產(chǎn)品技術(shù)轉(zhuǎn)移

ProductTechnicalTransfer產(chǎn)品技術(shù)轉(zhuǎn)移1Objective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(guò)程標(biāo)準(zhǔn)地運(yùn)作，有效地評(píng)估和控制新產(chǎn)品引入的風(fēng)險(xiǎn)，找出產(chǎn)品工藝和質(zhì)量控制的關(guān)鍵控制點(diǎn)，確保產(chǎn)品能順利穩(wěn)定地轉(zhuǎn)移至生產(chǎn)線進(jìn)展投產(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。2Scope范圍ThisSOPappliestothetechnicaltransferofalltheproductsfromdifferentresourcesincludingresearchinstitutesandcompaniescooperationwithSLP.本規(guī)程適用于所有來(lái)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。3Responsibilities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,QA、QC、生產(chǎn)及物控部門負(fù)責(zé)審核并監(jiān)視本規(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。4Definitions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工程組。5Procedures程序Classificationbyproductsource產(chǎn)品來(lái)源分類Domesticcontractprocessingproduct國(guó)內(nèi)委托加工產(chǎn)品DomesticcontractprocessingreferstotheprocessingproducingproductsbasingonthedrugregulationsofChinaandthetargetmarketwillbetheChinesemainland.國(guó)內(nèi)委托加工是指協(xié)助國(guó)內(nèi)企業(yè)按照中國(guó)法規(guī)要求生產(chǎn)且最終產(chǎn)品在中國(guó)境內(nèi)上市銷售的產(chǎn)品。Overseascontractprocessingproduct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(guó)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。Registryproduct公司注冊(cè)產(chǎn)品Othercompaniesorinstitutestransfertheirtechnicalachievement,technologyandinformationtoourcompanybyvariousmeans,andwewillhavetheallorpartoftheownershipoftheproduct.Forexample,ANDA,NDAandnewproductwhichwillbedeclaredindomestic.外部企業(yè)或研究單位通過(guò)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)的全部或局部所有權(quán)的產(chǎn)品，如ANDA、NDA、國(guó)內(nèi)新藥申報(bào)產(chǎn)品等。Procedureofproducttechnicaltransfer產(chǎn)品技術(shù)轉(zhuǎn)移程序Establishtheprojectofproducttechnicaltransfer建立產(chǎn)品技術(shù)轉(zhuǎn)移工程Confirmthedevelopmentstatusofprocessandanalyticalmethodsoftransferproject.確定產(chǎn)品技術(shù)轉(zhuǎn)移工程的產(chǎn)品的處方和工藝研發(fā)的狀態(tài)。Designatetheresponsiblepersonofthetransferorandthetransferee,establishtechnicaltransferteam.確定轉(zhuǎn)出方和接收方工程負(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(duì)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。Riskassessmentandchangecontroloftheproducttechnicaltransfer轉(zhuǎn)入產(chǎn)品技術(shù)轉(zhuǎn)移風(fēng)險(xiǎn)評(píng)估和變更控制Riskassessmentshouldfollowasthetwoways:新產(chǎn)品引入的風(fēng)險(xiǎn)評(píng)估分為以下兩個(gè)方面進(jìn)展：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(duì)引入的新產(chǎn)品可能對(duì)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(shí)驗(yàn)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(duì)新引入產(chǎn)品的影響進(jìn)展風(fēng)險(xiǎn)評(píng)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(xiǎn)分析表?。Projectmanagershouldorganizetheriskassessmentoftheprocessandqualitycontrolforthenewproduct.Identifytheoptimizationandvalidationactivitiesagainsttheproblemsandpotentialrisks.Referto<ProductProcessandQualityRiskAssessment>.