WPCC BE ).E6[Box, pw1F -T]:hE# k_ZFx=P HڍS +59O@b<|<)Ph)O$c4|o:A'@BB/@ʏ.5G4\ GAGT6S_!4ݥ >%+tŰk{6&s2܃i51섦JMU}x;>8?ޱ p+7'-קV)]OY^ԫi[T[47vst%0CoWsc!\Hqx˪9ZߩNHK<}$Any4PۍА@Зlw6$o ص5Wp|$ذNzmUqf"2mvGsr[tZzTNOiz49i⊍vࣱUeQUMUB6 %x~ 0t 0O 0 0 0\i 0 w 0g< 0 04 1UL 1 U Bi D3F 0  0= 0  AQc B  C I!!"S#9$&&x'&((N*a-r. //1z\345t267T899^: ; 1e<<n< 0r=?? 1m?????????w@@4\@p@6AAB\  `*Times New RomanTT' ELAB GLP Subcommittee Final Report  AG Products 0AG Products .   h:Default ParaDefault Paragraph FontXXXW\  `*Times New RomanTTW        W\  `*Times New RomanTTW8,para4para4  &&&W\  `*Times New RomanTTW        W\  `*Times New RomanTTW<5T.headerheader   !        >4X` hp x (#><5T.footerfooter   !        >4X` hp x (#>P8page numberpage numberXXXW\  `*Times New RomanTTW        W\  `*Times New RomanTTW<.LEVEL4LEVEL4&    &&&W\  `*Times New RomanTTW         W\  `*Times New RomanTTW'  D2LEVEL3.5LEVEL3.5  XXXW\  `*Times New RomanTTW         W\  `*Times New RomanTTW   ~B'n3n3n3      !X      ! !!!ELABGLPSubcommittee^!Page     ! 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Dallas,TX! !!!   !!      ?+ 4 <DL!!?(e2~B$ <!~J~J~J    $359=AEIMQ1""""""""$359=AEIMQ2 d'dxd Level 1 Level 2 Level 3 Level 4 Level 5(e2~B$ <!~J~J~J   ($    (e2~B$ <!~J~J~J   C<< g  ~B"n3n3n3   ?+ 4 <DL!X?  &7&n3n3&&7 CurrentEPALaboratory   &7&n3n3&&7 MonitoringProgram     &7&n3n3&&7??US.,d  ~B"n3n3n3   ?+ 4 <DL!X?&7&n3n3&&7More  preferreddd ~B"n3n3n3   ?+ 4 <DL!X? ~B"n3n3n3   ?+ 4 <DL!X? ~B"n3n3n3   ?+ 4 <DL!X? ~B"n3n3n3   ?+ 4 <DL!X? ~B"n3n3n3   ?+ 4 <DL!X?  ~B"n3n3n3   ?+ 4 <DL!X?  &7&n3n3&&7 ModificationofCurrentPrograms :    &7&n3n3&&7??US., / ~B"n3n3n3   ?+ 4 <DL!X?  &7&n3n3&&7 MajorEnhancementsof  CurrentPrograms : ~B"n3n3n3   ?+ 4 <DL!X? ~B"n3n3n3   ?+ 4 <DL!X? ~B"n3n3n3   ?+ 4 <DL!X? ~B"n3n3n3   ?+ 4 <DL!X?  ~B"n3n3n3   ?+ 4 <DL!X?  &7&n3n3&&7 Registration  List   &7&n3n3&&7Option5    &7&n3n3&&7??US., D ~B"n3n3n3   ?+ 4 <DL!X?  &7&n3n3&&7 Sponsor   &7&n3n3&&7 Monitoring  Input   &7&n3n3&&7Option3    &7&n3n3&&7??US., W ~B"n3n3n3   ?+ 4 <DL!X?  &7&n3n3&&7 Facility  Definition   Option1  (PhaseI) ~B"n3n3n3   ?+ 4 <DL!X? ~B"n3n3n3   ?+ 4 <DL!X?  ~B"n3n3n3   ?+ 4 <DL!X?  &7&n3n3&&7 IncreasedResourcesfor  OECA :  &7&n3n3&&7Option1(PhaseII)    &7&n3n3&&7??US., ~ ~B"n3n3n3   ?+ 4 <DL!X?  &7&n3n3&&7 LaboratoryAccreditation :    &7&n3n3&&7??US., p ~B"n3n3n3   ?+ 4 <DL!X?  &7&n3n3&&7 ThirdParty:   &7&n3n3&&7Option2   ~B"n3n3n3   ?+ 4 <DL!X? ~B"n3n3n3   ?+ 4 <DL!X? j ~B"n3n3n3   ?+ 4 <DL!X?  &7&n3n3&&7 NELAP:   &7&n3n3&&7Option4   ~B"n3n3n3   ?+ 4 <DL!X? ~B"n3n3n3   ?+ 4 <DL!X? ~B"n3n3n3   ?+ 4 <DL!X? ~B"n3n3n3   ?+ 4 <DL!X? ~B"n3n3n3   ?+ 4 <DL!X?  ~B"n3n3n3   ?+ 4 <DL!X?&7&n3n3&&7Less  preferred$35;AGMSY_31.1.1.1.1.1.1.1.3|x9\  `*Times New RomanTTC\  P6QP\  `*Times New RomanTTXXP\  P6QXP\  `*Times New RomanTT&&J\  P6Q&P\  `*Times New RomanTT^\  P6QP(J$~J~J~J  # e37=CIQYag1.a.i.(1)(a)(i)1)a) 012345678 9)e"Level 1Level 2Level 3Level 4Level 5Level 1Level 2Level 3Level 4Level 5Level 1Level 2Level 3Level 4Level 5Level 1Level 2Level 3Level 4Level 5 <!n3n3n3   w      n3  ELABGLPSubcommitteeExecutiveSummaryandFinalReport ' PreparedfortheJuly28,1997AnnualMeetingofELABXX  Summary:  C  n3XXInAprilof1996aSubcommitteeoftheEnvironmentalLaboratoryAdvisoryBoard(ELAB)wasformedto:1)CharacterizeEPAGoodLaboratoryPractice(GLP)laboratoryevaluationneeds,2)Evaluatealternativestoaccreditation,3)Examineimplementationoptions,4)DeterminebenefitsofGLPaccreditationtoEPAandothers,and5)DeterminehowactionbyEPAwouldimpacttheOrganizationforEconomicCooperationandDevelopment(OECD)programsandcommitments.TheSubcommitteedeveloped5primaryoptionsforconsiderationbytheELAB:1)AugmentthecurrentprogramandincreasefundsfortheEPAmonitoringprogram,2)Developa3rdpartyaccreditationsystemforGLPlaboratories,3)Increasethevalueofthecurrentsponsormonitoringprogram,4)DevelopaprocesswithintheNationalEnvironmentalLaboratoryAccreditationProgram(NELAP)toaccommodateEPAGLPstandards,and5)DeveloparegistrationlistforEPAsFederalFungicide,Insecticide,andRodenticideAct(FIFRA)andToxicSubstancesControlAct(TSCA)testinglaboratories.Anumberofsignificantneedsforintraagency,interagency,andinternationalharmonizationaswellastheimpactofpotentialEPAactionontheseneedswasdeveloped.ThecostofthecurrentEPAGLPprograms(includingthequalityassuranceoversighteffort)wasfoundtobesignificantandundervaluedbymuchoftheregulatoryoversightcommunity(especiallyinternationalregulators).TheoptionsdevelopedbytheSubcommitteewillvaryincostandimplementationcomplexityaswellastheirabilitytoaddressthevariousneedsexpressedinthisreport.ItisclearthatmoreresourcesshouldbemadeavailabletoEPAsGLPmonitoringandcomplianceprogramiftheseneedsaretobemet.However,thecostofaddingthesenewresourcesmustbebalancedwiththecostofthecurrentprogram.Anynewprocessesmustbevalueaddingandcosteffectivefortheentireindustry(regulatorsandregulatedcommunity)ifthesechangesaretobesuccessfullyimplemented.TheinternationaleffortstoharmonizeGLPprogramsandstandardsmustalsoweighheavilyinanychangestothecurrentprogram.TheSubcommitteethinkstheiroptionsprovideforsomeinterimrelieftothecurrentshortcomingsandalsoofferssuggestionsforlongertermimprovementstotheEPAGLPcompliancemonitoringprogram.TheSubcommitteerecommendsthat:1)TheGLPissuebedisengagedfromthecurrentNELAPactivityandtimeline,2)Interimreliefbeobtainedbyimplementingthesimpleraspectsofkeyoptionsoutlinedinthisreport,3)Therulemakingprocessbeutilizedtofacilitatealongtermsolutiontothecurrentproblems,and4)Theentireregulatedcommunitybedrawnintothereviewandcommentaspectofpossiblesolutionstoensureeachfacetofthenewprogramiscosteffective,valueadding,andredundancyisminimized.XXn3 Background:  k"D# n3XX  AseriesofOfficeofInspectorGeneral(OIG)reports(199192)concerningEPAoversightof(GLP)laboratoriesthatsubmitdatatobeusedinAgencydecisionmakingwereverycriticaloftheamountofauditingbeingdonebyEPAandtheuniverseoffacilitiesbeingaudited.Thereportsuggestedthata3rdpartyaccreditationprogrammightbeamoreeffectivewaytomanagetheoversightresponsibilitiesoftheAgency.AtthissametimeaneffortwasunderwaytocreateaNationalEnvironmentalLaboratoryAccreditationProgram(NELAP)tosetstandardsandnormalizeperformanceofenvironmentalmonitoringlaboratoriessubmittingdatatotheAgencyaswellastomanystateandlocaldecisionmakingbodies.InDecember,1994itwasdecidedtoincludeallorganizationsthatsubmitdatatoEPAintotheNELAP,includingthoseregulatedundertheGLPstandardsof40CFRpart160(FIFRA)and40CFRpart792TSCA.AstheGLPcommunitybegantointeractwiththosedevelopingNELAP,manyquestionswereraisedbyrepresentativesoftheGLPcommunityatthefirstNationalEnvironmentalLaboratoryAccreditationConference(NELAC)inFebruary,1995.TheEnvironmentalLaboratoryAdvisoryBoard(ELAB),formedduring1995,waschargedwiththeresponsibilitytoadviseEPAandNELACconcerningproblemareasrelatingtotheimplementationofthe -\'1    9      9NELAPprogram.SeveralELABsubcommittees(includingaGLPSubcommittee)wereorganizedtoexaminespecificworkwhichneededtobedoneinorderforNELAPtobecomefullyfunctional.TheELABGLPSubcommitteewasformedduringthefirstquarterof1996.    OnApril23,1996twentysixindividualsfromdifferentpartsoftheGLPregulatedcommunity,(privatesector,EPA,USDA,FDA)metviatelephoneconferencetodiscusstheirELABGLPSubcommitteecharterandbeginaprocessofdevelopingoptionsforconsiderationbytheELAB(seeAppendixAforthelistofSubcommitteemembers).ItwasdecidedthatbasictoanyoptionconsideredwastheneedtomaintainthecurrentGLPstandards,tomeettheneedsoftheinteragencyandinternationalcommunity,andbecosteffectiveformembersoftheGLPregulatedcommunity.WiththischargeinmindtheELABGLPSubcommitteedividedintothreesubteamstoaddresseachfacetofthischarge.Team1wastolookatoptionsforthelargerteamtoconsider.TheywerealsotoexaminethecurrentEPAGLPcomplianceprogramandusethisasaguidetobridgefrompresentpracticetopotentialoptionsforthefuture.Team2wastolookattheneedsofintergovernmentalagencies(EPA,FDA,etc.)andthoseoftheinternationalcommunity.Team3wastodevelopinformationfromacost/benefitperspectivewhichcouldbeusedtoevaluatethecosteffectivenessoftheoptionsselectedandfinallyrecommendedtotheELAB.    OnJune3,1996theELABGLPSubcommitteereceivedanoticefromtheEnvironmentalMonitoringManagementCouncil(EMMC)oftheEPAexpandingthecharteroftheELABGLPSubcommitteetoincludelookingattheGLPneedsofallFIFRAandTSCAprogramsandto:  C  $#>CB.u <DL!XB0 u 0u!u! u 2"3  0!!CharacterizetheGLPlaboratoryevaluationneedsoftheOfficeofPrevention,Pesticides,and h ToxicSubstances(OPPTS)andtheOfficeofEnforcementandComplianceAssurance(OECA). !! 0 u 0u!u! u 2"3  0!!EvaluatefeasiblealternativestoNELAPaccreditation.W!! 0 u 0u!u! u 2"3  0!!Examineprogramimplementationoptions(e.g.NELAC,privatesector,federalgovernment).!! 0 u 0u!u! u 2"3  0!!DeterminethebenefitsofGLPaccreditationtoEPAandothers.!! 0 u 0u!u! u 2"3  0!!DeterminehowpotentialactionswouldimpactOrganizationforEconomicCooperationand P Development(OECD)programsandcommitments. !! C  $$C  H+ 4 <DL!u XHTheELABGLPSubcommitteeintegratedthisexpandedcharterintotheexistingteamsandbegantoaddresseachoftheareasoffocuswiththeintentofpreparingafinalreportandrecommendationstotheELAB.ReportsofthethreeteamsoftheSubcommitteearesummarizedinthefollowingparagraphs.  XXn3 OriginalCharterTeamSummaries:  '! n3XX  Team1, DevelopmentofoptionsandexaminationofcurrentEPAGLPcomplianceprogram :  # AlistoflaboratoryevaluationneedswasdevelopedbasedoninputfromOPPTSandOECArepresentativestotheteam(AppendixB).Thelaboratoryevaluationneedsaresummarizedasfollows.AdditionalresourcesareneededtoenableEPAtoinspectover2,000laboratoriesgeneratingdataforEPAsubmission.Themajorityofthe2,000identifiedlaboratoriesactuallyparticipatedinfewerthanfivesubmittedstudiesduringthefiscalyears19931995(thesestatisticsarethemostcurrentlyavailable).Thecurrentinspectionprogramdoesnotprioritizefacilitiesbysizeornumberofstudiesconducted.AmeanstoidentifythefacilitiesgeneratingdataforEPAsubmissionisneeded.OECAcurrentlyreliesontheOPPTSdatabaseoffacilitynamesandaddressestakenfromthecoverpagesofstudyreports.ThesenamesandaddressescouldbeseveralyearsoldsincetheworkisoftendonelongbeforethestudyreportissubmittedtotheAgencyforreview.Timelyevaluationofstudiesforwhichregulatorydecisionsarependingisdesirable.OPPTSteammembersalsoindicatedthatitwouldbepreferabletoprioritizeinspectionsoffacilitieswithlargenumbersofstudiesunderwayaswellasthoseperforminglongtermandfieldstudies.PersonsperformingtheinspectionsshouldbecapableofidentifyingtechnicallymeaningfulissuesandprovidingOPPTSwithfeedbackregardingtheimportanceoftheseissues.Thislistofneedsalsoaddressedissuesraisedbythe19911992OIGreports.Fromthislistofneeds,Team1identifiedasetof35optionswhichwouldmeetvariousaspectsoftheOIGReportandalso _-(3 addresstheconcernsraisedaroundlaboratoryaccreditation.DiscussionswiththeentireSubcommitteeconcludedthatseveraloftheseoriginaloptionsoverlappedwithcertainaspectsofotheroptions,andeventuallytheoptionsetwasreducedto5whichwerethenevaluatedanddevelopedfurther.Thefollowingisageneraldescriptionofthefinal5options.Amoredetailedlistalongwithimplementationstrategies,strengths,andweaknessesisshowninAppendixCofthisreport.    ?+  <DL!X?0  Option1,Augmentationofthecurrentprogramandincreasedfundingandresources :The   existingEPAOECAGLPcompliancemonitoringprogramwouldbecontinuedbutinitiallyaugmentedinPhaseIbyredefiningtheuniverseofthefacilitiestobeinspectedwithfocusonfacilitieswithstudydirectorsandprimary/majordatagenerators.Subsequently,theoptioncouldbeexpandedwithincreasedfundinginPhaseIItoincreasethefrequencyofcompliancemonitoringsothatsitescouldbevisitedinamoretimelymanner(23yearsisthecurrentinternationalstandard).ResourcesfortheexpansioninPhaseIIwouldcomefromoneofthreeproposedsources:A)anincreaseintheEPAfundsdirectedtotheOECA,B)anincreaseinFIFRAregistrationfeescouldtargetfundsforEPAtoconductGLPinspections,orC)fundscouldbeobtainedfromanEPAOECAdirected"GLPInspection"fee.TheincreasedfrequencyofcompliancemonitoringwouldbeexpectedtoincreasethepublicconfidenceandinternationalacceptanceoftheUSEPAGLPprograms. !! 0   !! 0  Option2,ThirdpartyaccreditationforGoodLaboratoryPracticeStandards :The 7 developmentofaprivatethirdpartyaccreditationprogramwouldbesanctionedbyEPAforthepurposesofinspectingandaccreditinglaboratoriestoGLPstandards.EnforcementresponsibilitieswouldremainwiththeEPA.Theprogramwouldincluderegistrationoflaboratories,onsiteinspectionsofthetestsitefacility,alongwithtechnicalandqualityprograms.AcertificatewouldbeissuedforsuccessfulcompletionoftheGLPcomplianceinspection,whichwouldaddressinternationalconcernsandbroadenmarketacceptanceofthelaboratoryanddata.Thisoptioncouldfunctionaseitheramandatoryoravoluntaryprogramdependingonmethodofimplementation !! 0   !! 0  AstheAccreditingAuthority,theU.S.EPAOECAwouldestablishaprogramtorecognizethirdpartyaccreditingorganizationsorbodiestoprovidelaboratoryaccreditationtoaGLPstandard.Interestedstakeholders,includingthirdpartyaccreditingbodies,sponsors,contractlaboratoriesandotherswouldhelpdeveloprecommendationsfortheProgramDescriptionincluding:A)OECAsresponsibilityastheAccreditingAuthority,B)Criteriaforapprovingthirdpartyaccreditingbodies,andC)Criteriaforqualifyingandtrainingassessors. !!   0   !!   0  InterestedthirdpartyaccreditingbodieswoulddeveloptheirGLPaccreditationprogrambasedontheseconditions.TheseprogramswouldbereviewedbyOECAwhowouldsanctionacceptableprograms.ContinuedapprovalwoulddependonOECAsmonitoringandperiodicreapprovaloftheaccreditingprogram.AcceptedaccreditingbodiescouldpublicizetheirapprovalandexistingGLPaccreditingprogram,andbegintoacceptapplicationsandcompletetheaccreditationprocessasdescribed. !!   0   !!   0  Option3,Increasedvalueofsponsormonitoringprograms: TheexistingEPAGLP /& * ComplianceMonitoringProgramwouldbecontinuedwiththeadditionofrecognitionforsponsorscurrentandongoingGLPinspectionprograms.EventhoughinthecurrentprogramsponsorshavefullaccountabilityforthequalityandintegrityofthedatatheysubmittotheEPA,theEPAhasfullresponsibilityforallaspectsofcompliancemonitoring.InthisoptionEPAcontinuestheirinspection/auditprogramingenerallythesamemanner,butbyrecognizingcurrentvalueinexistingsponsorsGLPinspectionsofcontractfacilities,theOECAtargetingschemefromthelistof2000plusfacilitieswouldbealtered.Sponsors(registrants)wouldhaveanewresponsibilitytoreporttotheAgencyeachtimetheyvisitedandevaluatedacontractfacility,preferablyinanestablishedelectronicformat. !! 0  -(4!! 0  EPAwouldretaintheoptiontoinspectanytestsite,butwouldprioritizetheirscheduletofocusonregularinspectionsofsponsors,testingfacilitieswithstudydirectorsandfacilitiesgeneratingthemajorityoftheGLPdata.ByestablishingadatabaseofsponsorsGLPinspections,EPAwouldbeabletotrackthenumberofsponsorsinspectionsatsubcontractedtestsites.Usingthisinformation,theywouldprioritizetheirneedforinspectionsatremainingtestsitesthatgenerateonlyasmallamountofthedata.Bysupplementingtheirinspectionscheduleswithrecognitionofsponsorschedules,theEPAwouldbemuchmoreeffectiveinadequatelyschedulinginspectionoftestingfacilitiesthatgeneratethemajorityoftheGLPdata. !!   0   !!   0  Option4,NELAPaccreditationforGoodLaboratoryPracticeStandards: Inthisoptionthe g   currentfederallycontrolledEPAGLPProgram,utilizingthecurrentGLPstandards,wouldbeplacedundertheumbrellaofNELAPasaparallelprogramandwouldoperateindependentlyoftheotherNELAPprograms.FederalEPAinspectorswouldconductpriorityGLPcomplianceinspectionsanddataauditsaswellasparticipateintheactivitiesofNELAC,withadditionalinspectionsupportbeingprovidedbyEPAapprovedthirdpartyassessors. !! 0   !! 0  Theallocationofresponsibilitieswouldbeasfollows:EPAwouldcontinuetomanageanddirecttheactivitiesoftheEPAGLPprogram,tomaintainrecordsderivedfromGLPstudyandlaboratoryevaluations,andtoaddressbothinteragencyandinternationalharmonization,regulatoryandcomplianceissues.NELACwouldprovidetheadministrativesupportfortheaccreditationprogram.FundingoftheprogramwouldbelargelyderivedfrominspectionfeesleviedbyNELACand/orthirdpartyaccreditinggroup(s)foraccreditationinspections/assessments.Insummary,NELACwouldberesponsibleforfacilityaccreditationwhileEPAwouldretainoversightresponsibilitiesfortheGLPProgram. !!   0   !!   &7&n3&7&&&7      E+  <DL! XE0  n3&&7 Option5,FIFRA/TSCAGLPTestFacilityRegistration: Facilitieswhichintendtoperform  FIFRAandTSCAGLPstudiesforsubmissiontoEPAwouldberequiredtoregistertheirfacilitywithEPA.Facilityregistrationwouldinvolveaninitialsubmissionofinformationanddocumentsfromthefacilityforreviewtoestablishthebasicprofileforthefacility.Documentationcouldpossiblyinclude:Descriptionofsize,organization,andcapabilitiesofthefacility;theorganization,functions,andproceduresofthequalityassuranceunit;generaldescriptionofinstrumentsandequipmentusedatthesite,andthenumberandareasofexpertiseofstaff.Itmightalsoincludecurrentlistofstandardoperatingprocedures,resumes,CVsandtrainingrecordsofkeypersonnel,floorplansofthefacility,andacurrentmasterschedule.Onaperiodicschedule,facilitieswouldberequiredtoresubmitcertaindocumentsandinformation.&7&n3"!! 0  9n3&&7&7&n39 !! 0  n3&&7TheAgencyoradesignatedthirdpartycontractor(s)wouldauditthesubmitteddocuments. !2$ Registrationwouldnotconferapproval.FacilitieswithcorrectedminorGLPdeficiencieswouldbeprovisionallyregistered,whilefacilitieswithmajorGLPdeficiencieswouldbetargetsforinspection.PeriodicsubmissionofthefacilitysmasterschedulewouldberequiredandwouldprovideameansofmonitoringworkintendedforsubmissiontotheAgency.ThiswouldallowOECAtoprioritizeitsinspectionsandbeabletoconductinlifeauditreviewsofongoingstudies.Toremainontheregistrationlist,asubmitterwouldneedtocontinuetoremaininGLPcomplianceverifiedbyanEPAfacilityinspectionaudit.&7&n3 '!+!!  Dg     n3&&7n3n3    E+ 4 <DL! XE 'r", &   Team2,Interagencyandinternationalissuesconcerninglaboratoryaccreditation:  _  U.S.InteragencyIssuesPertainingtoU.S.EPALabAccreditationFDAPositionStatement     Departments,AgenciesandAdministrationsoutsideoftheU.S.EPApotentiallyaffectedbyaGLPaccreditationprogramincludetheUSDAprogramandtheFDAGLP.WhileinternallyUSDAdoesnothaveGLPrequirements,USDAprogramswhichcollectandsubmitdatatoEPAinsupportofpesticideregistrationdorequireGLPcomplianceprogramsaspartoftheirfundingrequirements.TheFDA,ontheotherhand,hasawellestablishedGLPprogram.TheoutcomeofthedebateondevelopinganationalGLPaccreditationprogramhasgreatestimpactonthisprogram.'_nNSince1978,theFDAhashadaprogramforinspectingGLPlaboratoriesconductingnonclinicalsafetystudiesforpharmaceuticals,veterinaryproducts,andmedicaldevicesprogram(frequencyevery23years).SuchstudiesareconductedandreportedinaccordancewiththeGLPregulationsfoundin21CFRpart58.TherearecurrentlynoplansbytheFDAtoadoptanaccreditationapproachtoregulateGLPlaboratories.TheprogramofinspectionsanddataauditscurrentlyinplaceattheFDAprovidesthenecessarylevelofdataqualityandintegritywithminimaloutlayofresources.Indevelopingitsapproachforregulatingtheselaboratories,theFDAconsideredseveraloptions,includingathirdpartyaccreditationprogram.TheFDAconcludedthataprogramofregularlaboratoryinspectionsanddataaudits,conductedbyFDApersonnel,wasthemostcosteffectiveandefficientmeanstoensurethequalityandintegrityofdatasubmittedtotheFDA.TheFDAreachedthisconclusioninpartbaseduponitsdecisiontoincludeintheregulationsarequirementthateachlaboratoryappointanindependentqualityassuranceunit,asaninternalmonitoringprocess.ThisselfregulationapproachwasfavoredbytheFDAastheleastburdensometoindustryandmostefficientforFDAoversight.TheadvantagesoftheFDAapproachtoregulatenonclinicalsafetytestinglaboratoriesisrecognizeddomesticallyandbyotheragenciesoftheU.S.governmentandinternationally,includingtheEPAandOECD.Implementationofanaccreditationprogrambyathirdpartywouldentailtheaddedexpenditureofresourcestoestablishaninfrastructureoftraining,oversightandadditionalregulations.TherehasbeennoinformationpresentedtotheFDAatthispointtosuggestanyjustificationforthisaddedexpense,nordoestheFDAhaveanyindicationthatitscurrentprogramhasbeenineffective.  