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A. 1) a.(1)(a) i) a)6i4footnote     . ;1uX` hp x (#;  #bb    8.` hp x (#8  #dd42LEVEL2E  8.` hp x (#8   Q\  `$Times NewRomanQ   8.` hp x (#8  &&&  Q\  `$Times NewRomanQ 86LEVEL1.II  ? *?;1X` hp x (#;  Q\  `$Times NewRomanQ #bb  /  H/8.` hp x (#8  &&&Q\  `$Times NewRomanQ #dd&0 d d 'dxd'dxd64LEVEL3.1 ; 5+ ` hp x (#5  XXX Q\  `$Times NewRomanQ   8.` hp x (#8  &&&  Q\  `$Times NewRomanQ 2UJ0LEVEL4 ; 5+ ` hp x (#5   8.` hp x (#8 0LO.para4    5+u u` hp x (#5    8.` hp x (#80OO.para2 N   8.` hp x (#8    8.` hp x (#8<P:List Bullet  8.` hp x (#8  &&&A(\ Y`SymbolA"..&&&Q\  `$Times NewRomanQ  8.` hp x (#8  (\ Y`Symbol0`].para1    ;1X` hp x (#;#bb    8.` hp x (#8#dd42LEVEL2B N 8.` hp x (#8   Q\  `$Times NewRomanQ   8.` hp x (#8  &&&  Q\  `$Times NewRomanQ 42LEVEL2C  8.` hp x (#8   Q\  `$Times NewRomanQ   8.` hp x (#8  &&&  Q\  `$Times NewRomanQ 42LEVEL2D  8.` hp x (#8   Q\  `$Times NewRomanQ   8.` hp x (#8  &&&  Q\  `$Times NewRomanQ 42LEVEL2A N 8.` hp x (#8   Q\  `$Times NewRomanQ   8.` hp x (#8  &&&  Q\  `$Times NewRomanQ 64LEVEL3.2 ; 5+ ` hp x (#5  XXX Q\  `$Times NewRomanQ   8.` hp x (#8  &&&  Q\  `$Times NewRomanQ 64LEVEL3.3 ; 5+ ` hp x (#5  XXX Q\  `$Times NewRomanQ   8.` hp x (#8  &&&  Q\  `$Times NewRomanQ 64LEVEL3.4 ; 5+ ` hp x (#5  XXX Q\  `$Times NewRomanQ   8.` hp x (#8  &&&  Q\  `$Times NewRomanQ 64LEVEL3.5 ; 5+ ` hp x (#5  XXX Q\  `$Times NewRomanQ   8.` hp x (#8  &&&  Q\  `$Times NewRomanQ 42LEVEL2F  8.` hp x (#8   Q\  `$Times NewRomanQ   8.` hp x (#8  &&&  Q\  `$Times NewRomanQ 64LEVEL1.I  A *A;1X` hp x (#;  Q\  `$Times NewRomanQ #bb  /  H/8.` hp x (#8  &&&Q\  `$Times NewRomanQ #dd:8LEVEL1.III J A *A;1X` hp x (#;  Q\  `$Times NewRomanQ #bb  /  H/8.` hp x (#8  &&&Q\  `$Times NewRomanQ #dd86LEVEL1.IV  A *A;1X` hp x (#;  Q\  `$Times NewRomanQ #bb  /  H/8.` hp x (#8  &&&Q\  `$Times NewRomanQ #dd64LEVEL1.V  A *A;1X` hp x (#;  Q\  `$Times NewRomanQ #bb  /  H/8.` hp x (#8  &&&Q\  `$Times NewRomanQ #dd86LEVEL1.VI  A *A;1X` hp x (#;  Q\  `$Times NewRomanQ #bb  /  H/8.` hp x (#8  &&&Q\  `$Times NewRomanQ #dd2A0Header  (#A7X` hp x (#A2A0Footer  (#A7X` hp x (#A0LO.para3 ;   5+ ` hp x (#5    8.` hp x (#84U[2PARA4.1    2(9 9 hp x (#2 K    8.` hp x (#8  4X[2para3.1    5+M M ` hp x (#5     8.` hp x (#8  4X[2para3.2    5+9 M ` hp x (#5     8.` hp x (#8  <jj:Page Number Q\  `$Times NewRomanQ&&&Q\  `$Times NewRomanQ42LEVEL2G  8.` hp x (#8   Q\  `$Times NewRomanQ   8.` hp x (#8  &&&  Q\  `$Times NewRomanQ ' DRAFT FINAL  AG Products 0 .     -'  :&%X:X&%%:&  ݛXBX%&&%XXB ELABGLPSubcommittee@$DraftReport;(#February6,1997  ТELABInterimMeeting$!$! (#Page  1  (e2$ 9#!  :&%X:X&%%:&   t    \R'3\  ;  N   -60'  :&%X:X&%%:&  ݛXXE1X` hp x (#XEXBX%&Ԁ&%XXB ;  dTable_A dTable_B#|xh(J#$  :&*%X:X&*%%:&*xhH  Z6Times New Roman Regular:X# e37=CIQYag1.a.i.(1)(a)(i)1)a) [_`a bdDe#fgDhs"ܪ|0fU AZ"Arial RegularFAZ"Arial Regular<77DMu:QuickFormat1F*%&*%  F*%&*%  9#!  :&%X:X&%%:&  ݛ    C  $#=CӢ,֣  .