工程負(fù)責(zé)人應(yīng)組織質(zhì)量研究和工藝研究人員對(duì)引入的新產(chǎn)品的工藝研究和質(zhì)量研究的情況進(jìn)展風(fēng)險(xiǎn)分析，針對(duì)存在的問(wèn)題和風(fēng)險(xiǎn)制訂相應(yīng)的優(yōu)化措施和驗(yàn)證措施。參見?新產(chǎn)品工藝和質(zhì)量風(fēng)險(xiǎn)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(xiǎn)評(píng)估的結(jié)果，對(duì)于可執(zhí)行的工程根據(jù)?變更控制?管理程序進(jìn)展過(guò)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，防止原有產(chǎn)品和新引入的產(chǎn)品的相互影響。5.2.3Preparetechnicaltransferplan編寫技術(shù)轉(zhuǎn)移方案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)移方案。Technicaltransferprotocolandtechnicaltransferlistshouldbewrittenbypersonnelassignedbytheresponsiblepersonfromthetransferee.Anditshouldbeapprovedbythequalitydirector.技術(shù)轉(zhuǎn)移方案由接收方工程負(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)移方案由接收方負(fù)責(zé)人負(fù)責(zé)組織進(jìn)展維護(hù)和修訂。Thetransferee’sresponsiblepersonshouldorganizedraftingtheproductvalidationmasterplanandmakeitaguidetothevalidationworkwhenanewproductisintroduced.Makesuretheintroductionprocessiseffectivelycontrolledandverified.接收方負(fù)責(zé)人負(fù)責(zé)組織編寫產(chǎn)品驗(yàn)證主方案，為新產(chǎn)品的引入所產(chǎn)生的驗(yàn)證工作提供文件指導(dǎo)和規(guī)劃，保證產(chǎn)品引入過(guò)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(yàn)證主方案的編號(hào)原那么：PVMP－工程編號(hào)－版本號(hào)，參見?驗(yàn)證的組織和實(shí)施?。Productvalidationmasterplanshouldincludebutnotlimitedto:Productintroductionandproduct-relatedvalidationplanintroductionResponsibilitiesofrelevantdepartmentsAcceptancecriteriaoftheprocessdevelopment,analyticaldevelopmentandcleaningresidueatdifferentstagesoftheproducttransferValidationlistofrelevantequipment,utilitiesandfacilitiesValidationlistofthemethodvalidation,cleaningvalidation,processvalidationandpackagingvalidation.Validationdocumentationlist產(chǎn)品驗(yàn)證主方案應(yīng)該包括但是不限于以下內(nèi)容：產(chǎn)品概述和產(chǎn)品相關(guān)驗(yàn)證的總體方案簡(jiǎn)介。產(chǎn)品引入相關(guān)部門的職責(zé)和分工。從產(chǎn)品轉(zhuǎn)移開場(chǎng)各階段的工藝研究、質(zhì)量研究和清潔殘留的承受標(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(yàn)證清單。引入產(chǎn)品的分析方法驗(yàn)證、清潔驗(yàn)證、工藝驗(yàn)證和包裝驗(yàn)證清單。相關(guān)驗(yàn)證文件列表。5.2.5Analyticaltestmethodstransfer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，確定工程質(zhì)量研究負(fù)責(zé)人，明確工程組成員工作職責(zé)分工。QualitydevelopmentteamimplementstheanalyticalmethodtransferaccordingtotechnicaltransferplanandSOP<AnalysisMethodTransfer>.質(zhì)量研究小組根據(jù)技術(shù)轉(zhuǎn)移工程方案和標(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.工程質(zhì)量研究負(fù)責(zé)人在制定分析方法轉(zhuǎn)移方案的同時(shí)應(yīng)制定分析方法培訓(xùn)方案，包括新產(chǎn)品分析方法講析和實(shí)際操作兩個(gè)方面。對(duì)負(fù)責(zé)轉(zhuǎn)移和承受分析方法操作的QC分析人員和相關(guān)QA人員進(jìn)展有效的培訓(xùn)，確保相關(guān)分析人員能正確理解分析程序，準(zhǔn)確無(wú)誤地執(zhí)行新產(chǎn)品分析方法的操作要領(lǐng)。5.2.6Pharmaceuticaltechnologytransfer工藝技術(shù)轉(zhuǎn)移Establishaprocessdevelopmentteamwhoisresponsiblefortheproductprocesstransfer.Assignresponsibilitiesfortheteamleaderandeveryteammember.