GLP 21 CFR part 58

GLP 21 CFR part 58

1. GLP OR GOOD LABORATORY PRACTICES
DR.K.VENKATESWARA RAJU
DEPT OF REGULATORY AFFAIRS
SHRI VISHNU COLLEGE OF PHARMACY

2. GLP OR GOOD LABORATORY PRACTICES
GLPisanFDAregulation.
Definition:GLPembodiesasetofprinciples
thatprovidesaframeworkwithinwhich
laboratorystudiesareplannedperformed,
monitored,reportedandarchived.
GLPissometimesconfusedwiththe
standardsoflaboratorysafetylikewearing
safetygoggles.

3. HISTORY
GLP is a formal regulation that was created by the FDA (United states food and drug
administration) in 1978.
Although GLP originated in the United States , it had a world wide impact.
Non-US companies that wanted to do business with the United states or register their
pharmacies in the United States had to comply with the United States GLP regulations.
They eventually started making GLP regulations in their home countries.
In 1981 an organization named OECD (organization for economic co-operation and
development ) produced GLP principles that are international standard.

4. WHY WAS GLP CREATED?
Intheearly70’sFDAbecameawareofcasesofpoorlaboratory
practiceallovertheUnitedStates.
FDAdecidedtodoanin-depthinvestigationon40toxicologylabs.
Theydiscoveredalotfraudulentactivitiesandalotofpoorlab
practices.
Examplesofsomeofthesepoorlabpracticesfoundwere
1.Equipmentnotbeencalibratedtostandardform,thereforegiving
wrongmeasurements.
2.Incorrect/inaccurateaccountsoftheactuallabstudy
3.Inadequatetestsystems

8. FAMOUS EXAMPLE
Oneofthelabsthatwentundersuchaninvestigationmadeheadlinenews.
ThenameoftheLabwasIndustrialBioTest.Thiswasabiglabthatrantestsforbigcompaniessuchas
ProcterandGamble.
Itwasdiscoveredthatmicethattheyhadusedtotestcosmeticssuchaslotionanddeodorantshad
developedcanceranddied.
IndustrialBioTestlabthrewthedeadmiceandcoveredresultsdeemingtheproductsgoodforhuman
consumption.
Thoseinvolvedinproduction,distributionandsalesforthelabeventuallyservedjailtime.

9. 21 CFR PART 58
CFRisCodeofFederalRegulationsisthecodificationofthegeneralandpermanentrulesandregulationssometimes
calledadministrativelaw)publishedintheFederalRegisterbytheexecutivedepartmentsandagenciesofthefederal
governmentoftheUnitedStates.
TheCFRispublishedbytheOfficeoftheFederalRegister,anagencyoftheNationalArchivesandRecords
Administration(NARA).TheCFRisdividedinto50titlesthatrepresentbroadareassubjecttoFederalregulations.
Outof50wewilluseTitle-21whichreferstoFood&Drugs.
Hencewecallit21-CFR.
This21-CFRisfurtherdividedinto1500parts.
Outofwhichwewillbeusingfrequently
11(i.e.21-CFRPart-11)forElectronicrecords
211(i.e.21-CFRPart-211)forGoodmanufacturingpractices
and58(i.e.21-CFRPart-58)forgoodlaboratorypracticesforconductingnonclinicallaboratorystudies.
21-CFRPart-58describesgoodlaboratorypracticesforconductingnonclinicallaboratorystudiesthatsupportorare
intendedtosupportapplicationsforresearchormarketingpermitsforproductsregulatedbytheFoodandDrug
Administration…compliancewiththispartisintendedtoassurethequalityandintegrityofthesafetydata…

10. SUBPART A -GENERAL PROVISIONS

11. SUBPART A -GENERAL PROVISIONS
SCOPE
Thispartprescribesgoodlaboratorypracticesforconductingnonclinicallaboratorystudiesthatsupportor
areintendedtosupportapplicationsforresearchormarketingpermitsforproductsregulatedbytheFood
andDrugAdministration,includingfoodandcoloradditives,animalfoodadditives,humanandanimal
drugs,medicaldevicesforhumanuse,biologicalproducts,andelectronicproducts.
Compliancewiththispartisintendedtoassurethequalityandintegrityofthesafetydatafiledpursuantto
sectionsoftheFederalFood,Drug,andCosmeticActandsectionsofthePublicHealthServiceAct.
ItprovidesdefinitionsofvarioustermsusedingoodlaboratorypracticeslikeACT,Testarticle,Control
article,Person,specimen
ItprovidesprovisionsforApplicabilitytostudiesperformedundergrantsandcontractsandInspectionofa
testingfacility

12. SUBPART B -ORGANIZATION AND PERSONNEL

13. PERSONNEL
Eachindividualengagedintheconductoforresponsibleforthesupervisionofanonclinicallaboratorystudyshallhave
education,training,andexperience,orcombinationthereof,toenablethatindividualtoperformtheassignedfunctions.
Eachtestingfacilityshallmaintainacurrentsummaryoftrainingandexperienceandjobdescriptionforeach
individualengagedinorsupervisingtheconductofanonclinicallaboratorystudy.
Thereshallbeasufficientnumberofpersonnelforthetimelyandproperconductofthestudyaccordingtothe
protocol.
Personnelshalltakenecessarypersonalsanitationandhealthprecautionsdesignedtoavoidcontaminationoftestand
controlarticlesandtestsystems.
Personnelengagedinanonclinicallaboratorystudyshallwearclothingappropriateforthedutiestheyperform.Such
clothingshallbechangedasoftenasnecessarytopreventmicrobiological,radiological,orchemicalcontaminationof
testsystemsandtestandcontrolarticles.
Anyindividualfoundatanytimetohaveanillnessthatmayadverselyaffectthequalityandintegrityofthenonclinical
laboratorystudyshallbeexcludedfromdirectcontactwithtestsystems,testandcontrolarticlesandanyother
operationorfunctionthatmayadverselyaffectthestudyuntiltheconditioniscorrected.Allpersonnelshallbe
instructedtoreporttotheirimmediatesupervisorsanyhealthormedicalconditionsthatmayreasonablybeconsidered
tohaveanadverseeffectonanonclinicallaboratorystudy.

