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PrinciplesofCleanroomValidation

Principles of Cleanroom
Validation
Sun, 11/06/2011 - 7:00pm

2 Comments

by David Muchemu

Acleanroomisamodularenvironmentinwhichthefollowing
environmentalfactorsarekeptundercontroltemperature,
airborneparticulates,microbes,relativehumidity,differential
pressure,andairflow.
CleanroomValidationisperformedforavarietyofreasons.To
ensurethatthedesignofthefacilityisfitforitsintended
purposetoensurethatthefacility,equipment,and
environmentmeetsUserRequirementSpecifications(URS)to
ensurethatthefacility,equipment,andenvironmentmeet
definedregulatoryrequirementstoensurethatthefacility,
equipment,anditsenvironmentfunctiontogetherasasystem
tomeetdefinedstandards.
Cleanroomsarevalidatedandthencertifiedtoachosenclass
ofISO146441.EachclassofISO145441hasitsunique
requirementsthatmustbemadeforafacilitytobeclassified
inthespecifiedclassification.
CLEANROOMVALIDATIONLIFECYCLE
Validationofanewcleanroomfollowsaspecifiedlifecycle.
Thelifecyclecomprisesfivephaseseachofwhich
accomplishesparticulartaskstocontrolvariationinthe
modularenvironment.
Cleanroomvalidationworkisaccomplishedthroughfive
phases.Itstartsoffwiththedesigncontrolphaseandends
withmonitorandcontrol.Changestoequipmentandcontrol
factorsafterthecleanroomhasbeenvalidatedaregroundsfor
cleanroomrevalidation.

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Image1

PHASEONE:DESIGNQUALIFICATION
CleanroomvalidationstartswithDesignQualification(DQ).
Thepurposeofthisphaseistoprovethroughobjective
evidencethatthedesignisfitforitsintendedpurpose.Design
Qualificationisaverificationexerciseagainstrequirements
definedintheacceptancecriteriaofyourDQprotocol.
Theprotocolshouldaddressthefollowing:
UserRequirementSpecifications(URS)
Vendordocumentsandspecifications
Facilitylayout
Purchaseorders
Designdocumentation
FactoryAcceptanceTests(FATs)
Asbuilddrawings
Datasheets
TheoutputoftheDesignQualificationphaseisaphasereport
andanStandardDocumentationList(SDL)filethat
documentsthefollowing:
1.Designrequirements
2.Biddingrequirements
3.Purchasingandorderdocumentation
4.Vendorsupplieddocumentslist
5.Asbuilddrawings
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6.Componentlists
7.Inspectionlists
8.FactoryAcceptanceTests
TheapprovaloftheDesignQualification,DQphaseisapre
requisitefortheinitiationoftheInstallationQualification,IQ
phase.
PHASETWO:INSTALLATIONQUALIFICATION
ThepurposeofthisInstallationQualification(IQ)phaseisto
confirmthroughverificationthatequipmentasinstalled
confirmstouserrequirementsanddesignrequirements.
Verificationisfocusedonthefollowingitemsthatshouldbe
calledforinyourIQprotocol:
HVACcalibration
P&IDloopverification
HEPAfilterintegritytestdatareview
Criticalequipmentcalibrationstatus
SiteAcceptanceTests(SATs)
InstallationQualificationtests
Pipingandweldingdocumentation
Utilityverification
Systemstandardoperatingproceduresandwork
instructions
TheoutputofthisphaseshouldbeanIQreportaddressingall
theaboveelements,andanSDLfilethatdocumentsthe
followingelements:
1.Projectchanges
2.IQtestsperformed
3.Calibration
4.Suppliersupplieddocuments
5.Equipmentcertificate
6.Installationdeviations
7.SiteAcceptanceTests(SAT)
8.Consumablelist
9.Sparepartlist
10.Environmentalreviewreport
11.ListofOperationalandInstructionaldocuments
IQapprovalisaprerequisiteforthestartoftheOperational
Qualification(OQ)phase.