%& ELABGLPSubcommitteeInterimReport P PreparedfortheFebruary6,1997InterimMeetingoftheNELAPELABExecutiveSummary  H   &%.   A1993OfficeofInspectorGeneralreportconcerningEPAoversightofGLPlaboratorieswhosubmitdatatobeusedinAgencydecisionmakingwasverycriticaloftheamountofauditingbeingdoneandtheuniverseoffacilitiesbeingaudited.ThereportsuggestedthataccreditationmaybeamoreeffectivewaytomanagetheoversightresponsibilitiesoftheAgency.AtthissametimeaneffortwasunderwaytocreateaNationalEnvironmentalLaboratoryAccreditationProgram(NELAP)tosetstandardsandnormalizeperformanceofenvironmentallaboratoriessubmittingdatatotheAgencyaswellastomanystateandlocaldecisionmakingbodies.In1994itwasdecidedtoincludeallorganizationswhosubmitdatatoEPAintotheNELAP,includingthoseregulatedundertheGLPstandardsof40CFR160andFIFRAandTSCAprogramregulations.AsthisnewcommunitybegantointeractwiththosedevelopingNELAP,manyGLPquestionswereraisedwhichultimatelyleadtotheestablishmentofaGLPSubcommitteeinMay,1995toidentifyoptionsconcerningtheGLPcommunity.TheEnvironmentalLaboratoryAdvisoryBoard(ELAB)ϢGLPSubcommitteewasformedduringthefirstquarterof1996.    OnApril23,1996peoplefrom19differentpartsoftheGLPcommunity,7fromtheEPA,1fromUSDA,and1fromFDAmetviatelephoneconferencetodiscusstheircharterandbeginaprocessofdevelopingoptionsforconsiderationbytheELAB.ItwasdecidedthattheseoptionsweretomaintainthecurrentGLPstandards,meettheneedsoftheinteragencyandinternationalcommunity,andbecosteffectiveforSponsorsandothermembersoftheGLPcommunitytobear.WiththischargeinmindtheSubcommitteedividedintothreesubteamstoaddresseachfacetofthischargeasquicklyandefficientlyaspossible.Team1wastolookatoptionsforthelargerteamtoconsider.TheywerealsotoexaminethecurrentEPAϢGLPcomplianceprogramandusethisasaguidetobridgefrompresentpracticetopotentialoptionsforthefuture.Team2wastolookattheneedsofintergovernmentalagencies(EPA,FDA,etc.)andthoseoftheinternationalcommunity.Team3wastodevelopinformationfromacost/benefitperspectivewhichcouldbeusedtoevaluatethecosteffectivenessoftheoptionsselectedandfinallyrecommendedtotheELAB.    OnJune3,1996theGLPSubcommitteereceivedanoticefromtheEnvironmentalMonitoringManagementCouncil(EMMC)oftheEPAexpandingthecharterofthesubcommitteetoincludelookingattheGLPneedsofallFIFRAandTSCAprogramsand:  ?+u u` hp x (#X? CharacterizethelaboratoryevaluationneedsofOPPTSandOECAprograms.Evaluatefeasiblealternativestoaccreditation.Examineprogramimplementationoptions(e.g.NELAC,privatesector,federalgovernment).DeterminethebenefitsofaccreditationtoEPAandothers.DeterminehowpotentialactionswouldimpactOECDprogramsandcommitments. ,E.` hp x (#uu` XE (t"'   ,  E.` hp x (#XEC  $$CThisexpandedcharteraddedconsiderablytothescopeandsignificanceoftheworktheSubcommitteefelttheyhadbeenaskedtoaccomplish.Italsoaddedtothetimethatwouldberequiredtoaccomplishthetask. ,  B.` hp x (#XB  X+%*   ,  E.