產(chǎn)品技術(shù)轉(zhuǎn)移

產(chǎn)品技術(shù)轉(zhuǎn)移（總17頁）-本頁僅作為文檔封面，使用時請直接刪除即可--內(nèi)頁可以根據(jù)需求調(diào)整合適字體及大小-ProductTechnicalTransfer

產(chǎn)品技術(shù)轉(zhuǎn)移Objective目的Thisproceduredefinestheprocedurefortheproducttechnicaltransferfromthetransferortotransferee.Makesurethetechnicaltransferfollowsastandardprocedure,toensurethatproductsareproducedandstoredaccordingtoappropriatedocumentationinordertoobtaintherequiredquality.本規(guī)程規(guī)定了產(chǎn)品技術(shù)由轉(zhuǎn)出方轉(zhuǎn)移到接收方的標(biāo)準(zhǔn)操作流程，使產(chǎn)品引入過程規(guī)范地運(yùn)作，有效地評估和控制新產(chǎn)品引入的風(fēng)險，找出產(chǎn)品工藝和質(zhì)量控制的關(guān)鍵控制點，確保產(chǎn)品能順利穩(wěn)定地轉(zhuǎn)移至生產(chǎn)線進(jìn)行投產(chǎn)，穩(wěn)定高效地生產(chǎn)出符合產(chǎn)品質(zhì)量標(biāo)準(zhǔn)的產(chǎn)品。Scope范圍ThisSOPappliestothetechnicaltransferofalltheproductsfromdifferentresourcesincludingresearchinstitutesandcompaniescooperationwithSLP.本規(guī)程適用于所有來源的產(chǎn)品，包括由研發(fā)機(jī)構(gòu)或其它公司向生產(chǎn)線技術(shù)轉(zhuǎn)移的所有產(chǎn)品。Responsibilities職責(zé)TDisresponsiblefordrafting,reviewing,revising,trainingandimplementingthisSOP.技術(shù)部負(fù)責(zé)本規(guī)程的起草、審核、修訂、培訓(xùn)和執(zhí)行。QA,QC,production,logisticdepartmentisresponsibleforreviewingandsupervisingtheimplementationofthisprocedure.QA、QC、生產(chǎn)及物控部門負(fù)責(zé)審核并監(jiān)督本規(guī)程的執(zhí)行。Qualitydirectorisresponsibleforapprovingthisprocedure.質(zhì)量總監(jiān)負(fù)責(zé)本規(guī)程的批準(zhǔn)。Technicaltransferstaffshouldunderstandandimplementthisprocedure.技術(shù)轉(zhuǎn)移相關(guān)人員理解并執(zhí)行本規(guī)程。Definitions定義Technicaltransferorreferstotheoriginalmanufactureorinstituteswhokeepthetechnicaldata.技術(shù)轉(zhuǎn)出方是指持有產(chǎn)品技術(shù)資料的原生產(chǎn)商或研究單位。TechnicaltransfereereferstotheteamthatconsistofTD,PD,QC,QA,etc..技術(shù)接收方是指由技術(shù)部、生產(chǎn)部、QC部、QA部等部門成員組成的項目組。Procedures程序Classificationbyproductsource產(chǎn)品來源分類contractprocessingproduct國內(nèi)委托加工產(chǎn)品DomesticcontractprocessingreferstotheprocessingproducingproductsbasingonthedrugregulationsofChinaandthetargetmarketwillbetheChinesemainland.國內(nèi)委托加工是指協(xié)助國內(nèi)企業(yè)按照中國法規(guī)要求生產(chǎn)且最終產(chǎn)品在中國境內(nèi)上市銷售的產(chǎn)品。contractprocessingproduct境外委托加工產(chǎn)品OverseascontractprocessingreferstocontractprocessingproducingproductsbasingonEP,USP,JP,BPect.andthetargetmarketwillbetheoverseas.境外代加工是指協(xié)助其它企業(yè)按照國外法規(guī)要求生產(chǎn)且最終產(chǎn)品在境外上市銷售的產(chǎn)品。product公司注冊產(chǎn)品Othercompaniesorinstitutestransfertheirtechnicalachievement,technologyandinformationtoourcompanybyvariousmeans,andwewillhavetheallorpartoftheownershipoftheproduct.Forexample,ANDA,NDAandnewproductwhichwillbedeclaredindomestic.外部企業(yè)或研究單位通過各種方式將科學(xué)技術(shù)成果、技術(shù)、信息轉(zhuǎn)讓給我公司，最終我公司擁有該技術(shù)的全部或部分所有權(quán)的產(chǎn)品，如ANDA、NDA、國內(nèi)新藥申報產(chǎn)品等。Procedureofproducttechnicaltransfer產(chǎn)品技術(shù)轉(zhuǎn)移程序theprojectofproducttechnicaltransfer建立產(chǎn)品技術(shù)轉(zhuǎn)移項目Confirmthedevelopmentstatusofprocessandanalyticalmethodsoftransferproject.確定產(chǎn)品技術(shù)轉(zhuǎn)移項目的產(chǎn)品的處方和工藝研發(fā)的狀態(tài)。Designatetheresponsiblepersonofthetransferorandthetransferee,establishtechnicaltransferteam.確定轉(zhuǎn)出方和接收方項目負(fù)責(zé)人，組建技術(shù)轉(zhuǎn)移小組。