Cleaning Validation Protocol for Pharmaceuticals.docx

Cleaning Validation Protocol for Pharmaceuticals.docx

《Cleaning Validation Protocol for Pharmaceuticals.docx》由会员分享，可在线阅读，更多相关《Cleaning Validation Protocol for Pharmaceuticals.docx（9页珍藏版）》请在冰豆网上搜索。

CleaningValidationProtocolforPharmaceuticals

CleaningValidationProtocolforPharmaceuticals

1Introduction

TheValidationoftheCleaningProceduresisestablishingdocumentedevidencethattheprocedureiseffectiveandcapableforremovingthecontaminantsassociatedwithpreviousproducts,residuesofcleaningagentsaswellasthecontrolofpotentialmicrobialcontaminants.

TheCleaningValidationisnotonlyensuringthecomplianceoftheregulatoryrequirements,butamoreimportantbenefitforperformingcleaningprocedurevalidationistheidentificationandthecorrectionofthepotentialproblemswhichcouldcompromisethesafety,efficacyorqualityofthesubsequentbatchesofdrugproduct.

2Objective

TheobjectiveoftheCleaningValidationistoverifytheeffectivenessofthecleaningprocedureforremovalofproductresidues,degradationproducts,preservatives,excipientsand/orcleaningagentssothattheanalyticalmonitoringmaybereducedtoaminimumintheroutinephase,andtoensurethatthereisnoriskassociatedwithcross-contaminationofactiveingredients.

TheobjectiveofValidationoftheCleaningProcedure（SOPNo._______________）usedforthecleaningofMachineName（MachineNo.________________）istoprovethattheproductcontactpartsoftheMachineName（MachineNo.________________）havebeencleanedandthatthecontaminationlevel（ChemicalandMicrobialContaminants）hasbeenreducedbelowtoanacceptablelevel.

Toachievetheseacceptablelevels,cleaningprocedure（SOPNo._______________）needtobeestablishedandvalidated;samplingandanalysiswillbecarriedoutforthispurposetoassurethatthecleaningofMachinecomplieswithspecifiedlimits.

CleaningValidationwillverifytheeffectivenessofcleaningprocedure.

3Scope

i.Thisdocumentoncleaningvalidationisintendedtoaddressspecialconsiderationandissuespertainingtovalidationofcleaningprocedure（SOPNo._______________）ofMachineName（MachineNo.________________）usedforTabletsCompressionofPharmaceuticalproducts.

ii.Thisdocumentisalsointendedtoestablishinspectionconsistencyanduniformitywithrespecttoequipmentcleaningprocedures.

iii.Thisdocumentisintendedtocovervalidationofequipmentcleaningfortheremovalofcontaminantsassociatedtothepreviousproduct,residuesofcleaningagentsaswellasthecontrolofpotentialmicrobialcontaminants.

4Responsibility

i.QA/QCManager

ii.ValidationTeamLeader

iii.ValidationOfficer

iv.RepresentativeofProductionDepartment

v.Analyst

vi.Microbiologist

5ValidationProgram

Equipmentcleaningvalidationmaybeperformedconcurrentlywithactualproductionstepsduringprocessdevelopmentandbulkmanufacturing.Validationprogramsshouldbecontinuedthroughfullscalecommercialproduction

Theconcept“Test-Until-Clean”willbeapplied.Thisconceptinvolvescleaning,samplingandtestingwithrepetitionofthissequenceuntilanacceptableresiduelimitisattained.

Avalidationprogramgenerallyencompassesatleastthreeconsecutivesuccessfulreplicatetoestablishthattheprocedureisreproduciblyeffective.

Iftheequipmentofthesimilarsize,designandconstructioniscleanedbythesameprocedure,studiesneednottobeconductedoneachunitaslongasatotalofthreesuccessfulreplicatesaredoneonsimilarpieceofequipment;thisconceptisknownasequipmentgrouping.

6ChangeControl

Anyofthefollowingproposedchangesareevaluatedfullyfortheirimpactonthevalidatedstateoftheprocedurechangesmaybe,

i.ChanginginMachine

ii.Changeincleaningagentsused（ifapplicable）

iii.Changeincleaningprocedures

Ifanyoftheabove-citedchangesarerequireditshouldbeperformedinaccordancewiththechangecontrolprocedure（SOPNo._________________）.

Aftertheapprovalofanychangeaccordingtoprocedure,itisrequiredtorevalidatetheCleaningProcedure.

7AcceptanceCriteria

TestingParameter

AcceptanceCriteria

1

Physicaldetermination

Thevisualexaminationoftheequipmentverifyingthatvisibleresiduesorparticulatematters.

