Biomaterials, medical devices, and combination products : biocompatibility testing and safety assessment

Content: Safety Evaluation of Medical DevicesIntroductionBiocompatibilityFundamentals of Biocompatibility TestsScope of Devices and the Medical Device MarketHistory Nonspecific Regulatory ConsiderationsReferencesRegulatory Aspects and Strategy in Medical Device and Biomaterials Safety EvaluationRegulatory BasisToxicity Testing: Medical DevicesReferencesRoad Map to Test SelectionsKey ConceptsReferencesMaterials in Medical Device DesignIntroductionMetalsCeramics and GlassesPolymersTextilesBiologically Sourced MaterialsSurface-Modifying MaterialsTissue Engineering ScaffoldsNanomaterialsReferencesWhat to Test: Sampling and Sample PreparationSamplingRandomizationSample PreparationReference MaterialsConclusionReferencesCytotoxicity TestingIntroductionBackgroundCrystal Violet StainingSilicone MicrophysiometerMicrotox TestNeutral Red Uptake (NRU) AssayMTTAgar Diffusion TestDirect Contact TestElution TestColony-Forming Assay (CFA)Correlation With In Vivo ResultsConclusionReferencesHemocompatibility (ISO 10993-4)Noncontact DevicesExternal Communicating DevicesImplant DevicesHemolysis TestsThe Osmotic Fragility TestErythrocyte StabilityWhole Blood Clotting TimeThrombogenicityComplement ActivationProtein AdsorptionCoagulationPlateletsConclusionReferencesLocal Tissue ToleranceDermal IrritationOcular Irritation TestingOther Nonparenteral Route Irritation TestsParenteral Irritation/ToleranceParenteral RoutesIntracutaneous IrritationFactors Affecting Irritation Responses and Test OutcomeReferencesImmunotoxicology (ISO 10993-20)Overview of the Immune SystemImmunotoxic EffectsImmunosuppressionImmunostimulationEvaluation of the Immune SystemImmunopathologic AssessmentsHumoral ImmunityCell-Mediated ImmunityNonspecific ImmunityHost-Resistance AssaysHypersensitivityLocal Lymph Node Assay (LLNA)ApproachesProblems and Future DirectionsReferencesImplantation Biology and StudiesUsp Implantation TestISO 10993 Implantation TestPreparation of Specimens for ImplantationTest Method for Implantation in Subcutaneous TissueReferencesAcute Systemic Toxicity Testing and Device Safety EvaluationIntroductionAcute Systemic Toxicity CharacterizationReferencesGenotoxicityIntroductionDNA StructureCytogeneticsReferencesSubchronic and Chronic Toxicity and Reproductive and Developmental ToxicityIntroductionObjectivesRegulatory ConsiderationsStudy Design and ConductParameters to MeasureHistopathologyStudy Interpretation and ReportingReproductive and Developmental ToxicityIntroductionICH Study DesignsMethodological IssuesData InterpretationReferencesCarcinogenicityAnimal ModelDose SelectionInterpretation of ResultsReferencesDegradation Products and Impurities Processes in Medical DevicesIntroductionMetalsCeramics and GlassesDegradation ProcessesEffects of SterilizationInterpretation of Sterility Test ResultsHeavy MetalsAcknowledgmentReferencesSpecial Case DevicesIntroductionRespiratory and Inhalation DevicesOphthalmic DevicesCardiovascular Devices and ProsthesesTamponsDevices for DentistryReferencesCombination ProductsDevice/Drug Combination ProductsHistorical BackgroundReferencesClinical Studies for Medical DevicesDesign ConsiderationsEpidemiologyConclusionReferencesLeachables and Extractables from Medical DevicesIntroductionSample PreparationGeneral Principles of Leachables and Extractables under ISO 10993Analytical MethodsRisk Assessment of Extracted MoietiesIntroduction to (Q)SAR for Leachable and Extractable EvaluationRisk Assessment for Leachables and ExtractablesReferencesToxicokinetics in Biomaterial and Device Safety EvaluationIntroductionRegulationsPrinciplesLaboratory MethodsPhysiologically Based Pharmacokinetic (PBPK) ModelingBiologically Derived MaterialsReferencesSpecial StudiesAnti-Infective MaterialsSpecific Tests21-Day Eye Irritation Study in RabbitsSystemic Injection TestProduction of Toxic Shock Syndrome Toxin-1 (TSST-1)Inflammatory Responses to BiomaterialsReferencesCase Histories and Problem ResolutionPhthalates Leaching From Polymer DevicesBPA: Bisphenol ATalc on Gloves and CondomsLatex AllergySilicones in Devices (Historical)Intrauterine DevicesToxic Shock Syndrome (Historical)ConclusionReferencesAppendix A: Selected Regulatory and Toxicological AcronymsAppendix B: Contract Testing LaboratoriesAppendix C: Notable Regulatory Internet AddressesAppendix D: Non-U.S. Medical Device Regulators