IP 2 Unit 4 NABL, OOS, GLP.pdf

The National accreditation Board for Testing and Calibration laboratories (NABL) is an independent organization operating under the supervision of the Department of Science and Technology, Government of India. Its primary objective is to provide certification to clinical labs in India for their testing and calibration activities.

1. NABLAccreditation
NATIONAL ACCREDITATION BOARD
FOR TESTING AND CALIBRATION
LABORATORIES (NABL),
& OOS, GLP
Dr. Kumara Swamy Samanthula
M. Pharm, Ph.D
A s s o c i a t e P r o f e s s o r
F a c u l t y o f P h a r m a c e u t i c a l S c i e n c e
A S S A M D O W N TO W N U N I V E R S I T Y

2. WhatisNABL?
TheNationalAccreditationBoardforTestingandCalibrationLaboratories(NABL)isan
autonomousbodyundertheguidanceoftheDept.OfScience&Technology,Govt.ofIndia,
whosepurposeistosupplyaccreditationtotestingandcalibrationofclinicallaboratories
withinthecountry.
NABLspecifiesthegeneralrequirementsforthecompetencetocarryouttestsand
calibrations,includingsampling.Itcoverstestingandcalibrationperformedusing
standardmethods,non-standardmethods,andlaboratory-developedmethods.
NationalAccreditationBoardforTestingandCalibrationLaboratories(NABL)isan
autonomousbodyunderDepartmentofScience&Technology,GovernmentofIndia,andis
registeredundertheSocietiesAct.
NABLhasbeenestablishedwiththeobjectivetoprovideGovernment,IndustryandSociety
ingeneralwithaschemeforthird-partyassessmentofthequalityandtechnical
competenceoftestingandcalibrationlaboratories.
GovernmentofIndiahasauthorizedNABLasthesoleaccreditationbodyforTestingand
Calibrationlaboratories.
Inordertoachievethisobjective,NABLprovideslaboratoryaccreditationservicesto
laboratoriesthatareperformingtests/calibrationsinaccordancewithNABLcriteriabased
oninternationallyacceptedstandardforlaboratoryaccreditationISO.

3. CONCEPT:TheconceptofLaboratoryAccreditationwasdevelopedto
provideameansforthird-partycertificationofthecompetenceof
laboratoriestoperformspecifictype(s)oftestingandcalibration.
LaboratoryAccreditationprovidesformalrecognitionofcompetent
laboratories,thusprovidingareadymeansforcustomerstofindreliable
testingandcalibrationservicesinordertomeettheirdemands.
LaboratoryAccreditationenhancescustomerconfidenceinaccepting
testing/calibrationreportsissuedbyaccreditedlaboratories.
TheglobalizationofIndianeconomyandtheliberalizationpoliciesinitiated
bytheGovernmentinreducingtradebarriersandprovidinggreaterthrust
toexportsmakesitimperativeforAccredited.

4. BenefitsofAccreditation:
⚫Potentialincreaseinbusinessduetoenhancedcustomerconfidenceand
satisfaction.
⚫Savingsintermsoftimeandmoneyduetoreductionoreliminationoftheneed
forre-testing.
⚫Bettercontroloflaboratoryoperationsandfeedbacktolaboratoriesasto
whethertheyhavesoundQualityAssuranceSystemand
⚫IncreaseofconfidenceinTesting/Calibrationdataandpersonnelperforming
work.
⚫CustomerscansearchandidentifythelaboratoriesaccreditedbyNABLfor
theirspecificrequirementsfromthedirectoryofAccreditedLaboratories.
⚫Usersofaccreditedlaboratorieswillenjoygreateraccessfortheirproducts,in
bothdomesticandinternationalmarkets,whentestedbyaccredited
laboratories.

5. TYPESOFLABORATORY CANSEEKACCREDITATION:
⚫Laboratoriesundertakinganysortoftestingorcalibrationin the
specifiedfields.
⚫Privateor governmentlaboratories.
⚫Smalloperationstolargemulti-fieldlaboratories.
⚫Sitefacilities,temporaryfieldoperationsandmobile
laboratories.

