如油脂，銹跡和顆粒。Nocoversfortanks,hoppersorsimilarmanufacturingequipment.罐體，料斗或類似的生產設備沒有蓋子。No/inadequateprecautionstakenwhenequipmentsuchasovenorautoclavecontainsmorethanoneproduct(possibilityofcross-contaminationormix-ups).(↑)同時存放有多個產品的生產設備如烘箱或滅菌柜沒有預防交叉污染或混淆的措施或措施不充分。Equipmentlocationdoesnotpreventcross-contaminationorpossiblemix-upsforoperationsperformedincommonarea.(↑)共用區域內設備的擺放位置不能防止交叉污染或混淆。PWsystemnotmaintainedoroperatedtoprovidewaterofadequatequality.(↑)純化水系統未很好地維護與操作，導致不能提供合格的水。Leakinggaskets.墊圈破漏Nocalibrationprogramforautomatic,mechanical,electronicormeasuringequipment/norecordsmaintained.自動化設備，機械設備，電子設備或測量設備沒有校驗計劃/沒有校驗記錄。Noequipmentusagelogs.沒有設備使用記錄。PersonnelC.02.006人員IndividualinchargeofQCorProductionforafabricator,packager/labellerortesterdoesnotholdauniversitydegreeinasciencerelatedtotheworkbeingconductedordoesnothavesufficientpracticalexperienceintheirresponsibilityarea.負責生產，包裝/貼簽或測試的質量管理或生產人員沒有相關領域的大學文憑同時缺少足夠的實踐經驗。IndividualinchargeofQCforadistributor,importerorwholesalerisnotqualifiedbyacademictrainingandexperience.負責分銷商，進口商或批發商的質量管理人員沒有達到應有的教育與工作經驗要求。DelegationofresponsibilitiesforQCorProductiontoinsufficientlyqualifiedpersons.質量管理與生產沒有足夠的合格人員以履行其職責。InsufficientpersonnelforQCorProductionoperationsresultinginahighprobabilityoferror.質量管理與生產人手不足導致錯誤率很高。InsufficienttrainingforpersonnelinvolvedinproductionandQCresultinginrelatedGMPdeviations.生產與質量管理人員培訓不足導致了相應的GMP偏差發生。SanitationC.02.007 C.02.00↑清潔Sanitationprogramnotinwritingbutpremisesinacceptablestateofcleanliness.廠房雖然潔凈但缺少書面的清潔計劃。NoStandardOperatingProcedure(SOP)formicrobial/environmentalmonitoring,noactionlimitsforareaswheresusceptiblenon-sterileproductsaremanufactured.沒有微生物/環境監控的標準操作流程，在易受污染的非無菌產品生產區域沒有設立監控措施限。Cleaningprocedureforproductionequipmentnotvalidated(includinganalyticalmethods).生產設備清潔方法沒做驗證（包括分析方法）Cleaningprocedureforproductionequipmentnotvalidatedwhennon-dedicatedequipmentisusedforhighriskproducts(↑).在非專用設備用于高風險類產品生產的情況下，設備清潔方法沒做驗證。Incompletehealthrequirements.不完整的健康要求。RawMaterialTesting C.02.009 C.02.010原料檢驗Reducetestingprograminplacewithoutadequatecertificationofthevendors/suppliers.在未對銷售商/供應商進行足夠資質認證的情況下減少測試項目。Waterusedintheformulationisnotofacceptablequality.配方用水質量達不到要求。Noidentitytestperformedbythemanufacturerafterreceiptonit’spremises/TestingforidentitynotdoneoneachcontainerforAPIsoraftermanipulationorrepackagingbythirdparty.收料后沒做鑒別/未對每桶原料做鑒別/經第三方處理或重包裝后未做鑒別。COAshowingincompletetesting.檢驗報告上的測試不完全。Incompletespecifications.標準不全。SpecificationsnotapprovedbyQC.標準未被質量管理部門批準。Testmethodsnotvalidated.檢驗方法沒有驗證。UseofAPIaftertheretestdatewithoutproperretesting.過再驗期的活性成分原料沒做再檢驗而直接使用。UseofinactiveRMaftertheexpirationdatewithoutproperretesting.未做檢驗而使用過期的非主成分原料。Multiplelotscomprisingonereceptionnotconsideredasseparateforsampling,testingandrelease.將多批物料做為一次收料而未分開采樣，測試與放行。