14. TESTING FACILITY MANAGEMENT
Foreachnonclinicallaboratorystudy,testingfacilitymanagementshall:
Designateastudydirectorbeforethestudyisinitiated.
Replacethestudydirectorpromptlyifitbecomesnecessarytodosoduringtheconductof
astudy.
Assurethatthereisaqualityassuranceunitasdescribedinprovisions.
Assurethattestandcontrolarticlesormixtureshavebeenappropriatelytestedfor
identity,strength,purity,stability,anduniformity,asapplicable.
Assurethatpersonnel,resources,facilities,equipment,materials,andmethodologiesare
availableasscheduled.
Assurethatpersonnelclearlyunderstandthefunctionstheyaretoperform.
Assurethatanydeviationsfromtheseregulationsreportedbythequalityassuranceunit
arecommunicatedtothestudydirectorandcorrectiveactionsaretakenanddocumented

15. STUDY DIRECTOR
Foreachnonclinicallaboratorystudy,ascientistorotherprofessionalofappropriateeducation,
training,andexperience,orcombinationthereof,shallbeidentifiedasthestudydirector.Thestudy
directorhasoverallresponsibilityforthetechnicalconductofthestudy,aswellasforthe
interpretation,analysis,documentationandreportingofresults,andrepresentsthesinglepointof
studycontrol.Thestudydirectorshallassurethat
Theprotocol,includinganychange,isapprovedandfollowed.
Allexperimentaldata,includingobservationsofunanticipatedresponsesofthetestsystemare
accuratelyrecordedandverified.
Unforeseencircumstancesthatmayaffectthequalityandintegrityofthenonclinicallaboratory
studyarenotedwhentheyoccur,andcorrectiveactionistakenanddocumented.
Testsystemsareasspecifiedintheprotocol.
Allapplicablegoodlaboratorypracticeregulationsarefollowed.
Allrawdata,documentation,protocols,specimens,andfinalreportsaretransferredtothe
archivesduringoratthecloseofthestudy.

16. QUALITY ASSURANCE UNIT
(a)Atestingfacilityshallhaveaqualityassuranceunitwhichshallberesponsibleformonitoringeachstudytoassuremanagementthatthe
facilities,equipment,personnel,methods,practices,records,andcontrolsareinconformancewiththeregulationsinthispart.Foranygivenstudy,
thequalityassuranceunitshallbeentirelyseparatefromandindependentofthepersonnelengagedinthedirectionandconductofthatstudy.
(b)Thequalityassuranceunitshall:Theprotocol,includinganychange,isapprovedandfollowed.
Maintainacopyofamasterschedulesheetofallnonclinicallaboratorystudiesconductedatthetestingfacilityindexedbytestarticleand
containingthetestsystem,natureofstudy,datestudywasinitiated,currentstatusofeachstudy,identityofthesponsor,andnameofthestudy
director.
Maintaincopiesofallprotocolspertainingtoallnonclinicallaboratorystudiesforwhichtheunitisresponsible.
Inspecteachnonclinicallaboratorystudyatintervalsadequatetoassuretheintegrityofthestudyandmaintainwrittenandproperlysigned
recordsofeachperiodicinspectionshowingthedateoftheinspection,thestudyinspected,thephaseorsegmentofthestudyinspected,the
personperformingtheinspection,findingsandproblems,actionrecommendedandtakentoresolveexistingproblems,andanyscheduleddate
forreinspection.Anyproblemsfoundduringthecourseofaninspectionwhicharelikelytoaffectstudyintegrityshallbebroughttothe
attentionofthestudydirectorandmanagementimmediately.
Periodicallysubmittomanagementandthestudydirectorwrittenstatusreportsoneachstudy,notinganyproblemsandthecorrectiveactions
taken.
Determinethatnodeviationsfromapprovedprotocolsorstandardoperatingproceduresweremadewithoutproperauthorizationand
documentation.
Reviewthefinalstudyreporttoassurethatsuchreportaccuratelydescribesthemethodsandstandardoperatingprocedures,andthatthe
reportedresultsaccuratelyreflecttherawdataofthenonclinicallaboratorystudy.
Prepareandsignastatementtobeincludedwiththefinalstudyreportwhichshallspecifythedatesinspectionsweremadeandfindings
reportedtomanagementandtothestudydirector.

