GMP培训(英文版)课件

MartinL.Jeiven,MS,RPh

President

JeivenPharmaceuticalConsulting,Inc.AComparisonofEUandUSGMPs(We’vemuchtolearnfromthose“acrossthepond”)ReliableGuidance1

MartinL.Jeiven,MS,RPh

PreTheEssentialWorldwide

PrincipleofGMPsProductQualitydependson:Quality,Safety,and Effectivenessmustbe designedandbuiltinto theproduct;Qualitycannotbetested intotheproduct;andEachstepinamanufacturingprocessmustbecontrolledtomaximizetheprobabilitythatthefinishedproductwillmeetallitsqualityanddesignspecifications.2TheEssentialWorldwide

PrincBriefGMPHistory1957:FirstGMPsissuedasagovernmentregulation(bytheCanadianSpecificationsBoardfordrugsuppliedtotheCanadianmilitary)1963/1978:USFDAGMPs1967:WHOGMPs1968/1973:UKGMPs1984:GMPsinmorethan25countries3BriefGMPHistory1957:FirstGUSvs.EUGMPs:OverviewInmostaspects,botharesimilarincontentandfocusonQualityThereareanumberofimportantdifferencesThereisconsiderablymoredetailintheEUGMPsFDAhasbeencriticizedforlackofdetailinvalidation,internalaudits,thedifferentrolesofQAandQC,etc.4USvs.EUGMPs:OverviewInmosUSvs.EUGMPs:Overview

(cont’d)FDA’sresponsetothecriticism:theGMPsareminimumrequirements,andindustry’sresponsibilityistoremaincurrentbyincorporatingintotheirproceduresinformationfromguidances,inspectionalguidelines,WarningLetters,FDApresentations,etc.MostcountrieswithintheEUupdatetheirGMPsevery1-5years;theUSGMPsaresubstantiallythesameasthe1978FinalRule5USvs.EUGMPs:Overview(cont

TheEUGMPsstress:TheexpectationsofQualityManagementandtheroleoftheQPTheexpectationfor,andextensivenessof,validationTheneedforself-inspection(=internalaudits)TrainingandassessmentofcompetenceTheroleofcontractmanufactureandanalysis6

TheEUGMPsstress:TheexpectEUCountries

(2005)AustriaCzechRepPortugalDenmarkHungaryNetherlandsSwedenSloveniaGermanyUKCyprusFinlandBelgiumEstoniaFranceItalyLatviaGreeceIrelandMaltaLuxembourgSpainPolandSlovakiaIceland–NonEUcountryLithuaniaNorway–NonEUcountry7EUCountries(2005)AustriaCzecInternationalGMPLexicon

ADR AdverseReactionCA CompetentAuthorityCRO ContractResearchOrganizationCT ClinicalTrialCTA ClinicalTrialApplicationCTD ClinicalTrialDirectiveCTM ClinicalTrialMaterialEC EuropeanCommunityEC EthicsCommitteeEEA EuropeanEconomicArea8InternationalGMPLexiconADR InternationalGMPLexicon(cont’d)EEC EuropeanEconomicCommunityEMEA EuropeanMedicinesEvaluationAgencyEU EuropeanUnionEUDRACT EuropeanClinicalTrialsDatabaseGCP GoodClinicalPracticeGMP GoodManufacturingPracticeHPFBI HealthProductandFoodInspection Branch(Canada)ICH InternationalConferenceofHarmonizationIMP InvestigationalMaterialsProduct9InternationalGMPLexicon(conInternationalGMPLexicon(cont’d)IMPD InvestigationalMaterialsProduct DossierMCA MedicinesControlAgencyMRA MutualRecognitionAgreementMS MemberStatePI PharmaceuticalInspectoratePIC PharmaceuticalInspectionConventionPIC/S PharmaceuticalInspection CooperationSchemePSF ProductSpecificationFileQP QualifiedPersonWHO WorldHealthOrganization10InternationalGMPLexicon(conInternationalGMPs:GMPsareineffectin104countriesTheymayberegulations(asintheUS,JapanorKorea),directives(asintheEU),guides(asintheUK),codes(asinAustralia),orWHOcode(asinmanySoutheastAsiacountries)Theintentisthesame:strictadherencetoconsistentlyassureproductquality11InternationalGMPs:GMPsareinFDAandEUInspections“FDAinspectorsinspectforcompliance;EUinspectorsinspectforadequatescience”.

