APIC 基于風(fēng)險(xiǎn)的數(shù)據(jù)完整性管理實(shí)踐指南-2019（中英文對(duì)照版）

lriskbasedguideformanagingdataintegrityVersionMarchAPIC翻譯JULIA頁(yè)1/60ACTIVEPHARMACEUTICALINGREDIENTSCOMMITTEEPracticalrisk-basedguideformanaging整性管理實(shí)踐指南Version1,March2019lriskbasedguideformanagingdataintegrityVersionMarchAPIC翻譯JULIA頁(yè)2/60teeAPICofCEFICmNVAndrvanderBiezenAspenOssB.V.teticiSpAciaSAlriskbasedguideformanagingdataintegrityVersionMarchAPIC翻譯JULIA頁(yè)3/60GeneralSectionnObjectivesandScopeOverallDataIntegrityApproach述BusinessProcessingMappingSystemIdentificationataandSystemCategorisation4.2SystemProfiling4.2.1Systemcategorization2Systemcategorizationrequirements4.3SystemAssessment5RiskAssessment6RiskManagement7References8ExampleslriskbasedguideformanagingdataintegrityVersionMarchAPIC翻譯JULIA頁(yè)4/601.GeneralSection通用部分1.1Introduction簡(jiǎn)介Dataintegrityreferstotheaccuracy,completenessandconsistencyofGxPdataoveritsentirelifecycle.Thestepsthatneedtobeoverseenincludetheinitialgenerationandrecording,theprocessing(incl.analysis,transformationormigration),theoutcome/use,theretention,retrieval,archiveandfinallythedestruction.數(shù)據(jù)完整性指GXP數(shù)據(jù)在其整個(gè)生命周期中的準(zhǔn)確性、完整性和持續(xù)性。需要監(jiān)管的步驟包括初始生成和記錄、處理(包括分析、轉(zhuǎn)化或遷移)、結(jié)果/使用、保存、檢索、歸檔和最終銷毀。Dataintegritymeansthatallthestepsdefinedabovearewellmanaged,controlledanddocumentedandthereforetherecordsoftheactivitiesfollowtheALCOAprinciplesdescribedintheguidelines.數(shù)據(jù)完整性意味著上述所有步驟均得到良好管理、控制和記錄，因此活動(dòng)的記錄遵守本指南中所述的ALCOA原則。TheALCOAandALCOA+principleshavebeeninplaceforseveralyearsintheindustryandarewidelyknownandimplemented.Achievingdataintegritycompliance,forpaper,electronicandhybridsystems,requirestranslationoftheseprinciplesintopracticalcontrolsinordertoassureGxP-impactingbusinessdecisionscanbeverifiedandinspectedthroughoutthedatalifecycle.ALCOA和ALCOA+原則在行業(yè)里已存在了數(shù)年，已得到廣泛理解和執(zhí)行。紙質(zhì)、電子和混合系統(tǒng)達(dá)成數(shù)據(jù)完整性合規(guī)需要將這些原則轉(zhuǎn)化為實(shí)用控制，以確保具GXP影響的業(yè)務(wù)決策可在其整個(gè)生命周期中得到確認(rèn)和檢查。Currentlyavailableregulatoryguidelineshavebeenusedtoelaboratetheapproachoutlinedinthispracticalguide(seealsosection7,References).目前已有的法規(guī)指南已被用來(lái)制訂本實(shí)操指南中所列的方法(參見第7部分，參考文獻(xiàn))。Thecurrentguidelinesondataintegrityrequirethatcompaniescompletedataintegritycriticalityandriskassessmentstoensurethattheorganizationalandtechnicalcontrolsthatareputinplacearecommensuratewiththelevelofrisktoqualityattributes.當(dāng)前對(duì)數(shù)據(jù)完整性的指南要求公司完成數(shù)據(jù)關(guān)鍵性和風(fēng)險(xiǎn)評(píng)估以確保所采用的組織和技術(shù)方面控制與質(zhì)量屬性風(fēng)險(xiǎn)水平相稱。Theguidelinesemphasisetheimportanceofcreatingandmaintainingaworkingenvironmentandorganisationalculturethatsupportsdataintegrity.Companiesshouldestablishdatagovernanceprogramsthataddresstechnical,proceduralandbehaviouralaspectstoassureconfidenceindataqualityandintegrity.指南強(qiáng)調(diào)了創(chuàng)建和維護(hù)支持?jǐn)?shù)據(jù)完整性的工作環(huán)境和組織文件的重要性。公司應(yīng)建立數(shù)據(jù)管理程序，從技術(shù)、程序和行為方面確保數(shù)據(jù)質(zhì)量和完整性可信度。