17. QUALITY ASSURANCE UNIT
(c)Theresponsibilitiesandproceduresapplicabletothequalityassuranceunit,
therecordsmaintainedbythequalityassuranceunit,andthemethodof
indexingsuchrecordsshallbeinwritingandshallbemaintained.Theseitems
includinginspectiondates,thestudyinspected,thephaseorsegmentofthe
studyinspected,andthenameoftheindividualperformingtheinspectionshall
bemadeavailableforinspectiontoauthorizedemployeesoftheFoodandDrug
Administration.
(d)AdesignatedrepresentativeoftheFoodandDrugAdministrationshall
haveaccesstothewrittenproceduresestablishedfortheinspectionandmay
requesttestingfacilitymanagementtocertifythatinspectionsarebeing
implemented,performed,documented,andfollowed-upinaccordancewith
provisions

18. SUBPART C -FACILITIES

19. SUBPART C -FACILITIES
Eachtestingfacilityshallbeofsuitablesizeandconstructiontofacilitatethe
properconductofnonclinicallaboratorystudies.Itshallbedesignedsothat
thereisadegreeofseparationthatwillpreventanyfunctionoractivityfrom
havinganadverseeffectonthestudy

20. ANIMAL CARE FACILITIES
(a)Atestingfacilityshallhaveasufficientnumberofanimalroomsorareas,asneeded,toassure
proper:(1)Separationofspeciesortestsystems,(2)isolationofindividualprojects,(3)quarantineof
animals,and(4)routineorspecializedhousingofanimals.
(b)Atestingfacilityshallhaveanumberofanimalroomsorareasseparatefromthosedescribedin
paragraph(a)ofthissectiontoensureisolationofstudiesbeingdonewithtestsystemsortestand
controlarticlesknowntobebiohazardous,includingvolatilesubstances,aerosols,radioactive
materials,andinfectiousagents.
(c)Separateareasshallbeprovided,asappropriate,forthediagnosis,treatment,andcontrolof
laboratoryanimaldiseases.Theseareasshallprovideeffectiveisolationforthehousingofanimals
eitherknownorsuspectedofbeingdiseased,orofbeingcarriersofdisease,fromotheranimals.
(d)Whenanimalsarehoused,facilitiesshallexistforthecollectionanddisposalofallanimalwaste
andrefuseorforsafesanitarystorageofwastebeforeremovalfromthetestingfacility.Disposal
facilitiesshallbesoprovidedandoperatedastominimizevermininfestation,odors,diseasehazards,
andenvironmentalcontamination

21. ANIMAL SUPPLY FACILITIES
Thereshallbestorageareas,asneeded,forfeed,bedding,supplies,and
equipment.Storageareasforfeedandbeddingshallbeseparatedfromareas
housingthetestsystemsandshallbeprotectedagainstinfestationor
contamination.Perishablesuppliesshallbepreservedbyappropriatemeans.

22. FACILITIES FOR HANDLING TEST AND
CONTROL ARTICLES
Asnecessarytopreventcontaminationormixups,thereshallbeseparateareas
for:
(1)Receiptandstorageofthetestandcontrolarticles.
(2)Mixingofthetestandcontrolarticleswithacarrier,e.g.,feed.
(3)Storageofthetestandcontrolarticlemixtures.
Storageareasforthetestand/orcontrolarticleandtestandcontrolmixtures
shallbeseparatefromareashousingthetestsystemsandshallbeadequateto
preservetheidentity,strength,purity,andstabilityofthearticlesand
mixtures.

23. LABORATORY OPERATION AREAS
Separatelaboratoryspaceshallbeprovided,asneeded,fortheperformanceof
theroutineandspecializedproceduresrequiredbynonclinicallaboratory
studies

24. SPECIMEN AND DATA STORAGE FACILITIES
Spaceshallbeprovidedforarchives,limitedtoaccessbyauthorizedpersonnel
only,forthestorageandretrievalofallrawdataandspecimensfrom
completedstudies.

25. SUBPART D -EQUIPMENT

26. EQUIPMENT -EQUIPMENT DESIGN
Equipmentusedinthegeneration,measurement,orassessmentofdataand
equipmentusedforfacilityenvironmentalcontrolshallbeofappropriate
designandadequatecapacitytofunctionaccordingtotheprotocolandshallbe
suitablylocatedforoperation,inspection,cleaning,andmaintenance.

27. MAINTENANCE AND CALIBRATION OF EQUIPMENT
Equipmentshallbeadequatelyinspected,cleaned,andmaintained.Equipmentusedforthe
generation,measurement,orassessmentofdatashallbeadequatelytested,calibratedand/or
standardized.
Thewrittenstandardoperatingproceduresrequiredunder§58.81(b)(11)shallsetforthin
sufficientdetailthemethods,materials,andschedulestobeusedintheroutineinspection,
cleaning,maintenance,testing,calibration,and/orstandardizationofequipment,andshall
specify,whenappropriate,remedialactiontobetakenintheeventoffailureormalfunctionof
equipment.Thewrittenstandardoperatingproceduresshalldesignatethepersonresponsiblefor
theperformanceofeachoperation.
Writtenrecordsshallbemaintainedofallinspection,maintenance,testing,calibratingand/or
standardizingoperations.Theserecords,containingthedateoftheoperation,shalldescribe
whetherthemaintenanceoperationswereroutineandfollowedthewrittenstandardoperating
procedures.
Writtenrecordsshallbekeptofnonroutinerepairsperformedonequipmentasaresultoffailure
andmalfunction.Suchrecordsshalldocumentthenatureofthedefect,howandwhenthedefect
wasdiscovered,andanyremedialactiontakeninresponsetothedefect.