AnFDAinspectormayspend80-90%ofthetimereviewingdocumentationrelatedtomanufacturingandtesting,lookingforevidenceofcomplianceandtheabsenceoffraud;theEUinspectorwillspend80-90%ofthetimeinterviewingstaffandmanagement,walkingthefacilitytoobservemanufacturingandtesting,andassessingthesoundnessoftheoperation.12FDAandEUInspections“FDAinsGMPInspectionsintheEU

Thekeydocumentcontrolling GMPinspectionsintheEUisthe CommissionDirective 2003/94/EC(8October2003).ItrepresentsaproposalbytheEU Commissiondesignedtoensure freedomofmovementofgoods, personnel,finances,andservices withintheEU.OnceapprovedbytheEuropeanParliament,implementationrequiresthateachmemberstateincorporatethedirectiveintoitsownnationallegislationwithinthreeyearsoforiginalpassage.13GMPInspectionsintheEUTheEUGMPs

Chapter1–QualityManagement

Principle TheholderofaManufacturingAuthorizationmustmanufacturemedicinalproductssoastoensurethattheyarefitfortheirintendeduse,complywiththerequirementsoftheMarketingAuthorizationanddonotplacepatientsatriskduetoinadequatesafety,qualityorefficacy.TheattainmentofthisQualityobjectiveistheresponsibilityofSeniorManagement,andrequirestheparticipationandcommitmentbystaffinmanydifferentdepartmentsandatalllevelswithinthecompany,bythecompany’ssuppliersandbythedistributors.14EUGMPs

Chapter1–QualityMEUGMPs

Chapter1–QualityManagement

(cont’d)

Principle(cont’d) ToachievetheQualityobjectivesreliably,theremustbeacomprehensivelydesignedandcorrectlyimplementedsystemofQAincorporatingGMPanditshouldbefullydocumentedanditseffectivenessmonitored.AllpartsoftheQAsystemshouldbeadequatelyresourcedwithcompetentpersonnel,andsuitableandsufficientpremises,equipmentandfacilities.15EUGMPs

Chapter1–QualityMQualityManagementandtheQualifiedPerson(QP)

IntheUS,FDAholdsSeniorManagementdirectlyandpersonallyresponsibleforcompliancetoGMPsInEurope,theQPisdirectlyandlegallyresponsibleforensuringthatapharmaceuticalproductcomplieswiththeGMPcommitmentsmadebythecompanyinitsapplicationtomarketproducts(ortestclinically).16QualityManagementandtheQuaQualityManagementandtheQualifiedPerson(QP)(cont’d)QPqualificationsinclude:universitydegreefromamemberstate,minimumof4yearstheoretical/practicalstudiesinpharmacy,veterinarymedicine,chemistryorbiology;minimumof2yearsworkingintheindustry,and(insomecountries),passageofanexamination.

17QualityManagementandtheQuaEUGMPs

Chapter1–QualityManagement

(cont’d)

Principle(cont’d)ThebasicconceptsofQA,GMPsandQCareinter-relatedandfundamentaltotheproductionandcontrolofmedicinalproducts.18EUGMPs

Chapter1–QualityMEUGMPs

Chapter2–Personnel

Principle

Theestablishmentand maintenanceofasatisfactorysystemofandthecorrectmanufactureof medicinalproductsrelies uponpeople.Theremustbesufficientqualified personneltocarryoutallthetasks.Individual responsibilitiesshouldbeclearlyunderstoodand recorded.Allpersonnelshouldbeawareofthe principlesofGMPthataffectthem,andreceive initialandcontinuingtrainingrelevanttotheirneeds.19EUGMPs

