Medical Product Regulatory Affairs: Pharmaceuticals, Diagnostics, Medical Devices

298 Pages·2008·7.32 MB·English

by  John J. Tobin

John J. Tobin and Gary Walsh
Medical Product Regulatory
Affairs
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John J. Tobin and Gary Walsh
Medical Product Regulatory Affairs
Pharmaceuticals, Diagnostics, Medical Devices
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V
Contents
Preface XIII
1 TheAimsandStructureofRegulations 1
1.1 Introduction 1
1.2 PurposeandPrinciplesofRegulation 1
1.3 TheLegalFrameworkforRegulation 3
1.3.1 NationalLegislativeProcess 3
1.3.2 EULegislativeProcess 4
1.3.3 WorkingwithLegalTexts 5
1.3.4 GuidanceDocuments 6
1.3.5 Pharmacopoeia 7
1.4 BasicLegislation 7
1.4.1 EULegislation 7
1.4.2 USLegislation 11
1.5 ScopeoftheLegislation 16
1.6 ChapterReview 19
1.7 FurtherReading 19
2 RegulatoryStrategy 21
2.1 ChapterIntroduction 21
2.2 BasicRegulatoryStrategy 21
2.2.1 ProductDevelopment 21
2.2.2 ProductManufacture 21
2.2.3 MarketVigilance 22
2.3 QualityAssuranceSystems 22
2.3.1 Personnel 23
2.3.2 Documentation 24
2.3.3 FacilitiesandEquipment 25
VI Contents
2.3.4 CorrectiveandPreventiveAction 25
2.4 Validation 26
2.5 RegulatoryBodies 27
2.5.1 EuropeanCommission 27
2.5.2 TheEMEA 29
2.5.3 NationalCompetentAuthorities 30
2.5.4 NotifiedBodies 32
2.5.5 TheFDA 32
2.5.6 USDepartmentofAgriculture 35
2.5.7 PharmacopoeiaAuthorities 36
2.6 InternationalHarmonisationBodies 36
2.7 InternationalConferenceonHarmonisation 36
2.7.1 VICH 39
2.7.2 TheGlobalHarmonisationTaskForce 39
2.8 PharmaceuticalInspectionCooperationScheme 40
2.9 TheWorldHealthOrganization(WHO) 42
2.10 ChapterReview 42
2.11 FurtherReading 42
3 DrugDiscoveryandDevelopment 43
3.1 ChapterIntroduction 43
3.2 DrugCategorisation 43
3.2.1 PrescriptionStatus 43
3.2.2 PhysicalProperties 44
3.2.3 ModeofAction 44
3.2.4 TherapeuticUse 45
3.3 DrugDiscovery 45
3.4 DrugDevelopment 50
3.5 DrugDelivery 52
3.5.1 Location 52
3.5.2 DrugCharacteristics 52
3.5.3 SpeedandDurationofTherapeuticEffect 53
3.5.4 Stability 55
3.6 ChapterReview 55
3.7 SuggestedReading 55
4 Non-ClinicalStudies 57
4.1 ChapterIntroduction 57
4.2 Non-ClinicalStudyObjectivesandTiming 57
4.3 PharmacologicalStudies 58
4.3.1 PharmacodynamicStudies 59
4.3.2 Pharmacokinetic/ToxicokineticStudies 62
4.4 BioavailabilityandBioequivalence 64
4.5 ToxicologyStudies 65
Contents VII
4.5.1 ToxicityStudies 65
4.5.2 GenotoxicityStudies 66
4.5.3 CarcinogenicityStudies 67
4.5.4 ReproductiveToxicologyStudies 67
4.6 Chemistry,ManufacturingandControlDevelopment
(CMC) 67
4.7 QualityofBiotechProducts 68
4.7.1 StabilityStudies 68
4.8 GoodLaboratoryPractice(GLP) 69
4.9 ChapterReview 69
4.10 FurtherReading 71
5 ClinicalTrials 73
5.1 ChapterIntroduction 73
5.2 ClinicalTrials 73
5.2.1 PhaseITrials 74
5.2.2 PhaseIITrials 74
5.2.3 PhaseIIITrials 75
5.3 ClinicalTrialDesign 76
5.4 GoodClinicalPractice 78
5.5 ClinicalTrialsintheEU 78
5.5.1 TheSponsor 80
5.5.2 TheInvestigator’sBrochure 80
5.5.3 TheInvestigator 81
5.5.4 TheTrialProtocol 81
5.5.5 TheInvestigationalMedicinalProductDossier 82
5.5.6 InformedConsent 82
5.5.7 ManufactureofInvestigationalMedicinalProduct 82
5.5.8 CompetentAuthorityClinicalTrialApplication 84
5.5.9 IndependentEthicsCommitteeCTA 85
5.5.10 AmendmentstoClinicalTrials 87
5.5.11 CaseReportForms 87
5.5.12 AdverseEventReporting 87