28. SUBPART E -TESTING FACILITIES OPERATION

29. STANDARD OPERATING PROCEDURES
(a)Atestingfacilityshallhavestandardoperatingproceduresinwritingsettingforthnonclinicallaboratorystudymethodsthatmanagementis
satisfiedareadequatetoinsurethequalityandintegrityofthedatageneratedinthecourseofastudy.Alldeviationsinastudyfromstandard
operatingproceduresshallbeauthorizedbythestudydirectorandshallbedocumentedintherawdata.Significantchangesinestablished
standardoperatingproceduresshallbeproperlyauthorizedinwritingbymanagement.
(b)Standardoperatingproceduresshallbeestablishedfor,butnotlimitedto,thefollowing:
Animalroompreparation.
Animalcare.
Receipt,identification,storage,handling,mixing,andmethodofsamplingofthetestandcontrolarticles.
Testsystemobservations.
Laboratorytests.
Handlingofanimalsfoundmoribundordeadduringstudy.
Necropsyofanimalsorpostmortemexaminationofanimals.
Collectionandidentificationofspecimens.
Histopathology.
Datahandling,storage,andretrieval.
Maintenanceandcalibrationofequipment.
Transfer,properplacement,andidentificationofanimals

30. STANDARD OPERATING PROCEDURES
(c)Eachlaboratoryareashallhaveimmediatelyavailablelaboratorymanuals
andstandardoperatingproceduresrelativetothelaboratoryproceduresbeing
performed.Publishedliteraturemaybeusedasasupplementtostandard
operatingprocedures.
(d)Ahistoricalfileofstandardoperatingprocedures,andallrevisionsthereof,
includingthedatesofsuchrevisions,shallbemaintained

31. REAGENTS AND SOLUTIONS.
Allreagentsandsolutionsinthelaboratoryareasshallbelabeledtoindicate
identity,titerorconcentration,storagerequirements,andexpirationdate.
Deterioratedoroutdatedreagentsandsolutionsshallnotbeused.

32. ANIMAL CARE
Thereshallbestandardoperatingproceduresforthehousing,feeding,handling,andcareofanimals.
Allnewlyreceivedanimalsfromoutsidesourcesshallbeisolatedandtheirhealthstatusshallbeevaluatedinaccordancewithacceptable
veterinarymedicalpractice.
Attheinitiationofanonclinicallaboratorystudy,animalsshallbefreeofanydiseaseorconditionthatmightinterferewiththepurposeor
conductofthestudy.If,duringthecourseofthestudy,theanimalscontractsuchadiseaseorcondition,thediseasedanimalsshallbeisolated,if
necessary.Theseanimalsmaybetreatedfordiseaseorsignsofdiseaseprovidedthatsuchtreatmentdoesnotinterferewiththestudy.The
diagnosis,authorizationsoftreatment,descriptionoftreatment,andeachdateoftreatmentshallbedocumentedandshallberetained.
Warm-bloodedanimals,excludingsucklingrodents,usedinlaboratoryproceduresthatrequiremanipulationsandobservationsoveran
extendedperiodoftimeorinstudiesthatrequiretheanimalstoberemovedfromandreturnedtotheirhomecagesforanyreason(e.g.,cage
cleaning,treatment,etc.),shallreceiveappropriateidentification.Allinformationneededtospecificallyidentifyeachanimalwithinananimal-
housingunitshallappearontheoutsideofthatunit.
Animalsofdifferentspeciesshallbehousedinseparateroomswhennecessary.Animalsofthesamespecies,butusedindifferentstudies,should
notordinarilybehousedinthesameroomwheninadvertentexposuretocontrolortestarticlesoranimalmixupcouldaffecttheoutcomeof
eitherstudy.Ifsuchmixedhousingisnecessary,adequatedifferentiationbyspaceandidentificationshallbemade.
Animalcages,racksandaccessoryequipmentshallbecleanedandsanitizedatappropriateintervals.
Feedandwaterusedfortheanimalsshallbeanalyzedperiodicallytoensurethatcontaminantsknowntobecapableofinterferingwiththe
studyandreasonablyexpectedtobepresentinsuchfeedorwaterarenotpresentatlevelsabovethosespecifiedintheprotocol.Documentation
ofsuchanalysesshallbemaintainedasrawdata.
Beddingusedinanimalcagesorpensshallnotinterferewiththepurposeorconductofthestudyandshallbechangedasoftenasnecessaryto
keeptheanimalsdryandclean
Ifanypestcontrolmaterialsareused,theuseshallbedocumented.Cleaningandpestcontrolmaterialsthatinterferewiththestudyshallnotbe
used

33. SUBPART F -TEST AND CONTROL ARTICLES

34. TEST AND CONTROL ARTICLE CHARACTERIZATION
Theidentity,strength,purity,andcompositionorothercharacteristicswhichwillappropriately
definethetestorcontrolarticleshallbedeterminedforeachbatchandshallbedocumented.
Methodsofsynthesis,fabrication,orderivationofthetestandcontrolarticlesshallbe
documentedbythesponsorrthetestingfacility.Inthosecaseswheremarketedproductsareused
ascontrolarticles,suchproductswillbecharacterizedbytheirlabeling.
Thestabilityofeachtestorcontrolarticleshallbedeterminedbythetestingfacilityorbythe
sponsoreither:(1)Beforestudyinitiation,or(2)concomitantlyaccordingtowrittenstandard
operatingprocedures,whichprovideforperiodicanalysisofeachbatch.
Eachstoragecontainerforatestorcontrolarticleshallbelabeledbyname,chemicalabstract
numberorcodenumber,batchnumber,expirationdate,ifany,and,whereappropriate,storage
conditionsnecessarytomaintaintheidentity,strength,purity,andcompositionofthetestor
controlarticle.Storagecontainersshallbeassignedtoaparticulartestarticleforthedurationof
thestudy.
Forstudiesofmorethan4weeks’duration,reservesamplesfromeachbatchoftestandcontrol
articlesshallberetainedfortheperiodoftimeprovidedby§58.195

35. TEST AND CONTROL ARTICLE HANDLING
Proceduresshallbeestablishedforasystemforthehandlingofthetestand
controlarticlestoensurethat:
Thereisproperstorage.
Distributionismadeinamannerdesignedtoprecludethepossibilityof
contamination,deterioration,ordamage.
Properidentificationismaintainedthroughoutthedistributionprocess.
Thereceiptanddistributionofeachbatchisdocumented.Such
documentationshallincludethedateandquantityofeachbatchdistributed
orreturned.

