123456789Q7條款12uctionCanarationalebeprovidedforthisdecision?Hasthedecisionbeendiscussedwiththerespectiveauthority?Arethequalitycriticalstepsidentified?QualityManagementrinciplessimplementedifyeslitypolicyHowisitbroughttotheattentionoftheemployees?ntedHowdoesManagementrevieweffectivenessofqualitysystemIstheQualityUnitQAQC)independentofproduction?Isthereanauthorizedperson(s)forthereleaseofIMandAPIs?Whoistheperson(s)?Arealldeviationsdocumentedandexplained?Arecriticaldeviationsinvestigatedinatimelymanner?Isthereawrittenprocedureforhandlinginvestigations(6.53)?Averagedaysforcompletion?beforecompletionofIfnotdonebyQUIsanappropriatesysteminplace?是否與有關藥政部門討論過該決定是否確認了關鍵質量步驟統是否通過認證(例如ISO9001)?(已通過者參見第20的效果解釋?如何保障未經質量部門(QU)完成評估的物料不會放行或使用?QU事。有否其它相應機構？2-35Averagetimeneededforinformation?ResponsibilitiesoftheQUU2.22Non-transferableresponsibilitiesofQU:IMAPI29establishsystemtorelease/rejectmaterialsandlabels建立物料和標簽放行/拒絕的體系30reviewofcriticalprocessstepsbatchrecords審核批記錄的關鍵工藝步驟31ensurecriticaldeviationsareinvestigated確保嚴重的偏離得到調查32approvingspecificationsandmasterinstructions批準質量標準和工藝規程33approvingallqualityrelateddocuments批準所有的有關質量的文件34ensuringconductionofinternalaudits確保進行自檢35approvingcontractmanufacturers批準合同制造商36approvingchangeswithqualityimpact批準涉及質量的變更37approvingvalidationdocuments批注驗證文件38ensurecomplaintsareresolved確保投訴得到處理39ensuringcalibrationsystemisfunctioningaccordingtoprocedureexecuted確保校驗工作按照既定程序進行40ensuringthatstabilitydataisgeneratedandreviewed確保穩定性數據得以記錄和審核41performingproductqualityreviews進行產品質量核查422.3ResponsibilitiesforProductionActivities生產活動職責43procedureforpreparing,reviewingandapprovinginstructions起草，審核批準指令的程序44reviewingbatchproductionrecords審核批生產記錄45ensurealldeviationsandinvestigationsarehandled確保對所有偏差進行調查處理46cleaningoffacilities設施得以清洗47calibrationsperformed校驗得以進行48validationdocumentsgenerated建立驗證文件49evaluationofproposedchanges評估變更申請50ensurethatfacilitiesandequipmentarequalified確保設施儀器得以確認512.4InternalAudits自檢35Areregularauditsperformed是否定期自檢？Isthereanauditschedule有無自檢計劃？Istheschedulefollowed自檢是否按計劃進行？Areauditfindingsandcorrectiveactionsdocumented?Proceduretonotifymanagementofauditfindings?Arecorrectiveactionscompletedwithinagreedtime(aretheresignificant是否按期改正(有無明顯拖延？)ProductQualityReview2.50AreregularProductQualityReviewsconductedforallproducts?是否對所有產品進行了定期質量審查？60Frequency(dedicated,campaign)?審查頻率(常規進行，偶爾?)61Content(atleast):審查至少包括下列內容：reviewofcriticalIPCandAPItestresults審查關鍵中間體和API化驗結果63reviewofallbatchesfailed審查所有的不合格批次64reviewofallcriticaldeviations審查所有的嚴重偏差65reviewofprocesschangesandimpactonquality審查工藝變更及其對質量的影響66reviewofchangestoanalyticalmethods審查分析方法的變更67reviewofresultsofongoingstabilityprogrammes審查正在進行的穩定性試驗結果reviewofreturns,complaints,recallsreviewofadequacyofcorrectiveactionsdefinedinpreviousreviewectiveactionstoaddressingrevalidation3nnelPersonnelQualificationsAdequatenumberofpersonnel?Qualificationofpersonnelsufficientatdifferentlevels?Areresponsibilitiesperiodicallyreviewedtoensuretheyarecurrent?3.12Isregulartrainingconducted?是否進行定期培訓？