Thisdocumentwillnotdescribealltheelementsrequiredforadatagovernanceprogramindetail.However,somefoundationalprinciplesaregivenbelow:本文件不會(huì)詳細(xì)講解數(shù)據(jù)管理程序所需的所有要素，但也在下面列出了一些基本原則：OrganisationalCulture組織文化Organisationalculturehasthepotentialtoincreasethepossibilityforlapsesindataintegrity;intentional(e.g.fraudorfalsification)orunintentional(e.g.lackofunderstandingofresponsibilitiesand/orrequirements).Toreducethispotential,organisationsshouldaspiretoanopenculturewheresubordinatescanchallengehierarchy,andfullreportingofasystemicorindividualfailureisabusinessexpectation.組織文化可能會(huì)有意(例如偽造或欺詐)或無(wú)意(例如缺乏對(duì)職責(zé)和/或需求的了解)地增加數(shù)據(jù)完整性出問題的可能性；。為降低這種可能性，組織應(yīng)鼓勵(lì)開放文化，下屬可挑戰(zhàn)等級(jí)制度，將全面地報(bào)告系統(tǒng)性或個(gè)人失敗作為一項(xiàng)業(yè)務(wù)要求。Awareness意識(shí)ItiscrucialthatemployeesatalllevelsunderstandtheimportanceofdataintegrityandtheimpactthattheycanhaveonGxPdatawiththeauthorisationsassignedfortheirjobroles.Trainingisamajorcomponentofraisingawarenessandshouldbeconductedperiodically.TheALCOA+concepts,andtheAPIC翻譯JULIA頁(yè)5/60acronymitself,arewidelyusedbyregulatorsandindustryandshouldbeincorporatedintotheprogram(e.g.withinstafftraining,policiesetc.).關(guān)鍵地的各層次員工了解數(shù)據(jù)完整性的重要性，及其對(duì)因工作原因獲得授權(quán)的GXP數(shù)據(jù)可能產(chǎn)生的影響。培訓(xùn)是提升意識(shí)的主要組成部分，應(yīng)定期進(jìn)行。ALCOA+概念及縮寫本身在藥監(jiān)機(jī)構(gòu)和行業(yè)里被廣泛使用，應(yīng)整合至程序中(例如，放在員工培訓(xùn)、方針等內(nèi))。SystemandProcessDesign系統(tǒng)和流程設(shè)計(jì)Compliancewithdataintegrityprinciplescanbeencouragedthroughtheconsiderationofeaseofaccess,usabilityandlocation.Forexample:可通過(guò)考慮易于獲得、易用和位置來(lái)鼓勵(lì)符合數(shù)據(jù)完整性原則：oControloverblankpapertemplatesforGxPdatarecordingo對(duì)GXP數(shù)據(jù)記錄用空白紙質(zhì)模板進(jìn)行控制oControlofspreadsheetsusedforcalculationso對(duì)用于計(jì)算的表格進(jìn)行控制oAccesstoappropriateclocksforrecordingtimedeventso可獲得適當(dāng)?shù)臅r(shí)鐘記錄需要計(jì)時(shí)的事件oAccessibilityofrecordsatthelocationswhereactivitiestakeplaceo在活動(dòng)發(fā)生的地方可訪問記錄oUseraccessrightsandpermissionsthatalignwithpersonnelresponsibilitieso用戶訪問權(quán)限和許可與人員職責(zé)相對(duì)應(yīng)oAutomationofGxPdatacapturewherepossibleo盡可能自動(dòng)捕獲GXP數(shù)據(jù)oAccesstoelectronicGxPdataforstaffperformingdatareviewactivitieso為執(zhí)行數(shù)據(jù)審核活動(dòng)的員工提供電子GXP數(shù)據(jù)訪問權(quán)限ManagementCommitment管理者承諾Seniormanagementshouldensurethatthereisawrittencommitmenttofollowaneffectivequalitymanagementsystemandprofessionalpracticestodelivergooddatamanagement.Thecommitmentsshouldinclude高級(jí)管理人員應(yīng)確保有書面承諾來(lái)執(zhí)行有效的質(zhì)量管理體系，以及專業(yè)性做法來(lái)實(shí)現(xiàn)良好的數(shù)據(jù)管理。包括：Anopenqualityculture開放的質(zhì)量文化Dataintegritygovernance數(shù)據(jù)完整性管理Allocationofappropriateresources適當(dāng)?shù)馁Y源配置Dataintegritytrainingforstaff員工數(shù)據(jù)完整性培訓(xùn)MonitoringofdataintegrityissueswithCAPAtakentoaddressissuesidentified監(jiān)測(cè)數(shù)據(jù)完整性問題，采取CAPA解決所識(shí)別出的問題Mechanismsforstafftoreportconcernstomanagement員工向管理層報(bào)告其擔(dān)憂的機(jī)制lriskbasedguideformanagingdataintegrityVersionMarchAPIC翻譯JULIA頁(yè)6/601.2ObjectivesandScope目的與范圍ThisdocumentisbasedongeneralDataIntegrityrequirementsandgatherspracticalexperiencesfromanumberofcompaniesoperatinginthesectorthatcanbeusedasguidancetoothers.Itisnotanall-inclusivelistofrequirementsbutproposesacomprehensiveapproachthatcompaniescanadopttohelpcarryouttheirdataintegrityriskassessments.本文件是基于通用數(shù)據(jù)完整性要求，匯集了在該領(lǐng)域運(yùn)營(yíng)的大量公司的實(shí)用經(jīng)驗(yàn)，可用于指導(dǎo)其它公司。它并非窮盡的需求清單，只是提出了一個(gè)全面的方法讓公司可以用來(lái)幫助執(zhí)行其數(shù)據(jù)完整性風(fēng)險(xiǎn)評(píng)估。