Ligand-Binding Assays: Development, Validation, and Implementation in the Drug Development Arena

422 Pages·2009·3.93 MB·English

by  Masood N. Khan

LIGAND-BINDING ASSAYS
DEVELOPMENT, VALIDATION, AND
IMPLEMENTATION IN THE DRUG
DEVELOPMENT ARENA
Editedby
Masood N. Khan
John W.A. Findlay

LIGAND-BINDING ASSAYS

LIGAND-BINDING ASSAYS
DEVELOPMENT, VALIDATION, AND
IMPLEMENTATION IN THE DRUG
DEVELOPMENT ARENA
Editedby
Masood N. Khan
John W.A. Findlay
Copyright(cid:2)2010byJohnWiley&Sons,Inc.Allrightsreserved.
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LibraryofCongressCataloging-in-PublicationData:
Ligandbindingassays : development,validation,andimplementationinthe
drugdevelopmentarena / [editedby]MasoodN.Khan,JohnW.A.Findlay.
p.;cm.
ISBN9780470041383(cloth)
1. Radioligandassay. 2. Drugdevelopment. I. Khan,MasoodN. II. Findlay,
JohnW.A.
[DNLM: 1. DrugDesign. 2. Immunoassay. 3. Ligands. 4. ProteinBinding.
QV744L7232009]
RS425.L542009
6150.19 dc22
2009036489
PrintedintheUnitedStatesofAmerica
10987654321
CONTENTS
Preface xi
Contributors xv
1 Ligand-BindingAssaysinDrugDevelopment:Introduction
andHistoricalPerspective 1
JohnW.A.FindlayandMasoodN.Khan
1.1 General 1
1.2 HistoricalReview 2
1.3 LBAsforMacromolecules 3
1.4 AdvantagesandLimitationsofLBAs 4
1.5 Ligand-BindingAssayBioanalyticalFocusGroupofAAPS 4
1.6 ScopeofthePresentVolume 8
References 11
2 Ligand-BindingAssaystoSupportDispositionStudies
ofMacromolecularTherapeutics 15
MarianM.Kelley,MarjorieA.Mohler,andJohnW.A.Findlay
2.1 Introduction 15
2.2 DifferencesBetweenLowMolecularWeightMolecules
andMacromolecules 16
2.3 LBAAssayConsiderationsRelativetoResearch
andDevelopmentStage 23
2.4 CriticalFutureChallengesforLigand-BindingAssays 30
2.5 Conclusions 32
References 32
3 DevelopmentofLigand-BindingAssaysforDrug
DevelopmentSupport 39
MasoodN.Khan,ProveenD.Dass,JohnH.Leete,RichardF.Schuman,
MicheleGunsior,andChanchalSadhu
3.1 Introduction 39
3.2 InherentComplexitiesofImmunoassayDevelopment 42
3.3 StepsintheDevelopmentofaValidatableImmunoassay 45
3.4 DevelopmentandOptimizationofanImmunoassay 58
v
vi CONTENTS
3.5 OptimizationofCommercialKit-BasedAssays 70
3.6 TroubleshootingImmunoassays 70
3.7. Conclusions 75
Acknowledgments 76
References 76
4 ValidationofLigand-BindingAssaystoSupport
PharmacokineticAssessmentsofBiotherapeutics 81
BinodhS.DeSilvaandRonaldR.Bowsher
4.1 Introduction 81
4.2 AssayDevelopmentandValidationParadigm 83
4.3 PrestudyValidationPhase 84
4.4 AnalyticalPerformanceCharacteristics 85
4.5 In-StudyValidationPhase 105
4.6 PartialValidations/MethodTransfer/Cross-Validation 107
4.7 Documentation 108
4.8 Conclusions 108
References 109
5 StatisticalConsiderationsintheValidation
ofLigand-BindingAssays 111
BrunoBoulanger,ViswanathDevanarayan,
andWalthe(cid:2)reDewe(cid:3)
5.1 Introduction 111
5.2 ObjectivesofAssayValidation 113
5.3 ValidationCriteria 115
5.4 EstimatingAssayPerformanceCharacteristics 119
5.5 DecisionRulesandRiskAssessmentinPrestudyValidation 122
5.6 DecisionRulesDuringIn-StudyPhase
andAssociatedRisks 123
5.7 ReconcilingValidationandRoutineDecisionRules 124
5.8 Conclusions 126
References 126
6 DevelopmentandValidationofLigand-BindingAssays
forBiomarkers 129
JeanW.Lee,YangPan,PeterJ.O’Brien,andRenXu
6.1 Introduction 129
6.2 PreanalyticalConsiderationsandMethodFeasibility 134
6.3 MethodDevelopmentandMethodQualification
forExploratoryApplications 142
6.4 MethodDevelopmentandMethodValidation
forAdvancedApplications 151
CONTENTS vii
6.5 PartialValidationforChangeControl 154
6.6 Documentation,RecordKeeping,andReporting 154
6.7 RegulatoryIssues 155
6.8 In-studyValidation 156
6.9 Conclusions 157
Acknowledgments 158
References 158
7 TheUseofCommercialAssayKitsforPK/PDAnalysis
inDrugDevelopment 163
JohnL.AllinsonandJohnD.Chappell
7.1 Introduction 163
7.2 ValidationDefinitionsThatMaybeInterpreted
Inconsistently 166
7.3 ValidationExperiments 168
7.4 Stability 180
7.5 ReoptimizingReagentConcentrations 184
7.6 TheUseofCommercialKitsforPKandTKAssays 186
7.7 MatrixProblems 189
7.8 ChangingMethodProtocol 190
7.9 Conclusions 191
References 191
8 DevelopmentandValidationofImmunogenicityAssays
forPreclinicalandClinicalStudies 193
ThomasH.Parish,DeborahFinco,andViswanathDevanarayan
8.1 Introduction 193
8.2 ImmunogenicityRisk-BasedStrategy 194
8.3 RegulatoryGuidance 195
8.4 AssayDesign 196
8.5 OptimizationandValidation:TotalBindingAntibodyAssays 204
8.6 OptimizationandValidation:NeutralizingAntibodyAssays 213
8.7 AssaysandRiskAssessment 220
8.8 ApplicationandInterpretationofData 224
8.9 Conclusions 225
8.10 Appendix8.A IllustrationofScreeningCutPointEvaluation 227
References 234
9 MacromolecularReferenceStandardsforBiotherapeutic
PharmacokineticAnalysis 239
MarieT.RockandStephenKeller
9.1 Introduction 239
9.2 UnitedStatesPharmacopeia 241