成立負(fù)責(zé)工藝技術(shù)轉(zhuǎn)移工作的工程工藝研究小組，確定工程工藝研究負(fù)責(zé)人，明確工程組成員工作職責(zé)分工。Processdevelopmentteamleaderorganizethereviewingoftheproductformulationandprocessdocumentsprovidedbythetransferor,including:FeasibilityoftheprocessRationaleofthequalityspecificationCurrentproductioncapacityagainsttheproductiondemand工程工藝研究負(fù)責(zé)人組織相關(guān)人員對(duì)產(chǎn)品轉(zhuǎn)出方提供的產(chǎn)品處方和工藝資料進(jìn)展產(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.工程工藝研究負(fù)責(zé)人將發(fā)現(xiàn)的問(wèn)題或存在的疑問(wèn)與產(chǎn)品轉(zhuǎn)出方相關(guān)人員進(jìn)展討論，確認(rèn)問(wèn)題的處理措施。.4Processdevelopmentteamleaderorganizetheteamtodraftaprocesstechnicaltransferprotocolbasingontheriskassessmentresults.Theformatoftheprotocolreferstotheprocesstechnicaltransferprotocoltemplate.Processtechnicaltransferprotocolshouldbedraftedaccordingtothetechnicaltransferagreement,couldincludebutnotlimitedto:Listoftherequiredmaterial,equipment,instrumentandsparepartsListoftheprocessdevelopmentTrialEvaluationofcleaningmethodforchemicalresidueProductprocesstransferplan工程工藝研究負(fù)責(zé)人根據(jù)風(fēng)險(xiǎn)分析的結(jié)果，組織工程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以下內(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(shí)驗(yàn)清單化學(xué)殘留清潔方法評(píng)估工藝技術(shù)轉(zhuǎn)移工作方案Processdevelopmentteamleadershoulddraftatechnologytransferplanaswellasatechnologytrainingplan.Thetechnologytrainingplanshouldincludetheexplainingandsiteoperation.ProcessdevelopmentteamleaderorganizethetrainingofproductionoperatorandQApersonnel,toensurethattraineescouldtounderstandtheprocedurescorrectly,andimplementthekeypointsofthenewprocessinanaccurateway.工程工藝研究負(fù)責(zé)人在制定工藝技術(shù)轉(zhuǎn)移方案的同時(shí)應(yīng)制定工藝技術(shù)培訓(xùn)方案，包括新產(chǎn)品工藝技術(shù)的講析和實(shí)際操作兩個(gè)方面。對(duì)負(fù)責(zé)轉(zhuǎn)移和承受工藝技術(shù)操作的生產(chǎn)一線人員和生產(chǎn)現(xiàn)場(chǎng)QA人員進(jìn)展有效的培訓(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(diǎn)，準(zhǔn)確無(wú)誤地執(zhí)行新產(chǎn)品工藝技術(shù)的操作要領(lǐng)。5.2.6.6Processdevelopmentteamsubmitsrequestsforrequiredmaterials,equipments,instrumentsandsparepartsaccordingtotheapprovedprocesstechnicaltransferprotocol.工程工藝研究組按照批準(zhǔn)的工藝技術(shù)轉(zhuǎn)移方案，申請(qǐng)采購(gòu)需要補(bǔ)充的物料、設(shè)備、儀器和耗材。5.2.6.7Processdevelopmentteamperformsformulationandprocessfeasibilitytrialaccordingtoapprovedprocessdevelopmentprotocol,andpreparesprocessfeasibilitytrialreports工程工藝研究組按照批準(zhǔn)的工藝研究方案對(duì)產(chǎn)品處方和工藝適應(yīng)性進(jìn)展確認(rèn)，編寫相應(yīng)的工藝適應(yīng)性研究報(bào)告。5.2.6.8Afterprocessfeasibilitytrial,theprojectteampreparesprocessoptimization,processscale-upandprocessqualificationprotocolbasingonthecriticalqualityattributesandprocessdesignrequirements,thenimplementtoinvestigateanddeterminethecriticalprocessparametersandequipmentoperationparameters.Referto<ProcessOptimize>,<ProcessScaleUp>,<ProcessQualification>.工藝適應(yīng)性研究完畢，工程組根據(jù)產(chǎn)品的關(guān)鍵質(zhì)量屬性和工藝設(shè)計(jì)要求，編寫工藝優(yōu)化、工藝放大和工藝確認(rèn)方案，進(jìn)展產(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)?。