Chapter2–Personnel EUGMPs

Chapter3–PremisesandEquipment

PrinciplePremisesandequipmentmustbelocated,designed,constructed,adaptedandmaintainedtosuittheoperationstobecarriedout.Theirlayoutanddesignmustaimtominimizetheriskoferrorsandpermiteffectivecleaningandmaintenanceinordertoavoidcross-contamination,buildupofdustordirtand,ingeneral,anyadverseeffectonthequalityofproducts.20EUGMPs

Chapter3–PremisesaEUGMPs

Chapter4-DocumentationPrincipleGooddocumentationconstitutesanessentialpartoftheQAsystem.ClearlywrittenDocumentationpreventserrorsfromspokencommunicationandpermitstracingorbatchhistory.Specifications,manufacturingformulasandinstructions,procedures,andrecordsmustbefreefromerrorsandavailableinwriting.Thelegibilityofdocumentsisofparamountimportance.

21EUGMPs

Chapter4-DocumentatEUGMPs

Chapter5–Production

Validation Validationstudiesshould reinforceGMPs,andbe conductedinaccordance withdefinedprocedures. Resultsandconclusions shouldberecorded.Whenanynewmanufacturingformulaormethodof preparationisadopted,stepsshouldbetakento demonstrateitssuitabilityforroutineprocessing. Thedefinedprocess,usingthematerialsand equipmentspecified,shouldbeshowntoyielda productconsistentlyoftherequiredQuality.22EUGMPs

Chapter5–ProductionEUGMPs

Chapter5–Production

(cont’d)Validation

(cont’d)Significantamendmentstothemanufacturingprocess,includinganychangeinequipmentormaterials,whichmayaffectproductqualityand/orthereproducibilityoftheprocessshouldbevalidated.Processesandproceduresshouldundergoperiodiccriticalre-validationtoensurethattheyremaincapableofachievingtheintendedresults.23EUGMPs

Chapter5–ProductionEUGMPs

Chapter6–QualityControl

Principle

QCisconcernedwithsampling,specifications andtestingaswellastheorganization, documentationandreleaseprocedureswhich ensurethatthenecessaryandrelevanttests arecarriedout,andthatmaterialsarenotreleasedforuse,

norproductsreleasedforsaleorsupply,untiltheirQuality hasbeenjudgedsatisfactory.QCisnotconfinedto laboratoryoperations,butmustbeinvolvedinalldecisions whichmayconcernthequalityoftheproduct.The independenceofQCfromProductionisconsidered fundamental.24EUGMPs

Chapter6–QualityCEUGMPs

Chapter7–ContractManufactureandAnalysis

Principle Contractmanufactureandanalysismustbecorrectlydefined,agreedandcontrolledinordertoavoidmisunderstandingswhichcouldresultinaproductorworkofunsatisfactoryquality.TheremustbeawrittencontractbetweentheContractGiverandtheContractAcceptorwhichclearlyestablishesthedutiesofeachparty.ThecontractmustclearlystatethewayinwhichtheQPreleasingeachbatchofproductforsale(orclinicaluse)exerciseshisfullresponsibility.25EUGMPs

Chapter7–ContractMEUGMPs

Principle Allcomplaintsandotherinformationconcerningpotentiallydefectiveproductsmustbereviewedcarefullyaccordingtowrittenprocedures.Inordertoprovideforallcontingencies,asystemshouldbedesignedtorecall,ifnecessary,promptlyandeffectivelyproductsknownorsuspectedtobedefectivefromthemarket(fortheclinic).Chapter8–ComplaintsandProductRecall26EUGMPs PrincipleChapter8–CEUGMPs

Chapter9–SelfInspection

PrincipleSelfinspectionsshouldbeconductedinordertomonitortheimplementationandcompliancewithGMPprinciplesandtoproposenecessarycorrectivemeasures.Personnelmatters,premises,equipment,documentation,production,QC,distributionofthemedicinalproducts,arrangementsfordealingwithcomplaintsandrecalls,andselfinspections,shouldbeexaminedatintervalsfollowingapre-arrangedprogrammeinordertoverifytheirconformitywiththeprinciplesofQA.27EUGMPs