Thetransfereeteamreviewthetechnicaldocumentsreferredbytransferor,accordingto<GeneralTechnologyTransferChecklist>.Signon<TechnicalTransferRecord>toconfirmtheycomplywithrequirement.Copyorscanreferencedocumentsusedintestmethodstransfer.技術(shù)轉(zhuǎn)移小組審核技術(shù)轉(zhuǎn)出方提交的轉(zhuǎn)移資料，審核工作參見《通用產(chǎn)品技術(shù)轉(zhuǎn)移檢查表》。核對文件清單，確認(rèn)符合要求和法規(guī)規(guī)定后在《技術(shù)轉(zhuǎn)移記錄》上簽字確認(rèn)。相關(guān)文件復(fù)印一份或掃描一份用于分析方法轉(zhuǎn)移工作。assessmentandchangecontroloftheproducttechnicaltransfer轉(zhuǎn)入產(chǎn)品技術(shù)轉(zhuǎn)移風(fēng)險評估和變更控制Riskassessmentshouldfollowasthetwoways:新產(chǎn)品引入的風(fēng)險評估分為下列兩個方面進(jìn)行：TDmanagershouldorganizetheriskassessmentregardingtotheinteractionfromthenewproductandcurrentproducts.Assesstheaffecttocurrentmaterials,premises,facilities,equipments,personnel,documentation,regulations,production,labcontrol,packaging,labeling.Identifythefeasibilityofthetransferandthefollowingwork.Referto<RiskAssessmentforProductTechnicalTransfer>.技術(shù)部經(jīng)理應(yīng)組織對引入的新產(chǎn)品可能對現(xiàn)有生產(chǎn)線的物料、廠房、設(shè)施、設(shè)備、人員、文件、法規(guī)、生產(chǎn)、實驗室控制、包裝與標(biāo)簽等相關(guān)方面產(chǎn)生的影響和生產(chǎn)線現(xiàn)有產(chǎn)品對新引入產(chǎn)品的影響進(jìn)行風(fēng)險評估，確定轉(zhuǎn)移的可行性和需要開展的工作。參見《新產(chǎn)品引入風(fēng)險分析表》。Projectmanagershouldorganizetheriskassessmentoftheprocessandqualitycontrolforthenewproduct.Identifytheoptimizationandvalidationactivitiesagainsttheproblemsandpotentialrisks.Referto<ProductProcessandQualityRiskAssessment>.項目負(fù)責(zé)人應(yīng)組織質(zhì)量研究和工藝研究人員對引入的新產(chǎn)品的工藝研究和質(zhì)量研究的情況進(jìn)行風(fēng)險分析，針對存在的問題和風(fēng)險制訂相應(yīng)的優(yōu)化措施和驗證措施。參見《新產(chǎn)品工藝和質(zhì)量風(fēng)險分析表》。Changecontrol變更控制Anewproducttransferintoplantisintherangeofchangecontrol,Basingontheresultofriskassessment,supervisetheprocessaccordingtothemanageprocedureof<ChangeControl>iftheprojectisfeasible,takecorrespondencemeasurescombinewiththeproducttransferprotocol,avoidtheinfluencebetweenoriginalproductsandthenewintroducedproduct.在生產(chǎn)線上引入新的產(chǎn)品屬于變更控制范圍，基于風(fēng)險評估的結(jié)果，對于可執(zhí)行的項目根據(jù)《變更控制》管理程序進(jìn)行過程的監(jiān)控，與產(chǎn)品轉(zhuǎn)移方案相結(jié)合采取相應(yīng)措施，避免原有產(chǎn)品和新引入的產(chǎn)品的相互影響。technicaltransferplan編寫技術(shù)轉(zhuǎn)移計劃Writetechnicaltransferplanaccordingtotheprocessflowandthecompany’stechnicaltransferstrategy.根據(jù)新引入產(chǎn)品的工藝流程和公司技術(shù)轉(zhuǎn)移策略等編寫技術(shù)轉(zhuǎn)移計劃。Technicaltransferprotocolandtechnicaltransferlistshouldbewrittenbypersonnelassignedbytheresponsiblepersonfromthetransferee.Anditshouldbeapprovedbythequalitydirector.技術(shù)轉(zhuǎn)移計劃由接收方項目負(fù)責(zé)人指定專人編寫，經(jīng)轉(zhuǎn)移小組審核后由質(zhì)量總監(jiān)批準(zhǔn)。Thetransferee’sresponsiblepersonshouldorganizethemaintenanceandamendmentofthetechnicaltransferplan.技術(shù)轉(zhuǎn)移計劃由接收方負(fù)責(zé)人負(fù)責(zé)組織進(jìn)行維護(hù)和修訂。transferee’sresponsiblepersonshouldorganizedraftingtheproductvalidationmasterplanandmakeitaguidetothevalidationworkwhenanewproductisintroduced.Makesuretheintroductionprocessiseffectivelycontrolledandverified.接收方負(fù)責(zé)人負(fù)責(zé)組織編寫產(chǎn)品驗證主計劃，為新產(chǎn)品的引入所產(chǎn)生的驗證工作提供文件指導(dǎo)和規(guī)劃，保證產(chǎn)品引入過程中相關(guān)工作得到有效的控制和確認(rèn)。