Theguideisessentiallypracticalandtherefore,afterthepresentationoftheapproachandofthetools,thedocumentincludessomeexamplesofexecutedassessments,categorisationsandcheckliststhatcanbeusedbyanycompanyaccordingtotheirindividualneeds.Eachcompanycanchoosetheappropriatetoolsandcategorisationsthatapplytotheirownbusinessprocessesandsystems.本指南基本是實(shí)用性的，因此在展示了方法和工具后，文件中包括了一些執(zhí)行、分類和檢查清單的實(shí)例，任何公司均可根據(jù)其自己需求加以使用。每個(gè)公司均可選擇其適當(dāng)?shù)墓ぞ吆头诸惙椒?，?yīng)用于其自己的業(yè)務(wù)流程和系統(tǒng)。ThisguidanceappliestoallGxPprocessesandGxPdatausedinthemanufactureandanalysisofAPIsforuseinhumanandveterinarydrugs.本指南適用于所有人藥和獸藥API生產(chǎn)和檢驗(yàn)所用的GXP流程和GXP數(shù)據(jù)。1.3Definitionsandabbreviations定義與縮寫B(tài)usinessprocess:asetofstructuredactivitiesortasksthatproduceaspecificserviceforaparticularcustomerorcustomers.Itisoftenvisualisedasaflowchartofasequenceofactivitieswithdecisionpoints.業(yè)務(wù)流程：一系列結(jié)構(gòu)化活動(dòng)或任務(wù)，為一個(gè)特定客戶或多個(gè)客戶提供特定的服務(wù)。通?？煽醋魇菐в袥Q策點(diǎn)的序列活動(dòng)的一個(gè)流程圖。Data:Facts,figuresandstatisticscollectedtogetherforreferenceoranalysis.Alloriginalrecordsandtruecopiesoforiginalrecords,includingsourceGxPdataandmetadataandallsubsequenttransformationsandreportsoftheseGxPdata,thataregeneratedorrecordedatthetimeoftheGxPactivityandallowfullandcompletereconstructionandevaluationoftheGxPactivity.數(shù)據(jù)：為參考或分析而一起采集的事實(shí)、數(shù)字和統(tǒng)計(jì)學(xué)內(nèi)容。所有原始記錄和原始記錄的真實(shí)副本，包括GXP源數(shù)據(jù)和元數(shù)據(jù)以及這些GXP數(shù)據(jù)后續(xù)的轉(zhuǎn)化和報(bào)告，這些數(shù)據(jù)是在GXP活動(dòng)執(zhí)行時(shí)生成或記錄的，使得可以全面完整重構(gòu)GXP活動(dòng)。Rawdata:Rawdataisdefinedastheoriginalrecord(data)whichcanbedescribedasthefirst-captureofGxPinformation,whetherrecordedonpaperorelectronically.Informationthatisoriginallycapturedinadynamicstateshouldremainavailableinthatstate.原數(shù)據(jù)：原數(shù)據(jù)定義為首次捕獲GXP信息的紙質(zhì)或電子原始記錄 (數(shù)據(jù))。原始以動(dòng)態(tài)狀態(tài)捕獲的電子信息應(yīng)保持可以該狀態(tài)獲得該Metadata:Metadataaredatathatdescribetheattributesofotherdataandprovidecontextandmeaning.Typically,thesearedatathatdescribethestructure,dataelements,inter-relationshipsandothercharacteristicsofdatae.g.audittrails.Metadataalsopermitdatatobeattributabletoanindividual(orifautomaticallygenerated,totheoriginaldatasource).元數(shù)據(jù)：描述其它數(shù)據(jù)屬性和提供環(huán)境與含義的數(shù)據(jù)為元數(shù)據(jù)。一般來(lái)說(shuō)，這些數(shù)據(jù)描述數(shù)據(jù)的結(jié)構(gòu)、數(shù)據(jù)要素、內(nèi)在關(guān)系和其它屬性，例如審計(jì)追蹤。元數(shù)據(jù)亦使得數(shù)據(jù)可追蹤至個(gè)人身份(或者如果是自動(dòng)生成的，追蹤到原始數(shù)據(jù)源)。Dataseverityassessment:withinGxPdata,differentlevelsofseveritycanbedefinedasafunctionofitsuse.Typically,thisislinkedtothestageofmanufacturingfollowingtheprincipleofincreasingGxPoutlinedinICHQ7.Alternatively,otherfactorssuchasimpactonfinalproductqualitycanbetakenintoaccounttofurtherdifferentiatebetweenseveritycategories.數(shù)據(jù)嚴(yán)重程度評(píng)估：在GXP數(shù)據(jù)中，不同級(jí)別的嚴(yán)重程度可定義為其用途的函數(shù)。一般來(lái)說(shuō)，這與生產(chǎn)階段有關(guān)，可按ICHQ7里所列的根據(jù)GXP漸增原則。其它因素如對(duì)最終產(chǎn)品質(zhì)量的影響性亦進(jìn)行考慮用于進(jìn)一步區(qū)別嚴(yán)重程度。Dataelements:(forthepurposeofthisdocument)individualGxPdataitemsthatarepartofrawGxPdataormetadata,e.g.anoperatorname,atestdate.數(shù)據(jù)要素：(本文件中)作為原GXP數(shù)據(jù)或元數(shù)據(jù)一部分的單個(gè)lriskbasedguideformanagingdataintegrityVersionMarchAPIC翻譯JULIA頁(yè)7/60GXP數(shù)據(jù)項(xiàng)目，例如，一個(gè)操作員的姓名、檢測(cè)日期)。