4-35Arerecordsoftrainingmaintained?ctivenessoftrainingevaluatedw3.2PersonnelHygiene3.21Dopersonnelwearcleanclothingsuitableforactivity?3.22HowisitensuredthatpersonnelhavenodirectcontactwithIMandAPIs?torageoffoodtakes3.23place?3.24Howarepersonnelwithinfectiousdiseasesoropenlesionsidentified?Isthereaprocedureinplacethatthesepersonshavenoproductcontact?3.3ConsultantsAreconsultantsusedtoadviseonanyGMPrelatedactivities?Isthereanassessmentofconsultantseducation,trainingandexperience?4BuildingsandFacilities4.1DesignandConstructionndedtoinationhowiscontaminationpreventedIsthereadequatespaceforplacementofequipmenttopreventmix-upor4.11contamination?4.12Outdoorequipmentraisesconcernsforcontamination?4.13Doesflowofmaterialsandpersonnelraiseconcernsforcontamination?4.14Definedareasorcontrolsystemsinplaceforthefollowingactivities:receipt,identification,samplingofincomingmaterialsquarantinebeforerelease/rejectSamplingofintermediatesorAPI’s在需要的崗位是否外加保護服？(例如，最終產品包裝室)抽煙，吃喝，保存食物?確定這些員工不得接觸產品?污染?絕之前的待驗35holdingofrejectedmaterialsbeforefurtherdisposition?Packagingandlabelingoperations?4.15Washingfacilitiesandtoiletsavailableforpersonnel?4.16Laboratoryareasseparatedfromproduction?4.2UtilitiesAretheutilitiesmonitoredandactionstakenwhenalertlimitsareexceeded?4.21Adequateventilation,airfiltrationandexhaustsystemsinplace?Arethesesystemsdesignedandoperatedtopreventcontamination?4.22Controlofre-circulatedairsufficienttoavoidcontamination?4.23Permanentlyinstalledpipeworkappropriatelyidentified?Ispipeworkmaintainedandlocatedinsuchawayastopreventcontamination?logicalcontamination4.24inareaswhereproductisexposed?4.3Water4.30Waterdemonstratedtobesuitableforintendeduse?4.31IsProcesswatermeetingdrinkingwaterqualityasaminimumstandard?Isadditionalwatertreatmentsysteminplace?IsqualityofallgradesofprocesswatermonitoredatpointsofuseforbjectionableorganismsAreactionstakenwhenlimitsareexceeded?4.32Tighterspecificationsneededtoensurequality?Whatarethespecifications?4.33Validationoftreatmentof(higher)watertreatment?4.34Ifclaimsaremadeforsterileorparenteraluse:Monitormicrobialcounts,objectionablemicroorganismsandendotoxins4.4Containment一步處理前的存放操作現場是否有足夠的通風，過濾和排風系統?水理/化學指標監測？取行動嗎？標是什么?的處理料：監測微生物計數，不良微生物和內毒素6-354.41Dedicatedproductionareaforhighpharmacologicalactivitytcforexamplemovingfromoneproductionareatoanother?4.5LightingAdequatelightingfore.g.cleaningandmaintenance4.6SewageandRefuse4.60Sewagetoberemovedtimely4.7SanitationandMaintenance4.70Buildingstobekeptproperlymaintained,repairedandcleaned4.71Writtenproceduresforcleaningforequipmentandfacilitiesinplace4.72Proceduresforpestcontrolinplace?5ProcessEquipment5.1DesignandConstruction5.10Equipmentsuitablylocated,easytocleanandmaintain?5.11Equipmentsurfacesdonotalterproductquality5.12Equipmentonlyusedwithinthequalifiedoperationrange?5.13Majorequipmentandpermanentlyinstalledpipeworkidentified5.15ForexampleadditionofseedsorsamplingArecurrentengineeringdrawingsavailableforequipment,installationsand5.16utilitysystems?5.2EquipmentMaintenanceandCleaning5.20Preventivemaintenanceprogrammeinplace?Schedulefollowed?是否建立防止人員物料交叉污染的措施？(例如，從一個生產區轉制藥車間是否從事高毒非藥物制品的生產(例如，殺蟲劑)？充足的照明(例如，清洗和維護)到適當的維修和清潔場有書面的設備和設施清潔程序影響產品質量認的運行范圍使用備和固定管線易于識別取樣)防性維修計劃？