Numberingoftheproductvalidationmasterplan:PVMP-Projectcode-SerialNo.,referto<ValidationOrganizationandImplementation>.產(chǎn)品驗證主計劃的編號原則：PVMP-項目編號-版本號，參見《驗證的組織和實施》。Productvalidationmasterplanshouldincludebutnotlimitedto:Productintroductionandproduct-relatedvalidationplanintroductionResponsibilitiesofrelevantdepartmentsAcceptancecriteriaoftheprocessdevelopment,analyticaldevelopmentandcleaningresidueatdifferentstagesoftheproducttransferValidationlistofrelevantequipment,utilitiesandfacilitiesValidationlistofthemethodvalidation,cleaningvalidation,processvalidationandpackagingvalidation.Validationdocumentationlist產(chǎn)品驗證主計劃應(yīng)該包括但是不限于下列內(nèi)容：產(chǎn)品概述和產(chǎn)品相關(guān)驗證的總體計劃簡介。?產(chǎn)品引入相關(guān)部門的職責(zé)和分工從產(chǎn)品轉(zhuǎn)移開始各階段的工藝研究、質(zhì)量研究和清潔殘留的接受標(biāo)準(zhǔn)。引入產(chǎn)品相關(guān)的設(shè)備、設(shè)施和公用系統(tǒng)的驗證清單。引入產(chǎn)品的分析方法驗證、清潔驗證、工藝驗證和包裝驗證清單。相關(guān)驗證文件列表。testmethodstransfer分析方法轉(zhuǎn)移Establishaqualitydevelopmentteamwhoisresponsiblefortheanalyticalmethodtransfer.Assignresponsibilitiesfortheteamleaderandeveryteammember.成立負(fù)責(zé)分析方法轉(zhuǎn)移工作的質(zhì)量研究小組，確定項目質(zhì)量研究負(fù)責(zé)人，明確項目組成員工作職責(zé)分工。QualitydevelopmentteamimplementstheanalyticalmethodtransferaccordingtotechnicaltransferplanandSOP<AnalysisMethodTransfer>.質(zhì)量研究小組根據(jù)技術(shù)轉(zhuǎn)移項目計劃和標(biāo)準(zhǔn)操作程序《分析方法轉(zhuǎn)移》的要求執(zhí)行分析方法轉(zhuǎn)移工作。Qualitydevelopmentteamleadershoulddraftananalyticalmethodtransferplanaswellasananalyticalmethodtrainingplan.Theanalyticalmethodtrainingplanshouldincludetheexplainingandsiteoperation.QualitydevelopmentteamleaderorganizethetrainingoftheanalystsandQApersonnel,toensurethattraineesunderstandtheprocedurescorrectly,andimplementthekeypointsofthenewmethodinanaccurateway.項目質(zhì)量研究負(fù)責(zé)人在制定分析方法轉(zhuǎn)移計劃的同時應(yīng)制定分析方法培訓(xùn)計劃，包括新產(chǎn)品分析方法講析和實際操作兩個方面。對負(fù)責(zé)轉(zhuǎn)移和接受分析方法操作的QC分析人員和相關(guān)QA人員進(jìn)行有效的培訓(xùn)，確保相關(guān)分析人員能正確理解分析程序，準(zhǔn)確無誤地執(zhí)行新產(chǎn)品分析方法的操作要領(lǐng)。technologytransfer工藝技術(shù)轉(zhuǎn)移Establishaprocessdevelopmentteamwhoisresponsiblefortheproductprocesstransfer.Assignresponsibilitiesfortheteamleaderandeveryteammember.成立負(fù)責(zé)工藝技術(shù)轉(zhuǎn)移工作的項目工藝研究小組，確定項目工藝研究負(fù)責(zé)人，明確項目組成員工作職責(zé)分工。Processdevelopmentteamleaderorganizethereviewingoftheproductformulationandprocessdocumentsprovidedbythetransferor,including:FeasibilityoftheprocessRationaleofthequalityspecificationCurrentproductioncapacityagainsttheproductiondemand項目工藝研究負(fù)責(zé)人組織相關(guān)人員對產(chǎn)品轉(zhuǎn)出方提供的產(chǎn)品處方和工藝資料進(jìn)行審核：產(chǎn)品工藝的可行性。質(zhì)量標(biāo)準(zhǔn)設(shè)置的合理性。公司現(xiàn)有生產(chǎn)工藝條件是否滿足產(chǎn)品生產(chǎn)需求。Processdevelopmentteamleadershoulddiscusstheproblemsdiscoveredandquestionswiththetransferor,andconfirmthesolutions.項目工藝研究負(fù)責(zé)人將發(fā)現(xiàn)的問題或存在的疑問與產(chǎn)品轉(zhuǎn)出方相關(guān)人員進(jìn)行討論，確認(rèn)問題的處理措施。Processdevelopmentteamleaderorganizetheteamtodraftaprocesstechnicaltransferprotocolbasingontheriskassessmentresults.Theformatoftheprotocolreferstotheprocesstechnicaltransferprotocoltemplate.Processtechnicaltransferprotocolshouldbedraftedaccordingtothetechnicaltransferagreement,couldincludebutnotlimitedto:Listoftherequiredmaterial,equipment,instrumentandsparepartsListoftheprocessdevelopmentTrialEvaluationofcleaningmethodforchemicalresidueProductprocesstransferplan項目工藝研究負(fù)責(zé)人根據(jù)風(fēng)險分析的結(jié)果，組織項目工藝研究小組起草工藝技術(shù)轉(zhuǎn)移方案，文件格式參照工藝技術(shù)轉(zhuǎn)移方案的模版。