InternationalIssuesPertainingtoU.S.EPAandtheOECDGLPPrograms:  "   ThedevelopmentofaUnitedStatesGLPstandardbytheFDAinthelate1970'spromptedinterestinGLPonthepartofotherOECDMembercountriesinordertoensurecontinuedacceptanceoftheirdatainthelargeU.S.market.OECD'sinvolvementflowedlogicallyfromaprinciplepurposeofallofitsprogramstheavoidanceofnontarifftradebarriersbetweenOECDMembercountriesasaconsequenceofnationalregulatoryprograms.ItisfrequentlystatedthatthegoaloftheOECDprogramisthe"internationalharmonization"ofGLPrequirements.Ingeneral,theOECDMembercountrieswithnationalGLPprogramshaveadoptedtheOECDPrinciplesofGLPasthebasicstandard,asrequiredbythe1981CouncilAct.Thisisespeciallytrueforthe15memberstatesoftheEuropeanUnion,(whosestandardistheOECDPrinciplesverbatim),Japan(MHW,MAFF,MITI),theUnitedStates(FDAandEPA),andSwitzerland.Ingeneral,thereisaveryhighdegreeofharmonizationamongstthesecountries.NewerprogramsbasedonGLParebeingdevelopedinCanada,MexicoandBrazil.EquallyrelevanttoanalyzingtheimpactandconditionsofaU.S.GLPaccreditationprogramistheevaluationofexistingbilateralagreementsandMOUbetweentheU.S.andOECDMembercountries.TheseagreementsreiterateprovisionsformeetingtheMutualAcceptanceofDataDecisionandgoals,includingpromotionofdataacceptanceandreciprocityamongstparticipatingcountries,andcontinuedcooperativerelationshipbetweencountries.Requirementscanbesummarizedintofourgeneralconditions:1)Adherencetostandards -(4 ofGLPbasedonnationalGLPprogramsandtheOECDCouncilRecommendationsandDecisions;2)Mutuallyconsistentnationalprograms,includingperiodic(approximatelyeverytwoyears)inspectionsbytrainedgovernmentinspectors,(orgovernmentsanctionedprograms);3)Nationalcomplianceprocedures,includingnotifyinglaboratoriesofobserveddeficienciesandrequirementsforcorrectiveaction;and4)Periodically,providingthesignatorieswithnamesandaddressesofnonclinicalhealthandenvironmentalsafetylaboratoriesoperatingwithinthecountryandthedatesofgovernmentorgovernmentsanctionedinspections,andcurrentGLPcompliancestatus.NoneoftheserequirementseithernegateorpromotetheconceptofdevelopingaU.S.GLPLaboratoryaccreditationprogram.Critical,however,toevaluatingtheimpactofaccreditationontheU.S.EPAGLPprogramisthepreambletothedocumententitled RevisedGuideforComplianceMonitoringProceduresforGoodLaboratoryPractices.Thepreamblestatesthat MembercountrieswilladoptGLPPrinciplesandestablishcompliancemonitoringproceduresaccordingtonationallegalandadministrativepractices..."Thus,itwouldappearevidentthatEPAcouldestablishathirdpartyaccreditationprogramaslongasEPAplayedanappropriateroleinestablishingandoverseeingtheprogram.ThisconclusionisconsistentwithprogramsalreadyinplaceinseveralEuropeancountries.XXn3  n3XX Team3 , Cost/BenefitAnalysisofCurrentProgramstoIndustryandProposedOptions : p    AsurveywasdevelopedanddistributedtotheEPAGLPcommunityinanattempttobetterunderstandthecostofthecurrentGLPregulationstotheregulatedcommunity.ThissurveywasconductedinandefforttodeterminetheimpactofGLPonthecostofresearchandtobreakoutthecostoftheQAUasitmonitorstheseprograms.Approximately900Cost/BenefitSurveyformsweremailedtomembersofSQA(400,membersoperatingunderEPAGLPregulations),NAICC(120),CSMA(300),andACPA(~80).Organizationsweretopoolresultsintoasingleresponsefortheentireorganization.Fiftytworesponseswerereturned(sponsors,16;ContractLabs,14;FieldCooperators,16;andothers6).ThesmallresponsewasinsufficienttoprovideareliableestimateofthetotalcostofGLPregulationstotheindustry.However,thecostoftheQAUdidprovidesomeinsightintothecostoftheQualityAssuranceportionoftheGLP.TheaveragecostofaQAprofessionalfromthecompaniesrepresentedinthesurveywasapproximately$70,000peryear(thiscostwouldincludebenefits,travel,andQAprogramcostinadditiontosalary).SincetherewasahigherresponseofsponsorsrelativetoindependentQArespondents,thisnumbermaybeanoverestimateoftheindustryaverage,howeveritshouldnotbedrasticallywrong.Ifthisnumberismultipliedbytheapproximate400membersofSQAassociatedwithEPAprograms,thenitisclearthatthecurrentdirectcosttoindustryforGLPQAprogramsapproaches$30millionannually.Additionalindirectcosts(i.e.archiving,training,etc.)drivethisvalueevenhigher.ThisnumberbecomesparticularlysignificantwhenitisrealizedthattheOIGReportsissuedbetween1991and1992didnotgiveanyconsideration/creditfortheimpactthatEPAregulatedindustryQAprogramshaveondataquality.TheFIFRAandTSCAtestingindustryGLPQAprogrameffortmustbeconsideredinwhateverfinaldecisionisreachedinthecurrentoversight/monitoringdebateifanacceptablecosteffectiverevisionistobesuccessfullyimplemented.XXn3Ԁ 7#& n3XX  XXn3 HowtheOptionsAddresstheExpandedCharter:  %X ) n3XX  ThecharteroftheSubcommitteewasexpandedbytheEMMCatsuchatime(June1996)thatconsiderationwasgiventothenewcharterthroughouttheworkoftheSubcommittee.MoredetailedresponsestotheindividualoptionsrelativetotheexpandedcharterobjectivesareincludedinAppendixC.Anoverviewofthefindingsrelativetotheindividualaspectsoftheexpandedcharterarepresentedbelow:  ̀ CharacterizethelaboratoryevaluationneedsofOPPTSandOECAprograms:  W+%0 9C  $$C9C  $$C  B.4` <DL!XB0 4 0` 4!4! 4 23  0` ` !` !Needtoknowwhoiscurrentlydoingthework(universeoflaboratories).Thereareover2000 ,&1 laboratoriescurrentlysupplyingdataforEPAreview. ` !` ! 0 4 0` 4!4! 4 23  0` ` !` !Needtoknowwhentheworkisbeingdone.Inlifeauditsarefarmorevaluableandmuchless -P(3 controversialthanpostmortemfindings.Thisistruebothfordeterminingthequalityoftheworkbeingdoneandimprovingthequalityforfuturework ` !` ! 0 4 0` 4!4! 4 23  0` ` !` !Needtoknowthelevelofcomplianceofthestudyduringthedatareviewphase,notafterthe  tolerancehasbeensetandaregistrationgranted. ` !` ! 0 4 0` 4!4! 4 23  0` ` !` !Needfortechnicallytrainedinspectorswhocanidentifymeaningfultechnicalissuesandassess   theirimpactonthestudy(administrativeproblemsarelessofanissuethantechnicalproblems)andthereviewprocess. ` !` ! 0 4 0` 4!4! 4 23  0` ` !` !Needtohavecriticalphaseandtimelyongoingauditsforlongtermstudies. x` !` ! 0 4 0` 4!4! 4 23  0` ` !` !Absoluterequirementfornecessaryresourcestoconducttimelyauditsandtoprovidereasonable  @ monitoringoversight. ` !` ! 0 4 0` 4!4! 4 23  0` ` !` !Needtobeabletobalanceworksoheaviestdatasuppliersgetreasonableoversight,butthatall /   facilitiesareauditedinatimelyregularmanner.Thisisparticularlycriticalasinternationalharmonizationactivitiesareincreasinglychangingthecompliancearena. ` !` ! C  $$C  H+ 4 <DL!4, XHB.S4 <DL!XB0 S Evaluatefeasiblealternativetoaccreditation: Threenonaccreditationoptionswereidentified O  whichwouldmeetvariousaspectsoftheneeds.Theyare: S!S! C  $$CH.4` <DL!S4XH0 4 0` 4!4! 4 23  0` ` !` !Augmentationofcurrentprogramsandincreasedfunding. ` !` ! 0 4 0` 4!4! 4 23  0` ` !` !Increasedvalueforsponsormonitoringprograms.H ` !` ! 0 4 0` 4!4! 4 23  0` ` !` !Laboratoryregistration.o` !` ! C  $$CH+ 4 <DL!4, XH  B.S4 <DL!XB0 S Examineprogramimplementationoptions :Specificexamplesofhoweachoftheoptionsdiscussed  wouldbeimplementedarediscussedwiththedetailedoptionsummaryinAppendixC.Therearegeneralissueswhichshouldberesolvednomatterwhichoptionisultimatelyselected.Theyare: S!S! C  $$CH.4` <DL!S4XH0 4 0` 4!4! 4 23  0` ` !` !Definethestandardwhichwillbeusedforthefuturemonitoringprogram.Thismaybeasbasic W asISOvs.GLPstandards,revisedGLPstandardstomeetnewOECDGLPPrinciples,ordevelopanewstandardforanaccreditationsystem(ifnecessary).TheSubcommitteeseesthegreatestvalueinamendingthecurrentUSGLPtomeettheharmonizationstandardoftherevisedOECDGLPwhichshouldbeissuedlaterthisyearorearlyin1998. ` !` ! 0 4 0` 4!4! 4 23  0` ` !` !ReaffirmthefederalprogrambasisforFIFRAandTSCAprograms.Thisseemstogowithout ? saying,butcontinuestobeakeypartofthedebaterelativetoNELAP. ` !` ! 0 4 0` 4!4! 4 23  0` ` !` !Nomatterwhichoptionorprogramispursuedinthefuturetheremaybearequirementfor p legislativechangestoFIFRAandTSCAaswellasamendmentsofthecurrentEPAGLPstandardstofacilitateimplementationofthenewprogram. ` !` ! 0 4 0` 4!4! 4 23  0` ` !` !Therewillbeaneedtoprovidetrainingandcertificationofnewauditorswhowillberequired '! tomeettheexpandedmonitoringrequirements. ` !` ! 0 4 0` 4!4! 4 23  0` ` !` !Theresourcefortheoverallprogramshouldbereevaluated.Ifthecurrentresources(dollars,  X# manpower,andtime)arenotadequatelymeetingtheneeds,thentheyshouldbeexaminedaspartofthewholeprocess.Ifnewcostsaretobeadded,everyeffortmustbemadetomakecertainthereisnotaredundancyinwhatisbeingdonebytheEPAandwhatisrequiredbytheindustry.  #&  Eachstepmustbevalueadding . #x'` !` ! C  $$C  H+ 4 <DL!4, XH  B.S4 <DL!XB0 S DeterminethebenefitsofaccreditationtoEPAandothers :Adetailedlistofthesebenefitsare g% ) presentedinthediscussionofOption2and4inAppendixC.Keyitemsarelistedhere,detailedbenefits /& *  and disadvantagesarelistedinAppendixC:&!+S!S! C  $$C  H.4` <DL!S4XH0 4 0` 4!4! 4 &7&n323  0` ` !` !Providesincreasedfrequencyofinspections,whileallowingOECAtoretainits '`", authorityandenforcementresponsibilities ` !` ! 0 4 0` 4!4! 4 23  0` ` !` !FacilitatesOECAsfocusondataauditss)$.` !` ! 0 4 0` 4!4! 4 23  0` ` !` !Providesan approveduniverseoflaboratoriesM*$/` !` ! 0 4 0` 4!4! 4 23  0` ` !` !Facilitatesintegrationofregulatoryandcommerceissues,andstreamlines '+%0 administrativeduties ` !` ! 0 4 0` 4!4! 4 23  0` ` !` !Meetsinternational(OECDGLP)requirements,|'2` !` ! 0 4 0` 4!4! 4 23  0` ` !` !Providesgreaterinternationalacceptanceoflaboratorytestingprogramsanddata-V(3` !` ! 0 4 0` 4!4! 4 23  0` ` !` !Financiallyselfsustaining,feewouldbeassessedtocoverprogramcost_` !` ! C  $$CH+ 4 <DL!4, XHn3&&7  B.S4 <DL!XB0 S 9&7&n3n3&&79 DeterminehowpotentialactionswouldimpactOECDprogramsandcommitments :TheOECD  GLPprinciplesarebeingrevisedatthecurrenttime.ItisexpectedthatthenewOECDprinciplesshouldbeissuedlaterthisyearorearlyin1998.Thesestandardsaregearedtodriveinternationalharmonizationofregulatoryworkandrequirements.TheUSEPAGLPSwillneedtobeamendedifwearetomeetthenewinternationalharmonizationstandardswhentheyarefinalized.Thenewstandardwillhelpdeterminethepotentialvalueofeachoftheoptionsdevelopedatthistime. S!S!   E+ 4 <DL!S4XE9&7&n3n3&&799&7&n39XXn3 Discussion: n3XX y   9&7&n3n3&&79  9&7&n3n3&&79Insummary,theSubcommitteehasdevelopedfiveprimaryoptionsforconsiderationbyELAB.Theseoptions(page3,AppendixC)willvaryincostandimplementationcomplexityaswellastheirabilitytoaddressvariousinteragencyandinternationalneedsexpressedearlierinthisdocument.Options1(PhaseI),3,and5,willallowtheAgencytoaugmenttheexistingcompliancemonitoringprogramwithminimalresourcedrainandaddedcost.But,theexpectationisthattheseoptions,asstandaloneoptions,areunlikelytomeetalloftheconcernsoftheinternationalcommunity,ortheOIGcommentsconcerningfrequencyofEPAGLPcompliancemonitoring.Additionalresources(bothmanpowerandcapital)willberequiredinordertosatisfythesemorecomplexconcerns.ThedecisiontreedepictedinFigure1identifiestheSubcommitteespreferenceforconsiderationofalternativemorecomprehensiveoptions,takingintoaccountnumerousrelevantfactors(complexity,cost,timing,valueaddingpotential,andeaseofimplementation)thatareexpandeduponthroughoutthisdocument.9&7&n3n3&&799&7&n3n3&&79TheELABshouldbeadvisedthatconcurrentwiththisinvestigationofoptionstoimprovethecurrentEPAGLPComplianceMonitoringprogramaretheeffortstoharmonizetheGLPStandardsinternationallythroughrevisionofOECDPrinciplesofGLPfollowedbytheiradoptionbyOECDMembercountries.Thisharmonizationinitiativeislikelytoimpacttosomedegreetheoptionsidentifiedinthisreport(particularlythelarger,morecomprehensiveoptions1(PhaseII),2,and4).Sincetherevisioneffortsarefairlyclosetobeingrealized,itisrecommendedthatdecisionscoveringoptions1(PhaseII),2,and4bedeferreduntilthenewOECDGLPPrinciplesarepublishedandtheharmonizationactivitiesareconcluded.  