DataFlow:diagramthatmapstheflowofinformationofanyprocessorsystem(inputs,outputs,storagepointsandroutesbetweeneachdestination).數(shù)據(jù)流：描繪出任何流程或系統(tǒng) (輸入、輸出、存貯點(diǎn)和每個(gè)終點(diǎn)之間的路徑)信息流的圖形。Dataprocessmapping:generationofavisualrepresentationofthecreationandmovementofdatathroughthebusinessprocessincludingdocumentationofthesystemsused.數(shù)據(jù)流程分析：將整個(gè)業(yè)務(wù)流程中數(shù)據(jù)創(chuàng)建和流向(包括所用系統(tǒng)的文件)以可視化方式呈現(xiàn)。DataAuditTrail:appropriateaudittrailelementssupportingtheacquisition,sequencing,processing,reportingandretentionofGxPdataforthereleaseofproduct.IncludingallrelevantorsignificantGxPdatagenerated,whichmayaffecttheproduct(suchas:analyticalmethodvalidation,stabilityanalysis,multiplesample/testruns,etc.),asdeterminedbyariskassessment.數(shù)據(jù)審計(jì)追蹤：支持產(chǎn)品放行用GXP數(shù)據(jù)的采集、排序、處理、報(bào)告和保存的適當(dāng)?shù)膶徲?jì)追蹤要素。包括按風(fēng)險(xiǎn)評(píng)估所決定的生成的所有可能影響產(chǎn)品的相關(guān)或重大GXP數(shù)據(jù)(如分析方法驗(yàn)證、穩(wěn)定性分析、多個(gè)樣品/檢測(cè)輪次等)。LIMS:LaboratoryInformationManagementSystemLIMS：實(shí)驗(yàn)室信息管理系統(tǒng)MES:ManufacturingExecutionSystemMES：生產(chǎn)執(zhí)行系統(tǒng)PCS/DCS:processcontrolsystems(PCS)/distributedcontrolsystems(DCS)PCS/DCS：工藝控制系統(tǒng)(PCS)/集散控制系統(tǒng)(DCS)Processmapping:activitiesinvolvedindefiningwhatabusinessentitydoes,whoisresponsible,towhatstandardabusinessprocessshouldbecompleted,andhowthesuccessofabusinessprocesscanbedetermined.流程分析：規(guī)定業(yè)務(wù)實(shí)體做什么、誰(shuí)負(fù)責(zé)、業(yè)務(wù)流程應(yīng)完成至什么標(biāo)準(zhǔn)以及業(yè)務(wù)流程的成功要如何確定中所涉及的活動(dòng)。SystemAuditTrail:arecordofalladministratorchanges.Thefrequencyofthisreviewshouldbedeterminedbasedonariskassessment.Thismaybeperformedaspartofthesystemperiodicreviewasappropriate.系統(tǒng)審計(jì)追蹤：一份所有管理員變更的記錄。該審核頻次應(yīng)根據(jù)風(fēng)險(xiǎn)評(píng)估來(lái)確定。適當(dāng)時(shí)可作為系統(tǒng)定期審核的一部分來(lái)執(zhí)行。Truecopy:Acopy(irrespectiveofthetypeofmediaused)oftheoriginalrecordthathasbeenverified(i.e.byadatedsignatureorbygenerationthroughavalidatedprocess)tohavethesameinformation,includingdatathatdescribethecontext,content,andstructure,astheoriginal真實(shí)副本：經(jīng)核查(即通過(guò)有日期的簽名或通過(guò)一個(gè)已驗(yàn)證的流程生成)具備相同信息，包括描述環(huán)境、內(nèi)容和結(jié)構(gòu)的數(shù)據(jù)的原始記錄副本(無(wú)論使用何種介質(zhì))。1.4OverallDataIntegrityApproach全面數(shù)據(jù)完整性方法Whenassessingdataintegrityriskswithinanorganisation,companiesmayfocusimmediatelyonthosesystemsorareasthatarethemostobviousinthiscontext,suchasaparticularsoftware,aspecificlabsystemorinstrumentetc.Doingsocreatestheriskofforgettinglessvisiblebutstillimportantareas,processesorsystems,oroffailingtoaddressintegrityissuesconcerningdataflowsbetweencontrolledenvironments.在一個(gè)組織內(nèi)評(píng)估數(shù)據(jù)完整性風(fēng)險(xiǎn)時(shí)，公司可能會(huì)直接關(guān)注在其環(huán)境中最明顯的那些系統(tǒng)或領(lǐng)域，如特別的軟件、特定的實(shí)驗(yàn)室系統(tǒng)或儀器等。如此可能會(huì)帶來(lái)忽視掉不顯見但仍很重要的領(lǐng)域、流程或系統(tǒng)的風(fēng)險(xiǎn)，或未能解決關(guān)于受控環(huán)境間數(shù)據(jù)流的完整性問題。Therefore,thisguideapproachesdataintegrityinaholisticmannerbylookingattheorganisationfromahigh-levelbusinessprocessperspective,subsequentlydivingdeeperintounderlyingsub-processesandonlyattheenddrillingdowntoindividualactivitiesorsystemsthatinvolveGxPdata.