工藝技術(shù)轉(zhuǎn)移方案內(nèi)容可以根據(jù)合作協(xié)議的要求編寫，可以參考但不僅限于下列內(nèi)容：新引入的產(chǎn)品所需的物料、設(shè)備、儀器和耗材清單工藝研究實驗清單化學(xué)殘留清潔方法評估工藝技術(shù)轉(zhuǎn)移工作計劃Processdevelopmentteamleadershoulddraftatechnologytransferplanaswellasatechnologytrainingplan.Thetechnologytrainingplanshouldincludetheexplainingandsiteoperation.ProcessdevelopmentteamleaderorganizethetrainingofproductionoperatorandQApersonnel,toensurethattraineescouldtounderstandtheprocedurescorrectly,andimplementthekeypointsofthenewprocessinanaccurateway.項目工藝研究負(fù)責(zé)人在制定工藝技術(shù)轉(zhuǎn)移計劃的同時應(yīng)制定工藝技術(shù)培訓(xùn)計劃，包括新產(chǎn)品工藝技術(shù)的講析和實際操作兩個方面。對負(fù)責(zé)轉(zhuǎn)移和接受工藝技術(shù)操作的生產(chǎn)一線人員和生產(chǎn)現(xiàn)場QA人員進(jìn)行有效的培訓(xùn)，確保相關(guān)人員能正確理解工藝步驟，熟悉新產(chǎn)品的關(guān)鍵工藝參數(shù)和關(guān)鍵控制點，準(zhǔn)確無誤地執(zhí)行新產(chǎn)品工藝技術(shù)的操作要領(lǐng)。Processdevelopmentteamsubmitsrequestsforrequiredmaterials,equipments,instrumentsandsparepartsaccordingtotheapprovedprocesstechnicaltransferprotocol.項目工藝研究組按照批準(zhǔn)的工藝技術(shù)轉(zhuǎn)移方案，申請采購需要補(bǔ)充的物料、設(shè)備、儀器和耗材。Processdevelopmentteamperformsformulationandprocessfeasibilitytrialaccordingtoapprovedprocessdevelopmentprotocol,andpreparesprocessfeasibilitytrialreports項目工藝研究組按照批準(zhǔn)的工藝研究方案對產(chǎn)品處方和工藝適應(yīng)性進(jìn)行確認(rèn)，編寫相應(yīng)的工藝適應(yīng)性研究報告。Afterprocessfeasibilitytrial,theprojectteampreparesprocessoptimization,processscale-upandprocessqualificationprotocolbasingonthecriticalqualityattributesandprocessdesignrequirements,thenimplementtoinvestigateanddeterminethecriticalprocessparametersandequipmentoperationparameters.Referto<ProcessOptimize>,<ProcessScaleUp>,<ProcessQualification>.工藝適應(yīng)性研究結(jié)束，項目組根據(jù)產(chǎn)品的關(guān)鍵質(zhì)量屬性和工藝設(shè)計要求，編寫工藝優(yōu)化、工藝放大和工藝確認(rèn)方案，進(jìn)行產(chǎn)品工藝優(yōu)化、工藝放大和工藝確認(rèn)工作，考察和確定關(guān)鍵工藝參數(shù)和設(shè)備運(yùn)行參數(shù)。參見《工藝優(yōu)化》、《工藝放大》和《工藝確認(rèn)》。Aftertheprocessqualificationbatch,ifthequalitycontrolitemsarecomplywithqualityspecifications,criticalprocessparametersandequipmentoperationparametersareconsistent,andthereportoftheprocessqualificationbatchisapproved,thentheprocesstechnicaltransferiscompleted.Thetransferredproductcouldbeputintoproductionofprocessperformancequalificationbatches.工藝確認(rèn)批生產(chǎn)結(jié)束，若產(chǎn)品的各項質(zhì)量控制項目均符合質(zhì)量標(biāo)準(zhǔn)，關(guān)鍵工藝控制參數(shù)和設(shè)備運(yùn)行參數(shù)穩(wěn)定，工藝確認(rèn)批生產(chǎn)報告批準(zhǔn)后，轉(zhuǎn)移產(chǎn)品可以進(jìn)入工藝性能確認(rèn)階段。Productionmanagerorganizerelevantpersonneltoestablishaprocessvalidationteamtoexecuteprocessperformancequalification.Referto<ProcessValidation>.生產(chǎn)經(jīng)理組織相關(guān)人員成立驗證小組組織實施產(chǎn)品的工藝性能確認(rèn)，參見《工藝驗證》。methoddevelopmentandverification產(chǎn)品清潔方法開發(fā)和確認(rèn)Newlyintroducedproductwillhaveanimpactonthevalidationstatusofcleaningmethodforexistingproducts.Processdevelopmentteamshouldcalculatethemaximumacceptableresiduelevelofeachactiveingredientonunitareaofcommonequipmentandchecksolubilityinthedetergentofnewlyintroducedactiveingredient.