6. TESTING
LABORATORIES
CALIBRATION
LABORATORIES
MEDICAL
LABORATORIES
PROFICIENCY
TESTING
PROVIDERS
REFERENCE
MATERIAL
PRODUCERS
Biological Electro-Technical ClinicalBiochemistry Testing ChemicalComposition
Chemical Mechanical ClinicalPathology Calibration Biological&Clinical
Electrical FluidFlowThermal Hematology& Medical Properties
ElectronicsFluid- &Optical Immunohematology Inspection PhysicalProperties
FlowMechanical Radiological Microbiology& EngineeringProperties
Non-Destructive Serology Miscellaneous
Testing Histopathology Properties
Photometry Cytopathology
Radiological Genetics
Thermal NuclearMedicine(in-
Forensic vitrotestsonly)

7. 10 StepApproachToAccreditation
⚫AwarenessTraining
⚫QualityPolicy&ObjectivesFinalization
⚫GapAnalysis
⚫Documentation/ProcessDesign
⚫Documentation/ProcessImplementation
⚫InternalAudit
⚫ManagementReviewMeeting
⚫ShadowAudit
⚫Corrective–PreventiveActions
⚫FinalCertificationAudit
Step1:AwarenessTraining
⚫100Separatetrainingsessionsfortopmanagement,middlemanagementandjuniorlevel
management.
⚫CreatesamotivatingenvironmentthroughouttheorganizationforISO17025implementation.

8. Step2:QualityPolicy&Objectives
⚫Work shopwithtopmanagementondevelopment ofquality policy.
⚫Workshopwithtopmanagementandmiddlelevelfunctionalmanagementon
developmentofqualityobjectives
Step3:GapAnalysis
⚫Understandingofalltheoperationsoftheorganization.
⚫Developmentofprocessmapfortheactivitiesof theorganization.
⚫Comparingexistingoperationswithrequirementsof ISO17025:2005standard.
Step4:Documentation/ProcessDesign
⚫QualityManual
⚫FunctionalProcedures
⚫WorkInstructions
⚫SystemProcedures
⚫Formats

9. Step5:Documentation/ProcessImplementation
⚫Work–shopon process/documentimplementation as perISO17025requirements.
⚫Departmental/Individualassistancein implementing thenewprocesses/documents.
Step6:InternalAudit
⚫InternalAuditTraining&Examination(Optional).
⚫Successfulemployeescarryoutinternalauditoftheorganizationcoveringallthedepartments andoperations.
⚫Suggestcorrectiveandpreventiveactionsforimprovementsineachoftheauditeddepartments.
Step7:ManagementReviewMeeting
⚫QualityPolicy&Objectives
⚫Resultsofinternalaudit
⚫Resultsofsupplierevaluation
⚫Resultsofcustomercomplaints
⚫Resultsofcustomerfeedbacketc.

10. Step8:ShadowAudit
ofthefinal
⚫Itisafinalcertificationaudit.
⚫FindsdegreeofcompliancewithISO 17025standard.
⚫Givesanideatotheemployeesabouttheconduct
certificationaudit.
Step9:Corrective–PreventiveActions
⚫Onthebasisofshadowauditconductedinthelaststep,allthenon-
conformitieswillbeassignedcorrectiveandpreventiveactions.
⚫Acheckwillensurethatallthepointsareclosedandtheorganizationis readyforthe
finalcertificationaudit.
Step10:FinalCertificationAudit
⚫Uponcompletionofvariousstagesofaccreditationaudit,theaudit,your organization
willbe awardedaccreditation.
⚫

11. OutofSpecifications(OOS):
Introduction:-Whenananalyticalortestresultofanybatchormaterialis
outofprescribedandpredeterminedlimitsorspecifications,itiscalledas
OOS.
OOSmayberaisedinthecaseofstabilitytesting,analysisofin-process,
testofrawmaterials,intermediatesandfinishedgoods(API).
InvestigationforOOSmaybeperformedwhilegettinganyunacceptable
andquestionableresults.