9&7&n3n3&&799&7&n3n3&&79 SubcommitteeevaluationofOptions  r   9&7&n3n3&&79EachoftheseoptionsaddresseddifferentissuesorconcernsraisedbymembersoftheSubcommitteeandaneffortwasmadetoconsolidatevariousoptionsintopackages.Eachoftheoptionsrepresenteddifferentapproachestomeetingtheneeds(dependingontheamountoftimeandresourcestobeappliedtotheproblem.Theoptionsalsospannedanumberofpotentialactivitieswhichwereverydivergentinnature.BasedontheseconsiderationstheSubcommitteeconcludedthatthedevelopmentofadecisiontreeviewoftheoptions(Figure1)wasmorerepresentativeoftheirconclusionsthanreducing/condensingtheprimaryoptionsetfurther.   8&7&n3n3&&78 I#& &   8&7&n3n3&&78Figure1.Decisiontreeviewofanimplementationschemeforthe5optionsdevelopedbytheELABGLPSubcommittee.8&7&n3n3&&788&7&n3n3&&78??US.,9ZJFz< x 0 @X@E/ /99ZJFz< x 0 @X@E/ /9,#8\LHz<,P 0 @@EX X88^NJz| 0 @@E{ {8,#8&7&n38US??.,8n3&&788&7&n3n3&&788&7&n3n3&&78fVR~ ,, 0 c@ dd@E  7&7&n3n3&&77??US.,iYU~<P  0 c@ dd@Ep_ p_ US??.,iYU~< ( 0 c@ dd@E  5&7&n3n3&&75??US., iYU~< ( 0 c@ dd@E x  !iYU~<( 0 c@ dd@E  US??.,4&7&n3n3&&74??US.,4444#\LHz<P 0 @@E  @ 2&7&n32US??.,2n3&&72"^NJz|F@  0 @@E"  " 2&7&n3n3&&72$iYU~<( 0 c@ dd@E ( ( 0&7&n3n3&&70??US.,%iYU~<, 0 c@ dd@E   &iYU~<  0 c@ dd@E   'iYU~< 0 c@ dd@E   US??.,??US.,(YIEz ,LH 0 @@E(H X(H )YIEz ,$ H 0 @@EH XHUS??.,*^NJz|fH 0 @@EB H XB H+iYU~< h 0 c@ dd@E'hH'h??US.,,iYU~<D 0 c@ dd@E ' 'US??.,??US.,-\LHz<$ @ 0 @@E X/\LHz<g 0 @@Eg 'g0iYU~< RL 0 c@ dd@EL , L 1iYU~<x 0 c@ dd@ET T 0  04iYU~<O 0 c@ dd@E+!+!5iYU~< R 0 c@ dd@E6iYU~<]R 0 c@ dd@E997iYU~<a  0 c@ dd@E==US??.,.^NJz|Z 0 @@EZ Z3k[W~|~f 0 c@ dd@EZ Z 8^NJz|(6 0 @@Eu u2^NJz|6l 0 @@Eul ,ul'_  TheSubcommitteeconsideredcomplexity,cost,timing,valueaddingpotential,andeaseofimplementationandthenthroughamultivotingprocessconcludedthatoptions1(PhaseI),3,and5wouldbetheeasiest(fastestandleastcostly)toimplement.TheSubcommitteerecognizedthatthesethreeoptionsbythemselvesorincombinationwereunlikelytoaddresskeyinternationalconcernssuchasfrequencyofauditingand/orcertification.Option1(PhaseII),notwithstandingthedifficultyinobtainingadditionalfunding,hasthegreatestpotentialofaddressingthemostneedswiththeleastdisruptionandcost.Option2mayrequiremoreresourcestoimplement.TherewasoneoverridingconsensuswithintheSubcommitteeandthatwasthatoption4wastheleastattractiveofalltheoptionsbecauseitposedthelargestnumberofissuesandconstraints(seeAppendixC).Itiscriticalthatanyadditionalprogramcostbeoffsetbyvalueaddingbenefitstoindustryforanyoftheseoptionstobeimplementedsuccessfully.  RECOMMENDATIONS:  '`", C 9 $$C  B.4 <DL!XB0   2  1  .3  0!!DisengagetheGLPissuefromtheNELAPactivityandtimeline.Therearetoomanypotentialproblems O)#. withthisoptionrelativetootheroptionsnotwithstandingthedifferencesinprogramneeds,resources,etc. !! 0   2  2  .3  0!!Focusimmediatelyonimplementingoptions1(PhaseI),3,and/or5toaugmentthecurrentOECA *%0 compliancemonitoringprogram.ShouldthismodificationinconcertwithharmonizationeffortswiththeOECDGLPPrinciplesstillnotaddresstheperceiveddeficienciesoftheOECAcompliancemonitoringprogram,thereafter,consideronalongertermscale,thevaluetobeaddedbyimplementingotheroptionsidentifiedinthisreport.-(4!! 0   2  3  .3  0!!UtilizetherulemakingprocesstoamendtheUSFIFRA/TSCAGLPstandardstomeetthenewOECD _ PrinciplesofGLPandforalignmentwiththemanyinternationalharmonizationeffortsunderwayatthecurrenttime. !! 0   2  4  .3  0!!Utilizetherulemakingprocesstoincludetheentireregulatedcommunityinthereviewandcomment X discussionofpossiblesolutionstoensurethateachfacetofthenewprogramiscosteffective,valueadding,andredundancyisminimized. G !! C 9 $$9C  E+ 4 <DL!, XE APPENDIXA.MembersoftheELABGLPSubcommittee  '   3 *QL!X30 * DavidAlexander  MaureenBarge Q FranDillon *!*! 0 * U.S.EPA  FMC Q StewartPesticideRegis.Assoc.G *!*! ? *eL!*QX?0 *  *!*! ? *QL!*eX?0 * DavidDull(cochair)  JimmyFlowers Q DebiGarvin L    x*!*! 0 * U.S.EPA  DowElanco Q PacificRimConsulting @*!*! B" *DL!*QXB0 *  *!*! < *QL!*X<0 * CliveHalder  LouiseHess Q WynnJohn(cochair)/  *!*! 0 * BayerCorporation  LancasterLaboratories Q DuPontAgProducts  *!*! E% *DL!*QXE0 *  *!*! < *QL!*X<0 * RobertKiefer  JohnD.Kobland Q FranciscaLiem( *!*! 0 * ChemicalSpecialties  AmericanCyanamid Q U.S.EPAO *!*! 0 * Mfrs.Assoc.,Inc.  AgProductsRes.Div. *!*! ? *QL!*QX?0 *  *!*! ? *QL!*QX?0 * DorisMason  RayMcAllister Q JohnMcCannH *!*! 0 * RhonePoulencAg  ACPA Q McCannAssociateso*!*! B" *DL!*QXB0 *  *!*! < *QL!*X<0 * ChrisOlinger  PatriciaOBrienPomerleau Q MickQualls*!*! 0 * U.S.EPA  CIIT Q QuallsAgLaboratoryh*!*! B" *DL!*QXB0 *  *!*! < *QL!*X<0 * RoxanneRobinson  GaryRoy Q PatriciaRoyalW*!*! 0 * A2LA  AlliedSignal,Toxicology Q QualitySystemsConsultants,Inc.*!*! 0 *  *!*! 0 * FredSiegelman  PaulSwidersky Q LeeWestP*!*! 0 * U.S.EPA  QualityAssociates,Inc. Q RDA&NAICCw*!*! 0 *  *!*! 0 * TammyWhite  StanWoollen Q *!*! E% *DL!*QXE0 * USDA,AgExper.Station  U.S.FDAp*!*! ?" *DL!*X?0 *  *!*! 0 * &7&n3 AdHoc _ *!*! 0 * n3&&7 *!*! B% *DL!*XB0 * TedCoopwood  GeorgeFong "*!*! 0 * EPA  FloridaEnvironmentalAdmin. j#*!*! 0 *  *!*! 0 * JohnHenshaw  JeanneMourrainY"%*!*! 0 * Monsanto  EPAAREAL !#&*!*!   H+ 4 <DL!*XHXXn3 AppendixB. n3XXԀ ELABGLPSUBCOMMITTEEGROUP1ASUMMARYREPORT  _  I. 4 Goals    4 Studyexistingcomplianceinspectionprogram 4 Gatheradditionalstatisticstodefineprogram 4 CharacterizelabevaluationneedsofOPPTSandOECA 4 CharacterizelabevaluationneedsoftheOfficeofToxicSubstance 4 CharacterizeuniverseofU.S.labssubjecttoEPAGLPCompliance 4 inspectionprogram II. 4 ExistingComplianceInspectionProgram     4 A. Objective:ForalldatageneratedandsubmittedtoEPAunderFIFRA P   4  sections3,4,5,8,18and24andundersections4and5ofTSCA, 4  1) assurethatfacilitiesconductingstudiesareincompliancewithEPA    4   GLPregulations; 4  2) assurethatdatasubmittedtoEPAhavebeenconductedin 8  4   compliancewithEPAGLPregulations; 4  3) assuretheintegrity,qualityandvalidityofdatathathavebeen '  4   submitted. 4 B. CurrentProgramDescription1995Data    4  1. Staffing17fulltimeequivalents(FTE),11whichconductinspectionsand   4    < audits.(DoesnotincludeFDAinspections) 4  2. Numberofinspectionsperformed82(4byFDA)OECAhasnoobligationto g  4    < conductacertainnumberofinspections.Thenumberofinspectionsvaries 4    < fromyeartoyeardependingonthebudgetandotherresources.There  isno 4    < mandateforinspectionof100%offacilities. `      4  3. Travelbudget$100,000currently.Historically,thetravelbudgethasnotbeen  "  4   verygood.SpecificinformationwasnotreleasedfromOECA. 4  4. Outsidecontractorsarenotused. o"% 0 4 0 4!4!0 ! ! 4   4  5. OECAhasdeterminedthatthereare2,000facilitiesinvolvedindata #' developmentforsubmissiontoEPAunderGLP.StatisticsprovidedforFiscalYears19931995showed3,040facilitiessubmitteddata(Table1).(Those3,040facilitieswereidentifiedaccordingtoeachdatarequirement,i.e.toxicology,efficacy,productchemistry,planteffects,animaleffects,environmentaleffects,andresiduechemistry.Therefore,asinglelaboratorycouldbecountedmorethanonceifitconductsstudiesinmultipledisciplines.)2,261(74.4%)ofthe3,040facilitiessubmitted5orfewerstudiesduringthat3yearperiod(Table2).1,703(56%)ofthe3,040facilitiessubmitted2,orfewerstudiesduringthat3yearperiod.  ! !   9%  <DL!X9Ӏ̀B+ 4 <DL! XB0 4 0 4!4! 4   4  6. OECAusesOPPandOPPTSdatabasesforthelaboratorylist.ThelistofFIFRA _-(3 laboratorieswillnotbeprovided.Alistofsponsorlabsisnotavailableatthistimeandwillnotbeprovided.AlistofTSCAlaboratoriesisnotavailableatthistimeandwillnotbeprovided.  ! ! 9%  <DL!X9ӀB+  <DL! XB0  0 !!      7. Eachtestsiteinastudyiscountedasafacilitybasedoninformationprovidedin   thefinalreportbythesponsor.Facilitieswhichareonetimefieldsitesareincluded.Alabcouldbelistedmorethanonceifitconductsmorethanonediscipline/guideline.During19931995,1,195or39.3%ofthefacilitieswereinvolvedinonly1submittedstudy.Thefacilitylistincludesafarmersfieldasafieldsiteifthesponsorsfinalreportidentifieditasafieldsite.OECAprefersthatsponsorsnotincludefarmersfieldsifalloftheworkisdonebythecooperatororsponsor.  ! ! ?%  <DL! X?ӀB+  <DL! XB0  0 !!      8. OECAdoesnothavethestafforbudgettoinspectall2,000facilities.Table3 `  showsprojectionsofbudgetandstaffrequirementstoachieveinspectionfrequenciesof2,3or5yearintervals.Eventhelongestinterval(5years)wouldrequirestaffingandabudgetofgreaterthan4timesthe1995level.  ! ! ?%  <DL! X?ӀB+  <DL! XB0  0 !!      9. AsanoutcomeofcriticisminanearlierreportfromtheOfficeoftheInspector H  General,thecurrentsystemdoesnottargetlabswhosubmitmostofthestudies.Thisshouldbereevaluatedinviewofthecurrentsituationandtheneedtomaximizeeffectivenessofresources.  ! ! ?%  <DL! X?Ӏ̀  <   OECAselectslabsforinspectionbasedonthefollowingcriteria: 0 Ѐ̀  <   a.  typeoflaboratory  Ѐ  <   b.  numberofstudiessubmittedtoEPA  Ѐ  <   c.  typeofstudiessubmittedtoEPA P Ѐ  <   d.  availabilityofinspectors w Ѐ  <   e.  availabilityoffinancialresources ? Ѐ  <   f.  typeofinspection(neutralschemeorforcause)  Ѐ  <   g.  geographicallocation(EPAregions) p Ѐ  <   h.  GLPcompliancestatementinthefinalreport 8 Ѐ  <   i.  studiesconductedafterthepromulgationofGLP _  Ѐ  <   j.  laboratoryparticipatedinthestudy '! ЀB+ 4 <DL! XB0 4 0 4!4! 4   4  10. OECAdefinesastudyforinspectionpurposesusingthesamedefinitionasgiven  X# intheGLPregulations.StudiesselectedforinspectionmusthaveavalidGLPcompliancestatementandhavebeenconductedafterthepromulgationoftheEPAGLP.WhileEPAattemptstoauditanentirestudy,thisisnotalwayspossiblewhenvariousfacilities/sitesareinvolved.  ! ! 9%  <DL!X9ӀB+ 4 <DL! XB0 4 0 4!4! 