新產(chǎn)品的引入將會對生產(chǎn)線原有產(chǎn)品的清潔方法驗證狀態(tài)產(chǎn)生影響，項目工藝研究組應(yīng)計算新引入產(chǎn)品與其它現(xiàn)有產(chǎn)品共用設(shè)備上單位面積表面允許的所有活性成份的最大允許殘留限度值，并確認(rèn)新產(chǎn)品的活性成份在現(xiàn)用清潔溶劑中的溶解度。Analyticaldevelopmentteamshouldpreparetheassaymethodandvalidationprotocolaccordingtothecontentoftheactiveingredient,andverifythechemicalresiduetestingmethod.項目質(zhì)量研究組參考新產(chǎn)品活性成份含量檢測方法開發(fā)和編寫確認(rèn)方案，對新產(chǎn)品活性成份的化學(xué)殘留檢測方法進(jìn)行確認(rèn)。Comparethemaximumacceptableresiduelevelandsolubilityinthedetergentoftheactiveingredientsinthenewlyintroducedproductsandexistingproducts.Basedonthecomparison,threedifferentmeasuresareasfollow:綜合比較生產(chǎn)線現(xiàn)有產(chǎn)品和新產(chǎn)品處方中活性成份的最大允許殘留限度值和活性成份在現(xiàn)用清潔溶劑中的溶解度。根據(jù)比較結(jié)果可以分下列三種情況處理：ClassI:ifthemaximumacceptableresiduelevelorsolubilityinthecurrentdetergentoftheactiveingredientinthenewlyintroducedproductislowerthanthatoftheexistingproducts,orthereisingredientintheproductformuladifficulttoclean,theefficiencyofthecleaningmethodshouldbeverifiedusingtheequipmentinpilotplant.I類：若新產(chǎn)品活性成份的最大允許殘留限度值或在現(xiàn)用清潔溶劑中的溶解度最低，或者新產(chǎn)品處方成份中有難以清潔的成份，應(yīng)在中試車間的工藝設(shè)備對清潔方法的清潔效果進(jìn)行確認(rèn)。ClassII:ifthemaximumacceptableresiduelevelandsolubilityinthecurrentdetergentoftheactiveingredientinthenewlyintroducedproductishigherthanthatoftheexistingproducts,theefficiencyofthecleaningmethodisnotnecessarytobeverifiedusingtheequipmentinpilotplant.II類：若新產(chǎn)品活性成份的最大允許殘留限度值和在現(xiàn)用清潔溶劑中的溶解度比現(xiàn)有產(chǎn)品的都大，則不需要在中試車間的工藝設(shè)備上對清潔方法的清潔效果進(jìn)行確認(rèn)。ClassIII:ifthemaximumacceptableresiduelevelofcurrentproductswillhavenegativeimpactonthenewlyintroducedproduct,arevisedmaximumacceptableresiduelevelshouldbeestablishedforcurrentproductsandperformre-validation.III類：如果現(xiàn)有產(chǎn)品活性成份的最大允許殘留限度值不符合新產(chǎn)品要求，應(yīng)對現(xiàn)有產(chǎn)品進(jìn)行限度修訂和清潔再驗證。FortheClassIproduct,ifcurrentcleaningmethodhasbeenverifiedonthepilotplantequipmentandtheresultshowsthatitissuitableforthenewproduct,then,thescale-upproductionaswellasthecleaningvalidationcanbeenforcedonthecommercialproductionline.對于I類中經(jīng)中試車間工藝設(shè)備確認(rèn)采用現(xiàn)有清潔方可以清潔干凈的產(chǎn)品，新產(chǎn)品可以正式轉(zhuǎn)入生產(chǎn)線進(jìn)行放大生產(chǎn)，同時進(jìn)行清潔驗證。ForClassIproductforwhichcurrentcleaningmethodcouldnotbeverifiedusingpilotplantequipment,anewcleaningmethodshouldbedevelopedandverifiedusingpilotplantequipmentbeforescale-upinproductionplant.Afterverification,scale-upproductionandcleaningvalidationinthecommercialproductionlinecouldbestarted.對于I類中經(jīng)中試車間工藝設(shè)備確認(rèn)采用生產(chǎn)線現(xiàn)有清潔方法難以清潔干凈的產(chǎn)品，應(yīng)開發(fā)針對該產(chǎn)品的清潔方法，并應(yīng)在進(jìn)入生產(chǎn)線進(jìn)行放大生產(chǎn)前，在中試車間對新開發(fā)清潔方法的清潔效果進(jìn)行確認(rèn)。確認(rèn)合格后，新產(chǎn)品可以正式轉(zhuǎn)入生產(chǎn)線進(jìn)行放大生產(chǎn)，同時進(jìn)行清潔驗證。ForClassIIproduct,theefficiencyofcleaningmethodshouldbefurtherverifiedduringscale-upproduction.CleaningvalidationreportshouldbeapprovedbyQualityDirector,thatindicatestheintroductionofnewproductwillnothavenegativeimpactonthecleaningvalidationstatusoftheproductionline.II類產(chǎn)品，在生產(chǎn)線進(jìn)行放大批生產(chǎn)的同時，應(yīng)對使用現(xiàn)有清潔方法的清潔效果進(jìn)行確認(rèn)，清潔確認(rèn)報告經(jīng)質(zhì)量總監(jiān)批準(zhǔn)后，標(biāo)志著新產(chǎn)品的引入不會影響生產(chǎn)線清潔方法的驗證狀態(tài)。