55.21Writtenproceduresforthecleaningofequipmentinplace?dstoredandwhere5.23forexampledegradantsorobjectionablelevelsofmicro-organisms?Isthecleaningfrequencyjustifiedanddocumented?5.24Isequipmentcleanedbetweenproductionofdifferentproducts?Formulti-purposeequipmentistheMaximumAcceptableCarryOverandother5.25Acceptancecriteriaforresiduesjustifiedanddetermined?Arethecleaningproceduresvalidated?5.26Equipmentidentifiedastoitscontentandcleanlinessstatus?5.3Calibration5.30InstrumentscriticalforIMand/orAPIqualityarecalibrated?Howiscriticaldefined?Writtenprocedureinplace?Schedulefollowed?5.31Calibrationdonewithstandardsthataretraceabletocertifiedstandards?5.32Recordsofcalibrationmaintained?5.33Calibrationstatusofinstrumentsknown?How(label,electronic)?5.34Howisitensuredthatinstrumentsoutofcalibrationarenotused?5.4ComputerisedSystems5.40AreGMPrelatedcomputersystemsvalidated?是否定期清洗防止積料或傳播洗狀態和內容物是否有標識牌？校驗使用的衡器是否可追朔到法定標準？？如發現儀表已過校驗有效期，是否進行偏差調查來決定是否放行有8-355.41hardware/softwaretoperformtask?Retrospectivevalidationforexistingsystemsifnotvalidatedattimeof5.42installation?5.43Whatcontrolsareinplacetopreventunauthorizedaccess?Whatcontrolsareinplacetopreventchangestodata?Whatcontrolsareinplacetopreventomissionsindata?ethechangewhenthechangewasmadeandofthepreviousentryWrittenproceduresfortheoperationandmaintenanceofcomputerizedsystems5.44available?5.45orsystemitself)?5.46investigatedaccordingtodefinedproceduresinvestigated?5.47Changestothecomputerizedsystemaremadeaccordingtoadefinedprocedure?5.48Howisdataprotectedincasesofsystembreakdowns?Back-upsystemprovided?IsRecoveryfromback-upstestedperiodically?6DocumentationandRecords6.1DocumentationSystemandSpecifications6.10anddistributionofallqualityrelateddocuments?6.11Howisrevision,supersedingandwithdrawalofdocumentscontrolled?Isarevisionhistorymaintained?6.12Procedureinplaceforretainingallappropriatedocuments?Retentionperiodspecified?6.13RetentionperiodforAPIswithexpirydate:1yearafterexpiry(min.)，何時進行的，原來輸入既定步驟進行調期進行從備份恢復系統的演練？文件的修訂，替代和撤銷？修訂歷史？9-356.14Arecorrectedentriesindocumentsdatedandsigned?Originalentrystillreadable?6.15Aredocumentspromptlyretrievable(copiesorelectronicmeansacceptable)?6.17Arespecificationsforallmaterials,IMandAPIsestablished?6.18Areelectronicsignaturesauthenticatedandsecure?6.2EquipmentCleaningandUseRecords6.20thefollowingproductandbatchnumberofeachbatchpersonwhoperformedcleaningpersonwhoperformedmaintenance6.3RecordsofRawMaterials,IM,APILabelingandPackagingMaterials6.30Recordsofeachdeliveryshouldcontain:nameofmanufacturer/supplierndquantitysuppliercontroloridentificationnumbernumberallocatedonreceiptteofreceiptacceptableconditionofreceivedgoodsassessedresultoftestsandconclusionderivedfromthisofusefinaldecisionreleaseorreject6.31Aremasterlabelsmaintained?6.4MasterProductionInstructions6.40AreMasterProductionInstructionsforeachIM/API文件是否可以迅速查找(印刷版或電子版都可以)？