Chapter9–SelfInspeEUGMPs

Chapter9–SelfInspection

(cont’d)Selfinspectionsshouldbeconductedinanindependentanddetailedwaybydesignatedcompetentperson(s)fromthecompany.Independentauditsbyexternalexpertsmayalsobeuseful.Allselfinspectionsshouldberecorded.Reportsshouldcontainalltheobservationsmadeduringtheinspectionsand,whereapplicable,proposalsforcorrectivemeasures.Statementsontheactionssubsequentlytakenshouldalsoberecorded.28EUGMPs

Chapter9–SelfInspeEUGMPs

The“OrangeGuide”

ThispublicationfromtheMedicinesControlAgencyincludesthemainpharmaceuticalRegulations,Directives,andguidances,includingtheGMPs,whichmanufacturersandwholesalesareexpectedtofollowwhenmanufacturinganddistributingmedicinalproductsintheEU.Thelatesteditionis2002andincludeskeyannexes,UK’sCodeofPracticeforQPs,andnotesonmutualrecognitionagreements.29EUGMPs

The“OrangeGuide” ThiCertificationbyaQualifiedPersonandBatchRelease–Annex16

Principle EachbatchoffinishedproductmustbecertifiedbyaQPwithintheEC/EEAorforexport. Thepurposeofcontrollingthebatchreleaseinthiswayis:Toensurethatthebatchhasbeenmanufacturedandcheckedinaccordancewiththerequirementsofitsmarketingauthorization,theprinciplesandguidelinesofECGMPortheGMPofathirdcountryrecognizedasequivalentunderanMRAandanyotherrelevantlegalrequirementbeforeitisplacedonthemarket30CertificationbyaQualifiedPCertificationbyaQualifiedPersonandBatchRelease–Annex16

(cont’d)

RoutinedutiesofaQualifiedPerson Beforecertifyingabatchpriortorelease,theQPdoingsoshouldensure,withreferencetotheguidanceabove,thatatleastthefollowingrequirementshavebeenmet:Thebatchanditsmanufacturecomplywiththeprovisionsofthemarketingauthorization(includingtheauthorizationrequiredforimportationwhererelevant);31CertificationbyaQualifiedPCertificationbyaQualifiedPersonandBatchRelease–Annex16

(cont’d)

RoutinedutiesofaQualifiedPerson

Allthenecessarychecksandtestshavebeenperformed,includinganyadditionalsampling,inspection,testsorchecksinitiatedbecauseofdeviationsorplannedchanges;AllnecessaryproductionandQCdocumentationhasbeencompletedandendorsedbythestaffauthorizedtodoso;AllauditshavebeencarriedoutasrequiredbytheQAsystem;TheQPshouldinadditiontakeintoaccountanyotherfactorsofwhichheisawarewhicharerelevanttothequalityofthebatch.32CertificationbyaQualifiedPCertificationbyaQualifiedPersonandBatchRelease–Annex16

(cont’d)RoutinedutiesofaQualifiedPerson

AQPwhoconfirmsthecomplianceofanintermediatestageofmanufacture,hasthesameobligationsasaboveinrelationtothatstageunlessspecifiedotherwiseintheagreementbetweentheQPsAQPshouldmaintainhisknowledgeandexperienceuptodateinthelightoftechnicalandscientificprogressandchangesinqualitymanagementrelevanttotheproductswhichheisrequiredtocertify.33CertificationbyaQualifiedPCertificationbyaQualifiedPersonandBatchRelease–Annex16

(cont’d)RoutinedutiesofaQualifiedPerson

IfaQPiscalledupontocertifyabatchofaproducttypewithwhichheisunfamiliar,heshouldfirstensurethathehasgainedtherelevantknowledgeandexperiencenecessarytofulfillthisduty.34CertificationbyaQualifiedPCertificationbyaQualifiedPersonandBatchRelease–Annex16

(cont’d)RoutinedutiesofaQualifiedPersonManufacturehasbeencarriedoutinaccordancewithGMPor,inthecaseofabatchimportedfromathirdcountry,inaccordancewithGMPstandardsatleastequivalenttoECGMP;Theprincipalmanufacturingandtestingprocesseshavebeenvalidated;withdocumentedproductionconditionsandmanufacturingrecords;DeviationsorplannedchangesinproductionorQChavebeenauthorizedbytheresponsibleperson(s).Anychangesrequiringvariationtothemarketingormanufacturingauthorizationhavebeenauthorizedbytherelevantauthority35CertificationbyaQualifiedPHarmonizationofAPIGMPs