12. IdentificationofOOS:
Reports ofLaboratory Investigation:-
ThisinvestigationisconductedwhenOOSisfoundinanalysis.Themain
purposeofobtainingOOSreportsistofindoutthesourceoftheresults
whichfalloutsidethespecifications.Inthisinitialinvestigation,alltheresults
shouldberecordedandwelldocumented.
Thedatashouldbeconveyedandforwardedtoqualitycontrol
department,sothatfullscaleanalysiscanbeperformed.

13. ResponsibilityofAnalystandSupervisor:-
Ananalysthastheprimaryresponsibilityforthelaboratorytesting
results.Heshouldhavesoundknowledgeabouttheprinciple,primary
requirementsandprocessoftheinvestigations.
Theaccurateandpreciseresultsareexpected,ifanywrongresultsare
foundthatshouldbeinformedtoconcernsuperiordepartmentand
assessmentshouldbeinitiatedwithimmediateeffect.
Thesupervisorofthelaboratoryshoulddiscusstheproblemsandthe
malfunctionedresultwiththeanalyst.Heshouldverifythefollowedcorrect
procedureandknowledgeoftheanalyst.

14. Heshouldoverlookthefollowingpoints:
1.Rawdataoftheresult.
2.Calculationsoftheresult.
3.Properfunctioningof instruments.
4.Procedureperformedbythe analyst.
5.Qualityparametersofsolvent's,reagents,standard solutions.
6.Knowledgeoftheanalystregardinginvestigation.
7.Methodvalidationandevaluationofperformance.
8.Preservationof theresultsobtained.

15. IdentificationofOOS:
ReportsofFuIl-ScaleInvestigation:Whenaninitialanalysisdoesnot
confirmtheerrorscausedbyOOSresultfromlabinvestigations,fullscale
investigationswithproperdesignshouldbeperformed.Theidentification
ofthesourceoftheerrorsandtheactiontakenforthecorrectnessare
themainobjectivesofthisinvestigation.
ThefollowingaretheimportantaspectsofOOSresultsidentificationwith
respecttofullscaleinvestigation.
1.Reviewofmanufacturing,productionandsampling.
2.Reviewof labinvestigationresult.
3.Supplementarylaboratorytestingprocedure.

16. ReviewofManufacturing,ProductionandSampling:-
TofindouttheOOSresults,reviewofmanufacturing, production
andsamplingisveryimportant.
Theerrorsandproblemsshouldbeinvestigatedandidentified.
Thedocumentsandrecordsofmanufacturingandproduction shouldbe
reviewed.
Theinvestigationsshouldbereviewedthroughawell-
documented manner.

17. ReviewofLabInvestigationResults:-
Itcontainsthefollowinginformation:
⚫Causeoftheinvestigation.
⚫Reviewandsummaryofmanufacturingprocess(whichmayhave
identifiedasmalfunctionedorcauseofOOSresults).
⚫Reviewofpreviousresultstofindoutthepossiblecauses
ofOOSresults.
⚫Reviewofdocumentedrecordstoanalyzethepossiblefactorsof
wrongresults.
⚫The actionstakento correct theprocess.

18. SupplementaryLaboratoryTestingProcedure:
ToinvestigateOOSresultsinfullscale,additionallaboratorytestingmay
beperformed.ThisincludesRe-testingandRe-sampling.
InRe-testing,aportionoforiginalsamplesaretestedagainaccordingto
thestandardprocedures.Theresultsarekeptinawelldocumented
manner.Thisprocesshelpstofindouttheproblemsencountereddueto
errorininstruments,process,dilutionorsamplehandling.
InRe-sampling,aspecimeniscollectedfromanyadditionalunitsfrom
originalsampleoranewsampleispreparedfromthesamebatchand
analyzedfurther.

