Cleaning-Validation-Protocol-for-Pharmaceuticals

CleaningValidationProtocolforPharmaceuticals1IntroductionTheValidationoftheCleaningProceduresisestablishingdocumentedevidencethattheprocedureiseffectiveandcapableforremovingthecontaminantsassociatedwithpreviousproducts,residuesofcleaningagentsaswellasthecontrolofpotentialmicrobialcontaminants.TheCleaningValidationisnotonlyensuringthecomplianceoftheregulatoryrequirements,butamoreimportantbenefitforperformingcleaningprocedurevalidationistheidentificationandthecorrectionofthepotentialproblemswhichcouldcompromisethesafety,efficacyorqualityofthesubsequentbatchesofdrugproduct.2ObjectiveTheobjectiveoftheCleaningValidationistoverifytheeffectivenessofthecleaningprocedureforremovalofproductresidues,degradationproducts,preservatives,excipientsand/orcleaningagentssothattheanalyticalmonitoringmaybereducedtoaminimumintheroutinephase,andtoensurethatthereisnoriskassociatedwithcross-contaminationofactiveingredients.TheobjectiveofValidationoftheCleaningProcedure(SOPNo._______________)usedforthecleaningofMachineName(MachineNo.________________)istoprovethattheproductcontactpartsoftheMachineName(MachineNo.________________)havebeencleanedandthatthecontaminationlevel(ChemicalandMicrobialContaminants)hasbeenreducedbelowtoanacceptablelevel.Toachievetheseacceptablelevels,cleaningprocedure(SOPNo._______________)needtobeestablishedandvalidated;samplingandanalysiswillbecarriedoutforthispurposetoassurethatthecleaningofMachinecomplieswithspecifiedlimits.CleaningValidationwillverifytheeffectivenessofcleaningprocedure.3Scopei.Thisdocumentoncleaningvalidationisintendedtoaddressspecialconsiderationandissuespertainingtovalidationofcleaningprocedure(SOPNo._______________)ofMachineName(MachineNo.________________)usedforTabletsCompressionofPharmaceuticalproducts.ii.Thisdocumentisalsointendedtoestablishinspectionconsistencyanduniformitywithrespecttoequipmentcleaningprocedures.iii.Thisdocumentisintendedtocovervalidationofequipmentcleaningfortheremovalofcontaminantsassociatedtothepreviousproduct,residuesofcleaningagentsaswellasthecontrolofpotentialmicrobialcontaminants.4Responsibilityi.QA/QCManagerii.ValidationTeamLeaderiii.ValidationOfficeriv.RepresentativeofProductionDepartmentv.Analystvi.Microbiologist5ValidationProgramEquipmentcleaningvalidationmaybeperformedconcurrentlywithactualproductionstepsduringprocessdevelopmentandbulkmanufacturing.ValidationprogramsshouldbecontinuedthroughfullscalecommercialproductionTheconcept“Test-Until-Clean”willbeapplied.Thisconceptinvolvescleaning,samplingandtestingwithrepetitionofthissequenceuntilanacceptableresiduelimitisattained.Avalidationprogramgenerallyencompassesatleastthreeconsecutivesuccessfulreplicatetoestablishthattheprocedureisreproduciblyeffective.Iftheequipmentofthesimilarsize,designandconstructioniscleanedbythesameprocedure,studiesneednottobeconductedoneachunitaslongasatotalofthreesuccessfulreplicatesaredoneonsimilarpieceofequipment;thisconceptisknownasequipmentgrouping.6ChangeControlAnyofthefollowingproposedchangesareevaluatedfullyfortheirimpactonthevalidatedstateoftheprocedurechangesmaybe,i.ChanginginMachineii.Changeincleaningagentsused(ifapplicable)iii.ChangeincleaningproceduresIfanyoftheabove-citedchangesarerequireditshouldbeperformedinaccordancewiththechangecontrolprocedure(SOPNo._________________).Aftertheapprovalofanychangeaccordingtoprocedure,itisrequiredtorevalidatetheCleaningProcedure.7AcceptanceCriteriaTestingParameterAcceptanceCriteria1PhysicaldeterminationThevisualexaminationoftheequipmentverifyingthatvisibleresiduesorparticulatematters.2ChemicalDetermination1.NMT0.1%ofthenormaltherapeuticdoseofanyproducttoappearinthemaximumdailydoseofthesubsequentproduct.2.NMT10ppmofanyproducttoappearinthenextproduct.3.Forcertainallergicingredients,penicillinescephalosporinofsteroidsandcytotoxic,thelimitshouldbebelowthelimitofdetection.3MicrobialContaminationTotalaerobicCountsa)BacterialCounts=NMT20CFUb)Molds=NMT02CFU8SamplingProcedureDirectSurfaceSampling(SwabMethod):a)Areadifficulttocleanandwhicharereasonablycleancanbeevaluatedbydirectsurfacesamplingmethod(SwabMethod),leadingtoestablishalevelofcontaminationorresiduepergivenareai.e.60–100in2.TheresiduethataredriedoutorareinsolublecanbesampledbySwabMethod.b)Thesuitabilityofthemethodtobeusedforsamplingandofsamplingmediumshouldbedetermined.Theabilitytorecoverthesampleaccuratelymaybeaffectedbythechoiceofsamplingmethod.Itisimportanttoassurethesamplingmediumandsolvent(usedforextractionfromthemedium)aresatisfactoryandcanbereadilyused.c)FordeterminationoftheMicrobiologicalContaminationonsurfacesistousesterilecottonswabsmoistenedwithsterilepeptonewater,WFI,orPhosphateBuffer.Usingsterileforcepsandaseptictechnique,anareaofpredeterminedsize,e.g.60-100in2,iswipedwithasterileswab.Theswabisthenasepticallytransferredtoasteriletubecontainingasuitablediluent.Thetubeisthenagitatedtosuspendanyviablemicroorganismsandaliquotsareplacedinasemisolidmediumtoobtainquantitativeresults.9CleaningProcedureThecleaningproceduresareperformedaccordingtoSOPNo.________________i.SwitchOfft