` hp x (#XEC  $$CBythetimeoftheannualmeetingoftheNationalEnvironmentalLaboratoryAccreditationConference(NELAC)inJulyof1996,theteamshadmadeconsiderableprogresstowardstheirgoals.Thirtyfivedifferentoptionshadbeenidentified.Anexcellentsummaryofwhatthekeyissueswerewiththecurrent -'- ТGLPprogramatEPAhadbeenprepared.ProgresswasbeingmadetodeterminetheneedsofotherAgenciesintheUSaswellastheinternationalcommunity.Anextensiveliteraturedatabasehadbeenaccumulated(over1200pages)fromwhichtobaserecommendationandtodevelopoptions.Astherecommendationsandoptionsweretakingshapetherequirementsforthecost/benefitdatabasewerealsobecomingclearandeffortbegantoformalizethesurveythatwouldserveasthebasisforthedatabase.AreportwaspresentedtotheELABwhichsummarizedtheprogresstodateandoutlinedthetimelineexpectedtocompletetheassignmentoftheSubcommittee. ,  B.` hp x (#XB  T    ,  E.` hp x (#XEC  $$CBetweenJulyandOctoberthecharacteristicsofeachofthe35optionswereidentifiedanddocumented.Adescriptionofthepotentialprogramalongwithitsadvantages,disadvantages,andanyconstraintsitmighthavewasprepared.TheseweresummarizedinamatrixandprovidedtotheSubcommitteeforreviewandcomment.InOctobertheentirecommitteemettogetherforthefirsttimetoreviewtheoptionsandcondensethemtoasetofmostpreferredoptionsforfutureworkandforcompletionofthecostbenefitanalysis.Thiswasaveryproductivesessionandresultedintheselectionof4optionsforfurtherworkandconsideration.Amajorconcernwasraisedatthismeetingregardingtheimpactofaccreditation/certificationmethodsorprocessesatEPAandhowtheywouldimpactworkdoneatFDA.SincemanylaboratoriessupplydatatoprogramsinbothAgenciesitwasmadeveryclearthattheimplicationofworkherewouldhaveasignificantimpactoncompatibilityofprogramsbetweenthetwoAgenciesinthefuture.StanWoollenfromFDAremindedtheSubcommitteethataccreditationandcertificationhadbeenconsideredextensivelyduringtheevaluationprocessinthe70sandearly80swhichresultedintheselectionoftheGLPsasthemostefficientandeffectivewaytobringdataqualityuptothestandardrequiredforregulatorydecisionmaking.ThisheightenedtheawarenessoftheSubcommitteeofthecriticalimplicationsoftherecommendationstheyweretocomeupwith.Progresshadalsobeenmadeontheinternationalarena.WiththereleaseofthedraftcopiesofthenewOECDGLPGuidelines,theimportanceofharmonizationeffortswasagainreinforcedtotheSubcommittee.AttheOctobermeetingthefoundationforthecostsurveywasalsofinalizedandtimelineanddistributionsystemdetermined.AttheconclusionoftheOctobermeetingitwasfeltthatmuchoftheworkofTeam1and2hadbeencompletedandthatthebigtasknowwastobettercharacterizethefouroptionsidentifiedatthemeeting.Fournewteamswereformedtopreparemoreformaldescriptionsoftheseoptions.Sincetherewasbroadinterestinsomeoftheoptionsafewpeopleworkedonmorethanoneteamduringthiswritingtime.Thefinalworkofteams1and2wasalsooutlinedwithafewpeopleworkingtofinalizethosephasesoftheproject. ,  B.` hp x (#XB      ,  E.` hp x (#XEC  $$CAsthenewteamsbeganpreparingthedescriptionsoftheoptionsafterthemeetingitbecameclearthattherewasafifthoptionthatshouldnotberuledoutyet.InaconferencecallwiththeentireteaminNovemberitwasdecidedtoaddthisfifthoptiontoourworkinglistforthenextphaseoftheprocess.Theoptionswere: ,  B.