5.5.13 AnnualSafetyReport 88
5.5.14 MonitoringofTrials 88
5.5.15 EndofTrial 88
5.5.16 TrialMasterFile 88
5.6 ClinicalTrialsinTheUS 89
5.6.1 InvestigationalNewDrugApplication(IND) 89
5.6.2 InstitutionalReviewBoard 91
5.6.3 CommunicationwiththeFDA 94
5.6.4 LabellingofInvestigationalDrugs 95
5.7 ChapterReview 95
5.8 FurtherReading 95
VIII Contents
6 MarketingAuthorisation 97
6.1 ChapterIntroduction 97
6.2 TheApplicationDossier 97
6.3 CTD 98
6.3.1 ModuleStructure 101
6.3.2 Module3:Quality 101
6.3.3 DrugMasterFiles 104
6.3.4 Module4:Non-ClinicalStudyReports 105
6.3.5 Module5:ClinicalStudyReports 105
6.3.6 Module2:Summaries 107
6.3.7 ModuleI:Region-Specific 110
6.3.8 Module1:EU 110
6.3.9 Module1:US 113
6.4 SubmissionandReviewProcessintheEU 114
6.4.1 CommunityAuthorisation 114
6.4.2 ScientificEvaluationProcess 119
6.4.3 Decision-MakingProcess 120
6.4.4 NationalAuthorisations 121
6.4.5 DecentralisedProcedure 121
6.4.6 MutualRecognitionProcedure 123
6.4.7 PlasmaMasterFilesandVaccineAntigenMasterFiles 124
6.5 SubmissionandReviewProcessintheUS 124
6.6 ChapterReview 127
6.7 FurtherReading 127
7 AuthorisationofVeterinaryMedicines 129
7.1 ChapterIntroduction 129
7.2 OverviewofDevelopmentProcessforVeterinary
Medicines 129
7.2.1 Pre-ClinicalStudies 130
7.2.2 ClinicalTrials 131
7.2.3 GoodClinicalPractices 131
7.3 AuthorisationofClinicalTrialsintheEU 134
7.4 AuthorisationofClinicalTrialsintheUS 135
7.5 MaximumResidueLimits 136
7.6 AuthorisationofVeterinaryMedicinesintheEU 138
7.6.1 ApplicationstoEstablishMRLs 138
7.6.2 ReviewofApplicationsandEstablishmentofMRLs 138
7.6.3 MarketingAuthorisations 142
7.6.4 PresentationoftheDossier 143
7.7 ApprovalofVeterinaryMedicinesintheUS 144
7.7.1 NewAnimalDrugApplication 144
7.7.2 ApprovalofVeterinaryBiologicalProducts 147
7.8 ChapterReview 148
7.9 FurtherReading 148
Contents IX
8 VariationstotheDrugAuthorisationProcess 149
8.1 ChapterIntroduction 149
8.2 ProvisionsinSupportofSpecialDrugApplications 149
8.2.1 OrphanDrugs 149
8.3 AcceleratedAccesstoNewDrugTherapies 151
8.3.1 EMEAAcceleratedReview 151
8.3.2 CompassionateUse 151
8.3.3 Fast-TrackProducts 152
8.3.4 TreatmentINDs 152
8.3.5 PaediatricApplications 152
8.4 ApprovalofNewDrugswhenHumanEfficacyStudiesare
notEthicalorFeasible 153
8.5 AnimalDrugsforMinorUseandMinorSpecies 153
8.5.1 ConditionalApproval 153
8.5.2 Indexing 154
8.5.3 Designation 154
8.6 UseofNon-AuthorisedDrugsforAnimalTreatmentintheEU 154
8.7 ChangestoanAuthorisedDrug 154
8.8 EUSystemforProcessingChanges 154
8.8.1 ExtensionApplications 155
8.8.2 MajorVariation(TypeII) 155
8.8.3 MinorVariation(TypeIAorIB) 156
8.9 ProcessingChangesintheUS 156
8.9.1 ManufacturingChangeSupplements 156
8.9.2 MajorChanges 157
8.9.3 ModerateChanges 157
8.9.4 MinorChanges 157
8.10 AuthorisationofGenericDrugs 158
8.10.1 EURegulations 158
8.10.2 USRegulations 159
8.11 ReferenceDrugExclusivity 159
8.12 OtherAuthorisationProcedures 161
8.12.1 Well-EstablishedMedicalUseProducts 161
8.12.2 CombinationProducts 161
8.12.3 HomeopathicMedicines 161
8.12.4 TraditionalHerbalMedicines 162
8.12.5 USRegulationofOTCDrugs 162
8.13 ChapterReview 164
8.14 FurtherReading 164
9 MedicalDevices 167
9.1 ChapterIntroduction 167
9.2 RegulatoryStrategyforMedicalDevicesintheEU 167
9.2.1 UseofStandardstoEstablishConformity 168
9.2.2 ClassificationofDevices 170