36. MIXTURES OF ARTICLES WITH CARRIERS
(a)Foreachtestorcontrolarticlethatismixedwithacarrier,testsbyappropriateanalyticalmethodsshallbeconducted:
(1)Todeterminetheuniformityofthemixtureandtodetermine,periodically,theconcentrationofthetestorcontrol
articleinthemixture.
(2)Todeterminethestabilityofthetestandcontrolarticlesinthemixtureasrequiredbytheconditionsofthestudyeither:
(i)Beforestudyinitiation,or
(ii)Concomitantlyaccordingtowrittenstandardoperatingprocedureswhichprovideforperiodicanalysisofthetest
andcontrolarticlesinthe
mixture.
(b)[Reserved]
(c)Whereanyofthecomponentsofthetestorcontrolarticlecarriermixturehasanexpirationdate,thatdateshallbe
clearlyshownonthecontainer.Ifmorethanonecomponenthasanexpirationdate,theearliestdateshallbeshown.

37. SUBPART G -PROTOCOL FOR AND CONDUCT
OF A NONCLINICAL LABORATORY STUDY

38. PROTOCOL
(a)Eachstudyshallhaveanapprovedwrittenprotocolthatclearlyindicatestheobjectivesandallmethodsfortheconductofthestudy.Theprotocolshall
contain,asapplicable,thefollowinginformation:
(1)Adescriptivetitleandstatementofthepurposeofthestudy.
(2)Identificationofthetestandcontrolarticlesbyname,chemicalabstractnumber,orcodenumber.
(3)Thenameofthesponsorandthenameandaddressofthetestingfacilityatwhichthestudyisbeingconducted.
(4)Thenumber,bodyweightrange,sex,sourceofsupply,species,strain,substrain,andageofthetestsystem.
(5)Theprocedureforidentificationofthetestsystem.
(6)Adescriptionoftheexperimentaldesign,includingthemethodsforthecontrolofbias.
(7)Adescriptionand/oridentificationofthedietusedinthestudyaswellassolvents,emulsifiers,and/orothermaterialsusedtosolubilizeorsuspendthetest
orcontrolarticlesbeforemixingwiththecarrier.Thedescriptionshallincludespecificationsforacceptablelevelsofcontaminantsthatarereasonably
expectedtobepresentinthedietarymaterialsandareknowntobecapableofinterferingwiththepurposeorconductofthestudyifpresentatlevelsgreater
thanestablishedbythespecifications.
(8)Eachdosagelevel,expressedinmilligramsperkilogramofbodyweightorotherappropriateunits,ofthetestorcontrolarticletobeadministeredandthe
methodandfrequencyofadministration.
(9)Thetypeandfrequencyoftests,analyses,andmeasurementstobemade.
(10)Therecordstobemaintained.
(11)Thedateofapprovaloftheprotocolbythesponsorandthedatedsignatureofthestudydirector.
(12)Astatementoftheproposedstatisticalmethodstobeused.
(b)Allchangesinorrevisionsofanapprovedprotocolandthereasonsthereforeshallbedocumented,signedbythestudydirector,dated,andmaintained
withtheprotocol.

39. CONDUCT OF A NONCLINICAL LABORATORY STUDY
(a)Thenonclinicallaboratorystudyshallbeconductedinaccordancewiththeprotocol.
(b)Thetestsystemsshallbemonitoredinconformitywiththeprotocol.
(c)Specimensshallbeidentifiedbytestsystem,study,nature,anddateofcollection.Thisinformationshallbelocatedon
thespecimencontainerorshallaccompanythespecimeninamannerthatprecludeserrorintherecordingandstorage
ofdata.
(d)Recordsofgrossfindingsforaspecimenfrompostmortemobservationsshouldbeavailabletoapathologistwhen
examiningthatspecimenhistopathologically.
(e)Alldatageneratedduringtheconductofanonclinicallaboratorystudy,exceptthosethataregeneratedbyautomated
datacollectionsystems,shallberecordeddirectly,promptly,andlegiblyinink.Alldataentriesshallbedatedonthe
dateofentryandsignedorinitialedbythepersonenteringthedata.Anychangeinentriesshallbemadesoasnotto
obscuretheoriginalentry,shallindicatethereasonforsuchchange,andshallbedatedandsignedoridentifiedatthe
timeofthechange.Inautomateddatacollectionsystems,theindividualresponsiblefordirectdatainputshallbe
identifiedatthetimeofdatainput.Anychangeinautomateddataentriesshallbemadesoasnottoobscurethe
originalentry,shallindicatethereasonforchange,shallbedated,andtheresponsibleindividualshallbeidentified