` hp x (#XB  @%$  C,B+ ` hp x (#XB Option1.ReevaluationofexistingEPAGLPcompliancemonitoringprogramswithaugmentationandincreasedfunding.Option2.ThirdpartyaccreditationforGoodLaboratoryPractices.Option3.Sponsormonitoringprogram.Option4.GLPprogramundertheumbrellaofNELAC.Option5.FIFRA/TSCAGLPTestingFacilityRegistration.  CE.` hp x (#` XEC  $$C  Theteamswereaskedtoprepareadetaileddescriptionforeachofthefiveoptionswithafulldescriptionoftheoption,asummaryofstrengthsandweaknessesoftheoption,andimplementationstrategy,andaconclusionconcerningtheoption.Asdiscussionoftheoptionscontinueditwasclearthattheoptionswere -'. notviewedequallybytheSubcommittee,howevereveryonefeltmuchmoreworkandinformationwouldberequiredbeforeafinaloptioncouldberecommended.Indeed,thequestionwasraisedastowhetheroneoftheseoptionswillemergeasafinalchoice,orifanewoptionutilizingfavoredportionsfromtheotheroptionswillemergefromthecostbenefitanalysistobedoneoverthenextfewmonths.TheseoptionsastheystandarestillverymuchworkingoptionsfortheSubcommitteeandarenotenvisionedatthistimetobereadyforfinalreleaseorrecommendation. ,  B.` hp x (#XB  x (   ,  E.` hp x (#XEC  $$CWorkoftheinteragencyandinternationalteamhasbeencompletedandagaintheimportanceofworkingcloselywithotherAgenciesandgovernmentsastheprocessiscompletedisheighten.FDAhaspreparedapositionstatementwhichclearlyindicatestheywillnotmovetoaccreditationnorwilltheyprovidecertificatesforlaboratorieswhichsupplydatafortheirconsideration.Aconsiderableamountofeffortwillyetbeneededtobalancethecurrentoptionswithbothinteragencyandinternationalrequirements. ,  B.` hp x (#XB  P    ,  E.` hp x (#XEC  $$CThecost/benefitsurveyhasbeensentoutandresultsarejustbeginningtoreturn.Thisactivityhascreatedconsiderablediscussionandconcernwithintheregulatedcommunity.Concernsoflossofcompetitiveadvantage,misuseofthedataoncegenerated,andsimplythefactthatthisinformationisnottypicallytrackedasalineiteminmostbusinesseshasmadethisparticularlychallengingfortheteam.Theyhavearrangedforawayfordatatobenormalizedtoprotecttheidentityofthoseprovidingthedataandfeelthattheynowhaveagoodsenseofcooperationwiththosewhowillbesubmittingthedata.ThereturnsareexpectedtobeintotheteambythemiddleofFebruarysothattheanalysiscanbecompletedduringthespring. ,  B.` hp x (#XB  \    ,  E.` hp x (#XEC  $$COveralltheSubcommitteehasmadeexcellentprogresswiththeproject.TheyareontracktoprovideafinalrecommendationtotheELABattheannualmeetinginJuly.ConsiderableefforthasbeenexpendedbythemembersoftheSubcommitteewhoalltookthesetasksonasaddonstoalreadyfullworkschedules.TimeconstraintshavebeenamajorbarrierforeveryonetocontendwithalongwiththefactthatwehaveteammemberslocatedallacrosstheUSA.Thisseparationbydistanceandtimehasbeenchallenging.TheuseofteleconferencingandelectronicmailhavebeentheprimarytoolsforcommunicatingandsharingoftheworkoftheSubcommittee.Severalcommitteemembersfeelthateventhoughwehavemadegoodprogressthepacehasbeenveryfast(possiblytoofast)andmoretimetodiscusswithintheregulatedcommunityandevenwithintheorganizationsparticipatingonthecommitteewouldleadtoahigherqualityproduct.WehopethattheCommitteesuseofthisreportwilldrawmoreinputfromalargerrangeofpeopletohelpresolvethisproblem.WeanticipateonemoretotalcommitteemeetinginthespringtofinalizeourrecommendationandreportfortheELABtobepresentedattheannualmeetingoftheNELACinJuly.   