4   4  11. OECAusesOPPTSsdatabasesfordetermininglabstobeinspected.Thereisno g% ) otherregistrationprogramforlabs.TheresultisthelagtimefromwhenthelaboratorystartsdevelopingdataforsubmissiontothetimewhenstudiesareactuallysubmittedandbecomeknowntoEPA.(Reregistrationrequiresprogressreports,butnewregistrationsdonot).  ! ! 9%  <DL!X9ӀB+  <DL! XB0  0 !!      12. TheOECAcomplianceinspectionprogramissupplementedbyinspection/ O)#. monitoringdonebyQAUnitsofsponsorcompanies.Thistypicallyincludesonsiteinspectionofeachfacility,protocolreview,reportreviewand,insomecases,datareview.ThisisallinadditiontothefacilityQAUmonitoringspecifiedinGLP.  ! !   E+ 4 <DL! XE  III. 4 LabEvaluationNeedsofOECA,OPPTSandIndustry  -(4 Ї 4 A. OECAPrioritiesfortheLabEvaluationProgram _ ?+  <DL!X?0  0 !!      1. Therearenospecificprogramrequirementswhichmustbesatisfied.Toinspect  2,000labsaccordingtothecurrentprogramdefinition,additionalresourcesarerequiredaslistedinTable3.  ! ! ?%  <DL! X?ӀB+  <DL! XB0  0 !!      2. Ameanstoaccuratelyidentifyallfacilitiescurrentlygeneratingdatafor   submissiontoEPA.  ! ! ?%  <DL! X?ӀB+  <DL! XB0  0 !!     B. OPPTSPrioritiesforComplianceInspectionsg   ! ! ?%  <DL! X?ӀB+ 4 <DL! XB0 4 0 4!4! 4   4  1. Studiesunderwayonchemicalforwhichregulatorydecisionsarepending   ! ! 9%  <DL!X9ӀB+  <DL! XB0  0 !!      2. Longtermandfieldstudies(  ! ! 0  0 !!     ! ! 0  0 !!      3. FacilitieswithlargenumbersofFIFRA/FFDCAstudiesunderway  ! ! ?%  <DL! X?ӀB+ 4 <DL! XB0 4 0 4!4! 4   4  4. Inspectorstrainedinconductingstudiesofthetypetheyinspecttoallowthemto H  focusonmeaningfulviolationsandpermitthemtoprovideOPPTSinformationregardingtheimportanceofproblemsobserved  ! ! 9%  <DL!X9Ӏ  < (NoteItemsIII.B13requirenotificationtoOECAofongoingstudy  schedules).̀B+ 4 <DL! XB0 4 0 4!4! 4   4 C. ToxicSubstancesPrioritiesforComplianceInspectorsW ! ! 9%  <DL!X9Ӏ̀  <   OTSdidnotrespondonthisissue.  ЀB+ 4 <DL! XB0 4 0 4!4! 4   4 D. IndustryPrioritiesforaComplianceInspectionProgramw ! ! <( 4 <DL!X<0 4   4!4! E+ 4 <DL!4 XE0 4 0 4!4! 4   4  1. Effectivemonitoringtoassuredataintegrity ! ! 0 4 0 4!4! 4    ! ! 0 4 0 4!4! 4   4  2. Addedvalueforanyprogramchangeswhichresultinincreasedcosts   @  @ to 8 industry  ! ! 0 4 0 4!4! 4    ! ! 0 4 0 4!4! 4   4  3. MaintainGLPandQAUasaneffectivequalitymanagementprogram" ! ! 0 4 0 4!4! 4    ! ! 0 4 0 4!4! 4   4  4. Acknowledgeindustrymonitoringofcontractfacilities! $ ! ! 0 4 0 4!4! 4    ! ! 0 4 0 4!4! 4   4  5. Reevaluatenumberandtypesoflabsthatneedinspectiontomaximize   @  @  #& utilizationofresources.Justifydecisionsasbusinessmustdo.  ! ! 0 4 0 4!4! 4    ! ! C 9 $$9C--C 9 $$9C--B.4 <DL!XB0 4 0 4!4!0 ! ! 2  1  .3  0 ! ! Minimizefinancialburdenonsmallbusinessesbyavoidingduplicative @  @  g% ) programs  ! ! C 9 $$9CH+ 4 <DL!X XH0 4 0 4!4!0 ! ! 4   4  7. Haveadequateinspection(compliancemonitoring)processtomeetinternational '`", needs. ((#- ! !   TABLE1  _   1. 4 Expandgoalstoincludecharacterizationoflabs/facilitiesandcharacterizationoflabsevaluation   4 needsofToxicSubstancesOffice.  [FacilityAnalysis,FranciscaLiemStudiessubmittedFY19931995(OPPTSPesticideAssessmentGuidelines)]   4 TypesofFIFRAlaboratories Types 4    < No.Facilities  (%) D   No.Studies(%)       4    <      D      L    Toxicology   < 724    (24%) D   11,696   L (57%) O  ProductEfficacy   < 303    (10%) D   1,536   L (8%)   ProductChemistry  < 465    (15%) D   1,675   L (8%) o EffectonPlant   < 225    (7%) D   700   L (3%)  EffectonAnimals  < 152    (5%) D   437   L (2%) 0 EffectonEnvironment  < 419    (14%) D   1,570   L (8%)   4 ResearchFarm  <   23   D      L 49 P  4 FieldCooperator/Consultant  91   D      L 425 w  4 University  <   25   D      L 83 ?  4 Foreignestablishment <   84   D     1,008   4 Laboratory  <   143   D     1,398 p  4 DomesticGovernment <   48   D      L 606 8  4 Miscellaneous  <   5   D      L 5 _  ResidueChemistry  <   752  (25%) D     2,841 L (14%) "  4 ResearchFarm  <   111   D      L 350 ! $  4 FieldCooperator/Consultant  222   D      L 2,068 G"%  4 University  <   78   D      L 211 #&  4 Foreignestablishment <   100   D      L 498 #x'  4 Laboratory  <   210   D      L 2,551 $@(  4 DomesticGovernment <   29   D      L 41 g% )  4 Miscellaneous  <   3   D      L 6 /& *   &!+   TABLE2  _ [FacilityAnalysis(Studies)FY9395]  No.ofsmalllaboratories(basedonno.ofstudiessubmittedinthelast3years)  No.Facilities  #Studies    No.Facilities    #Studies      4    <      D      L    Toxicology   <     ProductEfficacy   x  4 262   < 1     D 138     L 1 g    4 118   < 2     D 58     L 2 /    4 60   < 3     D 22     L 3     4 47   < 4     D 24     L 4 `   4 28   < 5     D 4     L 5 (  Total515(15studies) < 71%     D 246(15studies) L 81% O   ProductChemistry  <     EffectonPlants     4 172   < 1     D 102     L 1 o  4 90   < 2     D 29     L 2 7  4 36   < 3     D 23     L 3   4 26   < 4     D 18     L 4 h  4 19   < 5     D 10     L 5 0 Total343(15studies) < 74%     D 182(15studies) L 81% W  EffectonAnimals  <     EnvironmentalFate    4 63   < 1     D 165     L 1 w  4 26   < 2     D 64     L 2 ?  4 12   < 3     D 35     L 3   4 8   < 4     D 25     L 4 p  4 7   < 5     D 22     L 5 8 Total116(15studies) < 76%     D 311(includingfieldsites) _   4    <      D (15studies)   L 74% '!   ResidueChemistry   X#  4 293   < 1 G"%  4 123   < 2 #&  4 58   < 3 #x'  4 43   < 4 $@(  4 31   < 5 g% ) Total548(includingfieldsites) /& * 򀀀(15studies)  < 73% &!+ Smalllaboratories(submitted15studiesinthelast3years)is74%ofthetotalFIFRAGLPlabuniverse.  ((#-   TABLE3  _  ProjectedOECARequirementsoftheGLPInspectionProgram  X   Frequencyof  No.inspections    No.EPAstaff    Travelbudget   inspections  peryear <       x  4    <      D      L   2years 4   1000 <     160($12M)    $1,000,000 /   3years 4   700 <     120($9M)    $770,000 `  5years 4   400 <     68($5.1M)    $400,000  O  XX~J thathave AppendixC.DetaileddescriptionofoptionsdevelopedforELABconsiderationby _ theELABGLPSubcommittee ~JXX valuation  O XX~J 91  OPTION1 ~JXX 91  EXISTINGEPAFIFRAANDTSCAGLPCOMPLIANCEMONITORING  PROGRAMWITHAUGMENTATION(PhaseI)ANDINCREASEDFUNDING(PhaseII)XX~J 91    ~JXX 91   INTRODUCTIONXX~J 91  :   ( ~JXX     ThecurrentEPAFIFRAandTSCAGoodLaboratoryPractice(GLP)compliancemonitoringprogramisawellestablished,effective,nationallyandinternationallyrecognizedprogramformonitoringscientificresearch.ItisdesignedtoassurethequalityandintegrityofGLPstudiesconductedinthelaboratoryorintheenvironmenttosupportthesafetyand,insomecases,theefficacyofproducts.KeyelementsandproblemsofthecurrentEPAGLPprogramare:B.4 <DL!XB  Elements :   C  $$9C -- C  $$C -- K14 <DL!, XK0   2"3  0!!EPAOfficeofEnforcementandComplianceAssurance(OECA)/OfficeofCompliance(OC)conduct   periodiconsiteinspectionsanddataauditsoffacilitiesforGLPcompliance !! 0   2"3  0!!ThearchiveandretentionrequirementsareincludedforallcompletedGLPstudies!! 0   2"3  0!!AconsiderableamountofmonitoringandinspectingisperformedonstudiesconductedundertheGLP. x InadditiontotheEPAOECAGLPcompliancemonitoringprogram,anindependentQualityAssuranceUnit(QAU)isrequiredtocontinuallymonitoreachstudyforGLPcomplianceandkeepstudymanagementapprisedofGLPcomplianceissues.QAUinformsstudymanagementoftheneedforcorrectiveaction,ifappropriate,throughconfidentialQAUinspectionreports.TheQAUreviewmayincludecommentingoneachGLPstudyprotocol.QAUalwaysmonitors/inspectsatleastone,andoftenmany,"critical"phasesofeachGLPstudy.QAUroutinelyreviewseachGLPstudyfinalreportandaccompanyingdata.ThefinalreportincludesalistofQAUinspectionandreportingdatesforthestudy. !! 0   2"3  0!!ForstudiesconductedundertheGLPregulations,ithasbeenestimatedthatapproximately20,000final  reportsaresubmittedtoEPAinayear.Therefore,itispossiblethat60,000independentQAUreviewscouldhavebeenconductedonthesestudiesconductedundertheGLP.AdditionalsponsormonitoringandauditingmayalsobeconductedonGLPstudiessponsoredoutofhouse.Therefore,theestimateofpossibly60,000reviewsonstudiesconductedundertheGLPregulationscouldbeincreased. !! K.4 <DL! XK0   2"3  0!!Over13yearsofexperiencesincetheinceptionoftheEPAFIFRAandTSCAGLPfederalregulations   havedemonstratedthatthequalityandconsistencyoffinalreportssubmittedtoEPAhasgreatlyimproved. !! C  $$CE+ 4 <DL!, XEB.4 <DL!XB  Problems : W!# C  $$C -- 0   2"3  0!!WiththeinclusionoffieldstudiesintherevisedEPAGLPprogramover8yearsago,thenumberofGLP "% laboratories/facilitiesidentifiedbyEPAforonsiteinspectionsanddataauditsincreasedtoover2000. !! 0   2"3  0!!EPAOECAGLPonsiteinspectionsdonotcurrentlyfocusonlyontheprimary/majordatagenerating w$' facilities. !! 0   2"3  0!!OneofthedifficultiesnotedbytheEPA'sOfficeoftheInspectorGeneral(OIG)wasthatthefrequency & ) ofEPAonsiteGLPcompliancemonitoringofthelaboratories/facilitieswasconsideredinsufficient. !! 0   2"3  0!!ThenumberofEPAOECApersonnelwhoconductGLPcomplianceinspections(initially20fulltime '8"+ equivalents,currently11fulltimeequivalents)andthefundingresourceisnotcurrentlysufficienttoallowonsiteGLPinspectionfrequenciestosatisfyallconstituencies,includingthosewithinternationalrequirements. !! C  $$CE+ 4 <DL!, XE&&~J  B.4 <DL!XB0   ~J&&  XX~J     !! 0   ~JXX  DESCRIPTIONOFOPTION: ,"'1!! 0   &&~J    I-'2!! E+ 4 <DL!, XE~J&&  TheexistingEPAOECAGLPcompliancemonitoringprogramiscontinuedbutinitiallyaugmentedinPhase _ Ibyredefiningthescopeofthefacilitiestofocusontheprimary/majordatagenerators.Subsequently,theoptioncouldbeexpandedinPhaseIItoincreasethefrequencyofcompliancemonitoringsothatsitescanbevisitedinamoretimelymanner(internationalstandardisanauditevery2to3years).Thefundsfortheincreasedauditingfrequencycouldbeobtainedfromoneofthree&&~J  proposedsources:A)anincrease~J&&  inthe   EPAfundsdirectedtoOECA,B)anincreaseinproductregistrationfeeswiththeextrafeesdirectedtoOECAconductGLPinspections,orC)fundscouldbeobtainedfromanEPAOECAdirected"GLPInspection"fee.TheincreasedfrequencyofcompliancemonitoringbytheEPA(oritsdesignate(s))willenhancepublicconfidenceandinternationalacceptanceoftheUSEPAGLPprograms.