40. SUBPARTS H–I [RESERVED]

41. SUBPART J—RECORDS AND REPORTS

42. REPORTING OF NONCLINICAL LABORATORY STUDY RESULTS
(a)Afinalreportshallbepreparedforeachnonclinicallaboratorystudyandshallinclude,butnotnecessarilybelimitedto,thefollowing:
(1)Nameandaddressofthefacilityperformingthestudyandthedatesonwhichthestudywasinitiatedandcompleted.
(2)Objectivesandproceduresstatedintheapprovedprotocol,includinganychangesintheoriginalprotocol.
(3)Statisticalmethodsemployedforanalyzingthedata.
(4)Thetestandcontrolarticlesidentifiedbyname,chemicalabstractsnumberorcodenumber,strength,purity,andcompositionorotherappropriatecharacteristics.
(5)Stabilityofthetestandcontrolarticlesundertheconditionsofadministration.
(6)Adescriptionofthemethodsused.
(7)Adescriptionofthetestsystemused.Whereapplicable,thefinalreportshallincludethenumberofanimalsused,sex,bodyweightrange,sourceofsupply,species,strainandsubstrain,
age,andprocedureusedforidentification.
(8)Adescriptionofthedosage,dosageregimen,routeofadministration,andduration.
(9)Adescriptionofallcircumstancesthatmayhaveaffectedthequalityorintegrityofthedata.
(10)Thenameofthestudydirector,thenamesofotherscientistsorprofessionals,andthenamesofallsupervisorypersonnel,involvedinthestudy.
(11)Adescriptionofthetransformations,calculations,oroperationsperformedonthedata,asummaryandanalysisofthedata,andastatementoftheconclusionsdrawnfromtheanalysis.
(12)Thesignedanddatedreportsofeachoftheindividualscientistsorotherprofessionalsinvolvedinthestudy.
(13)Thelocationswhereallspecimens,rawdata,andthefinalreportaretobestored.
(14)Thestatementpreparedandsignedbythequalityassuranceunitasdescribedin§58.35(b)(7).
(b)Thefinalreportshallbesignedanddatedbythestudydirector.(c)Correctionsoradditionstoafinalreportshallbeintheformofanamendmentbythestudydirector.Theamendment
shallclearlyidentifythatpartofthefinalreportthatisbeingaddedtoorcorrectedandthereasonsforthecorrectionoraddition,andshallbesignedanddatedbythepersonresponsible.

43. STORAGE AND RETRIEVAL OF
RECORDS AND DATA
(a)Allrawdata,documentation,protocols,finalreports,andspecimens(exceptthosespecimensobtainedfrom
mutagenicitytestsandwetspecimensofblood,urine,feces,andbiologicalfluids)generatedasaresultofa
nonclinicallaboratorystudyshallberetained.
(b)Thereshallbearchivesfororderlystorageandexpedientretrievalofallrawdata,documentation,
protocols,specimens,andinterimandfinalreports.Conditionsofstorageshallminimizedeteriorationof
thedocumentsorspecimensinaccordancewiththerequirementsforthetimeperiodoftheirretentionand
thenatureofthedocumentsorspecimens.Atestingfacilitymaycontractwithcommercialarchivesto
providearepositoryforallmaterialtoberetained.Rawdataandspecimensmayberetainedelsewhere
providedthatthearchiveshavespecificreferencetothoseotherlocations.
(c)Anindividualshallbeidentifiedasresponsibleforthearchives.
(d)Onlyauthorizedpersonnelshallenterthearchives.
(e)Materialretainedorreferredtointhearchivesshallbeindexedtopermitexpedientretrieval.

44. RETENTION OF RECORDS
(a)Recordretentionrequirementssetforthinthissectiondonotsupersedetherecordretentionrequirementsofanyotherregulationsin
thischapter.
(b)Exceptasprovidedinparagraph(c)ofthissection,documentationrecords,rawdataandspecimenspertainingtoanonclinical
laboratorystudyandrequiredtobemadebythispartshallberetainedinthearchive(s)forwhicheverofthefollowingperiodsisshortest:
(1)Aperiodofatleast2yearsfollowingthedateonwhichanapplicationforaresearchormarketingpermit,insupportofwhichthe
resultsofthenonclinicallaboratorystudyweresubmitted,isapprovedbytheFoodandDrugAdministration.Thisrequirementdoesnot
applytostudiessupportinginvestigationalnewdrugapplications(IND’s)orapplicationsforinvestigationaldeviceexemptions(IDE’s),
recordsofwhichshallbegovernedbytheprovisionsofparagraph(b)(2)ofthissection.
(2)Aperiodofatleast5yearsfollowingthedateonwhichtheresultsofthenonclinicallaboratorystudyaresubmittedtotheFoodand
DrugAdministrationinsupportofanapplicationforaresearchormarketingpermit.
(3)Inothersituations(e.g.,wherethenonclinicallaboratorystudydoesnotresultinthesubmissionofthestudyinsupportofan
applicationforaresearchormarketingpermit),aperiodofatleast2yearsfollowingthedateonwhichthestudyiscompleted,
terminated,ordiscontinued.
(c)Wetspecimens(exceptthosespecimensobtainedfrommutagenicitytestsandwetspecimensofblood,urine,feces,andbiological
fluids),samplesoftestorcontrolarticles,andspeciallypreparedmaterial,whicharerelativelyfragileanddiffermarkedlyinstabilityand
qualityduringstorage,shallberetainedonlyaslongasthequalityofthepreparationaffordsevaluation.Innocaseshallretentionbe
requiredforlongerperiodsthanthosesetforthinparagraphs(a)and(b)ofthissection.