Theproceduresofestablishmentofresiduallimits,microbialacceptancecriteria,detergentresiduallimitsandsamplingmethodshouldbereferringto<CleaningValidation>.關(guān)于殘留物、微生物、清潔劑殘留的可接受限度建立和取樣方法等程序參見《清潔驗證》。technicaltransferreport產(chǎn)品技術(shù)轉(zhuǎn)移報告Whenthetransferoftestmethodsandpharmaceuticaltechnologyarefinished,Atechnicaltransferreportshouldbedraftedbypersonnelfromtransfereeandreviewedbythetransferoraswellasthetransferee.Itshouldbeapprovedbythequalitydirectorfinally,thatmeansthetechnicaltransfersuccessful.Refertoannex2〈ProductTransferReportOutline〉.分析方法和工藝技術(shù)轉(zhuǎn)移成功完成之后，技術(shù)接收方負(fù)責(zé)編寫技術(shù)轉(zhuǎn)移報告，由技術(shù)轉(zhuǎn)出和接收方負(fù)責(zé)人審核后交質(zhì)量總監(jiān)批準(zhǔn)確認(rèn)產(chǎn)品技術(shù)轉(zhuǎn)移工作完畢。參見附錄2《產(chǎn)品轉(zhuǎn)移報告提綱》。Managementofprojectdocuments產(chǎn)品技術(shù)轉(zhuǎn)移的項目文件管理Allthedocumentsgeneratedduringthetechnicaltransferprocessshouldbenumbered,archivedandretrievedaccordingto<ProductDevelopmentDocumentsManagement>.Thedocumentadministratorshouldcheckandsortingallthedocumentsandmakesuretheyareputawayattheendofaworkstage.技術(shù)轉(zhuǎn)移過程中產(chǎn)生的所有文件應(yīng)按《研發(fā)項目文件管理》的要求分階段進(jìn)行整理，每一個工作結(jié)束，技術(shù)部文件管理人員應(yīng)對文件整理工作進(jìn)行檢查，確認(rèn)所有相關(guān)文件已經(jīng)按照要求整理好。thescale-upandprocessqualificationbatch,theprotocolofscale-upandprocessqualification,analyticalmethodstandardoperationproceduresandproductspecificationshouldbeapprovedbythequalitydirector.ThecopiesofanalyticalmethodstandardoperationproceduresandproductspecificationsshouldbesenttoQAandQC,theoriginalshouldbearchivedinprojectdocumentfolder.產(chǎn)品進(jìn)行工藝放大和工藝確認(rèn)前，工藝放大（確認(rèn)）方案、分析方法操作規(guī)程和質(zhì)量標(biāo)準(zhǔn)草案應(yīng)經(jīng)過質(zhì)量總監(jiān)批準(zhǔn)。分析方法操作規(guī)程和質(zhì)量標(biāo)準(zhǔn)草案的復(fù)印件兩份分別轉(zhuǎn)移給QC和QA,原件存在產(chǎn)品轉(zhuǎn)移項目文件夾內(nèi)。processqualification,projectteamleadershouldorganizetheteammembers,productionsupervisor,QCsupervisorandQApersonneltoreviewtheanalyticalmethodstandardoperationproceduresandthespecificationsofAPI,excipients,intermediateproductsandfinishproduct,identifyproblemsanddeterminethecorrespondingmeasures.工藝確認(rèn)結(jié)束后，產(chǎn)品轉(zhuǎn)移項目負(fù)責(zé)人應(yīng)召集項目組成員、生產(chǎn)主管、QC主管、QA等相關(guān)人員對新產(chǎn)品分析方法操作規(guī)程和原料、輔料、中間產(chǎn)品、成品的質(zhì)量標(biāo)準(zhǔn)草案進(jìn)行審核，找出文件中存在的問題確定修改方案。theprocessperformancequalificationbatches,QCandQAdepartmentshouldpreparetheSOPsofanalyticalmethodandspecificationsaccordingtotherevisedproposalanddocumentformatspecialforourcompany..工藝驗證批（生物批）生產(chǎn)前，QC和QA部門負(fù)責(zé)按照確定的修改方案和公司的文件格式要求起草商業(yè)生產(chǎn)用的產(chǎn)品分析方法標(biāo)準(zhǔn)操作規(guī)程和原料、輔料、中間產(chǎn)品、成品的質(zhì)量標(biāo)準(zhǔn)。managerorganizerelevantpersonneltopreparemasterformula,batchprocessingrecord,batchpackagingrecord,processvalidationprotocolandotherproductionstandardoperationproceduresneeded.生產(chǎn)經(jīng)理組織相關(guān)人員編寫工藝規(guī)程、批生產(chǎn)記錄、批包裝記錄、工藝性能確認(rèn)方案或其他需要增加的生產(chǎn)標(biāo)準(zhǔn)操作規(guī)程。