19. ANALYSISOFINVESTIGATEDRESULTS:-THEREPORTED RESULTS SHOULD BEANALYZED AND
INTERPRETED TOFINDOUTTHEPOSSIBLE,PROBABLE ANDACTUALCAUSESOFOOSRESULTS.SOME
POSSIBILITIESAREDISCUSSEDBELOW:
AnalysisofInvestigated Results

20. AnalysisofInvestigatedResults

21. ChangeControl:-
Introduction:-Inpharmaceuticalindustrychangecontrolisan
importantpartofqualityassurance.
Thechangesproposedandmadeinanyprocedureorprocessshouldbe
reviewed,established,documentedandapprovedbytheconcerned
authorities.
Changecontrolisthesystemtoimplementthisapprovedchangetoconfirm
theregulatoryrequirements.
Definition:-Changecontrolcanbedefinedasaformalsystembywhich
qualifiedrepresentativesofappropriatedisciplinesreviewproposedor
actualchangesthatmightaffectthevalidatedstatusoffacilities,systems,
equipmentorprocesses.Theintentistodeterminetheneedforactionthat
wouldensureanddocumentthatthesystemismaintainedinavalidated
state.

22. Function:Anychangeinmanufacturingprocess.equipment,materials
usedthatmaycausealterationinproductqualityshouldbevalidated.The
mainfunctionsofchangecontrolare:
1.Identificationofthechangesmade.
2.Reviewofthechange.
3.Approvalofthechange.
4.Validatingthechangeswhichcanaltertheproductquality, regulatoryor
GMPrequirements.
5.Analysisofthechangeandmonitoringoftheimpactof
change

23. AreaofChange:
1.Manufacture:Followingchangesare concerned:
⚫Rawmaterials,
⚫Equipment's,
⚫Process/parameters,
⚫Testing/validationprocedures,
⚫Packagingmaterials,
⚫Cleaningprocess
2.Qualitycontroland qualityassurance:Followingchangesareconsidered:
⚫Qualitytestingparameters,
⚫Samplingsize,
⚫Validationprocess,
⚫Specificationsofrawmaterials,intermediatesandfinalproduct,
⚫Documentation,
⚫Standardoperatingprocedures(SOPs).

24. 3.Researchanddevelopment: Itincludesthechangein:-
⚫Manufacturingprocess(anyadditionofeliminationofsteps),
⚫Rawmaterials(anyadditionofomissionoftheproduct)
⚫Specificationsofrawmaterials,intermediatesandfinalproduct,
⚫Quantitativeaspectsofrawmaterialsandfinishedproducts,
⚫Manufacturingconditionsandstorageconditions,
⚫Testing/validationprocedures.
4.Engineering:
⚫Equipmentused,
⚫Validationoftheequipment,
⚫Partsofequipment,
⚫Workinganddesignlayout,
⚫Software/HardwareorChangeinanyprogram.

25. 5.Marketing:Written Procedures&Documentation:
Proceduresinwritingshouldbekeptattheproperplacetodescribethe
changesmaderelatedtothematerials,equipmentandmethodof
manufacturingortestingconditionsoranyotherchangethatcanaffect
thequalityoftheproduct.
Standardoperatingprocedure(SOP)andrecordsofchangecontrol
documentsarerequiredforthedocumentation.TheChangeControlForm
(CCF)isanimportantdocumentationpartofchangecontrol.
Itcontainstheformrelatedtoinitiatedepartmentfortheproposed
change,proposedchangedetails,commentsfromQAHead,categoryof
thechanges,supportivedocuments,managementreviewformand
assessmentofCCF.