NoSOPforconditionsoftransportationandstorage.沒有規定運輸儲藏條件的SOP。Certificationofbrokersorwholesalersallowedwithoutproperdocumentation.對所許可的中間商或批發商缺少書面的的授權。ManufacturingControls C.02.011 C.02.012生產控制MasterFormulaeprepared/verifiedbyunqualifiedpersonnel.主處方由無資質人員編寫/核對。Complexproductionprocessesnotvalidated.(↑)復雜生產工藝沒有驗證。Incompletevalidationstudies/reportsforcomplexmanufacturingprocess(lackofevaluation/approval).復雜生產工藝的驗證研究/報告不完整（缺少評估/批準）Changeoverproceduresformanufacturingofmedicinal/non-medicinalproductsarenotvalidatedornotavailable.藥品/非藥品生產的改換規程沒有驗證/缺失。Unapproved/undocumentedmajorchangescomparedtoMasterProductionDocuments.(↑)生產工藝上的重大改變沒有經過批準/沒有書面記錄。DeviationsfrominstructionsduringproductionnotdocumentedandnotapprovedbyQC.對生產指令的偏差未做書面記錄同時未經質量管理部門認可。Discrepanciesinyieldorreconciliationfollowingproductionnotinvestigated.對生產收率或物料平衡的差異未作調查。LineclearancebetweenproductionofdifferentproductsnotcoveredbySOPandnotdocumented.沒有不同產品之間清場的SOP同時沒有書面記錄。Noregularchecksformeasuringdevices/norecords.測量儀器沒有定期檢查/沒有記錄。Lackofproperidentificationofin-processmaterialsandproductionroomsresultinginahighprobabilityofmix-ups.生產區域和中間物料沒有適當的標識非常容易造成混淆。Inadequatelabelling/storageofrejectedmaterialsandproductsthatcouldgeneratemix-ups.報廢物料沒有標識不清，儲藏空間不夠，易引起混淆。Uponreceipt,bulkandin-processdrugs,RMandPMnotheldinquarantineuntilreleasedbyQC.收料后，在由質量管理部門放行之前，粗制品，中間體，原料和包材沒有放置到待檢區域。Productionpersonnelusingbulkandin-processdrugs,RMandPMwithoutpriorauthorizationbyQC.(↑)未經質量管理部門的授權，生產人員使用粗制品，中間體，原料和包材。Inadequate/inaccuratelabellingofbulk/in-processdrugs,RMandPM.粗制品，中間體，原料和包材標識不清/不正確RMdispensingnotdonebyqualifiedpersons,accordingtoanSOP.沒有按照SOP，由有資質的人員完成配料。MasterFormulaeincompleteorshowinginaccuraciesintheprocessingoperations.主處方不完整或在生產過程中顯示出不夠準確。Changesinbatchsizenotprepared/verifiedbyqualifiedpersonnel.產品規格更換沒有由有資質的人員完成/審核。Inaccurate/incompleteinformationinmanufacturing/packagingbatchdocuments.生產包裝批文件信息不準確/不完整。Althoughdocumented,combinationofbatchesdonewithoutQCapproval/notcoveredbySOP.盡管有文件記錄，但未經質量管理部門批準合并批號/沒有SOP涵蓋此內容。Nowrittenproceduresforpackagingoperations.包裝操作沒有書面規程規定。Non-standardoccurrencesduringpackagingnotinvestigatedbyqualifiedpersonnel.有資質的人員未對包裝過程中出現的非正常情況進行調查。Inadequatecontrolofcodedandnon-codedprintedPM(includingstorage,dispensing,printing,disposal).編碼，未編碼打印的包裝材料（儲藏，發放，打印和銷毀）控制不嚴。Noorinadequateself-inspectionprogram/ProgramdoesnotaddressallapplicablesectionsofGMPs/Recordsincompleteornotmaintained.自檢計劃缺少或不完全/自檢計劃沒能涵蓋所應涉及的GMP領域/自檢記錄不完整或沒有保存。ProductsimportedfromforeignsitesthatarenotlistedontheForeignSiteAnnexoftheEstablishmentLicence(↑)產品由海外工廠進口，但海外工廠沒有在企業許可證附件-海外工廠中列出。Recall:召回：Absenceofrecallprocedurecombinedwithdistributionpracticesthatwouldnotpermitanadequaterecall(distributionrecordsunavailableornotkept).缺少召回程序同時發貨操作的方式導致不可能完全召回（發貨記錄缺失或未留記錄）Improperquarantineanddisposalpracticesthatwouldallowrecalled/rejectedunitstobereturnedforsale.