FDAandmanyoftheEUmemberstateshaveroutinelyconductedinspectionsofAPImanufacturerssince1979.Followingthedeathof87childreninHaitifromcontaminatedacetaminophenliquid,andrealizingthattherewasalackofclearGMPregulationsandguidelinesforAPImanufacture,ICHenactedaninternationalsetofGMPsgoverningthemanufacture,testing,anddistributionofAPIs:theICH-Q7AguidelinehasbeenadoptedaslawintheUS,EU,Japan,andothercountries.

36HarmonizationofAPIGMPs FDASelf-Inspection

Theroleofself-inspectionisnot discussed,orrequired,intheUS GMPs;howeverthisplaysamajor roleintheEuropeanandWHOGMPs. TheEuropeanGMPsdescribeself-inspectionsinthefollowingway:

Self-inspectionsshouldbeconductedinordertomonitortheimplementationandcompliancewithGMPprinciplesandtoproposenecessarycorrectivemeasures.37Self-Inspection TheroleofseSelf-Inspection(cont’d)

Personnelmatters,premises,equipment,documentation,production,QC,distributionofthemedicinalproducts,arrangementsfordealingwithcomplaintsandrecalls,andself-inspection,shouldbeexaminedatintervalsfollowingapre-arrangedprograminordertoverifytheirconformitywiththeprinciplesofQA.38Self-Inspection(cont’d) PersoSelf-Inspection

(cont’d)

WhilethisisdeemedintheUStobethefunctionofinternalauditprograms,suchauditprogramsare“offlimits”toFDAinspectorsandarenotroutinelyreviewedforadequacyofself-inspection,orforadequacyofthefollow-upactionsthatmightbenecessitatedfromsuchaselfinspection.Withoutquestion,theroleofself-inspectionisvitaltoassurefinalproductqualityandtoattempttoattaincontinuousimprovementintheworkplace.39Self-Inspection(cont’d) WhileSelf-Inspection

(cont’d)

Self-inspectionsshouldbeconductedinanindependentanddetailedwaybydesignatedcompetentperson(s)fromthecompany.Independentauditsbyexternalexpertsmayalsobeuseful.Allselfinspectionsshouldberecorded.Reportsshouldcontainalltheobservationsmadeduringtheinspectionsand,whereapplicable,proposalsforcorrectivemeasures.Statementsontheactionssubsequentlytakenshouldalsoberecorded.40Self-Inspection(cont’d) Self-Directive2001/20/EC(GCPDirective)ThisdirectivehasGMPimplicationswithrespecttomanufacturing,packaging,labeling,storage,distribution,returns,destructionandimportationintotheEUofIMPs.TheClinicalTrialsDirective41Directive2001/20/EC(GCPDireClinicalTrialAuthorization(CTA)Article9(2)ofDirective2001/20/ECrequiresthatarequestforauthorisationtoconducttheclinicaltrialbemadetotheCompetentAuthority(=QP)ineachmemberstateinwhichthesponsorplanstocarryoutthetrial.CTAmustbeapprovedbytheQPbeforeatrialcanstart.CTAcomprisestheClinicalTrialDossier(CTD)andInvestigationalMaterialsProductDossier(IMPD)42ClinicalTrialAuthorization(GMPConsiderationsBeforeaClinicalTrialisInitiatedTechnicalAgreementsareinplace.Manufacturingandassemblyactivitieshave been,andwillbe,conductedinaccordance withEUGMPs.CTAisapproved,andtheQPhasaccesstoits contents.PSFcontainsallthenecessarydocumentsandis accessibletotheQP.Comparatorsaresourcedfromqualifiedvendors.Shipmentconditionsareappropriate,andwillberecorded.TestingrequirementsfortheIMPareclear.43GMPConsiderationsBeforeaTeAnnex13-GMPManufacturingofInvestigationalMedicinalProductsDocumentationManufacturingPackagingmaterialsComparatorproductsBlindingoperationsRandomizationcodesPackagingLabelingQualityControlProductReleaseShippingComplaintsRecalls&ReturnsDistribution44Annex13-GMPManufacturingIMP(=CTM)CertificationbyaQualifiedPersonandBatchRelease–Annex16