&&~J  ~J&&  IMPLEMENTATIONSTRATEGY:  S   &&~J  ~J&&  ThecurrentEPAGLPcompliancemonitoringprogramofonsiteEPAinspectionsanddataauditsaswellas   independentQAUmonitoringandinspectingforGLPcompliancewouldcontinue.ToinitiallyaugmentthecurrentprograminPhaseI,thescopeandfocusoftheEPAonsiteinspectionswouldberedefined.ThescopewouldberedefinedtoincludefacilitieswithStudyDirector(s).ThefocusoftheEPAonsiteGLPcompliancemonitoringwouldincludefacilitieswithstudydirectorsandprimary/majordatageneratingfacilities.Theoptiontovisitalldatageneratingfacilitieswouldbemaintained.ThisredefinitioncouldbeimplementedbyEPAwithareasonableeffortandwithinareasonableperiodoftimeandwouldmaximizeEPA'seffectiveness.FundingincreasessuggestedinPhaseIIshouldbedirectedtotheEPAOECAGLPcompliancemonitoringprogram.Thefundscouldbeobtaineddirectlyfrom:A)theEPAbudget,B)fromanincreaseintheFIFRAorTSCApetitionregistrationfees,orC)froma"GLPInspection"fee.Inallthesecases,legislativeapprovalandimplementationtimewouldberequired.TheseadditionalresourceswouldallowOECAtoincreasethefrequencyofcompliancemonitoringauditsandtocomeintoalignmentwithinternationalauditfrequency(currentlyinternationalfacilitiesreceivearegulatoryauditevery23years).&&~J  ~J&& oftheEP STRENGTHS:  ` &&~J oftheEP C  $$C -- B.4 <DL!XB0   ~J&& oftheEP 2"3  0!!Thisoptionpreservestheintegrity,structureandharmonizationoftheGLPinternationalstandards.The a federalgovernment'sofficialsfromEPAwouldcontinuetoconductonsiteGLPcompliancemonitoring.ThisoptionshouldmeettheperceivedneedsofEPA,FDA,industry,andtheinternationalOECDGLPcommunityandnotinterferewithharmonizationagreementswithFDA.BecauseEPAconductstheGLPcompliancemonitoringinspections,theGLPfacilitywouldbeprovidedwithfairenforcementpracticesandremoval/minimizationofperceivedconflictofinterestandconfidentialityissues.Withareasonableeffort,EPAcouldinitiallyaugmentthecurrentOECAGLPcomplianceprogram'sresourceutilizationbyredefiningtheGLPfacilities,andfocusinginspectionsontheprimary/majordatageneratingfacilities.ThisPhaseIapproachwouldprovideconsistencywiththeinternationalGLPcommunity'scurrentrevisioneffortsonredefiningGLPfacilities. !! 0   2"3  0!!Thesubsequentexpansionoftheoption(PhaseII)withincreaseddirectedEPAOECAfundinghasa 1$' primarybenefitofprovidingEPAwithexpandedGLPinspectioncapabilities.ThismayprovideamechanismandincreasedcapabilitiesforEPAtoauditscientificsafetydatapriortofinalproductassessmentbyOPPTS.Theregistrationpetitionreviewprocesscouldpotentiallybeacceleratedandthereforeprovideanoffsetbenefitand'valueadded'totheregistrant.TheadditionaldirectedfundingwillhelpoffsetcurrentEPAOECAresourceconstraints.Thisapproachshouldsatisfytherequirementsofallconstituencies,includingthosewithinternationalrequirements.ItmayserveasanationalandinternationalbenefitenhancingthenationalconfidenceandinternationalacceptanceoftheUSEPAGLPcompliancemonitoringprogram. !! C  $$CE+ 4 <DL!, XEXX~J oftheEP  ~JXX oftheEP WEAKNESSES:  ),&1 &&~J oftheEP C  $$C -- B.4 <DL!XB0   ~J&& oftheEP 2"3  0!!ByredefiningtheGLPfacilitiesandfocusingonsiteinspectionstowardtheprimary/majordatagenerating -l(3 facilities(PhaseI),thefrequencyofEPAonsiteinspectionsofsometestsitesmaybereduced.ThisconcernmaybeovercomebyestablishingafeedbackmechanismbetweenEPAandtheregulatedcommunity. !! 0   2"3  0!!Theexpansionoftheoption(PhaseII)withdirectedfunding,thelongtermbenefitofincreasingthe X numberofGLPfacilitiesinspectedbyEPAwilloutweighthetimeconstraintsforlegislativeauthorizationandimplementation.ItmayinvolveadditionalcosttoEPA,theregistrant,ortheGLPfacility.Iffundingisincreasedfromaregistrationor"GLPInspection"fee,afairandequitablefeestructurewillhave&&~J oftheEP to~J&& oftheEP be   established.Testingfacilitiesorsponsorswithnointernationalneedscouldbejeopardizedbythesefeesandsponsor'smaybearanunfairshareofthecosts.ThiscouldresultinhighercostofalreadyexpensiveGLPstudieswithoutaddedvalueontheintegrityandqualityofdata.ItcouldpotentiallydrivestudiesoutoftheUSforcostreasons,imposeanontarifftradebarrier,andbeanunnecessaryburdenforsmallhighlyspecializedbusinesses. !! C  $$CE+ 4 <DL!, XE&&~J oftheEP ~J&& oftheEP CONCLUSION:  L  &&~J oftheEP ~J&& oftheEP Adequateandappropriatemonitoring,performedbyqualifiedEPAinspectors,ofscientificresearch M  laboratoriesconductingFIFRAandTSCAstudiesundertheGLPregulationsisofparamountimportancetotheregulatedcommunity,theinternationalcommunity,and,ultimatelytothepublic.ThisoptionmaintainstheintegrityoftheEPAGLPcompliancemonitoringprogram,includingtheQAUGLPcompliancemonitoring.NationalandinternationalGLPprogramharmonizationismaintained.WithareasonableeffortinPhaseI,programaugmentationthroughredefinitionandfocuscouldenhancetheeffectivenessofthecurrentGLPcompliancemonitoringprogram.TheincreasedfundingforexpansionoftheoptioninPhaseIIwillresultsinincreasedEPAGLPinspectioncapabilitiesandfrequencies,meetingtheneedsofEPA,includingtheOIG,FDA,theindustryandtheinternationalcommunity.ThisexpandedoptionhasthepotentialtoenhancetheEPAregistrationpetitionreviewprocess.DirectedfundingresourcesmayrequiretimeforapprovalandimplementationbutwillresultinincreasedEPAGLPcompliancemonitoringcapabilities.Withthisoption,EPAremainsastheGLPcompliancemonitoringentity.  XX~J oftheEP Option2:~JXX oftheEP THIRDPARTYACCREDITATIONFORGOODLABORATORYPRACTICE = PROGRAMSXX~J oftheEP  - ~JXX oftheEP &&~J oftheEP ~J&& oftheEP INTRODUCTION:  p  &&~J oftheEP   ~J&& p   In1994,theOECDGLPPanelissuedastatementonGLPaccreditationprograms.Here,theOECD q " acknowledgedthequasiaccreditationprograms,andstatedthatsuchprogramsmustbebasedonOECDGLPPrinciplesandnotISOGuide25,andhavegovernmentoversight.Forthesereasons,thisaccreditationoptionisbasedonGLPstandards,withtheU.S.EPAhavingprimarycontrolandactingastheAccreditingAuthority.  &&~J p   ~J&& p   DESCRIPTIONOFTHEPROGRAM:  k$ ' &&~J p     ~J&& p   ThedevelopmentofaprivatethirdpartyaccreditationprogramwouldbesanctionedbyEPAforthepurposes  & ) ofinspectingandaccreditinglaboratoriestoGLPstandards.EnforcementresponsibilitieswouldremainwiththeEPA.Theprogramwouldincluderegistrationoflaboratories,onsiteinspectionsofthetestsitefacility,alongwithtechnicalandqualityprograms.AcertificatewouldbeissuedforsuccessfulcompletionoftheGLPcomplianceinspection,whichwouldaddressinternationalconcernsandbroadenmarketacceptanceofthelaboratory,anddata.AstheAccreditingAuthority,theU.S.EPAOfficeofEnforcementandComplianceAssurance(OECA)wouldestablishaprogramtorecognizethirdpartyaccreditingorganizationorbodiestoprovidelaboratoryaccreditationtoaGLPstandard.Interestedstakeholders,includingthirdpartyaccreditingbodies,sponsors,contractlaboratoriesandotherswoulddeveloptheProgramDescription;including: -~(3    4 OECAsresponsibilityastheAccreditingAuthority 4 Criteriaforapprovingthirdpartyaccreditingbodies 4 Criteriaforqualifyingandtrainingassessors.  InterestedthirdpartyaccreditingbodieswoulddeveloptheirGLPaccreditationprogrambasedontheseconditions.TheseprogramswouldbereviewedbyOECAandsanctionacceptableprograms.ContinuedapprovalwoulddependonOECAsmonitoringandperiodicreapprovaloftheaccreditingprogram.AcceptedaccreditingbodiescouldpublicizetheirapprovalandexistingGLPaccreditingprogram,andbegintoacceptapplicationsandcompletetheaccreditationprocessasdescribed.  &&~J p   ~J&& p   ACCREDITINGPROCESS:     XX~J p     ~JXX p   Theaccreditingprocesswouldbeginuponsubmissionofacompletedapplicationandfeesforaccreditation b  bythelaboratorytotheaccreditingorganization.Afterinitialreview,theaccreditingorganizationwouldcontactthelaboratorytoacknowledgereceiptoftheapplicationandtodiscusstheassignmentoftrainedassessors.TheobjectoftheassessmentistodeterminewhetherornotalaboratorycomplieswiththeGLPrequirementsforaccreditation,andcancompetentlyperformthetypesoftestsforwhichaccreditationissought.AtthedirectionofOECA,dataauditsofselectedstudiescouldalsobeperformed.Theassessorwouldclosetheonsiteportionoftheassessmentwithanexitbriefing.Awrittenreportoftheassessorsfindings,includinganydeficienciesoritemsneedingcorrectiveactionwouldbereviewedattheexitbriefingandleftwiththelaboratory.Ifdeficienciesarecited,thelaboratorymustsubmitawrittenplanofcorrectiveaction,withanticipateddatesofcompletion.Theaccreditingbodywouldreviewthecorrectiveactionforcompleteness.Theinspectionreport,alongwithanycorrectiveactionwouldbesenttotheaccreditingreviewpanelforadecisiononaccreditation.Onceaccreditationisapproved,thelaboratorywouldbeissuedacertificatebytheaccreditingbody.AcopyofthelaboratorycertificateandscopeofaccreditationisprovidedtoOECA.  &&~J p   ~J&& p   STRENGTHS:   &&~J p   ~J&& p    4 Providesincreasedfrequencyofinspections,whileallowingOECAtoretainitsauthority &! ?+  <DL!X?  andenforcementresponsibilitiesE+ 4 <DL! XE 4 FacilitatesOECAsfocusondataaudits 4 Providesan approveduniverseoflaboratories 4 Facilitatesintegrationofregulatoryandcommerceissues,andstreamlinesadministrative?+  <DL!X?  dutiesE+ 4 <DL! XE 4 Meetsinternational(OECDGLP)requirements 4 Providesgreaterinternationalacceptanceoflaboratorytestingprogramsanddata 4 Financiallyselfsustaining&&~J p   &  ~J&& p   &&~J p   ~J&& p   WEAKNESSES:  g'"+ &&~J p   ~J&& p    4 Additionalcosttoparticipatinglaboratories  )#-  4 PerceivedinternalmanagementfocusawayfrominternalQAU 4 Confidentialityofproprietaryinformation&&~J p   'g'~J&& p   CONCLUSION:  ;,&1 &&~J p     ~J&& p   ThedevelopmentofathirdpartyaccreditationprogramforGLPpromotestheuseoftheGLPstandardswhich -~(3 ensurescontinuedOECDharmonizationandinternationalacceptanceofdata.RelianceonthirdpartyaccreditorsfostersincreasedinspectionfrequencyandaddressesconcernsoftheInspectorGeneralandinternationalcommunity.ControlismaintainedbyU.S.EPA,astheAccreditingAuthorityandEnforcementEntity.Thisprogramwouldmostlikelybeacceptedinternationally.Thecurrentlyanticipatedaccreditationcostsappearreasonableandtimetoimplementtheprogramwouldbeminimal.XX~J p      ~JXX p   XX~J p   OPTION3&&X p   :~J& p   INCREASEDVALUEFORCURRENTSPONSORMONITORINGPROGRAMS:&&~J p    7  ~J&& p   &&~J p   ~J&& p   INTRODUCTION:      &&~J p   ~J&&    ThecurrentEPAlistoffacilitiesgeneratingGLPdataisover2000facilities,andtheEPAdoesnothave  D  adequatestaffandresourcestoinspectthemallonaregularschedule.ThislistisgeneratedbylistingstudytestingfacilitiesplusallsubcontractedtestsitesidentifiedinthefinalreportsofstudiesconductedundertheGLPregulations.BasedoninformationfromFranciscaLiemoftheEPA,themajorityofthesetestsitesgenerateonlyasmallamountofthedata.Currently,theEPAdoesnotprioritizetheirinspectionscheduletofocusonfacilitiesthatgeneratethemajorityoftheGLPdata.InadditiontoAgencyinspections,sponsorsalsoinspecttheirsubcontractedtestsitesforGLPcompliance.FDAandEPAGLPregulationsbothassignsponsors(registrants)theresponsibilityforGLPcomplianceofastudy,regardlessofwherethestudyisconducted.Inresponsetothisrequirement,sponsorshavedeveloped L GLPinspectionprogramsfortheircontractfacilities.SponsorsmustattesttotheGLPcomplianceoftheentirestudy,includingworkconductedatsubcontractedtestsites,whenastudyissubmittedtotheAgency.ThisresponsibilitywasreinforcedbyEPAsEnforcementResponsePolicy,wheremonetaryfinesandpenaltiesfornoncompliancewithGLParemuchgreaterforsponsorsthatsubmittedstudiesthanforcontractfacilitiesthatconductedstudies.