Cleaning Process Development and Validation

CleaningProcessDevelopmentandValidationJune16,2006BrianKimVPofQualityTanox,Inc.PartIRegulatory/ComplianceOverviewApplicableregulationsandrequirements21CFR211.65a)Equipment….surfaceswhichcontactcomponents,in-processmaterials,ordrugproductsshallnotbereactive,additiveorabsorptive…..21CFR211.67Equipmentandutensil….cleaned,maintained,andsanitizedatappropriateintervalstoprevent…orcontaminationthatwouldalterthesafety,identity,strength,quality,orpurity……Regulatory/ComplianceOverview21CFR211.182WrittencleaningProcedureCleaninganduselogCholestyramineResinUSPrecallduetothelowlevelcontaminationwithintermediatesanddegradantsafterreuseofrecoveredsolventsfrompesticideproduction–increasedFDAawareness.Regulatory/ComplianceOverviewGuidanceGuidetoInspectionforValidationofCleaningProcesses.FDA,1993ICHQ7A,GMPforPharmaceuticalActiveIngredientsRegulatory/ComplianceOverviewFDA21CenturyRisk-BasedQualitySystemInitiativeDefinecriticalproductattributesandcontrolofcriticalprocesses(ProcessCapacity)toensure:SAFETY,PURITY,EFFICACY,QUALITYDesign“Quality”intoprocessesScience-basedriskmanagementRealtimeQACleaningValidationOverviewObjectivesAssuranceofproductpurity,safety,efficacyandqualityPreventionofproductcrosscontaminationbybyproduct,residualproduct,microbialresidueandresidualdetergentWhencleaningvalidationisrequiredIntroductionofnewequipment/productManufacturing/cleaningprocesschangesRawmaterial/cleaningagentchangesCleaningValidationOverviewGoodsystemdesignComprehensiveMasterValidationProgramEffectivecleaningprocessdevelopmentAdequateanalyticaltechniqueJustifiableacceptancecriteria–productspecific(HowCleanisClean?)ContinuousdatamonitoringandevaluationAcceptancecriteriaadjustmentasnecessaryCleaningValidationOverviewRoutinereviewofdeviations,excursionsandchangecontrolrelatedtocleaningprocessparameters,equipment,andmaterialsRe-validationasrequiredDefinewhatandhowtorevalidateDefinewhentorevalidateApplicationofvalidationlifecyclemanagementCleaningValidationOverviewCleaningValidationLifecycleManagementValidationMasterPlanCleaningCycleDevelopment(Re)Validation(IQ/OQ/PQ)Newproduct/EquipmentRoutineTestingRegularDataReviewEvaluationofCleaningParametersCleaningCycleDevelopmentElementstoconsiderDesign/ConstructioncomplexityofequipmentCharacteristicsofresiduals/producttocleanCleaningagentsTypeofcleaningprocess(Automatedvs.Manual)ManufacturingprocessAnalyticalmethodsandtheirsensitivityEquipmentDesign/ConstructionforEffectiveCleaningAdequatedesign/structuralcomplexityandconfigurationMaterialandSurfaceNon-ReactiveandcleanabilityCompatibilitywithdetergentsStageofManufacturingProcessUpstreamDownstreamIncreasedRiskDrugproductEquipmentDesign/ConstructionforEffectiveCleaningStructural/designcomplexitySizeandprocesspipingconfigurationforCIPPotentialdeadleg/spaceAdequateturbulenceAdequateslopeNozzledesignandlocationsBranchpipingorientationEquipmentDesign/ConstructionforEffectiveCleaningInstrumentTeeforCIP:L/D1.5DLAdequateturbulence(Flowrate)forCIP½ft/sec5ft/sec5ft/secEquipmentDesign/ConstructionforEffectiveCleaningCIPReturnCIPReturnGoodBadEquipmentDesign/ConstructionforEffectiveCleaningBranchpipingorientationBadDesignGoodDesignUpDownParallelCharacteristicsofProductsUnderstand(Bio)chemicalcharacteristicsofProduct(s)ProductmatrixTypeofactivemolecule(e.g.,protein,DNA,peptide,smallmolecule)Excipients/ProcessrelatedcomponentsProductmatrixisacriticalelementfor:CleaningprocessdesignForthedeterminationofadetergentandprocessparametersCharacteristicsofProductsPhysicochemicalcharacteristicsSolubilitywithmedium(e.g.,water,organicsolvent)ReactivityisacriticalelementforthedeterminationofprocessparametersDegreeofareactionwithadetergentormediumatdifferentconditions.DegradantsChemicalstateLiquidSemi-solidSolidCharacteristicsofProductsMicrobestaticpropertyCriticalfordetergentselectionToxicity/PharmacologicalpotencyCriticalforacceptancecriteriaPotentialproductand/orcomponentdegradantsafterreactionwithadetergentCriticalforacceptancecriteriaCleaningAgentSelectionSelectionofaCleaningAgentDependingontheparticulartypeofchemicals(soils)toremoveconsidering:Chemical/Physicalnatureofthemolecule(soil)toremoveReactivityPhysicochemicalcharacteristicsofthemoleculeChemicalstateofsoilsCleaningAgentSelectionTypeofDetergentAcidicAlkalineInorganicsoilsaremoresolubleinacidicdetergentWorkswellasblendsofseveralacidsMakeorganicsoilswatersolubleviathechangeofchemical/physicalnatureoforganicsoilsEasytochooseEquipmentcorrosionDifficulttochooseLesscompatiblewithothercleaningcomponentsPrecipitationofwaterhardnessNocleaningeffectonmineralresiduesLimitedtoorganicsVeryconcentrationdependentCleaningAgentSelectionBiologicalsoils–alkalineBlendingofothercleaningcomponentswithalkalinedetergentenhancescleaningeffects.Builders–thegroupofcomplexingagentsthatenhancethecleaningeffectandtheeffectofsurfactantEDTA,polyphosphate,NTA,citratesCleaningAgentSelectionSurfactants–severaltypesbasedontheioncharacteristicsoft