隔離和銷毀操作不當，可能導致召回產品，退貨重新被銷售。QualityControlDepartmentC.02.013 C.02.014 C.02.015質量管理部門Inadequatefacilities,personnelandtestingequipment.設施，人員和測試儀器不足Noauthoritytoenterproductionareas.(↑)無權進入生產區域NoSOPsapprovedandavailableforsampling,inspectionandtestingofmaterials.物料抽樣，檢查和測試的SOP未被批準或無法獲得。ProductsmadeavailableforsalewithoutapprovalofQCdepartment.(↑)產品未經質量管理部門批準便可以銷售。ProductsreleasedforsalebyQCwithoutproperverificationofmanufacturingandpackagingdocumentation.質量管理部門未核對生產與包裝的文件，便批準銷售產品。Deviationsandborderlineconformancesnotproperlyinvestigatedanddocumented,accordingtoaSOP.偏差和緊扣質量底線的合格情況沒能按照SOP進行完全的調查并做書面記錄。RM/PMusedinproductionwithoutpriorapprovalofQC.原料與包材未經質量管理部門批準便已用于生產。Reprocessing/ReworkingdonewithoutpriorapprovalofQCdepartment.(↑)未經質量管理部門批準而進行再制/返工操作。Nosystemforcomplainthandlingandreturnedgoods.沒有投訴與退處理貨的系統。SOPscoveringoperationsthatcanaffectthequalityofaproductsuchastransportation,storage,etc.notapprovedbyQCdepartment/notimplemented.可能影響產品品質的操作如運輸，存儲等等的SOP沒有經質量管理部門批準/沒有被執行。Absenceofchangecontrolsystem.缺少更改控制Fortestinglaboratories,(inhouseorcontract)thesystemsandcontrolsinplacefortheproperqualification,operation,calibrationandmaintenanceofequipment,standards,solutions,andrecordskeepingdonotassurethattheresultsandconclusionsgeneratedareaccurate,preciseandreliable.(↑)測試實驗室（內部或外部）的現場管理與監控體系（包括驗證，操作，校驗，設備維護，標準品，各種溶液，記錄保存）無法保障其出具數據的準確，精密和可靠。PackagingMaterialTestingC.02.016C.02.017包材檢驗Reducetestingprograminplacewithoutadequatecertificationofvendors/suppliers.在未對銷售商/供應商進行足夠資質認證的情況下減少測試項目。AbsenceoftestingofPM.缺少包材檢驗SpecificationsnotapprovedbyQC.質量標準沒有被質量管理部門批準。Noidentitytestdonebythepackager/labellerafterreceiptonitspremises.包裝/貼簽人員領料后未做鑒別測試。Certificationofbrokersorwholesalersdonewithoutproperdocumentation.對中間商或批發商所做認證沒有正確地書面歸檔。FinishedProductTestingC.02.01↑C.02.019成品檢驗Noncompliantproductsmadeavailableforsalewithoutproperjustification.(↑)沒有充分的解釋而銷售不合格品。Incomplete/inadequatespecifications.不完整/不正確的質量標準FinishedproductspecificationsnotapprovedbyQC.成品標準未經質量管理部門批準。Incompletetesting.測試不完全。NoidentitytestinguponreceiptinCanadafromnon-MRAcountryandnoperiodiccompleteconfirmatorytesting.從非互認國家進口到加拿大的產品未做鑒別試驗同時沒有周期性的全項檢驗。Testmethodsnotvalidated.分析方法沒有驗證。NoSOPforconditionsoftransportationandstorage.沒有SOP規定儲藏運輸的條件。Useofuniqueidentifierprinciplesnotmeetingtheacceptableoptions.使用不被接受的特殊鑒別方法RecordsC.02.020toC.02.024記錄AbsenceofMasterProductionDocuments.缺少生產主記錄Unavailabilityofdocumentationfromsuppliersinatimelymanner.供應商提供文件不及時。SamplesC.02.025C.02.026樣品Retainedsamplesnotkeptforfinishedproducts.成品未做留樣。Failuretosubmitretainedsampleswhenalternativesampleretentiongranted.沒有遞交留樣而擅自改變留樣計劃。StabilityC.02.027C.02.02↑穩定性Insufficientnumberoflots/insufficientdatatoestablishshelf-life.用于建立效期的數據和樣品數量不夠。Noactiontakenwhendatashowsth