&&~J    ~J&&    DESCRIPTIONOFOPTION3SPONSORMONITORINGPROGRAM:  5 &&~J     ~J&&    TheexistingEPAGLPComplianceMonitoringProgramiscontinuedwiththeadditionofrecognitionfor x sponsorsinspectionprograms.TheEPAretainsfullresponsibilityforallaspectsofcompliancemonitoringandcontinuestheirinspection/auditprogramingenerallythesamemanner.ByrecognizingvalueinsponsorsGLPinspectionsofcontractfacilities,theirtargetingschemefromthelistof2000plusfacilitieswouldbealtered.Sponsors(registrants)wouldhaveanewresponsibilitytoreporttotheAgencyeachtimetheyvisitedandevaluatedacontractfacility,preferablyinanestablishedelectronicformat.EPAretainstheoptiontoinspectanytestsite,butwouldprioritizetheirscheduletofocusonregularinspectionsofsponsors,testingfacilitieswithstudydirectorsandfacilitiesgeneratingthemajorityoftheGLPdata.ByestablishingadatabaseofsponsorsGLPinspections,EPAwouldbeabletotrackthenumberofsponsorsinspectionsatsubcontractedtestsites.Usingthisinformation,theywouldprioritizetheirneedforinspectionsatremainingtestsitesthatgenerateonlyasmallamountofthedata.Bysupplementingtheirinspectionscheduleswithsponsorschedules,theEPAwouldbemuchmoreeffectiveinadequatelyinspectingtestingfacilitiesthatgeneratethemajorityoftheGLPdata.B.r4 <DL!XB0 r &&~J     r!r! E+ 4 <DL!r4XE~J&&    &&~J    ~J&&    IMPLEMENTATIONSTRATEGY:  'B"+ &&~J     ~J&&    SponsorswouldreporttheirGLPcomplianceinspectionschedulesofcontractfacilitiestotheEPA,preferably C)#- inaestablishedelectronicformat.Informationreportedwouldbestandardizedandincludethedate(s)ofvisit(s),lengthofvisit,systemsandtypesofoperationsobserved,andpertinentinformationotherthaninspectionfindings.Asdescribedunder InspectionofatestingfacilityintheGLPStandards,the QualityAssuranceUnitrecordsoffindingsandproblems,ortoactionsrecommendedandtaken,wouldnotbeprovidedtotheEPA. -(3 EPAwouldthenincorporatethisinformationintoadatabase.EPAwouldfocustheirinspection/auditresourcesfirstonsponsors,testingfacilitieswithstudydirectorsandfacilities&&~J    ~J&&    generatingthemajorityoftheGLPdata. ' Presumingalaboratory/testsitethatgeneratedasmallamountofdatawas&&~J    ~J&&    evaluatedwith&&~J    ~J&&    someregularityby  sponsors,itwouldnotroutinelybeinspectedbyEPAforGLPcompliance,thoughtheyretaintheoptiontodosoatanytime.Ifatestsitewasnotvisitedregularlybymultiplesponsors,presumablythattestsitewouldbetargetedforinspection.Anotherfactorinfluencingthenumberofinspectionsrequiredwouldbethegeographicallocationandcropsettingthatafieldstationconducted.Minorusetypefieldlaboratories(minorcropinanisolatedlocal)wouldrequirelessmonitoringthanaheavilyusedfieldorchemicalanalysislaboratory(majorcropintheheartofamajoruse/productionarea.)  &&~J     ~J&&    STRENGTHS:  e   &&~J       C  $$C --   B.4 <DL!XB0   ~J&&    2"3  0!!Sponsorshavealreadyinvestedinmonitoringprogramsforcontractfacilitiesbecausetheyareresponsible   andliableforcomplianceatthesefacilities.ByrecognizingthevalueofsponsorsinspectionsasasupplementalpartoftheEPAGLPComplianceMonitoringprogram,theirinspection/auditingschedulewouldbegreatlyenhanced.EPAcanprioritizeandbalancetheirinspectionresourcestofocusonfacilitiesgeneratingthemajorityofdataandwheretherearesuspectedorobviousproblems. !! 0   2"3  0!! CostsassociatedwiththisOptionwouldbeminimumforbothEPAandsponsorsbecauseitutilizes   existingprograms.ThesponsorreportingprocesswillresultinaminorincreaseincosttoGLPregulatedcommunityandpotentialcostbenefit.  !! 0   2"3  0!! QualityofGLPdataremainshighbecausetheintegrityofexistingprogramsdoesnotreallychange. G (Undertheexistingprogram,thequalityofdatahasbeenconsideredgood.TheconcernhasbeenwiththenumberoffacilitiesandnotbeingabletoscheduleEPAinspectionsonanacceptablefrequency.) x!! 0   2"3  0!! EPAsinspectionsaretheprimaryenforcementtypeinspectionsandoverallcontrolofGLPcompliance @ resideswithEPA.ItisanimportantadvantagebecauseGLPareafederalregulationandprimaryresponsibilityformonitoringcompliancemustresidewithEPAsOfficeofCompliance(OC).EPAsinspectorshavethenecessarybackgroundandexperiencewithGLPtoprovideindustrywithfairenforcementpracticesandcomplianceassistance. `!! 0   2"3  0!! TheinformationrequiredforEPAtoeffectivelymonitorsponsorsinspectionprogramsisavailableto ( themunderthecurrentGLPregulation[160.35(c)].AtestingfacilityswrittenproceduresforconductinginspectionsandauditsareevaluatedduringEPAinspections,aswellastrainingrecordsforQAUpersonnel.UnderexistingGLPregulations,recordsofinspectionsconductedbyaQAU(nottheresults)areavailabletorepresentativesoftheEPAorFDA.IftheEPAfindsthatatestingfacilitysQAUproceduresarenotadequateduringaninspection,theycouldcitethemasfindingsintheirGLPinspectionreport. 7 "!! 0   2"3  0!! EPAisnotdependentonthequalityoftheinspectionsofanyonesponsor.Byestablishingadatabase  # forsponsorsinspections,theEPAwouldknowhowmanysponsorshaveinspectedatestingfacilityandhowfrequentlythefacilityhadbeeninspected.TheInspectorGeneralsreportstatedthatGLPfacilitieswerenotadequatelyinspectedandOCdidnothavetheresourcestomonitorsomanytestsites,butitdidnottakeintoaccountorevaluatetheongoingGLPmonitoringofcontractfacilitiesbysponsors.BecauseofsponsorsliabilityandEPAsEnforcementResponsePolicy,U.S.testingfacilitieslikelyhaveundergonemoreGLPinspectionsthananyplaceintheworld. %P )!! 0   2"3  0!! Withadatabaseofsponsorsinspections,theEPAwouldknowtheidentityoffacilitiesactively w&!* conductingstudiesunderGLPregulations.Currently,thisinformationbecomesavailableaftertheworkhasbeencompletedandthefinalreporthasbeensubmittedtoEPA. (",!! C  $$CE+ 4 <DL!, XE &&~J    ~J&& 3   WEAKNESSES: )J$. &&~J 3     C  $$C -- B.4 <DL!XB0   ~J&& 3   2"3  0!!Thereisapotentialconflictofinterestbyallowingsponsorstowatchoverthecontracttestsiteswhoare K+%0 conductingthestudiesforthem.Somesponsorsmaynotbediligentintheirassessmentofthetestsites,andmayjustdoacursoryevaluation.Eveniftheprogramwasconductedproperly,thepublic'sperceptionofthisprogrammayhavenegativeconnotations.-D(3!! 0   2"3  0!!IfacontractlabthoughtthatitwouldbeunlikelythattheAgencywouldinspectit(becauseitwasvisited _ byitsclients),itmayonlymeettheminimumstandardsrequiredtokeepitsclients. !! 0   2"3  0!!Internationalconcernsabouta CertificateofGLPcompliancearenotaddressed.!! 0   2"3  0!!NoprovisiontogathernonGLPcomplianceinformationifasponsorchoosesnottoreportit.The X frequencyofauditingmaybemisleadinginreflectingalabsqualificationtodoGLPwork. !! 0   2"3  0!!NoothercountryusessponsorauditingasameasureofGLPcomplianceorasanaugmentationtoAgency G  monitoringsystems. !! C  $$CE+ 4 <DL!, XE&&~J 3   ~J&& 3   CONCLUSION:   R &&~J 3      ~J&& 3   Option3SponsorMonitoringProgramdependsonthecontinuationofEPAsGLPComplianceMonitoring S   Program.ImplementationwouldbesimpleandcosteffectivebecauseitutilizestheexistingGLPcompliancemonitoringinspectionprogramsofEPAandindustry.EPAwouldprioritizetheirinspectionscheduletofocusonfacilitiesgeneratingthemajorityofdataandwheretherearesuspectedorobviousproblems.TheirprogramwouldbesupplementedwithadatabaseofsponsorsGLPinspectionsofcontractfacilities.Sponsorswouldonlyhaveaddedreportingresponsibilities.TheAgencystartupandmaintenancecostsforadatabasewouldbeminimizedbytheaddedbenefitsofprioritizingtheirinspectionschedules.TheOptionisinconformancewithexistingGLPregulationssotherearenolegalramifications.SponsorshaveprimaryresponsibilityforGLPcompliancewhenstudiesorphasesofstudiesareperformedatcontractedfacilities.ThisOptionshouldnotpresentaconflictwithFDAregulationsorInternationalAgencies.UnderFDAGLP,sponsorsalsohaveresponsibilitytomonitortheircontractfacilities.InternationalAgencyinspectionshavebeenprimarilydirectedattestingfacilitieswithstudydirectors,butarenowstartingtoinspecttestingsites(withoutstudydirectors).  Option3couldbecombinedwithOption1toaugmenttheexistingEPAComplianceMonitoringProgramand/orwithOption5,aregistrationlistprogramtofacilitatetrackingoffacilitiesandtestsitesconductingGLPstudies.  &&~J 3     ~J&& 3   XX~J 3   OPTION4~JX 3   INCLUSIONOFGLPPROGRAMUNDERTHEUMBRELLAOFNELAP:XX~J 3    = ~JXX 3   XX~J 3    ~JXX 3   GENERALDESCRIPTION :  XX~J 3      ~JXX 3   InthisoptionthefederallycontrolledEPAGLPProgram,utilizingthecurrentGLPstandards,wouldbeplaced v! undertheumbrellaofNELAPasaparallelprogramandwouldoperateindependentlyoftheotherNELAPprograms.FederalEPAinspectorswouldconductpriorityGLPcomplianceinspectionsanddataauditsaswellasmonitortheactivitiesofNELAC,withadditionalinspectionsupportbeingprovidedbyEPAapprovedthirdpartyassessors.Theallocationofresponsibilitieswouldbeasfollows:EPAwouldcontinuetomanageanddirecttheactivitiesoftheEPAGLPprogram,tomaintainrecordsderivedfromGLPstudyandlaboratoryevaluations,andtoaddressbothinteragencyandinternationalharmonization,regulatoryandcomplianceissues.NELACwouldprovidetheadministrativesupportfortheaccreditationprogram.FundingoftheprogramwouldbelargelyderivedfrominspectionfeesleviedbyNELACand/orthirdpartyaccreditinggroup(s)foraccreditationinspections/assessments.Insummary,NELACwouldberesponsibleforfacilityaccreditationwhileEPAwouldretainoversightresponsibilitiesfortheGLPProgram.  XX~J 3   ~JXX 3   STRENGTHOFOPTION:  *%/ XX~J 3    C  $$C -- C  $$C --   0 4  ~JXX 3   2"3  044!4!InspectionfeescollectedbyNELACcouldprovideadditionalmanpowerandfundingto&&~J 3   ~J&& 3   OECA,F'14!4! 0 4  2"3  044!4!AslongasnochangesaremadeintheGLPStandardstoaccommodateNELAC,theGLP - (2 harmonizationeffortswithFDAwouldnotbedisrupted,therebyretainingasinglenationalGLPStandard 4!4! 0 4  2"3  044!4!Couldincreasefrequencyofinspectionsandpossiblyresultinacertificateofaccreditationwhich  wouldbeacceptabletotheinternationalcommunity 4!4! 