PrincipleEachbatchoffinishedIMPmustbecertifiedbyaQPwithintheEC/EEAorforexport.ControllingthereleaseensuresthatIMPshavebeenmanufacturedtotherequirementsofitsmarketingauthorization,theprinciplesandguidelinesofECGMPsortheGMPsofathirdcountryrecognizedasequivalentunderaMRAandanyotherrelevantlegalrequirements.45IMP(=CTM)CertificationbyaQResponsibilityoftheQPforGMPComplianceAnnex16(section5)givesguidancewhendifferentsitesanddifferentQPsareinvolvedindifferentstagesoftheprocess.ThegeneralprincipleisthattheQPwhoisresponsibleforcertifyingthefinalpackagedproductmaytakepersonalresponsibilityforallstagesormaytakeaccountoftheconfirmationofearlierstagesbytherelevantQPresponsibleforthosestages.46ResponsibilityoftheCertificationbyaQPandIMPBatchRelease–Annex16

RoutinedutiesofaQualifiedPerson

Checksandtestshavebeenperformed,includinganyadditionalsampling,inspection,testsorchecksinitiatedbecauseofdeviationsorplannedchanges;ProductionandQCdocumentationhasbeencompletedandendorsedbythestaffauthorized;AuditshavebeencarriedoutasrequiredbyQA47CertificationbyaQPandIMPTheRoleofQualifiedPersonforCTMTheresponsibilitiesoftheClinicalTrialsQParegenerallythesameasexistingarrangementsformarketedproducts.Forexample:BatchcertificationisrecordedinaregisterQPsarerequiredtomaintaintheirknowledgeandexperienceQPsarerequiredtohavetheknowledgerelevanttotheproducttypetheyarecertifyingPersonallyresponsible/liablefortheirdecisions.CTMcanbereleasedbythe‘local’countryQPifdelivereddirectlytoanindividualMS48TheRoleofQualifiedPersonfPSFResponsibilityoftheQPforCTM(cont’d)TheQPneedstoknowthecontentsofeachstudyfile,wheretheyarekeptandwhoiscontactattheappropriatesites.TherewillneedtobearigorouschangecontrolsysteminplacetoensurethattheQPknowsaboutthechangesandcertifieseachbatchagainstcurrent

data.49PSFResponsibilityoftheQPfResponsibilityoftheQPforComparatorProductsusedinClinicalTrialsForcomparatorproductssourcedintheEU,orwithaMAintheEU,QPcertificationislimitedtoensuringthattheproductisusedaccordingtotheMAconductthetrialandisblinded,packagedandlabeled,storedanddistributedappropriately.IMPfromnon-EUsourcesmustbecertifiedasmanufacturedunderEUGMPsUseofnon-EUsourcedcomparatorsinEUtrialswillbeachallenge50ResponsibilityoftheQPforCImportationofIMPsImportationofIMPintotheEUrequirestheimportertohaveaManufacturer’sLicenseandtonameaQPonthatlicense.Thelicensewillincludetheproducttypes(e.g.:tablets,injectables,etc.)thatthecompanycanimportTherearevariationsbetweenmemberstates.SomeMSswillconducttestingofIMPaspartoftheirrelease.OtherMSs,includingtheUK,leaveittotheQPtodecide51ImportationofIMPsImportatiInternationalGMPs:FutureDirections