5.2.6.9Aftertheprocessqualificationbatch,ifthequalitycontrolitemsarecomplywithqualityspecifications,criticalprocessparametersandequipmentoperationparametersareconsistent,andthereportoftheprocessqualificationbatchisapproved,thentheprocesstechnicaltransferiscompleted.Thetransferredproductcouldbeputintoproductionofprocessperformancequalificationbatches.工藝確認(rèn)批生產(chǎn)完畢，假設(shè)產(chǎn)品的各項(xiàng)質(zhì)量控制工程均符合質(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(bào)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。5.2.6.10Productionmanagerorganizerelevantpersonneltoestablishaprocessvalidationteamtoexecuteprocessperformancequalification.Referto<ProcessValidation>.生產(chǎn)經(jīng)理組織相關(guān)人員成立驗(yàn)證小組組織實(shí)施產(chǎn)品的工藝性能確認(rèn)，參見?工藝驗(yàn)證?。5.2.7Cleaningmethoddevelopmentandverification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(huì)對(duì)生產(chǎn)線原有產(chǎn)品的清潔方法驗(yàn)證狀態(tài)產(chǎn)生影響，工程工藝研究組應(yīng)計(jì)算新引入產(chǎn)品與其它現(xiàn)有產(chǎn)品共用設(shè)備上單位面積外表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.工程質(zhì)量研究組參考新產(chǎn)品活性成份含量檢測(cè)方法開發(fā)和編寫確認(rèn)方案，對(duì)新產(chǎn)品活性成份的化學(xué)殘留檢測(cè)方法進(jìn)展確認(rèn)。Comparethemaximumacceptableresiduelevelandsolubilityinthedetergentoftheactiveingredientsinthenewlyintroducedproductsandexistingproducts.Basedonthecomparison,threedifferentmeasuresareasfollow:綜合比擬生產(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)比擬結(jié)果可以分以下三種情況處理：ClassI:ifthemaximumacceptableresiduelevelorsolubilityinthecurrentdetergentoftheactiveingredientinthenewlyintroducedproductislowerthanthatoftheexistingproducts,orthereisingredientintheproductformuladifficulttoclean,theefficiencyofthecleaningmethodshouldbeverifiedusingtheequipmentinpilotplant.=1\*ROMANI類：假設(shè)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(duì)清潔方法的清潔效果進(jìn)展確認(rèn)。ClassII:ifthemaximumacceptableresiduelevelandsolubilityinthecurrentdetergentoftheactiveingredientinthenewlyintroducedproductishigherthanthatoftheexistingproducts,theefficiencyofthecleaningmethodisnotnecessarytobeverifiedusingtheequipmentinpilotplant.=2\*ROMANII類：假設(shè)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，那么不需要在中試車間的工藝設(shè)備上對(duì)清潔方法的清潔效果進(jìn)展確認(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(duì)現(xiàn)有產(chǎn)品進(jìn)展限度修訂和清潔再驗(yàn)證。.4FortheClassIproduct,ifcurrentcleaningmethodhasbeenverifiedonthepilotplantequipmentandtheresultshowsthatitissuitableforthenewproduct,then,thescale-upproductionaswellasthecleaningvalidationcanbeenforcedonthecommercialproductionline.對(duì)于=1\*ROMANI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)展放大生產(chǎn)，同時(shí)進(jìn)展清潔驗(yàn)證。ForClassIproductforwhichcurrentcleaningmethodcouldnotbeverifiedusingpilotplantequipment,anewcleaningmethodshouldbedevelopedandverifiedusingpilotplantequipmentbeforescale-upinproductionplant.Afterverification,scale-upproductionandcleaningvalidationinthecommercialproductionlinecouldbestarted.