因此，本指南的數(shù)據(jù)完整性方法是從較高水平的業(yè)務(wù)流程角度來(lái)對(duì)組織進(jìn)行全面查看，然后進(jìn)一步深入至底層子流程，最后挖掘到涉及GXP數(shù)據(jù)的單個(gè)活動(dòng)或系統(tǒng)。Figure1isagraphicalrepresentationofthisapproachandthesequenceofstepsthatshouldhelpassessorstoobtainacompleteandprofounddataintegrityriskassessment.圖1采用圖形方式展示了該方法和步驟順序，有助于評(píng)估人得到完整深入的數(shù)據(jù)完整性風(fēng)險(xiǎn)評(píng)估。ItshouldbenotedthattheproposedapproachissuitablenotonlytoassessrisksrelatedtosystemsorprocessesalreadypresentintheorganisationbutalsotoproactivelyevaluatetherequirementsoflriskbasedguideformanagingdataintegrityVersionMarchAPIC翻譯JULIA頁(yè)8/60newsystems.要注意的是所提議的方法不僅適用于評(píng)估與組織內(nèi)現(xiàn)有系統(tǒng)或流程有關(guān)的風(fēng)險(xiǎn)，亦可用于提前評(píng)估新系統(tǒng)的需求。Belowisashortdescriptionofthesequenceactionsthatareillustratedinthediagram.Detailsforthemajorstepswillbefurtherelaboratedinthefollowingsectionsofthisguideline(thosesectionsarealsocross-referencedinFigure1).以下是圖中展示的動(dòng)作順序的簡(jiǎn)單說(shuō)明。主要步驟的詳細(xì)情況將在本指南后續(xù)部分里進(jìn)一步說(shuō)明(那些部分亦在圖1中做了交叉引用)。?Identifythecompany’shigh-levelGxPbusinessprocesses(orhavinglinkstoGxPactivities)(ref.tosection2)?識(shí)別公司的高水平GXP業(yè)務(wù)流程(或與GXP活動(dòng)有關(guān)的)(參考第2部分)?MapeachoftheGxPbusinessprocessesandtheirsub-processesdowntolevelofprocessflowsthatconsistofindividualactivities(refertosection0)?分析每個(gè)GXP業(yè)務(wù)流程及其子流程直至單項(xiàng)活動(dòng)構(gòu)成的流程水平?IdentifytheGxPdataelementsandthewaythedataflows(IN/OUT)betweenthedifferentprocessstepsoractivities(DataProcessMapping);(refertosection0)?識(shí)別出GXP數(shù)據(jù)要素，以及不同流程步驟或活動(dòng)之間的數(shù)據(jù)流(進(jìn)/出)途徑(數(shù)據(jù)流程分析)(參見第0部分)?Identifyandisolatetheindividualsystems(bothpaperandelectronic)thatmanage(generate,store,transferorprocess)GxPdata(refertosection0)?識(shí)別并分隔出單個(gè)管理(生成、存貯、轉(zhuǎn)移或處理)GXP數(shù)據(jù)的系統(tǒng)(紙質(zhì)和電子的)(參見?AssignGxPdatatoaspecificcategorybasedonaseverityassessment(refertosection4.1)?根據(jù)嚴(yán)重程度評(píng)估結(jié)果，將GXP數(shù)據(jù)分類至具體的類別(參照第4.1部分)?CreateaprofileofeachsystembasedonthewayGxPdataishandledbythatsystem(e.g.datageneration,storage,processing,transferoracombinationthereof)andassignacategorytothesystembasedonitsprofile;(refertosection4.2)?根據(jù)該系統(tǒng)處理GXP數(shù)據(jù)的方法，為每個(gè)系統(tǒng)創(chuàng)建一份概況說(shuō)明(例如，數(shù)據(jù)生成、存貯、處理、轉(zhuǎn)移或后續(xù)組合)，并根據(jù)其概況將系統(tǒng)分類至一個(gè)類別(參見第4.2部分)?Identifythegapbetweenthe“asis”stateofthesystemandthedesiredstate(i.e.thesetofdataintegrityrequirementslinkedtotheparticularsystemcategory);acheck-listshouldbeusedtoaccomplishthistask;(refertosection4.3)?識(shí)別系統(tǒng)當(dāng)前狀態(tài)與所需狀態(tài)之間的差距(即，與特定系統(tǒng)類別相關(guān)的一系列數(shù)據(jù)完整性需求)；應(yīng)使用檢查清單來(lái)完成此任務(wù)(參考第4.3部分)?Analysethedataintegrityriskconsideringthegapsidentifiedabove,whichisanassessmentofthefailuremode,usingseverity,occurrenceanddetectabilitythatarepartoftheriskassessmentmethodology(e.g.FMEA);(refertosection5)?分析數(shù)據(jù)完整性風(fēng)險(xiǎn)，同時(shí)考慮上述已識(shí)別的差距，這是一種失效模式分析，采用嚴(yán)重程度、發(fā)生可能性與檢出能力作為風(fēng)險(xiǎn)評(píng)估方法學(xué)的一部分(例如FMEA)(參見第5部分)?Establisharemediationplantoremediatethegapsandsetprioritiesbasedonthemagnitudeoftherisk(refertosection6)?