processperformancequalificationbatchesarefinished,projectteamleadershouldorganizedocumentadministratorofTDanddocumentspecialisttochecktheprojectdocuments.Ensureallthedocumentshavebeenarchivedinproductfilefolderalready.Refertoannex3<ProductTechnicalTransferDocumentList>.工藝性能確認(rèn)工作結(jié)束，產(chǎn)品轉(zhuǎn)移項目負(fù)責(zé)人應(yīng)組織技術(shù)文件管理員、QA文件控制專員等對項目文件進(jìn)行檢查，確認(rèn)所有項目文件資料已經(jīng)歸入相應(yīng)的產(chǎn)品檔案之中，參見附錄3《產(chǎn)品技術(shù)轉(zhuǎn)移文件清單》。6Annex附錄Annex1:ProductTechnicalTransferflowchart附錄1：產(chǎn)品技術(shù)轉(zhuǎn)移流程圖ProductTransferReportOutline附錄2：產(chǎn)品轉(zhuǎn)移報告提綱ProductTechnicalTransferDocumentList附錄3：產(chǎn)品技術(shù)轉(zhuǎn)移文件清單TemplateofProtocolforPharmaceuticalTransfer附錄4：工藝技術(shù)轉(zhuǎn)移方案模板F-07-0035RiskAssessmentforProductTechnicalTransfer新產(chǎn)品引入風(fēng)險分析表F-07-0036GeneralTechnologyTransferChecklist通用產(chǎn)品技術(shù)轉(zhuǎn)移檢查表F-07-0037TechnicalTransferRecord技術(shù)轉(zhuǎn)移記錄F-07-0021RiskAssessmentforProcessandQualityControl新產(chǎn)品工藝和質(zhì)量風(fēng)險分析表RelatedDocuments相關(guān)文件SOP01601ChangeControl變更控制SOP01613QualityRiskManagement質(zhì)量風(fēng)險管理SOP01801ValidationOrganizationandImplementation驗證的組織和實施SOP07019AnalysisMethodTransfer分析方法轉(zhuǎn)移SOP07010ProductDevelopmentDocumentsManagement研發(fā)項目文件管理SOP07045ProcessOptimize工藝優(yōu)化SOP07047ProcessScaleUp工藝放大SOP07048ProcessQualification工藝確認(rèn)SOP04015ProcessValidation工藝驗證SOP04016CleaningValidation清潔驗證Reference參考資料None無Annex1：附錄1：Annex2:ProductTransferReportOutline附錄2：產(chǎn)品轉(zhuǎn)移報告提綱Pharmaceuticaldevelopmentsummary藥物研發(fā)總結(jié)Includeashortdescriptionofthedrugproductdevelopmenthistory.包括對藥物研發(fā)過程的概述。Scale-upSummary放大概述Provideashortdescriptionofthemanufacturingdevelopmenthistoryfrompilotscaletofullscale.提供對中試規(guī)模到大生產(chǎn)的研發(fā)過程的概述。ProductComposition產(chǎn)品成分Compareeachseparateingredientintheproductandcorrespondingquantitativecompositionbetweenthedevelopmentsiteandmanufacturingsite.比較研發(fā)的和生產(chǎn)的產(chǎn)品中所含的不同成分及其含量。Explainanydifferencesencounteredbetweenthedevelopmentsiteandmanufacturingsite.解釋在研發(fā)地點和生產(chǎn)地點的不同之處的原因。RawMaterials原輔料Compareeachseparaterawmaterialandcorrespondingcodenumber,supplier,trademarkandspecificationreferencebetweenthedevelopmentsiteandmanufacturingsite.比較在研發(fā)地點和生產(chǎn)地點的原輔料和相應(yīng)的代號、供應(yīng)商、商標(biāo)和參照的質(zhì)量標(biāo)準(zhǔn)。Explainanydifferencesencounteredbetweenthedevelopmentsiteandmanufacturingsite.解釋在研發(fā)地點和生產(chǎn)地點的不同之處的原因。Immediatecontainer內(nèi)包裝Compareeachimmediatecontainercomponent,supplierandspecificationreferencebetweenthedevelopmentsiteandmanufacturingsite.比較在研發(fā)地點和生產(chǎn)地點的內(nèi)包裝材料的成分、供應(yīng)商和參照的質(zhì)量標(biāo)準(zhǔn)。Explainanydifferencesencounteredbetweenthedevelopmentsiteandmanufacturingsite.解釋在研發(fā)地點和生產(chǎn)地點的不同之處的原因。Productspecificationsandtestmethods質(zhì)量標(biāo)準(zhǔn)和檢驗方法Includeasummarytableidentifyingthetest,specificationandcorrespondinganalyticalmethod.包括一個匯總表格列出檢驗、質(zhì)量標(biāo)準(zhǔn)和對應(yīng)的分析方法。Manufacturingprocess生產(chǎn)工藝Comparethemanufacturingequipment,operationparametersandIPClimitsforeachstepoftheprocessbetweenthedevelopmentsiteandthemanufacturingsite.