對(duì)于=1\*ROMANI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(duì)該產(chǎn)品的清潔方法，并應(yīng)在進(jìn)入生產(chǎn)線進(jìn)展放大生產(chǎn)前，在中試車間對(duì)新開發(fā)清潔方法的清潔效果進(jìn)展確認(rèn)。確認(rèn)合格后，新產(chǎn)品可以正式轉(zhuǎn)入生產(chǎn)線進(jìn)展放大生產(chǎn)，同時(shí)進(jìn)展清潔驗(yàn)證。ForClassIIproduct,theefficiencyofcleaningmethodshouldbefurtherverifiedduringscale-upproduction.CleaningvalidationreportshouldbeapprovedbyQualityDirector,thatindicatestheintroductionofnewproductwillnothavenegativeimpactonthecleaningvalidationstatusoftheproductionline.=2\*ROMANII類產(chǎn)品，在生產(chǎn)線進(jìn)展放大批生產(chǎn)的同時(shí)，應(yīng)對(duì)使用現(xiàn)有清潔方法的清潔效果進(jìn)展確認(rèn)，清潔確認(rèn)報(bào)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(huì)影響生產(chǎn)線清潔方法的驗(yàn)證狀態(tài)。Theproceduresofestablishmentofresiduallimits,microbialacceptancecriteria,detergentresiduallimitsandsamplingmethodshouldbereferringto<CleaningValidation>.關(guān)于殘留物、微生物、清潔劑殘留的可承受限度建立和取樣方法等程序參見?清潔驗(yàn)證?。Producttechnicaltransferreport產(chǎn)品技術(shù)轉(zhuǎn)移報(bào)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(bào)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(bào)告提綱?。Managementofprojectdocuments產(chǎn)品技術(shù)轉(zhuǎn)移的工程文件管理Allthedocumentsgeneratedduringthetechnicaltransferprocessshouldbenumbered,archivedandretrievedaccordingto<ProductDevelopmentDocumentsManagement>.Thedocumentadministratorshouldcheckandsortingallthedocumentsandmakesuretheyareputawayattheendofaworkstage.技術(shù)轉(zhuǎn)移過(guò)程中產(chǎn)生的所有文件應(yīng)按?研發(fā)工程文件管理?的要求分階段進(jìn)展整理，每一個(gè)工作完畢，技術(shù)部文件管理人員應(yīng)對(duì)文件整理工作進(jìn)展檢查，確認(rèn)所有相關(guān)文件已經(jīng)按照要求整理好。Beforethescale-upandprocessqualificationbatch,theprotocolofscale-upandprocessqualification,analyticalmethodstandardoperationproceduresandproductspecificationshouldbeapprovedbythequalitydirector.ThecopiesofanalyticalmethodstandardoperationproceduresandproductspecificationsshouldbesenttoQAandQC,theoriginalshouldbearchivedinprojectdocumentfolder.產(chǎn)品進(jìn)展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(guò)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)移工程文件夾內(nèi)。5.3.2Afterprocessqualification,projectteamleadershouldorganizetheteammembers,productionsupervisor,QCsupervisorandQApersonneltoreviewtheanalyticalmethodstandardoperationproceduresandthespecificationsofAPI,excipients,intermediateproductsandfinishproduct,identifyproblemsanddeterminethecorrespondingmeasures.工藝確認(rèn)完畢后，產(chǎn)品轉(zhuǎn)移工程負(fù)責(zé)人應(yīng)召集工程組成員、生產(chǎn)主管、QC主管、QA等相關(guān)人員對(duì)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)展審核，找出文件中存在的問(wèn)題確定修改方案。5.3.3Beforetheprocessperformancequalificationbatches,QCandQAdepartmentshouldpreparetheSOPsofanalyticalmethodandspecificationsaccordingtotherevisedproposalanddocumentformatspecialforourcompany..工藝驗(yàn)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)。