GMP培训(英文版)

MartinL.Jeiven,MS,RPhPresidentJeivenPharmaceuticalConsulting,Inc.AComparisonofEUandUSGMPs(We’vemuchtolearnfromthose“acrossthepond”)ReliableGuidanceTheEssentialWorldwidePrincipleofGMPsProductQualitydependson:Quality,Safety,andEffectivenessmustbedesignedandbuiltintotheproduct;Qualitycannotbetestedintotheproduct;andEachstepinamanufacturingprocessmustbecontrolledtomaximizetheprobabilitythatthefinishedproductwillmeetallitsqualityanddesignspecifications.BriefGMPHistory1957:FirstGMPsissuedasagovernmentregulation(bytheCanadianSpecificationsBoardfordrugsuppliedtotheCanadianmilitary)1963/1978:USFDAGMPs1967:WHOGMPs1968/1973:UKGMPs1984:GMPsinmorethan25countriesUSvs.EUGMPs:OverviewInmostaspects,botharesimilarincontentandfocusonQualityThereareanumberofimportantdifferencesThereisconsiderablymoredetailintheEUGMPsFDAhasbeencriticizedforlackofdetailinvalidation,internalaudits,thedifferentrolesofQAandQC,etc.USvs.EUGMPs:Overview(cont’d)FDA’sresponsetothecriticism:theGMPsareminimumrequirements,andindustry’sresponsibilityistoremaincurrentbyincorporatingintotheirproceduresinformationfromguidances,inspectionalguidelines,WarningLetters,FDApresentations,etc.MostcountrieswithintheEUupdatetheirGMPsevery1-5years;theUSGMPsaresubstantiallythesameasthe1978FinalRuleTheEUGMPsstress:TheexpectationsofQualityManagementandtheroleoftheQPTheexpectationfor,andextensivenessof,validationTheneedforself-inspection(=internalaudits)TrainingandassessmentofcompetenceTheroleofcontractmanufactureandanalysisEUCountries(2005)AustriaCzechRepPortugalDenmarkHungaryNetherlandsSwedenSloveniaGermanyUKCyprusFinlandBelgiumEstoniaFranceItalyLatviaGreeceIrelandMaltaLuxembourgSpainPolandSlovakiaIceland–NonEUcountryLithuaniaNorway–NonEUcountryInternationalGMPLexiconADRAdverseReactionCACompetentAuthorityCROContractResearchOrganizationCTClinicalTrialCTAClinicalTrialApplicationCTDClinicalTrialDirectiveCTMClinicalTrialMaterialECEuropeanCommunityECEthicsCommitteeEEAEuropeanEconomicAreaInternationalGMPLexicon(cont’d)EECEuropeanEconomicCommunityEMEAEuropeanMedicinesEvaluationAgencyEUEuropeanUnionEUDRACTEuropeanClinicalTrialsDatabaseGCPGoodClinicalPracticeGMPGoodManufacturingPracticeHPFBIHealthProductandFoodInspectionBranch(Canada)ICHInternationalConferenceofHarmonizationIMPInvestigationalMaterialsProductInternationalGMPLexicon(cont’d)IMPDInvestigationalMaterialsProductDossierMCAMedicinesControlAgencyMRAMutualRecognitionAgreementMSMemberStatePIPharmaceuticalInspectoratePICPharmaceuticalInspectionConventionPIC/SPharmaceuticalInspectionCooperationSchemePSFProductSpecificationFileQPQualifiedPersonWHOWorldHealthOrganizationInternationalGMPs:GMPsareineffectin104countriesTheymayberegulations(asintheUS,JapanorKorea),directives(asintheEU),guides(asintheUK),codes(asinAustralia),orWHOcode(asinmanySoutheastAsiacountries)Theintentisthesame:strictadherencetoconsistentlyassureproductqualityFDAandEUInspections“FDAinspectorsinspectforcompliance;EUinspectorsinspectforadequatescience”.AnFDAinspectormayspend80-90%ofthetimereviewingdocumentationrelatedtomanufacturingandtesting,lookingforevidenceofcomplianceandtheabsenceoffraud;theEUinspectorwillspend80-90%ofthetimeinterviewingstaffandmanagement,walkingthefacilitytoobservemanufacturingandtesting,andassessingthesoundnessoftheoperation.GMPInspectionsintheEUThekeydocumentcontrollingGMPinspectionsintheEUistheCommissionDirective2003/94/EC(8October2003).ItrepresentsaproposalbytheEUCommissiondesignedtoensurefreedomofmovementofgoods,personnel,finances,andserviceswithintheEU.OnceapprovedbytheEuropeanParliament,implementationrequiresthateachmemberstateincorporatethedirectiveintoitsownnationallegislationwithinthreeyearsoforiginalpassage.EUGMPsChapter1–QualityManagementPrincipleTheholderofaManufacturingAuthorizationmustmanufacturemedicinalproductssoastoensurethattheyarefitfortheirintendeduse,complywiththerequirementsoftheMarketingAuthorizationanddonotplacepatientsatriskduetoinadequatesafety,qualityorefficacy.TheattainmentofthisQualityobjectiveistheresponsibilityofSeniorManagement,andrequirestheparticipationandcommitmentbystaffinmanydifferentdepartmentsandatalllevelswithinthecompany,bythecompany’ssuppliersandbythedistributors.EUGMPsChapter1–QualityManagement(cont’d)Principle(cont’d)ToachievetheQualityobjectivesreliably,theremustbeacomprehensivelydesignedandcorrectlyimplementedsystemofQAincorporatingGMPanditshouldbefullydocumentedanditseffectivenessmonitored.AllpartsoftheQAsystemshouldbeadequatelyresourcedwithcompetentpersonnel,andsuitableandsufficientpremises,equipmentandfacilities.QualityManagementandtheQualifiedPerson(QP)IntheUS,FDAholdsSeniorManagementdirectlyandpersonallyresponsibleforcompliancetoGMPsInEurope,theQPisdirectlyandlegallyresponsibleforensuringthatapharmaceuticalproductcomplieswiththeGMPcommitmentsmadebythecompanyinitsapplicationtomarketproducts(ortestclinically).QualityManagementandtheQualifiedPerson(QP)(cont’d)QPqualificationsinclude:universitydegreefromamemberstate,minimumof4yearstheoretical/practicalstudiesinpharm