制訂補(bǔ)救計(jì)劃對(duì)差距進(jìn)行彌補(bǔ)，并根據(jù)風(fēng)險(xiǎn)的重要性設(shè)定優(yōu)先順序(參見第6部分)lriskbasedguideformanagingdataintegrityVersionMarchAPIC翻譯JULIA頁(yè)9/60rofileX.xBusinessprocess12stepNstep1rofileX.xBusinessprocess12stepNstep1step2-IdentifyD-Isolate3MIPCINTAPI4.2.2equirementtionprofiling464.2.1rityGeneralConceptofthisguideXtochapterXBusinessBusinessprocessN-1SubprocessXINshat4.1y4.1+tity5encexdetect5nttionseAPIC翻譯JULIA頁(yè)10/60 ……當(dāng)前改進(jìn)后段落X公司X.x進(jìn)4.1 ……當(dāng)前改進(jìn)后段落X公司X.x進(jìn)4.1 流流進(jìn)2-識(shí)別數(shù)據(jù)流-3、中控、中間體、原料藥.1系統(tǒng)概況系統(tǒng)需求56出+442BusinessProcessingMapping業(yè)務(wù)流程分析BusinessProcessmappingshouldbeusedinordertoprovideaglobaloverviewonallkindsofactivitiesperformedinacompany,includingoperational,supportiveandstrategicprocesses.Examplesinclude:應(yīng)對(duì)業(yè)務(wù)流程進(jìn)行分析以提供公司內(nèi)所實(shí)施的所有類型活動(dòng)的全球概況，包括運(yùn)作、支持和策略流程。實(shí)例包括：Production(Development&ControlofMasterBatchRecord,ManufactureofaProduct)生產(chǎn)(主批記錄的制訂&控制、產(chǎn)品生產(chǎn))Laboratories(AnalysisofMaterialSample,Qualification&CalibrationofInstruments)實(shí)驗(yàn)室(物料樣品的分析、儀器確認(rèn)&校正)APIC翻譯JULIA頁(yè)11/60ControlofPackaging&Labels包裝&標(biāo)簽控制Quality(ChangeControl,ComplaintManagement)質(zhì)量(變更控制、投訴管理)MaterialsManagement(DistributionofFinalProduct)物料管理(最終產(chǎn)品的銷售運(yùn)輸)FacilitiesandEquipment(Calibration)設(shè)施與設(shè)備(校正)Thisapproachnotonlyhelpstovisualizeallactivitiessequencingwithinaprocess,butalsointeractionsbetweentheseactivitiesaswellasinteractionsbetweenprocesses.該方法不僅有助于實(shí)現(xiàn)流程內(nèi)所有活動(dòng)排序的可視化，亦有助于這些活動(dòng)之間的相互作用和流程之間的相互作用。BusinessProcessMappingisanapproachtovisuallyrepresentflowsforgivenprocesses.Itisintendedtoprovideaclearschematicviewoftheactivitiesperformed,stepbystepfromstarttofinish.業(yè)務(wù)流程分析是一種以可視方式呈現(xiàn)指定流程的業(yè)務(wù)流，意在為所實(shí)施的活動(dòng)從開始到結(jié)束按步驟順序提供一個(gè)清晰的示意圖。AfterdefiningwhichbusinessprocessesareGxPrelevantthenextphaseistomapthemindetail.Itisessentialtoformacrossfunctionalteamtoperformthemappingwhichinvolvestherelevantsubjectmatterexperts(SMEs)andbusinessprocessowners.Thisiscommonlydonebyidentifyingeachstepoftheprocess,asanactionordecisionpoint,andtobuildthesequencedprocess.Dependingonthelevelofdetail,astepcanalsobesubdividedinsub-steps(whichcanbemappedseparately).在指定了哪些業(yè)務(wù)流程與GXP有關(guān)后，下一步是將其詳細(xì)畫出。這是形成一個(gè)涉及相關(guān)主題專家 (SME)和業(yè)務(wù)流程所有者的交叉功能團(tuán)隊(duì)以執(zhí)行流程分析畫出流程圖基本要求。一般是通過(guò)識(shí)別流程每個(gè)步驟來(lái)實(shí)現(xiàn)此工作，作為一個(gè)行動(dòng)或決策點(diǎn)，以及建立有序流程。根據(jù)詳細(xì)程序不同，一個(gè)步驟亦可進(jìn)一步細(xì)分為子步驟(可以分別畫出流程圖)。Theexamplesdisplayedinsection8illustratetheapproach.在第8部分展示的例子說(shuō)明了此方式。lriskbasedguideformanagingdataintegrityVersionMarchAPIC翻譯JULIA頁(yè)12/60ebookinginedateleIDAnalystmeDatessFloweageleworkgenerationebookinginedateleIDAnalystmeDatessFloweageleworkgenerationACB(單流程流)存貯作指令mIDACBFollowingtheexecutionofbusinessprocessmappingincludingthemappingofsub-processes,thefollowingstepsareperformed:在實(shí)施了業(yè)務(wù)流程包括子流程分析和畫出流程圖后，執(zhí)行以下步驟：A.Identifythesystems(bothpaperandelectronic)involvedintheprocessingofGxPdataB.識(shí)別GXP數(shù)據(jù)處理中涉及的系統(tǒng)(紙質(zhì)和電子)C.DefineindividualGxPdataelementsD.定義單個(gè)GXP數(shù)據(jù)要素E.IdentifyGxPdataelementsthatcanbemodified,deletedorre-processedaftercreation(atthenon-administratorleveli.e.eitheraccidentallyordeliberately).F.