Productionmanagerorganizerelevantpersonneltopreparemasterformula,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。Whenprocessperformancequalificationbatchesarefinished,projectteamleadershouldorganizedocumentadministratorofTDanddocumentspecialisttochecktheprojectdocuments.Ensureallthedocumentshavebeenarchivedinproductalready.Refertoannex3<ProductTechnicalTransferDocumentList>.工藝性能確認(rèn)工作完畢，產(chǎn)品轉(zhuǎn)移工程負(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(duì)工程文件進(jìn)展檢查，確認(rèn)所有工程文件資料已經(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Annex2:ProductTransferReportOutline附錄2：產(chǎn)品轉(zhuǎn)移報(bào)告提綱Annex3:ProductTechnicalTransferDocumentList附錄3：產(chǎn)品技術(shù)轉(zhuǎn)移文件清單6.4Annex4:TemplateofProtocolforPharmaceuticalTransfer附錄4：工藝技術(shù)轉(zhuǎn)移方案模板6.5F-07-0035RiskAssessmentforProductTechnicalTransfer新產(chǎn)品引入風(fēng)險(xiǎn)分析表6.6F-07-0036GeneralTechnologyTransferChecklist通用產(chǎn)品技術(shù)轉(zhuǎn)移檢查表6.7F-07-0037TechnicalTransferRecord技術(shù)轉(zhuǎn)移記錄6.8F-07-0021RiskAssessmentforProcessandQualityControl新產(chǎn)品工藝和質(zhì)量風(fēng)險(xiǎn)分析表7RelatedDocuments相關(guān)文件SOP01601ChangeControl變更控制SOP01613QualityRiskManagement質(zhì)量風(fēng)險(xiǎn)管理SOP01801ValidationOrganizationandImplementation驗(yàn)證的組織和實(shí)施SOP07019AnalysisMethodTransfer分析方法轉(zhuǎn)移SOP07010ProductDevelopmentDocumentsManagement研發(fā)工程文件管理SOP07045ProcessOptimize工藝優(yōu)化SOP07047ProcessScaleUp工藝放大SOP07048ProcessQualification工藝確認(rèn)SOP04015ProcessValidation工藝驗(yàn)證SOP04016CleaningValidation清潔驗(yàn)證8Reference參考資料None無(wú)Annex1：

附錄1：Annex2:ProductTransferReportOutline附錄2：產(chǎn)品轉(zhuǎn)移報(bào)告提綱1Pharmaceuticaldevelopmentsummary藥物研發(fā)總結(jié)Includeashortdescriptionofthedrugproductdevelopmenthistory.包括對(duì)藥物研發(fā)過(guò)程的概述。2Scale-upSummary放大概述Provideashortdescriptionofthemanufacturingdevelopmenthistoryfrompilotscaletofullscale.提供對(duì)中試規(guī)模到大生產(chǎn)的研發(fā)過(guò)程的概述。3ProductComposition產(chǎn)品成分Compareeachseparateingredientintheproductandcorrespondingquantitativecompositionbetweenthedevelopmentsiteandmanufacturingsite.比擬研發(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(diǎn)和生產(chǎn)地點(diǎn)的不同之處的原因。4RawMaterials原輔料Compareeachseparaterawmaterialandcorrespondingcodenumber,supplier,trademarkandspecificationreferencebetweenthedevelopmentsiteandmanufacturingsite.比擬在研發(fā)地點(diǎn)和生產(chǎn)地點(diǎn)的原輔料和相應(yīng)的代號(hào)、供給商、商標(biāo)和參照的質(zhì)量標(biāo)準(zhǔn)。Explainanydifferencesencounteredbetweenthedevelopmentsiteandmanufacturingsite.解釋在研發(fā)地點(diǎn)和生產(chǎn)地點(diǎn)的不同之處的原因。5Immediatecontainer內(nèi)包裝Compareeachimmediatecontainercomponent,supplierandspecificationreferencebetweenthedevelopmentsiteandmanufacturingsite.比擬在研發(fā)地點(diǎn)和生產(chǎn)地點(diǎn)的內(nèi)包裝材料的成分、供給商和參照的質(zhì)量標(biāo)準(zhǔn)。Explainanydifferencesencounteredbetweenthedevelopmentsiteandmanufacturingsite.解釋在研發(fā)地點(diǎn)和生產(chǎn)地點(diǎn)的不同之處的原因。