WHO药品生产技术转移指南Annex7

285©WorldHealthOrganizationWHOTechnicalReportSeries,No.961,2011Annex7WHOguidelinesontransferoftechnologyinpharmaceuticalmanufacturing1.Introduction2.Scope3.Glossary4.Organizationandmanagement5.Production:transfer(processing,packagingandcleaning)6.Qualitycontrol:analyticalmethodtransfer7.Premisesandequipment8.Documentation9.QualificationandvalidationReferences2861.IntroductionTheseguidingprinciplesontransferoftechnologyareintendedtoserveasaframeworkwhichcanbeappliedinaflexiblemannerratherthanasstrictrigidguidance.Focushasbeenplacedonthequalityaspects,inlinewithWHO’smandate.1.1Transferofprocessestoanalternativesiteoccursatsomestageinthelife-cycleofmostproducts,fromdevelopment,scale-up,manufacturing,productionandlaunch,tothepost-approvalphase.1.2Transferoftechnologyisdefinedas“alogicalprocedurethatcontrolsthetransferofanyprocesstogetherwithitsdocumentationandprofessionalexpertisebetweendevelopmentandmanufactureorbetweenmanufacturesites”.Itisasystematicprocedurethatisfollowedinordertopassthedocumentedknowledgeandexperiencegainedduringdevelopmentandorcommercializationtoanappropriate,responsibleandauthorizedparty.Technologytransferembodiesboththetransferofdocumentationandthedemonstratedabilityofthereceivingunit(RU)toeffectivelyperformthecriticalelementsofthetransferredtechnology,tothesatisfactionofallpartiesandanyapplicableregulatorybodies.1.3Literaturesearchesrevealedlittleinformationonthesubjectoriginatingfromnationalorregionalregulatorybodies.GuidanceonintracompanytransferswaspreparedbytheInternationalSocietyforPharmaceuticalEngineering(ISPE)(1).1.4Theeverchangingbusinessstrategiesofpharmaceuticalcompaniesincreasinglyinvolveintra-andintercompanytransfersoftechnologyforreasonssuchastheneedforadditionalcapacity,relocationofoperationsorconsolidationsandmergers.TheWHOExpertCommitteeonSpecificationsforPharmaceuticalPreparations,therefore,recommendedinitsforty-secondreportthatWHOaddressthisissuethroughpreparationofWHOguidelinesonthismatter(2).1.5Transferoftechnologyrequiresadocumented,plannedapproachusingtrainedandknowledgeablepersonnelworkingwithinaqualitysystem,withdocumentationofdatacoveringallaspectsofdevelopment,productionandqualitycontrol.Usuallythereisasendingunit(SU),areceivingunitandtheunitmanagingtheprocess,whichmayormaynotbeaseparateentity.For“contractmanufacturing”pleaseseegoodmanufacturingpractices(GMP)(3).1.6Forthetransfertobesuccessful,thefollowinggeneralprinciplesandrequirementsshouldbemet:•theprojectplanshouldencompassthequalityaspectsoftheprojectandbebasedupontheprinciplesofqualityriskmanagement;287•thecapabilitiesoftheSUandattheRUshouldbesimilar,butnotnecessarilyidentical,andfacilitiesandequipmentshouldoperateaccordingtosimilaroperatingprinciples;•acomprehensivetechnicalgapanalysisbetweentheSUandRUincludingtechnicalriskassessmentandpotentialregulatorygaps,shouldbeperformedasneeded;•adequatelytrainedstaffshouldbeavailableorshouldbetrainedattheRU:—regulatoryrequirementsinthecountriesoftheSUandtheRU,andinanycountrieswheretheproductisintendedtobesupplied,shouldbetakenintoaccountandinterpretedconsistentlythroughoutanytransferprogrammeproject;and—thereshouldbeeffectiveprocessandproductknowledgetransfer.1.7TechnologytransfercanbeconsideredsuccessfulifthereisdocumentedevidencethattheRUcanroutinelyreproducethetransferredproduct,processormethodagainstapredefinedsetofspecificationsasagreedwiththeSU.1.8IntheeventthattheRUidentifiesparticularproblemswiththeprocessduringthetransfer,theRUshouldcommunicatethembacktotheSUtoensurecontinuingknowledgemanagement.1.9Technologytransferprojects,particularlythosebetweendifferentcompanies,havelegalandeconomicimplications.Ifsuchissues,whichmayincludeintellectualpropertyrights,royalties,pricing,conflictofinterestandconfidentiality,areexpectedtoimpactonopencommunicationoftechnicalmattersinanyway,theyshouldbeaddressedbeforeandduringplanningandexecutionofthetransfer.1.10Anylackoftransparencymayleadtoineffectivetransferoftechnology.1.11Someoftheprinciplesoutlinedinthisdocumentmayalsobeapplicabletomanufacturinginvestigationalpharmaceuticalproductsforclinicaltrialsaspartofresearchanddevelopment,butthisisnotthemainfocusofthisguidanceandhasbeenexcludedduetothecomplexityoftheprocesses.1.12SomeoftheresponsibilitiesoutlinedinthisdocumentfortheSUmayalsobeconsideredtobepartofthemanagementunitresponsibilities.2.ScopeNote:Thissectionspecificallyprovidesfortransferofqualitycontrol(QC)methodswhereatechnicalagreementexists(SUmanufacturertoRUmanufacturerorSUmanufacturertoRUQClaboratory).Wherenosuchtechnicalagreementsexist(e.g.testingbynationallaboratoriesortesting288forprocurementagencies)anumberofthepointslistedinsection2.4maynotbeworkable,andalternativeapproachesmayberequired.2.1Thisdocumentgivesguidanceinprincipleandprovidesgeneralrecommendationsontheactivitiesnecessarytoconductasuccessfulintra-orintersitetransferoftechnologyasdescribedintheIntroductiontotheseguidelines.Theintentionistoaddressthebasicconsiderationsneededforasuccessfultransferinordertosatisfytheregulatoryauthoritydefinedforthetransferp