2

ChemicalDetermination

1.NMT0.1%ofthenormaltherapeuticdoseofanyproductto appearinthemaximumdailydoseofthesubsequentproduct.

2.NMT10ppmofanyproducttoappearinthenextproduct.

3.Forcertainallergicingredients,penicillinescephalosporinofsteroidsandcytotoxic,thelimitshouldbebelowthelimitofdetection.

3

MicrobialContamination

TotalaerobicCounts

a） BacterialCounts=NMT20CFU

b） Molds=NMT02CFU

8SamplingProcedure

DirectSurfaceSampling（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.

9CleaningProcedure

ThecleaningproceduresareperformedaccordingtoSOPNo.________________

i.SwitchOfftheMachine

ii.Writedowncompletecleaningprocedurestepwise

iii.AftercleaningpasteCleaningStatusLabelandenterinLogbook

10TestingProcedure

PhysicalTesting

Alongwithtakingsamples,itisimportanttoperformvisualinspectionaswelltoensuretheprocessacceptability.

ChemicalTesting

WritedowntheanalyticalprocedurefordeterminationoftracesatleastthreeActivePharmaceuticalIngredients.

MicrobiologicalTesting

SwabTest

▪CottonSwabspreparedonS.Ssticksaresterilized.

▪PhosphatebufferpH7.2preparedanddispensed5mlineachscrewcappedtesttubesissterilized.

▪Materialistransferredintosterileareaforswabtestafterdisinfection.

▪Removethesterilizedswab,soakinphosphatebufferandtouchtothesurfacetobechecked

▪2½x2½inch2areaistouchedagainsteachsoakedswab.

▪Placebacktheswabintothetubecontainingphosphatebufferandlabelthetubewiththetestingpartanddate.

▪Transferthetestedswabtomicrolab.formicrobiologicaltest.

▪Pourplatemethodisusedtocheckthecontaminants.

▪Platesareincubatedfor48hours,theresultsaredeclaredasnumberofCFUperpartorsurface.

11OverallValidationProcedure

i.IntimatetheProductionDepartmentfortheCleaningValidationofMachineName（MachineNo.________________）beforestartingtheactivitythroughCleaningValidationSchedule.

ii.AfterCleaningoftheMachineName（MachineNo.________________）accordingtoprocedure（SOPNo.____________）ProductionDepartmentinformtheValidationSectionforconductingtheValidationactivities.

iii.ValidationOfficertakestheSwabSampleforChemicalDetermination,whereasMicrobiologisttakestheSwabSampleforMicrobiologicalDetermination.

iv.SendthesamplestoQCalongwithTechnicalInformationSheetforanalysis.

v.QCDanalyzesthesampleaccordingtoprocedureandprovidetheresultstoValidationSection.

vi.Repeatthestepsii,iiiandivafterthechangeofconsecutivethreedifferentproducts.

vii.ValidationSectionanalyzesalltheresultsandcompilesthereport.

viii.IftheresultscomplywiththespecifiedlimitsthantheMachineName（MachineNo.________________）isconsideredascleanedandtheCleaningProcedure（SOPNo._____________）isconsideredasValidated.

ix.Iftheresultsdonotcomplywiththespecifiedlimits,thenrepeattheoverallValidationactivesforfurthertwoconsecutivechangesofdifferentproductsi.e.toprovidethevalidationdataofthreeconsecutiveAPI’s.

x.Ifthevalidationresultsdonotcomplywiththespecification,improvethecleaningprocedureandcontinueituntilalltheresultscomplywiththespecifiedlimits.

12InspectionCriteria（forthreeconsecutiveproducts）

12.1PreviousProduct

BatchNo.

WhiletakingsamplesfromMachineName（MachineNo.________________）,notedownthefollowingpoints.

·        Descriptionofmachine/equipment/area:

·        MajorProductcontactcomponents:

·        ProductContactArea:

·        PreviousBatchcompletedon:

·        Equipmentcleanedon:

·        Detergent/Solventused:

·        Compositionofthedetergentused:

·        CleaningTools:

·         AncillaryUtilities:

·         CleaningCycles:

·         Cleanedby:

·         Supervisedby:

·         Sampledby（Chemical）

·        Sampledby（Microbiological）

·        AftercleaningtheEquipmentusedon:

·        SubsequentProduct:

·        BatchNo.

·        NameofAPI:

·        BatchSizeofthesubsequentproduct:

·        MaximumdailydoseofthesubsequentProduct:

12.2PreviousProduct

      BatchNo.

WhiletakingsamplesfromMachineName（MachineNo.________________）,notedownthefollowing