分別比較在研發(fā)地點和生產(chǎn)地點的每一工藝步驟的生產(chǎn)設(shè)備、操作參數(shù)和IPC限度。Explainanydifferencesencounteredbetweenthedevelopmentsiteandmanufacturingsite.解釋在研發(fā)地點和生產(chǎn)地點的不同之處的原因。Includeaprocessflowdiagram.包括一個工藝流程圖。Packaging包裝工藝Providedescriptionofpackagingpresentation,includingreferencetospecifications.提供一份詳細(xì)包裝描述，包括參照的標(biāo)準(zhǔn)。Validation驗證ProvideAnalysisMethodandcleaningvalidationstrategyand/orreports.提供分析方法驗證和清潔驗證的方法或者報告。Providesterilizationvalidationstrategyand/orreports(ifapplicable).如果需要，提供滅菌驗證的方法和報告。Stability穩(wěn)定性Provideregistrationstabilitystrategyandstabilityprotocol.提供為注冊資料申報準(zhǔn)備的穩(wěn)定性實驗的方法和穩(wěn)定性實驗的方案。Conclusions結(jié)論P(yáng)rovideconclusionsregardingtheproducttechnicaltransferexperiences.為產(chǎn)品技術(shù)轉(zhuǎn)移提供總結(jié)。ApprovalsignaturesfromtheDevelopmentteamandOperationsteam.轉(zhuǎn)出方和接受方的簽名批準(zhǔn)。

Annex3:ProductTechnicalTransferDocumentList附錄3：產(chǎn)品技術(shù)轉(zhuǎn)移文件清單No.Item項目1CustomerDocuments&Information合作方的文件和信息Contracts合同Priceagreement價格合同Purchaseorder-supplycontract采購訂單合同Annualpurchasingplan年度采購計戈1JQAagreement質(zhì)量協(xié)議APIAPI-Vendor&Qualification原料藥-供應(yīng)商和供應(yīng)商審計API-AnalyticalMethods&Specification原料藥-分析方法和質(zhì)量標(biāo)準(zhǔn)API-Residues-AnalyticalMethods(forCleaningValidation)原料藥殘留-分析方法(清潔驗證)SDS-SafetyDataSheet安全數(shù)據(jù)表Excipents,Blister(ALU,PVC),Box,Leaflet,BulkTabletContainer,Transportbox,Cleaning輔料、內(nèi)包裝材料、紙盒、說明書、半成品包裝容器、外箱、清潔方法Materials-Vendor&Qualification物料-供應(yīng)商和供應(yīng)商審計Materials-AnalyticalMethods&Specification物料-分析方法和質(zhì)量標(biāo)準(zhǔn)DetergentResidues-AnalyticalMethod(forCleaningQualification)清潔劑殘留-分析方法(清潔驗證)DrugProduct&intermediates成品和中間產(chǎn)品Specification質(zhì)量標(biāo)準(zhǔn)Identification鑒別方法Assay含量測定方法ContentUniformity含量均勻度測定方法RelatedSubstances有關(guān)物質(zhì)測定方法Dissolution溶出度測定方法MicrobiologicalPurity微生物測定方法Formula&Process處方和工藝Formula&ProcessDescription處方和工藝描述BatchRecord批記錄ValidationProtocol驗證方案DesignDrawings設(shè)計圖紙PunchesanddiesDesignDrawing沖模和中模設(shè)計圖紙BlisterDesignDrawing鋁塑板設(shè)計圖紙BottleandCapDesignDrawing瓶和蓋設(shè)計圖紙BoxDesignDrawing紙盒設(shè)計圖紙TransportboxDesignDrawing外箱設(shè)計圖紙

Equipment&InstrumentsandMateriallist設(shè)備、儀器和物料清單EquipmentList設(shè)備清單InstrumentsList儀器清單MaterialList物料清單ImportfromCustoms合作方輸入CustomsDocumentsforImportofMaterials物料文件PurchaseOrder/Contract采購訂單或合同BusinessLicenseofManufacturer（OnlyinLegalProvisionsList）物料制造商的營業(yè)執(zhí)照（僅適應(yīng)于法定清單內(nèi)物料）MaterialsList物料清單Material’sSanitationPermit（OnlyinLegalProvisionsList）物料制造商的衛(wèi)生許可證（僅適應(yīng)于法定清單內(nèi)物料）GMPCertificateofManufacturer物料制造商的GMP證書CustomsDocumentsforImportofRLD標(biāo)準(zhǔn)對照品（成品）文件PurchaseOrder采購訂單CustomsDocumentsforImportofCRS標(biāo)準(zhǔn)品（工作對照品）文件PurchaseOrder采購訂單Export出口CustomsDocumentsforExportofDrugProduct出口產(chǎn)品的合作方文件Customer'sMA（MarketingAuthorization）ofeachTabletStrength每個規(guī)格產(chǎn)品的上市許可證BusinessLicenseofCustoms合作方的營業(yè)執(zhí)照BusinessLicenseofManufacturer（English）公司的營業(yè)執(zhí)照（英文版）GMPCertificateofManufacturer公司的GMP證書Transportation運(yùn)輸Decision:AirorSeaShipment運(yùn)輸方式：空運(yùn)或海運(yùn)PriceQuotations報價PriceAgreement價格合同Carri