U *&UE1X` hp x (#XE .%&.. #bbdd  #6  2  I  .3    INTRODUCTION#6J7݌ &% Ќ <u'%!A< XXX &%..&%& #ddbb  C  Hu'%!CB.` hp x (#XB N NN B.` hp x (#XB .%& ..   g9   2  A  .3    HistoryofNELAP/GLPIssuesg9K:݌ Q("' Ќ NN! XX! &%..  &%&    NN  B.` hp x (#XB  ;  TheNationalEnvironmentalLaboratoryAccreditationConference(NELAC)helditsfirstinterim l*$) meetingDecember68,1995.ThiswasthefirstmeetingfollowingtheannouncementthatthescopeoftheNationalEnvironmentalLaboratoryAccreditationProgram(NELAP)wouldbeexpandedtoincludealltestingwhichwouldresultinsubmissionofdatatoEPA,includingtestinggovernedbyearlierGLPstatutes.Theattendanceatthemeetingfarexceededthatanticipatedby -'- theorganizers,andtheregulatedcommunityplacedmanyissuesontheflooroftheconferencewhichdidnotappeartohavebeenaddressedpreviouslybytheNELAPBoardofDirectors.TheresultsofthismeetingweretheformalestablishmentoftheNELACandtheclearindicationthatthescopeoftheNELAPwouldnotchange.ItwasalsoclearthattherewasanintentbytheNELAPtohaveanaccreditationprogramforGLPsincludedundertheirumbrellaofaccreditedprogramsbytheyear2000.JusthowtheGLPswouldfitintothisvoluntaryparticipationprogramwasnotdefinedatthattime.TheQualitySystemsbeingdevelopedfortheNELAPwerebasedontheISOGuide25PrincipleandalthoughtherearesimilaritiesbetweentheGLPsandISOGuide25Principles,therearealsosignificantdifferences.;,<݌̌ NN  ! XX!  NB.` hp x (#XB N NN  B.` hp x (#XB  FB  EarlydiscussionsbetweentheregulatorsandtheregulatedcommunityparticipatinginthemeetingcenteredaroundthepossibleinclusionofGLPsintheNELAP,nationalandinternationalperspectivesforGLPorISOGuide25accreditationprograms,expectationofvoluntaryparticipationinNELACbyindustriesalreadystatutorilyrequiredtocomplywithGLPregulations,developmentofstandardsandsystemswhichcouldmeettheexpectationsofallplayers,andcostofsuchaprogramtosmallbusinesswhichprovideessentialservicestotheindustry.LegalissuesregardingEPAsabilitytodelegateauthoritytoNELACforaccreditationprograms,toacceptdataonlyfromnonaccreditedlaboratories,toacceptuserfeestohelpdefraycostsoftheprogramstillneedtobedecided.Mostimportantlytoindustry(ParticipantsintheNELAC),iswhetherthereisanyvaluetoaddedbyincludingGLPsunderNELAP.FBB݌̌ NN  ! XX!  NB.` hp x (#XB N NN B.` hp x (#XB .%& ..   =G   2  B  .3    ELABandtheGLPSubcommittee=G!H݌ \  Ќ NN! XX! &%..  &%&    NN  B.