識(shí)別可在創(chuàng)建之后進(jìn)行修改、刪除或重新處理的GXP數(shù)據(jù)(在非管理員層次，即有意或無(wú)Theexecutionofthesestepsallowsforefficiencyintheexecutionoftheriskassessmentinthenextstageoftheprocess.這些步驟的執(zhí)行可提高流程下一階段中執(zhí)行風(fēng)險(xiǎn)評(píng)估的效率。Figure2Exampleofanindividualsub-processmapping(samplebookingstep)圖2單個(gè)子流程分析舉例(樣品記錄步驟)ereceiptocessflow)mID圖2單個(gè)子流程分析舉例(樣品記錄步驟)錄入日期lriskbasedguideformanagingdataintegrityVersionMarchAPIC翻譯JULIA頁(yè)13/604DataandSystemCategorisation數(shù)據(jù)和系統(tǒng)分類4.1DataSeverityAssessment數(shù)據(jù)嚴(yán)重程度評(píng)估Aproposedapproachistousethestageofmanufacturingastheprimarydeterminantforseverityclassification(high-medium-low),followingtheprincipleofincreasingGxPrequirementsoutlinedinICHQ7.However,additionalfactorssuchasimpactonfinalproductqualitycanbeconsideredtofurtherdifferentiatewithinaseveritycategory(high/veryhigh–medium/mediumhigh所提議的方法可使用生產(chǎn)階段作為嚴(yán)重程度分級(jí)的初步確定(高-中-低)，遵從ICHQ7中逐步增加GXP要求的原則。但是，可考慮引入更多因子如對(duì)最終產(chǎn)品質(zhì)量的影響來(lái)進(jìn)一步區(qū)分同一嚴(yán)重級(jí)別內(nèi)的差異(高/非常高-中等/中高)。Remark:incasecertainGxPdata,dependingonitsuse,belongstodifferentseveritycategoriesthehighestseverityismaintained.(seealsotable3ofchapter5‘Riskassessment’toclarifyseverityrating)注：根據(jù)其用途不同，如果有些GXP數(shù)據(jù)屬于不同嚴(yán)重級(jí)別，則保持最高嚴(yán)重級(jí)別(參見第5章“風(fēng)險(xiǎn)評(píng)估”表3對(duì)嚴(yán)重程度分級(jí)的說(shuō)明)High/veryhighseveritydata:GxPDatageneratedduringanddirectlyassociatedwiththefinalstageofAPIsynthesis(directimpactonproductquality/patientsafety)高/極高嚴(yán)重性數(shù)據(jù)：在API合成最后階段或與之直接相關(guān)生成的GXP數(shù)據(jù)(直接影響產(chǎn)品質(zhì)量/患者安全)Examples(notexhaustive):例子包括(但不僅限于)oTemperatureoffinalcrystallisationo最終結(jié)晶溫度oWeighinganddispensingofcriticalrawmaterialso關(guān)鍵原料稱重和分料oAnalyticaltestingrecordsofAPIoAPI分析檢驗(yàn)記錄oCalibrationofinstrumentscontrollingcriticalprocessparameterso控制關(guān)鍵工藝參數(shù)的儀器校正oCalibrationrecordsofQCinstrumentsoQC儀器校正記錄oCleaningrecordsofaproductionequipmento生產(chǎn)設(shè)備清潔記錄Medium/mediumhighseveritydata:GxPDatageneratedduringanddirectlyassociatedwiththeproductionofAPIintermediatesandrawmaterialstesting.中等/中高級(jí)嚴(yán)重性數(shù)據(jù)：在API中間體生產(chǎn)和原料檢測(cè)中生成或與其直接有關(guān)的GXP數(shù)據(jù)Examples(notexhaustive):例子包括(但不僅限于)oReactionconditionsduringAPIintermediateproductionoAPI中間體生產(chǎn)中的反應(yīng)條件oAnalyticaltestingrecordsofrawmaterialsandintermediates(fromregulatorystartingrawmaterialonwards)o原料和中間體分析檢測(cè)記錄(自注冊(cè)起始物料往后)oCalibrationofinstrumentscontrollingnon-criticalparameterso控制非關(guān)鍵參數(shù)的儀器校正oRecordsofin-processcontrolsforAPIintermediatemanufactureoAPI中間體生產(chǎn)中控記錄APIC翻譯JULIA頁(yè)14/60Lowseveritydata:GxPDatathatisGxPrelevantbutisnotdirectlyassociatedwithrawmaterialtesting,APIintermediateproductionortestingorAPIfinalstageproductionortesting.嚴(yán)重性較低的數(shù)據(jù)：具有GXP相關(guān)性但不直接與原料檢測(cè)、API中間體生產(chǎn)或檢測(cè)，或API最終階段生產(chǎn)或檢測(cè)有關(guān)的GXP數(shù)據(jù)Examples(notexhaustive):例子包括(但不僅限于)oRecordsthatdonotdirectlyimpactoperationsandnotdescribedinthebatchproductionrecord(BPR)oranalyticalmethodso不直接影響操作，未在批生產(chǎn)記錄(BPR)或檢驗(yàn)方法中描述的記錄oLocationandtransfersofmaterials(nottemperaturesensitive)ormaterialtransferrequestso物料位置和轉(zhuǎn)移(對(duì)溫度不敏感)或物料轉(zhuǎn)移請(qǐng)求oAutoclaveGxPdataforwastemediadisposalo廢棄培養(yǎng)基處理的滅菌器GXP數(shù)據(jù)oOperatoraccesstoproductionareao操作員進(jìn)出生產