AnimportantfuturedirectionforGMPinspectionsindevelopedcountriesisriskassessment.Canadianinspectionsintheearly1970s:firstattempttoestablisharisk-basedapproachtoGMPcomplianceCanadianHPFBIclassifiesbothdrugproductsandGMPnon-complianceobservationsfoundundertheir“RiskClassificationofGMPObservations”scheme.Theyalsocategorizecriticalproducts.Australianinspectorstakeasimilarapproach.FDAispursuingrisk-basedinspectionsasoneofitsinitiatives.52InternationalGMPs:FutureDirInternationalGMPs:FutureDirections(cont’d)TrainingValidation,orcompetencytestingofpersonnel,appearstobethenextareatobeofficiallyaddressed.GoingbeyondUSGMPs[211.25(a)],theUKisnowrequiringtechnicalstafftobecertifiedasmeetingNationalVocationalQualification(NVQ)standards53InternationalGMPs:FutureDirQUESTIONS?THANKYOU!5454演讲完毕，谢谢观看！演讲完毕，谢谢观看！

MartinL.Jeiven,MS,RPh

President

JeivenPharmaceuticalConsulting,Inc.AComparisonofEUandUSGMPs(We’vemuchtolearnfromthose“acrossthepond”)ReliableGuidance56

MartinL.Jeiven,MS,RPh

PreTheEssentialWorldwide

PrincipleofGMPsProductQualitydependson:Quality,Safety,and Effectivenessmustbe designedandbuiltinto theproduct;Qualitycannotbetested intotheproduct;andEachstepinamanufacturingprocessmustbecontrolledtomaximizetheprobabilitythatthefinishedproductwillmeetallitsqualityanddesignspecifications.57TheEssentialWorldwide

PrincBriefGMPHistory1957:FirstGMPsissuedasagovernmentregulation(bytheCanadianSpecificationsBoardfordrugsuppliedtotheCanadianmilitary)1963/1978:USFDAGMPs1967:WHOGMPs1968/1973:UKGMPs1984:GMPsinmorethan25countries58BriefGMPHistory1957:FirstGUSvs.EUGMPs:OverviewInmostaspects,botharesimilarincontentandfocusonQualityThereareanumberofimportantdifferencesThereisconsiderablymoredetailintheEUGMPsFDAhasbeencriticizedforlackofdetailinvalidation,internalaudits,thedifferentrolesofQAandQC,etc.59USvs.EUGMPs:OverviewInmosUSvs.EUGMPs:Overview

(cont’d)FDA’sresponsetothecriticism:theGMPsareminimumrequirements,andindustry’sresponsibilityistoremaincurrentbyincorporatingintotheirproceduresinformationfromguidances,inspectionalguidelines,WarningLetters,FDApresentations,etc.MostcountrieswithintheEUupdatetheirGMPsevery1-5years;theUSGMPsaresubstantiallythesameasthe1978FinalRule60USvs.EUGMPs:Overview(cont

TheEUGMPsstress:TheexpectationsofQualityManagementandtheroleoftheQPTheexpectationfor,andextensivenessof,validationTheneedforself-inspection(=internalaudits)TrainingandassessmentofcompetenceTheroleofcontractmanufactureandanalysis61

TheEUGMPsstress:TheexpectEUCountries

(2005)AustriaCzechRepPortugalDenmarkHungaryNetherlandsSwedenSloveniaGermanyUKCyprusFinlandBelgiumEstoniaFranceItalyLatviaGreeceIrelandMaltaLuxembourgSpainPolandSlovakiaIceland–NonEUcountryLithuaniaNorway–NonEUcountry62EUCountries(2005)AustriaCzecInternationalGMPLexicon

ADR AdverseReactionCA CompetentAuthorityCRO ContractResearchOrganizationCT ClinicalTrialCTA ClinicalTrialApplicationCTD ClinicalTrialDirectiveCTM ClinicalTrialMaterialEC EuropeanCommunityEC EthicsCommitteeEEA EuropeanEconomicArea63InternationalGMPLexiconADR InternationalGMPLexicon(cont’d)EEC EuropeanEconomicCommunityEMEA EuropeanMedicinesEvaluationAgencyEU EuropeanUnionEUDRACT EuropeanClinicalTrialsDatabaseGCP GoodClinicalPracticeGMP GoodManufacturingPracticeHPFBI HealthProductandFoodInspection Branch(Canada)ICH InternationalConferenceofHarmonizationIMP InvestigationalMaterialsProduct64InternationalGMPLexicon(conInternationalGMPLexicon(cont’d)IMP