0 4  2"3  044!4!EstablishedGLPtrainedthirdpartyassessment/compliancegroup(s)couldassistEPAinlaboratory   evaluations 4!4! 0 4  2"3  044!4!TheEPAGLPProgramunderNELACumbrellawouldprovideaprocessbywhichEPAcoulduse   approvedforfeethirdpartyassessmentgroupswithoutreceivingfundsdirectlyfromtheregulatedcommunity 4!4! 0 4  2"3  044!4!Somelaboratories,particularlycontractlaboratories,mayderiveabusinessincentivetobecoming g   accredited 4!4! C  $$C  XX~J 3   ~JXX 3   WEAKNESSESOFOPTION:    XX~J 3   C  $$C --   0 4  ~JXX 3   2"3  044!4!WouldneedtoresolveplacingafederallymandatedGLPprogramunderavoluntarystateprogram@ 4!4! 0 4  2"3  044!4!WouldsubjectNELACtointensecriticismandchallengesiftheregulatedcommunitywasnot g  allowedintheNELACconstitutiontoimpactNELACactivities/standardsduringtheirrulemakingproceduresbyusingcommentperiodsandpublichearings,etc. 4!4! 0 4  2"3  044!4!InternationalandinteragencyacceptancefortheprogramcouldbejeopardizediftheGLPStandards, ` ortheharmonizationefforts,arechangedtoaccommodateNELAC 4!4! 0 4  2"3  044!4!WouldneedtoresolveEPAdelegatingspecificGLPComplianceProgramresponsibilitiestostatesO4!4! 0 4  2"3  044!4!Wouldneedtoestablishproceduresforprocessingfederalenforcementactionsresultingfromstate  andthirdpartyevaluations/inspections 4!4! 0 4  2"3  044!4!Couldrequirestatestobecomeinvolvedinsharingoversightworkload,training,andthedevelopment H ofenforcementcasesfortheGLPprogramwithlittleincentiveforthestates 4!4! 0 4  2"3  044!4!WouldrequireharmonizationbetweenUSandinternationalaccreditationprogramssoastonotplace 7 USbusinessesatacompetitivedisadvantage 4!4! 0 4  2"3  044!4!MightnotaccommodateOPPTSneedstohaveappropriatelytimedauditinformationh4!4! 0 4  2"3  044!4!ProvideslittleincentiveforOECAtostreamline/improveexistingprogram04!4! 0 4  2 "3  044!4!Wouldprovidetheregulatedcommunitylittle valueaddedimpactforincreasedcostof W accreditation 4!4! 0 4  2 "3  044!4!Unlessprogramisadjustedtomakeallowancesforthenumberoffacilitiesinspected,frequencyof  inspections,timelinessofreportingandqualityofscientificreviews,stakeholderswouldreceivelittlebenefitfromtheincreasednumberoffacilitiesinspected 4!4! 0 4  2 "3  044!4!Smallspecialtylaboratoriesmightbeadverselyaffectedbyincreasedcost? "4!4! 0 4  2 "3  044!4!AccreditationwillincreasecostoftestingintheUSwhichmightdrivesomelaboratoriesoutofthe !# country 4!4! 0 4  2 "3  044!4!WouldneedtoestablishproceduresforEPAtodirectthirdpartyforfeeinspections/assessments"8%4!4! 0 4  2"3  044!4!Wouldneedtoestablishappropriateandreasonablefeestructuresthroughouttheprogram_#&4!4! 0 4  2"3  044!4!WouldneedtoprovideOECAwithadditionalresourcestomonitortheactivitiesofNELACand '$' thirdpartygroups,toprovideappropriatetraining,schedulingandtrackinginspections,archivingandprocessinginspectionfindings 4!4! C  $$C CONCLUSION:  G'!+   TheEPAGLPprogramcouldbeplacedundertheumbrellaofNELAPifitweretreatedasaseparateandindependentprogramsoastonotinterferewiththesuccessofthecurrentFederallymandatedGLPmonitoringandcomplianceprogram.TheadditionalresourcesthatcouldbeprovidedtotheEPAGLPprogrambythestatesorthirdpartyassessmentgroup(s)couldbeusedtoincreasetheresponsivenessoftheAgencysGLPprogram,however,ownershipandcontroloftheprogramwouldbeverycumbersomeinthisdualoversightsystem.BynotchangingtheGLPregulationstoaccommodateNELAPrequirements,thereshouldbelittleadverseaffectontheharmonizationofseveralregulationswithinEPA,withFDAor -((3 theinternationalGLPcommunity.DueconsiderationwouldhavetobegiventoallowtheGLPregulatedcommunitytorespondtochangesmadeintheregulationsordirectionofenforcementactions(rulemaking,commentperiods,etc.).SuchproblemareasastheconcernsoftheregulatedGLPcommunity;thelegalityofdelegationofEPAGLPresponsibilitiestoStates;theuseof forfeethirdpartyassessors;theestablishmentofareasonablefeestructure;thearchiving,trackingandprocessingofinspection/assessmentdata,etc.,allshouldbeaddressedbeforethisoptioncanbeseriouslyconsidered.XX~J 3   ~JXX 3   XX~J 3   ~JXX 3   XX~J 3   OPTION5~JXX 3   FIFRA/TSCAGLPTESTINGFACILITYREGISTRATIONXX~J 3        ~JXX 3     & X   &&~J&&&&      ~J&& riorityGL    BACKGROUND  ri   H   'ity      ~J~J~J~J'X '    &&~J&&&&      ~J&& riorityGL OneofthedifficultiesfacedbyOECA,inadditiontonothavingthestaffresourcesorbudgettoinspectthe 7  estimated2000facilitiesidentifiedasdevelopingdataforsubmissiontoEPAunderGLPs,isthatitcannotidentifythefulluniverseoftestinglaboratories.OECAusesOPPandOTSdatabasesforthelaboratorylistwhichisgeneratedfrominformationprovidedinthefinalreportbythesponsor.TheresultisalagtimefromwhenthelaboratorybeginsdevelopingdataforsubmissiontothetimewhenstudiesareactuallysubmittedandbecomeknowntoEPAandtowhentheselabsareinspected.Eachtestsiteinastudyiscountedasafacilitybasedoninformationprovidedinthefinalreportbythesponsor.EPAhasdataontestfacilitiesbutitisincomplete. 'riority ri )ity    ~J~J~J~J      &&~J&&&&      ~J&& riorityGL OnesolutionEPAhasbeenlookingat,toimplementtheEPAsOfficeoftheInspectorGenerals(OIG) ? recommendations,isthemandatoryregistrationofallfacilitiesparticipatinginGLPregulatedstudies,basedondocumentsubmissionandassessment.u.ity    ~J~J~J~J     & X   &&~J&&&&      ~J&& riorityGL    DESCRIPTIONOFOPTION  ri  _  0ity      ~J~J~J~J'X_0    &&~J&&&&      ~J&& riorityGL FacilitieswhichintendtoperformFIFRAandTSCAGLPstudiesforsubmissiontoEPAwouldberequired  toregistertheirfacilitywithEPA.Facilityregistrationwouldinvolveaninitialsubmissionofinformationanddocumentsfromthefacilityforreviewtoestablishthebasicprofileforthefacility.Documentationcouldpossiblyinclude:descriptionofsize,organization,andcapabilitiesofthefacility;theorganization,functions,andproceduresofthequalityassuranceunit;generaldescriptionofinstrumentsandequipmentusedatthesite,andthenumberandareasofexpertiseofstaff.Itmightalsoincludecurrentlistofstandardoperatingprocedures,resumes,CVsandtrainingrecordsofkeypersonnel,floorplansoffacility,andacurrentmasterschedule.Onaperiodicschedule,facilitieswouldberequiredtoresubmitcertaindocumentsandinformation. 'riorityri 2ity    ~J~J~J~J      &&~J&&&&      ~J&& riorityGL TheAgencyoradesignatedthirdpartycontractorwouldauditthesubmitteddocuments.Registrationwould !$ notconferapproval.Facilitieswithcorrectedminordeficiencieswouldbeprovisionallyregistered,whilefacilitieswithmajordeficiencieswouldbetargetsforinspection.PeriodicsubmissionofthefacilitysmasterschedulewouldberequiredandwouldprovideameansofmonitoringworkintendedforsubmissiontotheAgency.ThiswouldallowOECAtoprioritizeitsinspectionsandbeabletoconductinlifeauditreviewsofongoingstudies.Toremainontheregistrationlist,asubmitterwouldneedtocontinuetoremaininGLPcomplianceverifiedbyanEPAfacilityinspectionaudit.7ity    ~J~J~J~J     & X   &&~J&&&&      ~J&& riorityGL    IMPLEMENTATIONSTRATEGY  ri  7(",  ;ity      ~J~J~J~J'X7(;    &&~J&&&&      ~J&& riorityGL Aregistrationfeewouldbechargedwhichwouldcoverallparticipantsinastudy,andwouldbebyfacility )h$. (sitesactuallyconductingworkaspartofthestudy),notbycompanyorcorporation.Theregistrationfee,whichwouldrequirecongressionalauthorization,wouldbelargeenoughtoadministerandmaintaintheregistrationlistandreviewofdocumentsubmissions.EPAwouldhavetoidentifyanddevelopfaircriteriastandards.Afterareasonableperiodforregistrationtobeimplemented,theAgencycouldrejectanystudiesutilizingunregisteredfacilities,iftheregistrationsystemistosucceed. 'riority ri  -P(3 =ity    ~J~J~J~J     & X   &&~J&&&&      ~J&& riorityGL    STRENGTHS  ri  '  Aity      ~J~J~J~J'X'A    &&~J&&&&      ~J&& riorityGL Withlittleeffort,amandatoryregistrationlistwouldprovideEPAwithacompletedatabaseor known X populationofGLPtestingfacilities.ThiswouldmeettheOIGsrecommendationsthattheAgencyhaveassuranceofalaboratorysawarenessofandabilitytomeetGLPrequirementsandtheprovisionofanindustrywidelaboratoryenvironmentmoreconducivetoGLPcompliancewiththequalityofthedataremaininghigh. 'riority ri City    ~J~J~J~J      &&~J&&&&      ~J&& riorityGL Inaddition,aregistrationlistwouldprovidetheAgencywithascreeningcapabilityandwouldpermitmore g   efficienttargetinganduseofresources.ItwouldalsopermittheAgencytomakeapreliminaryassessmentofpreviouslyuninspectedfacilities,andutilizelimitedresourcestoinspectfacilitieswhichappeartohavethemostseriousdeficiencies.AssessmentofGLPcompliancecontinuestoremainwithEPA.IfEPAweretoimplementthisprogram,concernsforconflictsofinterestandconfidentialitywouldbeminimized.Gity    ~J~J~J~J      &&~J&&&&      ~J&& riorityGL EPAcouldprovidethelistofregisteredGLPlaboratoriestointernationalgovernments,whichmayaddress   internationalconcerns.Additionally,theregistrationlistcouldbeannotatedwiththedatesofEPAfacilityinspections.Jity    ~J~J~J~J     & X   &&~J&&&&      ~J&& riorityGL    WEAKNESSES  ri  7  Lity      ~J~J~J~J'X7L    &&~J&&&&      ~J&& riorityGL TherewillbeanadditionalminimalregistrationcosttotheGLPtestingfacilitiestocoveradministrationofthe h registrationlist.RegistrationcoststoGLPcommunitymaybegreaterforsmallcompaniesandcompanieswithmultipletestingfacilities.Inaddition,EPAwouldincuraninitialadministrativecosttostarttheprogramandmaintainit.Therewouldbeno valueaddedtocurrentGLPcompliancefordataquality. 'riority ri Nity    ~J~J~J~J      &&~J&&&&      ~J&& riorityGL Onsiteevaluationswouldstillberequired,andasnotedbeforeEPAlackssufficientresourcestoadequately P inspectallGLPlaboratories,butitwouldbebetterinformedofwhichlabsandwhichstudieswerebeingconductedsoitcouldprioritizeitsinspections.A voluntaryregistrationlistwouldbecounterproductivebecauseitwouldnotprovidetheAgencywithan approveduniverseoflabs. Rity    ~J~J~J~J     & X   &&~J&&&&      ~J&& riorityGL    CONCLUSION  ri  8  Uity      ~J~J~J~J'XU    &&~J&&&&      ~J&& riorityGL ThealternativeprogramsbeingproposedtohelpaugmentthecurrentEPAGLPcompliancemonitoringsystem '! representaprogressivelistofoptionsthatcanbeimplementedbythemselvesorincombinationwitheachother.TheregistrationlistwasnotincludedintheoptionforthereevaluationofexistingEPAGLPcompliancemonitoringprogramwithfundingconsiderations,becausethegroupfelt,byitself,itwouldnotsolvetheEPAsproblemswithfundingandresourcesforconductingfacilitysiteinspections.However,theregistrationlistcouldproveusefulinconjunctionwithotherproposedoptions. 'riorityri Vity    ~J~J~J~J