記錄稱制或標識碼和檢驗結論拒絕的最后決定權eparedindependentlycheckedbyQU6.41DoMasterProductionInstructionscontainthefollowing:nameofproductincludingdocumentreferencecodecompletelistofrawmaterialsaccuratestatementofquantitiesneededorcalculationofquantityproductionlocationandmajorequipmenttobeuseddetailedproductioninstructionsincludingsequences,rangesofparameters,samplinginstructions,IPC,timelimits,expectedyielductionsforstorage6.5BatchProductionRecords6.50AreBatchProductionRecordscheckedbeforeissuanceforcorrectversion?6.52Thebatchrecordshouldcontainthefollowing:date(s)andtimes(ifappropriate)ntityofmajorequipmentidentificationofmaterialsusedactualresultsgperformedsignaturesoftheperson(s)performingtheoperationIPClaboratorytestresultsactualyield,ifappropriatedescriptionofpackagingandlabelsuseddeviation/investigationresultsofreleasetesting6.6LaboratoryControlRecords6.60Laboratoryrecordsshouldcontainthefollowing:名稱包括其文獻編碼表達所需的數量或計算方法和使用的主要設備批記錄是否有唯一的批號(非連續性生產)？日期和時間(如適用)備的物料referencetotestmethodcompleterecordofallrawdatarecordofallcalculationsstatementoftestresultiftheycomplywithspecificationssignatureanddateofperson(s)performingthetestingsignatureofsecondpersondemonstratingreviewforaccuracy,completeness6.61Otherrecordstobemaintained:modificationtotestmethodcalibrationoflaboratoryinstrumentsstabilitytestingperformedOOSinvestigations6.7BatchProductionRecordReviewIsawrittenprocedureforthehandlingofbatch(laboratory)recordreview6.70available?6.71Arebatch(laboratory)recordsofcriticalstepsreviewedbytheQU?AretheyreviewedbeforethereleaseoftheAPI?6.72review?7MaterialsManagement7.1GeneralControlsArewrittenproceduresavailableforhandlingofreceipt,identification,7.10quarantine,storage,sampling,testing,approvalorrejectionofmaterials?7.11Systemtoevaluatesuppliersofcriticalmaterialsinplace?品數據的記錄果是否達標的結論名和日期確認準確性和完整性的復核人簽名更是否建立了審閱批(化驗室)記錄的書面程序？質量部門是否審閱批(化驗室)記錄的關鍵步驟？物料的接收，識別，待驗，存放，取樣，化驗，批注或拒絕是否有立關鍵物料供應商的評估系統？Evaluationmustshowthatsuppliercanconsistentlyprovidematerialmeetingspecifications(7.31)7.12Materialspurchasedagainstagreedspecifications?Purchasedfromanapproved(byQU)supplier?7.13Ifsupplierisnotthemanufacturer,istheoriginalmanufacturerknown?7.1413)?7.2ReceiptandQuarantine7.20UponreceiptmaterialsvisuallyexaminedforcorrectlabelingontainerdamagebrokensealstamperingorcontaminationArematerialsheldunderquarantineuntilreleasedforuse?Howisthisdone?7.21Incomingmaterialsarereleasedbeforemixedwithexistingstocks?Areproceduresinplacetopreventdischargingmaterialswrongly?edtodemonstratenocontamination(oneormoreofthefollowing):certificateofcleaningtestingfortraceimpuritiesauditofthesupplier7.24Iseachdeliveryofmaterialsidentified(codeorbatchnumber)?Isthereasysteminplacetoidentifythestatusofeachbatch?7.3SamplingandTestingofIncomingProductionMaterials7.30Isatleastonetestconductedtoverifytheidentityofincomingmaterials?IfsuppliersCertificateofAnalysisisusedinsteadoftestingasystemforevaluationmustbeinplace.7.31(seealso7.11)平谷必須表明供應商能夠持續提供符合質量標準的物料(7.31)對發放的物料如何識別(編碼或批號)？樣和化驗對于收到的物料是否最少進行一種鑒別測試？Are3fullanalysesconductedbeforereducingtesting?Isafullanalysisperformedatappropriateintervalsandcomparedwiththesupplierscertificateofanalysis?Aresamplingmethodsdescribedwithatleastnumberofcontainerstobesampledwhichpartofthecontaineramountofsampletobetaken7.34Issamplingdoneatdefinedlocationspreventingcontamination?7.35Arecontainersfromwhichsamplesaretakenidentified?7.4Storage7.40Ismaterialstoredinamannertopreventdegradationandcontamination?7.41Arefiberdrums,bagsandboxesstoredoffthefloor?Isstoredmaterialsuitablyspacedtopermitcleaningandinspection?7.42Domaterialsmettheirrespectivestorageconditions?IstheFIFOprinciplefollowed?7.43Incasematerialsisstoredoutdoors:dolabelsremainlegiblearethecontainerscleanedbeforeopeningisitdescribedinaprocedure7.44Howarerejectedmaterialsheldunderaquarantinesystem?8ProductionandInProcessControls8.1ProductionOperationsArethedevicesperiodicallycalibratedwithcertifiedreferences?8.11Docontainerswithsubdividedmaterialcontainthefollowinginformation:nameofmaterialcodeorcontrolnumberweight,ifapplicable括的包裝容器數量取樣清晰是否進行清潔和中間控制裝有多次分發物料的容器是否提供下列信息：控制碼retestdate,ifapplicable8.12Howarecriticalweighing,measuringorsubdividingoperationwitnessed?Isanequivalentcontrolused?Ifsowhat?8.16Howistheprocessingstatusofmajorunitsofequipmentindicated?8.2TimeLimitsAreallspecifiedtimelimitsoftheoperatinginstructionsmet?8.21HowarestorageconditionsforIMheldforfurtherprocessingdetermined?8.3In-processSamplingandControlsltheperformanceofthes8.32ArecriticalIPCapprovedbytheQU?productionpersonneldocumentedif8.33theyperformtheIPC?8.34AresamplingmethodsforIPCdescribedinwriting?Doesin-processsamplingnotcausethecontaminationofsampleand/orproduct?8.4BlendingofBatchesofIMorAPIs8.41AreOOSbatchesblendedwithotherbatchesmeetingthespecifications?Areallbatchesindividuallytestedpriortoblending?Anddotheyallmeetion8.43conformancetospecifications?8.44batches?8.45thisstepareknowntobecritical?8.46Howisitdemonstratedthattheblendedbatchdoesnotaffectstability?復驗期(如適用)在混批前，是否對個批號分別化驗？是否全部合格？定性？8.47Istheexpiry/retestdatebasedontheoldestbatchintheblend?8.5ContaminationControlsintosuccessivebatchesof.50thesameIM/APIdonotaffecttheimpurityprofileoftheAPI?8.51WhatmeasuresaretakeninproductiontopreventcontaminationofIM/API?WhatspecificprecautionsaretakentoavoidcontaminationoftheAPIafter8.52purification?9PackagingandIdentificationLabellingofAPIsandIM9.1General9.10Arewrittenproceduresavailabledescribingttinexaminationtestingeofpackagingmaterialsandlabels?9.11Arespecificationsforallpackagingmaterialsandlabelsestablished?9.12Arerecordsofeachdeliveryofpackagingmaterialsandlabelskept?9.2PackagingMaterialsCancontainers/packagingmaterialusedprovideadequateprotectionagainst9.20deteriorationorcontaminationduringtransportation?9.21Arecontainerscleanedsothattheyaresuitablefortheirintendeduse?9.22Arewrittenproceduresforcleaninginplaceforre-usedcontainers?Areallpreviouslabelsremovedordefaced?9.3LabelIssuanceandControl9.30Isaccesstolabelstoragearealimitedtoauthorizedpersonnel??所用的容器/包材在運輸過程中是否受到足夠的保護，以防止變形或被移除或涂掉？否只有授權的人員才能進入標簽存放區？Areproceduresinplacetoreconcilethequantitiesoflabelsissuedandused?ArediscrepanciesinvestigatedandapprovedbytheQU?9.33Areallout-datedandobsoletelabelsdestroyed?in4batchrecord?9.36Isarepresentativelabelincludedinthebatchrecord?9.4PackagingandLabellingOperationsArewrittenproceduresinplaceensuringthatcorrectpackagingmaterialsand9.40labelsareused?9.41aredoneatthesametime?9.42Labelsshouldindicatethefollowinginformation(atleast):nameofproductidentifyingcodeandbatchnumberstorageconditions,whensuchinformationiscriticaltoassurequality9.43aswellasrequirementsof9.42contain:nameandaddressofmanufactureryspecialtransportconditions,ifapplicablespecialstorageconditions,ifapplicable(10.22)legalrequirements,ifapplicablesForAPIswithretestdate:datetobeincludedonlabeland/orcertificateofisIMAPI的標簽是否正確進行核查(9.45)？