26. GLP(GoodLaboratoryPractice):-
Introduction:-GLPwasintroducedforthenon-clinicalsafetystudiesin1976.In
late90'sthispracticealongwithOECD(OrganizationforEconomicCo-operation
andDevelopment)wasacceptedasindustrystandards.
GLPhasbeenintroducedduetothepooranddishonestpracticeinlaboratoryin
theearly70's.Thepoorlabpracticesincludewrongcalibrationofequipments,
inaccuratetestsystemsandaccounts.
In1983,IndustrialBioTestLaboratory(1952-1978)ofNewYorkwasfoundguilty
asitprovidedwrongandinaccurateresearchdatatotheGovernment.
Thecompanyprovidedfake,fabricatedandconcealeddataofthetestsonrodents
involvingTrichlorobanilide(deodorantsoapadditives),Naprosyn(arthritisdrug),
Sencor(Herbicide)andNemacur(Pesticide).

27. Definition:-AccordingtoValcarcelM.,GLPisasetofrules,operating
proceduresandpracticesestablishedbyanorganizationtoensurethequality
andaccurateresultsinalaboratorypractice.Inthispractice,thegiven
organizationsetstheprinciplesandthelaboratoryworksareplanned,operated,
overlookedandreported.
FundamentalsofGLP:
Resources:Itincludesthefollowing:
1.OrganizationandManagement:Managementhastheoverallresponsibilityfor
theimplementationofbothgoodscienceandgoodorganizationwithintheir
institutions.Goodscienceincludesproperdefinitionofexperimentaldesign,
knowledgeofscientificprinciples,documentationofexperimentaland
environmentalvariables,completeevaluationoftheresultsandreportingof
results.
Whereas,goodorganizationshouldprovideproperplanningofstudies,qualified
skilledpersonnel,adequatefacilities,infrastructures,properconductionofstudies
andverificationprocessforthestudyresults

28. 2.Personnel:Thedetailedrecordsshouldbemaintainedforevery
individualstaffoftheinstitution.Therecordsincludethedetailcurriculum
vitae,trainingrecordsandtheirjobdescriptions.Theserecordsshould
meettheGLPrequirementsandthesearemaintainedtoestablishthat
everystaffhasthecompetence,education,experienceandtrainingto
performthetests.
3.AvailabilityofFacilities:Adequatefacilitieswithstate-of-the-art
infrastructureshouldbeprovidedbytheinstitutionandmanagementto
ensurethevalidationofthestudies.Thecleaning,maintenanceand
documentsofthesiteplanshouldsatisfytheguidelines.
4.AvailabilityofEquipments:Adequateequipmentsmustbeavailable
forthestudyintheorganization.Thesuitabilityoftheequipmentand
calibratedinstrumentsshouldbeprovidedbythemanagement.

29. C.Characterization:-Itincludes:
1.TestItems:Itmaybeanactiveingredientforamedicine,apesticide,a
foodadditive,avaccine,anindustriallyusedchemical,abiomassoran
extractionfromplants.Theseitemsarecharacterizedbyanalyticalprofile
likechemicalidentificationtest,solubility,stabilityetc.Thetestitems
shouldbestoredproperlytoavoidthecontamination.
2.TestSystems:Thetestsystemscouldbetheanimals,bacteria,cells,
organsandplants.Sometimestheymaybeanalyticalequipmentsalso.
Thetestsystemsshouldbehandledinsuchawaythatitmustcomply
withtheGLPguidelinesandwiththenationalanimalwelfarelaw.

30. C.Rules:-
1.StudyProtocols:Thestudyplanorprotocoldescribeshowthestudyis
designedandhowitistobeconducted.Theplanshouldincludethe
expectedtimeframeofthestudy.
2.WrittenProcedures:WrittenproceduresareoftenknownasSOPs
(StandardOperatingProcedures).SOPsprovidetheinstructionshow
eachtechnicalprocedureshouldbeperformed,howtoensurethesound
organizationofthestudy,environmentalvariablesanddata.