(chǎn)區(qū)域oGxPdatageneratedduringthedevelopmentofprocessorsystemsorequipment,priortothevalidationorqualificationo在工藝或系統(tǒng)或設(shè)備開發(fā)期間驗(yàn)證或確認(rèn)之前生成的GXP數(shù)據(jù)oShiftschedulingo排班表oPlanningdata(productionschedule)o計(jì)劃數(shù)據(jù)(生產(chǎn)計(jì)劃)oShiftchangenoteso交接班日志oTimeandattendanceinformation(timeandattendancesystemmaynotbequalified,butmaybeusedduringinvestigations)o時(shí)間和考勤信息(時(shí)間和考勤系統(tǒng)可不確認(rèn)，但可能會(huì)在調(diào)查中使用)oSafetytrainingo安全培訓(xùn)oAnalysisofchemicalsbeforestartingmaterialso起始物料之前的化學(xué)品分析oForinformationonlyinprocesscontrolso僅供過(guò)程控制參考的信息4.2SystemProfiling系統(tǒng)概況分析Oncethesystemisidentified,itcanbefurthercategorisedbasedupontheGxPdatathatisgeneratedinandbythesystem.Thissystemcategorisationwillhelpselectingthenecessaryquestionsduringthesystemassessmentinthenextstep.(seesection4.3).一旦對(duì)系統(tǒng)進(jìn)行了識(shí)別，即可進(jìn)一步將其根據(jù)其中生所的GXP數(shù)據(jù)和系統(tǒng)類別進(jìn)行分類。此系統(tǒng)分類有助于在下一步系統(tǒng)評(píng)估中選擇必要的問題(參見第4.3部分)。Remark:pleasenotethatthesecategoriesaredifferentfromcategoriesasdefinedinGAMPguidesincethefocushereisonthedatalifecycleinsteadofonthesystem.注：請(qǐng)注意這些類型與GAMP指南中所定義的類別是不同的，因?yàn)檫@里關(guān)注的是數(shù)據(jù)生命周期而不是系lriskbasedguideformanagingdataintegrityVersionMarchAPIC翻譯JULIA頁(yè)15/604.2.1Systemcategorization系統(tǒng)分類Thefollowing6categoriesareproposed.提議分為以下6類Remark:備注(1)ItisimportanttoevaluatethesysteminrelationtoallGxPdataitprocesses.Incaseofdifferentoutcomes,thehighestcategoryismaintained.Forhybridsystemsbothcategorieshavetobetakenintoaccount.重點(diǎn)是要評(píng)估與其所處理的所有GXP數(shù)據(jù)有關(guān)的系統(tǒng)。如果有不同結(jié)果，使用最高類別?；旌舷到y(tǒng)則要考慮兩種類別。(2)ItisimportantthattheevaluationisdonefromthepointofviewofthesystemwheretheGxPdataisgeneratedandnotwheretheGxPdataisbeingtransferredto.重點(diǎn)是要從生成GXP數(shù)據(jù)的系統(tǒng)而不是GXP數(shù)據(jù)被轉(zhuǎn)移到的系統(tǒng)的角度進(jìn)行評(píng)估。Category1:Anon-electronicsystem.NoGxPdataarestored.Typicalexamplesarebagsealers,pHpaper,densitymeters,CAPAlogbook.第1類非電子系統(tǒng)。沒有存貯GXP數(shù)據(jù)。典型的例子是袋子封簽，pH重計(jì)、CAPA臺(tái)賬Category2:AnelectronicsystemandthegeneratedGxPdataisnotstoredandmanuallytransferredonpaper.TypicalexamplescouldincludepHmeters,balances,polarimeterswithmanualadjustableawavelength,pressuregaugewithdisplay.第2類生成GXP數(shù)據(jù)但不存貯，而是手動(dòng)轉(zhuǎn)移至紙上的電子系統(tǒng)。典型的例子可包括pH計(jì)、天平、可手動(dòng)調(diào)節(jié)波長(zhǎng)的折光計(jì)、有顯示的壓力Category3:AnelectronicsystemwithsomelimitedmanualadjustableinputdataandthegeneratedGxPdataisnotstoredbutprintedout.TypicalexamplescouldbepotentiometrictitratorsnotconnectedtoaPC,balanceswithprinter.第3類電子系統(tǒng)，可手動(dòng)手限調(diào)整輸入數(shù)據(jù)并生成GXP數(shù)據(jù)，不能存貯但可以打印出來(lái)。典型例子是未連接至電腦的滴定儀、接有打印機(jī)的天Category4:AnelectronicsystemwithsomelimitedmanualadjustableinputdataandthegeneratedGxPdataisnotstoredbutsentviaaninterfacetoanothersystem,e.g.acat5or6.Typicalexamplescouldbetemperaturesensors.第4類電子系統(tǒng)，可手動(dòng)有限調(diào)整輸入數(shù)據(jù)并生成GXP數(shù)據(jù)，不能存貯但經(jīng)過(guò)接口傳輸至另一個(gè)系統(tǒng)，例如五類線和六類線，典型例子是溫度Category5:AnelectronicsystemwhereGxPdataarepermanentlystored,andtheseGxPdataarenotmodifiedbytheusertogenerateresults(staticGxPdata).ExamplescouldincludeUVinstrumentsorIRinstrumentsusedforidentificationtesting,inlineparticlesizeandTOCtestin