作批號是，應標示其條件地址輸條件，如適用特殊儲存條件，如適用(10.22)適用Arepackagingandlabelingfacilitiesinspectedbeforeusetoensurethatallmaterialsnotneededareremoved?Isthisinspectiondocumented?yhavebeenalteredPleasespecifyStorageandDistributionWarehousingProceduresArefacilitiesforthestorageofmaterialsavailablesupportingtheclaimedstorageconditionsegtemperature,humidity)?物料儲存設施是否滿足物料的儲存條件(例如，溫度，濕度)？Arerecordsofthestorageconditionskept?Areseparatestorageareasprovidedforquarantined,rejected,returnedorrecalledproductsOrisanalternativesystemused?Ifso,howisitdesignedandqualified?DistributionProceduresllHowdoesthemanufacturerensurethatthetransporterknowsandfollowsthe量造成不良影響?appropriatetransportandstorageconditions?LaboratoryControlsGeneralControlsAreadequatelaboratoryfacilitiesavailable?esreviewedandapprovedbytheQUDothespecificationssetfortheAPIsincludeacontroloftheimpurities?413appropriateactionlimitshavebeenestablished?如果API設置了微生物和/或內毒素限度，那確定的行動限是什么？11.15AreallOOSresultsinvestigated?IsresamplingafterOOSdescribedinaprocedure?11.17Areprimaryreferencestandardsstoredunderappropriateconditions?Isthesourceoftheprimarystandarddocumented?imarystandarddapprovesecondary11.19referencestandards?Aresecondaryreferencestandardsperiodicallyre-qualified?11.2TestingofIntermediatesandAPIs11.21IsthereanimpurityprofileestablishedforeveryAPI?intheregulatorysubmissionoragainsthistoricaldata11.3ValidationofAnalyticalProceduresSeesection12.811.4CertificatesofAnalysis11.40AreauthenticCertificatesofAnalysisissuedforeachbatchofIM/API?11.41InformationontheCertificateofAnalysis:nameofIM/APIbatchnumberandcodenumber?teofreleaseexpirydate,ifapplicableretestdate,ifdesired明用11.42OntheCertificateofAnalysis,arealltestsperformedlisted,togetherwith化驗報告是否列明所有檢驗項目，及其合格標準和得到的數值？ained11.43CertificatesofAnalysisshouldbesignedbyauthorizedpersonneloftheQUshowname,addressandtelephonenumberofmanufacturernumberofthelaboratorythatperformedthetestsmustbeshown.ertificateofAnalysis11.5StabilityMonitoringofAPIs11.50Isanon-goingstabilitytestingprogrammeconducted?Dotheresultsofthestabilityprogrammejustifystorageconditionsandexpiry/retestdates(seealso11.61)?11.51Arethetestmethodsusedinstabilityvalidatedandstabilityindicating?11.52containers?11.53Arethefirstthreecommercialproductionbatchesplacedonstability?Thereafter,isatleastonebatchperyearaddedtothestabilitymonitoring11.54programme?Areannuallytestsperformedtoconfirmstability?11.55ForAPIswithlessthan1yearstability:11.6ExpiryandRetestDating11.60controlofthecompany?門授權的人簽名名稱，地址和電話如果由代理商發放的化驗報告(見18節)必須注明代理商的名稱，存條件和失效期/復驗期是否相應(見11.61)？20-35Reserve/RetentionSamplesArereservesamplesstoredfor1yearafterexpirydateor3yearsafterdistributionwhateverislonger)?ForAPIsarereservesamplesstoredforatleast3yearsaftercomplete留樣是否保留至有效期后一年或發貨后三年(取其中長者)？ibutionarketedValidationValidationPolicyIsthecompanysoverallvalidationpolicydocumented?withrfromhistorical)Aretheoperatingrangesdefined?Areallcriticaloperationstepsvalidated?ValidationDocumentationdationprotocolestablishedIsitapprovedbytheQU?Isthefollowingspecifiedinthevalidationprotocol:criticalprocessstepsacceptancecriteriaypeofvalidationnumberofprocessruns?Isavalidationreportpreparedsummarisingtheresultsobtained,includingrecommendationofchangestocorrectdeficiencies?