31. D.Results:-
Itincludesrawdata,finalreportsanddataarchiving.
1.RawData:Theoriginalrecordandthedataneededforthereconstruction
shouldberecorded.Therawdatashouldinclude'what‘wasdone,'how'itwas
done,'when’theworkwasdoneand’who’performedthework.Therecordeddata
shouldclarifytheprocessbywhichitisgeneratedandshouldconfirmtheprocess
hasbeenperformedaspertheguidelinesandSOPs.
2.FinalResults:Finalresultsaretheresponsibilityofthestudydirector.These
resultsshoulddescribethestudyaccuratelyandthescientificinterpretation.
Theresultsshouldreflectaccuratelytherawdata.Thereviewandauditofthese
reportsshouldbedone.Allacceptedchangesintheresultsapprovedbythe
reviewershouldbeincorporatedbeforethefinalizationoftheresults.

32. 3Archives:Archivingisasafedepositingofallinformation.Itis
consideredtobeacenterforthecompilationanddistributionofsummary
documents.Thearchivingofdocumenthelpsthereconstructionofstudies
performedearlier.
E.QualityAssurance:Therequirementofthe quality
assuranceistovalidatetheexperimentalresults.Quality
assuranceunit(QAU)orsimplyQAmustreviewallphasesofpreclinical
research,organizationframework,staffdocuments,studyproceduresand
SOPs.TheinternalauditsandinspectionsshouldbeperformedbytheQA
officers.TheQAperformsthestudy-basedaudit,facilityandsystems-
basedinspectionandprocess-basedinspections.

33. GLPPrinciples:-GLPprinciplesaresetoforganizationalrequirements.GLPisaregulationcoveringthequality
managementofnon-clinicalsafetystudies.Theaimoftheregulationistoencouragescientiststoorganizeandperform
theirstudiesinawaywhichpromotesthequalityandvalidityofthetestdata.
GLPdealswiththefollowingissues:
⚫Thefacilityprovidedbytheorganization.
⚫Efficientandtrainedpersonnel.
⚫Qualityofvalidatedequipmentandreagents.
⚫Predeterminedstudydesign.
⚫SOPs,processvalidationandtestprocedures.
⚫Correctnessoftheresults.
⚫Qualityassurancelaboratory(QAL)andQualityassuranceprogram(QAP).
⚫Recordedanddocumentedresultsandtheirstorage.
Theorganizationsshouldfulfillallthecriteriatoprovideallthefacilitiesforthegoodpracticeinlaboratory.Thepersonnel
shouldhaveenoughknowledgeabouttheprinciplesandworkingofthepractices.IntheelementsofGLP,SOPisan
importantpartwithrespecttoqualityassurance.Tomaintaintheproductivityoftheresult,awelldocumentedSOPis
required;moreover,thepersonnelshouldhavecompleteinformationmentionedinSOPs.

34. SOPsdefinethecompleteprocessflowandworkstepswhichhelpto
achievetheaccurateandprecisedresults.Validatedmodernequipments
andadequatefacilitiesshouldbeprovidedbytheorganizationtomaintain
thegoodpracticeinlaboratory.Thecompletespecificationsandstorageof
reagentsandmaterialsshouldbeprovided.
QAlaboratoryshouldhavethepropertestprocedures(physical,chemical
andbiological)andcharacterizeddataforboththetestandreference
materials.
Qualityassuranceunit(QAU)bearstheresponsibilitytoassure
theGLPandthisunitisattachedwithQALandQAP.
Theauditofthelaboratoryandverificationofthequalityparametersarethe
majorresponsibilitiesoftheQAU.Thereportedstudyresultsshouldbe
storedandretainedwithwelldocumentedmanner.

35. AimofGLP:-
1.GLPhelpstoreducethenumberoffalsenegativesarisingfromthe
studies.Falsenegativeresultforatoxicitystudyfalselyintimatedthatthe
testitemisnottoxic,butinrealtheitemistoxic.
2.GLPalsohelpstoreducethechanceoffalsepositives.Inthecaseofa
non-clinicalsafetystudy,theresultswronglypredictthatthetestitemis
toxic,whenreallyitisnot.
3.GLPpromotesinternationalrecognitionofstudydata.Whenstudiesare
performedaccordingtoOECDGLPprinciples,thentheacceptabilityand
reliabilityofthedataarerecognizedintheinternationallevelbytheOECD
memberstates.