45. RETENTION OF RECORDS
(d)Themasterschedulesheet,copiesofprotocols,andrecordsofqualityassuranceinspections,asrequiredby§58.35(c)shallbe
maintainedbythequalityassuranceunitasaneasilyaccessiblesystemofrecordsfortheperiodoftimespecifiedinparagraphs(a)and(b)
ofthissection.
(e)Summariesoftrainingandexperienceandjobdescriptionsrequiredtobemaintainedby§58.29(b)mayberetainedalongwithall
othertestingfacilityemploymentrecordsforthelengthoftimespecifiedinparagraphs(a)and(b)ofthissection.
(f)Recordsandreportsofthemaintenanceandcalibrationandinspectionofequipment,asrequiredby§58.63(b)and(c),shallbe
retainedforthelengthoftimespecifiedinparagraph(b)ofthissection.
(g)Recordsrequiredbythispartmayberetainedeitherasoriginalrecordsorastruecopiessuchasphotocopies,microfilm,microfiche,
orotheraccuratereproductionsoftheoriginalrecords.
(h)Ifafacilityconductingnonclinicaltestinggoesoutofbusiness,allrawdata,documentation,andothermaterialspecifiedinthissection
shallbetransferredtothearchivesofthesponsorofthestudy.TheFoodandDrugAdministrationshallbenotifiedinwritingofsucha
transfer.

46. SUBPART K—DISQUALIFICATION OF TESTING FACILITIES

47. PURPOSE
(a)Thepurposesofdisqualificationare:
(1)Topermittheexclusionfromconsiderationofcompletedstudiesthatwereconductedbyatestingfacility
whichhasfailedtocomplywiththerequirementsofthegoodlaboratorypracticeregulationsuntilitcanbe
adequatelydemonstratedthatsuchnoncompliancedidnotoccurduring,ordidnotaffectthevalidityor
acceptabilityofdatageneratedby,aparticularstudy;and
(2)Toexcludefromconsiderationallstudiescompletedafterthedateofdisqualificationuntilthefacilitycan
satisfytheCommissionerthatitwillconductstudiesincompliancewithsuchregulations.
(b)Thedeterminationthatanonclinicallaboratorystudymaynotbeconsideredinsupportofanapplication
foraresearchormarketingpermitdoesnot,however,relievetheapplicantforsuchapermitofanyobligation
underanyotherapplicableregulationtosubmittheresultsofthestudytotheFoodandDrugAdministration

48. GROUNDS FOR DISQUALIFICATION
TheCommissionermaydisqualifyatestingfacilityuponfindingallofthefollowing:
(a)Thetestingfacilityfailedtocomplywithoneormoreoftheregulationssetforthinthis
part(oranyotherregulationsregardingsuchfacilitiesinthischapter);
(b)Thenoncomplianceadverselyaffectedthevalidityofthenonclinicallaboratorystudies;
and
(c)Otherlesserregulatoryactions(e.g.,warningsorrejectionofindividualstudies)havenot
beenorwillprobablynotbeadequatetoachievecompliancewiththegoodlaboratory
practiceregulations.

49. NOTICE OF AND OPPORTUNITY FOR HEARING ON PROPOSED DISQUALIFICATI ON
(a)WhenevertheCommissionerhasinformationindicatingthatgroundsexist
under§58.202whichinhisopinionjustifydisqualificationofatestingfacility,
hemayissuetothetestingfacilityawrittennoticeproposingthatthefacilitybe
disqualified.
(b)Ahearingonthedisqualificationshallbeconductedinaccordancewiththe
requirementsforaregulatoryhearingsetforthinpart16ofthischapter

50. FINAL ORDER ON DISQUALIFICATION.
(a)IftheCommissioner,aftertheregulatoryhearing,orafterthetimeforrequestinga
hearingexpireswithoutarequestbeingmade,uponanevaluationoftheadministrative
recordofthedisqualificationproceeding,makeshefindingsrequiredin§58.202,heshall
issueafinalorderdisqualifyingthefacility.Suchordershallincludeastatementofthebasis
forthatdetermination.Uponissuingafinalorder,theCommissionershallnotify(witha
copyoftheorder)thetestingfacilityoftheaction.
(b)IftheCommissioner,afteraregulatoryhearingorafterthetimeforrequestingahearing
expireswithoutarequestbeingmade,uponanevaluationoftheadministrativerecordof
thedisqualificationproceeding,doesnotmakethefindingsrequiredin§58.202,heshall
issueafinalorderterminatingthedisqualificationproceeding.Suchordershallincludea
statementofthebasisforthatdetermination.UponissuingafinalordertheCommissioner
shallnotifythetestingfacilityandprovideacopyoftheorder.

51. ACTIONS UPON DISQUALIFICATION.
(a)Onceatestingfacilityhasbeendisqualified,eachapplicationforaresearchormarketingpermit,whetherapproved
ornot,containingorrelyinguponanynonclinicallaboratorystudyconductedbythedisqualifiedtestingfacilitymay
beexaminedtodeterminewhethersuchstudywasorwouldbeessentialtoadecision.Ifitisdeterminedthatastudy
wasorwouldbeessential,theFoodandDrugAdministrationshallalsodeterminewhetherthestudyisacceptable,
notwithstandingthedisqualificationofthefacility.Anystudydonebyatestingfacilitybeforeorafterdisqualification
maybepresumedtobeunacceptable,andthepersonrelyingonthestudymayberequiredtoestablishthatthestudy
wasnotaffectedbythecircumstancesthatledtothedisqualification,e.g.,bysubmittingvalidatinginformation.Ifthe
studyisthendeterminedtobeunacceptable,suchdatawillbeeliminatedfromconsiderationinsupportofthe
application;andsucheliminationmayserveasnewinformationjustifyingtheterminationorwithdrawalofapproval
oftheapplication.
(b)Nononclinicallaboratorystudybegunbyatestingfacilityafterthedateofthefacility’sdisqualificationshallbe
consideredinsupportofanyapplicationforaresearchormarketingpermit,unlessthefacilityhasbeenreinstated
under§58.219.Thedeterminationthatastudymaynotbeconsideredinsupportofanapplicationforaresearchor
marketingpermitdoesnot,however,relievetheapplicantforsuchapermitofanyobligationunderanyother
applicableregulationtosubmittheresultsofthestudytotheFoodandDrugAdministration.