是否有驗證報告對驗證結果加以總結，包括對不足之處改進建議？Arevariationsfromthevalidationprotocoldocumentedandjustified?478Qualification確認21-3512.30IstherepolicyorprocedureforQualification/Validation?.IsValidationMasterPlanavailable?validationactivities?12.4ApproachestoProcessValidationIsprocessvalidation(PV)conductedbeforecommercialdistributionofAPI12.10batches?sthejustification12.42ofperformingothertypes?12.44followingrequirementsmet:criticalprocessparametershavebeenidentifiedappropriatein-processcriteriahavebeenestablishednosignificantprocessfailureshaveoccurredimpurityprofileshavebeenestablishedfortheexistingAPI2.45madeduringthereviewperiod?12.5ProcessValidationProgramme12.50concurrentvalidation?12.6PeriodicReviewofValidatedSystems對關鍵設備及其附屬系統是否進行適當的確認(DQ,IQ,OQ,PQ)?經確定發生重大的工藝失敗22-35atedtoverifythattheyarestilloperatinginavalidmanneregthroughproductqualityreview)?12.7CleaningValidation12.70Arecleaningproceduresvalidated?Ifnot,isthereajustification?entativeAPIIMselectedforcleaningvalidationtability12.72Doesthecleaningvalidationprotocolincludeequipmenttobecleanedproceduresmaterialsusedacceptablecleaninglevelsparameterstobemonitoredanalyticalmethodstypeofsamples(swab,rinse)howsamplesarecollectedandlabeled12.73Doesthetypeofsamplingdetectinsolubleandsolubleresidues?IsthesamplingmethodcapabletoquantitativelymeasurelevelsofremainingesaminatesHowareresiduelimitsestablished(onminimumknownpharmacological,toxicologicalorphysiologicalactivityorthemostdeleteriouscomponent)?是否定期評估系統和工藝過程以確認它們運轉正常(例如，通過審(基于溶解性，清洗難度和殘留限度的計算基于效力，毒性和穩定水平取樣方式(擦拭，沖洗)何收集和標示如何建立殘留限度(根據已知的藥理，毒理或生理活性或最有害組23-35rvalstoensuretheirsValidationofAnalyticalMethodsAretheanalyticalmethodsdevelopedbythecompanyvalidated?HowarePharmacopoeialmethodsqualified?如何確定分析驗證級別(例如不同的生產階段)是合理的？alyticalequipmentqualifiedArerecordsofmodifiedvalidatedanalyticalmethodsmaintained?Isthereasonforthemodificationdocumented?ChangeControlIsaformalchangecontrolsysteminplacecapableofevaluatingallchanges?Writtenproceduresshouldbeprovidedfortheidentification,documentation,reviewandapprovalofchanges.別，文件，審核和批準應當有書面規定AreallchangesimpactingthequalityoftheAPI/IMapprovedbytheQU?Arechangesclassified(e.g.major,minor)?變更是否分類(重大的，小的)？Ifnot,howistheimpactonthequalityoftheAPIbeingevaluated?Howisleveloftesting,validation,documentationdetermined(scientific如何確定測試，驗證，文件的級別(科學判斷)？Howisitensuredthatafterachangeallaffecteddocumentsarerevised?Arethefirstbatchesevaluatedafterthechangehasbeenimplemented?Ifcriticalchangeshavebeenmade,hastheimpactonexpiry/retestdatesandprocessvalidationbeenevaluated?變更對于API質量(特別是物理指標)可能造成的影響是否通知了alattributesRejectionandRe-UseofMaterials和再利用物料onAreIM/APIsfailingtomeetspecificationsidentified?How?541Reprocessing返工24-35Areallstepswherereprocessingisconductedpartofthefilingdocuments?ngIsaninvestigationperformedbeforeadecisionistakentoreworkabatch?Havereworkedbatchesbeensubjectedtoappropriateevaluationitytestingtoshowequivalencytooriginalprocess?藝等效Isconcurrentvalidationperformedifmorethanonebatchisaffected?Isareport