6Productspecificationsandtestmethods質(zhì)量標(biāo)準(zhǔn)和檢驗(yàn)方法Includeasummarytableidentifyingthetest,specificationandcorrespondinganalyticalmethod.包括一個(gè)匯總表格列出檢驗(yàn)、質(zhì)量標(biāo)準(zhǔn)和對(duì)應(yīng)的分析方法。7Manufacturingprocess生產(chǎn)工藝Comparethemanufacturingequipment,operationparametersandIPClimitsforeachstepoftheprocessbetweenthedevelopmentsiteandthemanufacturingsite.分別比擬在研發(fā)地點(diǎn)和生產(chǎn)地點(diǎn)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(diǎn)和生產(chǎn)地點(diǎn)的不同之處的原因。Includeaprocessflowdiagram.包括一個(gè)工藝流程圖。8Packaging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)。9Validation驗(yàn)證ProvideAnalysisMethodandcleaningvalidationstrategyand/orreports.提供分析方法驗(yàn)證和清潔驗(yàn)證的方法或者報(bào)告。Providesterilizationvalidationstrategyand/orreports(ifapplicable).如果需要，提供滅菌驗(yàn)證的方法和報(bào)告。10Stability穩(wěn)定性Provideregistrationstabilitystrategyandstabilityprotocol.提供為注冊(cè)資料申報(bào)準(zhǔn)備的穩(wěn)定性實(shí)驗(yàn)的方法和穩(wěn)定性實(shí)驗(yàn)的方案。11Conclusions結(jié)論P(yáng)rovideconclusionsregardingtheproducttechnicaltransferexperiences.為產(chǎn)品技術(shù)轉(zhuǎn)移提供總結(jié)。ApprovalsignaturesfromtheDevelopmentteamandOperationsteam.轉(zhuǎn)出方和承受方的簽名批準(zhǔn)。

Annex3:ProductTechnicalTransferDocumentList

附錄3：產(chǎn)品技術(shù)轉(zhuǎn)移文件清單No.Item工程1CustomerDocuments&Information

合作方的文件和信息Contracts合同Priceagreement價(jià)格合同Purchaseorder-supplycontract采購(gòu)訂單合同Annualpurchasingplan年度采購(gòu)方案 QAagreement質(zhì)量協(xié)議APIAPI-Vendor&Qualification原料藥－供給商和供給商審計(jì)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(yàn)證〕SDS-SafetyDataSheet

平安數(shù)據(jù)表Excipents,Blister(ALU,PVC),Box,Leaflet,BulkTabletContainer,Transportbox,Cleaning

輔料、內(nèi)包裝材料、紙盒、說(shuō)明書、半成品包裝容器、外箱、清潔方法Materials-Vendor&Qualification物料－供給商和供給商審計(jì)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(yàn)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(cè)定方法ContentUniformity含量均勻度測(cè)定方法RelatedSubstances有關(guān)物質(zhì)測(cè)定方法Dissolution溶出度測(cè)定方法MicrobiologicalPurity微生物測(cè)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(yàn)證方案DesignDrawings設(shè)計(jì)圖紙PunchesanddiesDesignDrawing沖模和中模設(shè)計(jì)圖紙BlisterDesignDrawing鋁塑板設(shè)計(jì)圖紙BottleandCapDesignDrawing瓶和蓋設(shè)計(jì)圖紙BoxDesignDrawing紙盒設(shè)計(jì)圖紙TransportboxDesignDrawing外箱設(shè)計(jì)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(gòu)訂單或合同BusinessLicenseofManufacturer(OnlyinLegalProvisionsList)

物料制造商的營(yíng)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(duì)照品〔成品〕文件PurchaseOrder采購(gòu)訂單CustomsDocumentsforImportofCRS標(biāo)準(zhǔn)品〔工作對(duì)照品〕文件PurchaseOrder采購(gòu)訂單Export出口CustomsDocumentsforExportofDrugProduct

出口產(chǎn)品的合作方文件Customer’sMA(MarketingAuthorization)ofeachTabletStrength

每個(gè)規(guī)格產(chǎn)品的上市許可證BusinessLicenseofCustoms

合作方的營(yíng)業(yè)執(zhí)照BusinessLicenseofManufacturer(English)

公司的營(yíng)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(bào)價(jià)PriceAgreement價(jià)格合同CarrierContract承運(yùn)人合同2.