52. PUBLIC DISCLOSURE OF INFORMATION REGARDING DISQUALIFICATION
(a)Uponissuanceofafinalorderdisqualifyingatestingfacilityunder§58.206(a),theCommissionermaynotifyallor
anyinterestedpersons.SuchnoticemaybegivenatthediscretionoftheCommissionerwheneverhebelievesthat
suchdisclosurewouldfurtherthepublicinterestorwouldpromotecompliancewiththegoodlaboratorypractice
regulationssetforthinthispart.Suchnotice,ifgiven,shallincludeacopyofthefinalorderissuedunder§58.206(a)
andshallstatethatthedisqualificationconstitutesadeterminationbytheFoodandDrugAdministrationthat
nonclinicallaboratorystudiesperformedbythefacilitywillnotbeconsideredbytheFoodandDrugAdministration
insupportofanyapplicationforaresearchormarketingpermit.IfsuchnoticeissenttoanotherFederal
Governmentagency,theFoodandDrugAdministrationwillrecommendthattheagencyalsoconsiderwhetherornot
itshouldacceptnonclinicallaboratorystudiesperformedbythetestingfacility.Ifsuchnoticeissenttoanyother
person,itshallstatethatitisgivenbecauseoftherelationshipbetweenthetestingfacilityandthepersonbeing
notifiedandthattheFoodandDrugAdministrationisnotadvisingorrecommendingthatanyactionbetakenbythe
personnotified.
(b)Adeterminationthatatestingfacilityhasbeendisqualifiedandtheadministrativerecordregardingsuch
determinationaredisclosabletothepublicunderpart20ofthischapter.

53. ALTERNATIVE OR ADDITIONAL ACTIONS TO DISQUALIFICATION.
(a)Disqualificationofatestingfacilityunderthissubpartisindependentof,andneitherinlieuofnorapreconditionto,
otherproceedingsoractionsauthorizedbytheact.TheFoodandDrugAdministrationmay,atanytime,institute
againstatestingfacilityand/oragainstthesponsorofanonclinicallaboratorystudythathasbeensubmittedtothe
FoodandDrugAdministrationanyappropriatejudicialproceedings(civilorcriminal)andanyotherappropriate
regulatoryaction,inadditiontoorinlieuof,andpriorto,simultaneouslywith,orsubsequentto,disqualification.The
FoodandDrugAdministrationmayalsoreferthemattertoanotherFederal,State,orlocalgovernmentlaw
enforcementorregulatoryagencyforsuchactionasthatagencydeemsappropriate.
(b)TheFoodandDrugAdministrationmayrefusetoconsideranyparticularnonclinicallaboratorystudyinsupportof
anapplicationforaresearchormarketingpermit,ifitfindsthatthestudywasnotconductedinaccordancewiththe
goodlaboratorypracticeregulationssetforthinthispart,withoutdisqualifyingthetestingfacilitythatconductedthe
studyorundertakingotherregulatoryaction.

54. SUSPENSION OR TERMINATION OF A TESTING FACILITY BY A SPONSOR..
Terminationofatestingfacilitybyasponsorisindependentof,andneitherinlieuofnora
preconditionto,proceedingsoractionsauthorizedbythissubpart.Ifasponsorterminates
orsuspendsatestingfacilityfromfurtherparticipationinanonclinicallaboratorystudy
thatisbeingconductedaspartofanyapplicationforaresearchormarketingpermitthat
hasbeensubmittedtoanyCenteroftheFoodandDrugAdministration(whetherapproved
ornot),itshallnotifythatCenterinwritingwithin15workingdaysoftheaction;thenotice
shallincludeastatementofthereasonsforsuchaction.Suspensionorterminationofa
testingfacilitybyasponsordoesnotrelieveitofanyobligationunderanyotherapplicable
regulationtosubmittheresultsofthestudytotheFoodandDrugAdministration.

55. REINSTATEMENT OF A DISQUALIFIED TESTING FACILITY
Atestingfacilitythathasbeendisqualifiedmaybereinstatedasanacceptablesourceofnonclinicallaboratory
studiestobesubmittedtotheFoodandDrugAdministrationiftheCommissionerdetermines,uponan
evaluationofthesubmissionofthetestingfacility,thatthefacilitycanadequatelyassurethatitwillconduct
futurenonclinicallaboratorystudiesincompliancewiththegoodlaboratorypracticeregulationssetforthin
thispartand,ifanystudiesarecurrentlybeingconducted,thatthequalityandintegrityofsuchstudieshave
notbeenseriouslycompromised.Adisqualifiedtestingfacilitythatwishestobesoreinstatedshallpresentin
writingtotheCommissionerreasonswhyitbelievesitshouldbereinstatedandadetaileddescriptionofthe
correctiveactionsithastakenorintendstotaketoassurethattheactsoromissionswhichledtoits
disqualificationwillnotrecur.TheCommissionermayconditionreinstatementuponthetestingfacilitybeing
foundincompliancewiththegoodlaboratorypracticeregulationsuponaninspection.Ifatestingfacilityis
reinstated,theCommissionershallsonotifythetestingfacilityandallorganizationsandpersonswhowere
notified,under§58.213ofthedisqualificationofthetestingfacility.Adeterminationthatatestingfacilityhas
beenreinstatedisdisclosabletothepublicunderpart20ofthischapter.

56. Thank you