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PHASETHREE:OPERATIONQUALIFICATION
TheobjectiveforthisOperationalQualification(OQ)phaseis
toshowthroughobjectiveevidencethatthecleanroom
operatesinconformancewithdesignrequirementsanduser
definedrequirements,andthatitconsistentlyoperateswithin
adefinedrangeofconditions.
TheOQprotocolshouldaddressthefollowing:
TestingHVAC(HeatingVentilationAirConditioner)
systemoperationagainstspecifiedfunctional
requirements
CriticalAlarms
InterlockAlarms
Criticaloperatingparametersdefinedontheroomdata
sheet
Filterintegritytests
Standardoperationforthecleanroom
Airspeedandairflow
Airflowpatterns
Pressuredifferential
TheOQphaseshouldalsoaddressworstcasescenarios.To
designtheworstcasescenariofortheoperationofthe
cleanroom,criticaloperatingparametersareidentifiedfrom
thecleanroomdatasheet.Operationranges,andextreme
ranges,aresetforeachcriticalparameterandaworstcase
designedanddocumented.Itshouldincludethefollowing:
1.Maximumandminimumtemperatures
2.Maximumandminimumhumidity
3.Maintenanceschedules
4.Personnelcontamination
Theworstcasescenarioisusuallycarriedoutatthespecified
HighandspecifiedLowparameters.
TheoutputofthisphaseisanOQreportaddressingalarms
andfunctionalrequirementsofthecleanroomspecifiedinthe
userrequirementspecifications.
PHASEFOUR:PERFORMANCEQUALIFICATION
ThepurposeofPerformanceQualification(PQ)ofthe
cleanroomistodemonstratewithobjectiveevidencethatthe
cleanroomconsistentlyoperateswithindefinedparametersto
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producethedefined,desiredenvironmentaloutcome.
Cleanroomperformancequalificationinvolvestestingand
monitoringofthefollowing:
1.Airborneparticulatelevels
2.Surfaceparticulatelevels
3.Viablemicrobialparticulates
4.Relativehumidity
5.Differentialpressure
6.Temperature
TheoutputofthePQphaseisaPQreportthatanalyzesthe
performanceofthecleanroomusingspecifiedequipment
parameters.PQisaprerequisiteforcertification.

Table1

Table2

CLEANROOMCERTIFICATION
Validatedcleanroomsarevalidatedtoarequiredclassof
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cleanliness.Thelevelofcleanlinesschosenisdrivenbyuser
requirements.CleanroomclassesaredefinedinISO14641:
MethodsforevaluationandmeasurementsforCertificationare
specifiedinISO146443.Itcallsoutforthefollowingten
tests.
1.Airborneparticlecounttest
2.Airflowtest
3.Airpressuredifferencialtest
4.Filterleakagetest
5.Flowvizualizationtest
6.Airflowdirectiontest
7.Temperaturetest
8.Humiditytest
9.Recoverytest
10.Containmentleaktest
Oncecertifiedtoaparticularclassthecleanroomfactorsare
monitoredtoensurethatparametershavenotdrifted,or
changed,andthattheenvironmentisundercontrol.
MONITORANDCONTROL
Aconstantmonitoringprogramisrequiredaftercertification.
RequirementsforcompliancearefoundinISO146442.
Statisticalanalysisforcleanroomparametersisencouragedas
atoolformonitoringthecleanroomaftercertificationto
ensurecompliance.Thetoolofchoiceisstatisticalprocess
control,SPC.

DavidMuchemuisthecofounderandCEOofCGMP
UniversityInc.Heisaseniorconsultantforpharmaceutical,
medicaldevice,tissueanddietarysupplements.Hespecializes
inprocessvalidation,qualitysystemdesign,andCAPAand
changecontrol.Hispassionisproactivequalitymanagement
throughprocesscontrol.Heisanestablishedauthorof
severalCGMPbooks.

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v.srikanthgoud ayearago

Goodmeansoflearningforfreshers

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SaiKing 2yearsago

niceexplaination

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