PDA-TR49-2010-Points-to-Consider-for-Biotechnology

2010TechnicalReportNo.49PointstoConsiderforBiotechnologyCleaningValidationPointstoConsiderforBiotechnologyCleaningValidationTaskForceTaskForceAuthorsRoseBicksler,Johnson&Johnson,Inc.JennaCarlson,Genentech,Inc.EsmaeilEktefaie,BaxterAGMichaelGuyader,LonzaGroupLtd.NorbertHentschel,BoehringerIngelheimPharmaceuticalsDestinA.LeBlanc,CleaningValidationTechnologies,Co-ChairPeterF.Levy,PLConsultingAnuragS.Rathore,IndianInstituteofTechnology,Co-ChairDestrySillivan,U.S.FoodandDrugAdministrationBruceStevens,BiogenIdec,Inc.TaskForceContributorsLeahFrautschy,Genentech,Inc.JohnM.Hyde,JMHydeConsulting,Inc.NitinRathore,PhD,AmgenInc.OtherContributorsBoChi,PhD,U.S.FoodandDrugAdministrationBillJones,HumanGenomeSciences,Inc.RobLynch,HumanGenomeSciences,Inc.AnnaE.Sayani,Bristol-MyersSquibbCompanyRichardTaylor,BayerHealthcareGeorgeVerghese,STERISCorporationThecontentandviewsexpressedinthisTechnicalReportrepresenttheworkoftheTaskForcevolunteersandarenotnecessarilytheviewsoftheorganizationstheyrepresent.PointstoConsiderforBiotechnologyCleaningValidationTechnicalReportNo.49ISBN:978-0-939459-30-8©2010ParenteralDrugAssociation,Inc.Allrightsreserved.TableofContents1.0INTRoduCTIoN..................................................31.1Purpose/Scope...............................................32.0GlossaRyoFTeRms........................................53.0CleaNINGPRoCessdesIGNaNddeVeloPmeNT..........................................63.1Introduction....................................................63.2CleaningProcessControls(Inputs)andMeasurements(Outputs).........................63.2.1CleaningCycleDesign........................63.2.2Physical-ChemicalAspects................73.3MeasurementsUsedtoDetermineCleaningEffectiveness....................................83.4EquipmentandPlantDesignConsiderations....................................83.4.1Piping..................................................83.4.2Automatedvs.ManualSystems.........93.4.3CentralizedCIPvs.DiscreteCleaningofIsolatedEquipment...........93.4.4CleanOutofPlace(COP)....................93.5SoilEvaluationandCategorization..................93.5.1SoilCategories....................................93.5.2SoilRemoval.....................................103.5.3CleaningComparabilityBasedonSoilandSurface................113.5.4SoilSelectionforLaboratoryEvaluations.....................123.6PerformingCleaningDevelopmentExperiments............................123.6.1ParameterSelection..........................133.6.2ParameterInteractions......................133.7CleaningProcessScale-Up...........................133.7.1SettingProcessControls...................143.7.2IntroductionofNewSoilstoaValidatedCleaningSystem........143.8Applyingthe“DesignSpace”ConcepttoCleaningProcesses....................154.0aCCePTaNCelImITs.......................................174.1KeyIssuesinLimitsforActives....................174.1.1EstablishingLimitsforActivesinFormulationandFinalFill..................184.1.2EstablishingLimitsforActivesinBulkManufacture.............184.1.3LimitsBasedonToxicityData...........194.2LimitsforCleaningAgents............................204.2.1LimitsforCommodityChemicals......204.2.2LimitsforFormulatedCleaningAgents................................204.3BioburdenLimits...........................................214.4EndotoxinLimits...........................................214.5VisualCleanCriterion....................................214.6ModifyingLimits...........................................225.0samPlINGmeThods......................................235.1SamplingMethodSelection..........................235.1.1DirectSamplingMethods.................235.1.2RinseSampling.................................235.1.3SwabSampling.................................245.1.4ComparisonofSwabandRinseSampling..........................255.2PlaceboSampling.........................................265.3SamplingforMicrobialandEndotoxinAnalysis.................................265.4SamplingRecoveryStudies..........................265.4.1GeneralConsiderations.....................265.4.2SwabRecovery.................................275.4.3RinseRecovery................................275.4.4“Recovery”inVisualInspection........285.4.5RecoveryforBioburdenandEndotoxinSampling...................285.5TrainingandQualificationofSamplers..........295.5.1KeyIssuesforTrainingforSwabSampling...........................295.5.2KeyIssuesforTrainingforRinseSampling............................305.5.3TrainingforVisualInspection............306.0aNalyTICalmeThods...................................316.1SpecificAnalyticalMethods.........................316.2ImpactofInactivation/DegradationoftheActive.................................................316.3NonspecificAnalyticalMethods...................326.3.1TotalOrganicCarbon(TOC)...............326.3.2TotalProtein......................................336.3.3Conductivity......................................336.3.4VisualInspection...............................346.4MicrobialTestMethods........