` hp x (#XB  I  Inordertoaddressthemanyissuesraisedatthefirstinterimmeeting,theEnvironmental w' LaboratoryAdvisoryBoard(ELAB)wasestablishedbyEPAundertheFederalAdvisoryCommitteeActtoproviderecommendationsandcommenttotheAgencyontheprocessandproceduresusedtodevelopandoperatetheNELAP.TheELABallowstheEPAtoobtainadviceorrecommendationsfromthoseotherthanfulltimeequivalents(FTEs).TheELABauthorizedaSubcommitteetobeformedtoaddressGLPissuesrelatingtotheNELAP.ThiscommitteewaschargedwithdevelopingasetofrecommendationsfortheELABSconsiderationconcerningtheapplicationoftheNELAC/NELAPprogramtotestfacilitiescurrentlysubjecttotheEPAsGoodLaboratoryPracticeStandards.Thesubcommitteeconsistsof27participants(20industry/7government)representingagriculturalchemicalproductscompanies,tradeassociations,professionalorganizations,acedmia(USDA),contracttestingfacilities(laboratoryandfield),consultants,thirdpartyaccreditors,andEPA/FDA/USDA.TheSubcommitteeisjointlychairedbyamemberfromindustryandonefromtheEPA.TheSubcommitteewasorganizedandhelditsfirstmeetingonApril23,1996.IJ݌̌ NN  ! XX!  NB.` hp x (#XB N NN  B.` hp x (#XB  O  TheSubcommitteeacceptedasitscharterresponsibilitytodevelopasetofoptionsfortheELABtoconsiderandprovidearecommendationrelativetothoseoptions.ItwasagreedthattheoptionsmustmaintainGLP/QAqualityimprovementprocesses,itmusthaveinteragencyandinternationalacceptance,anditmustbecosteffective.Withtheseobjectivesinmind,theSubcommitteedecidedthefastestprogresswouldbemadebydividingactivitiesamongthemembersfordevelopmentofspecificrecommendationsforthelargerteamtocomebackanddiscuss/review.TheSubcommitteethereforedividedintothreetaskgroupstoworkonthefollowingtopics:ODP݌̌ NN  ! XX!  NB.` hp x (#XB _-'-  ;% ;;  ?+ ` hp x (#X?  %S  Group1.ProgramOptions: AssesstheeffectivenessoftheexistingEPAGLPcompliance P monitoringandenforcementprograms.Baseduponitsanalysisoftheexistingprograms,thegroupwoulddefineanddevelopthestructureforalternativeapproaches.Theseapproacheswouldinclude,butnotbelimitedto:1)accreditationeitherwithinoroutsideoftheNELAC/NELAPframework,2)afeebasedinspectionprogramoperatedbyEPAorathirdparty(s)selectedbyEPA,3)sponsorprogramsthatassesscontractfacilityperformance,4)othersthatwouldemergeintheprocess.%S@T݌̌ ;;  ! X` X!  X;?+ ` hp x (#X?  T    ;X% ;;  ?+ ` hp x (#X?  %W  Group2.International/InteragencyIssues: Exploretheinternationalandinteragency 0  implicationsofdevelopinganEPAaccreditationprogram.TheroleoftheOECDGLPprogram(i.e.specificissuesraisedbyGermany,Brazil,etc.wereastartingpoint)aswellastheimpactofaccreditationprogramsonexistingagreementsonGLPswillbeassessed.ThepreferenceofsomenonOECDcountries(i.e.Brazil)forISOGuide25asaqualitystandardinsteadoftheOECDGLPwasassessed,aswellasthefactthattheWorldTradeOrganization(WTO)recognizestheISOstandardandnottheOECDGLPsinthecontextoftheGeneralAgreementonTariffsandTrade.Assessthecurrentstate/progressofinternationalharmonizationanddeterminetheimpactthismayhaveonactionstakenbytheEPAintheUS.%WX݌̌ ;;  ! X` X!  X;?+ ` hp x (#X?     ;X% ;;  ?+ ` hp x (#X?  %o\  Nationally,therole,interaction,andparticipationoftheFDAandtheUSDAindevelopingthestructureofapossiblefutureEPAaccreditationprogrammustbeassessed.Determinetheprogressofthe RestructuringGovernmentInitiativeintheUSandassessitsimpactin 0 interagencyneeds,requirements,andexpectations.%o\\݌̌ ;;  ! X` X!  X;?+ ` hp x (#X?  8   ;X% ;;  ?+ ` hp x (#X?  %L_  Group3.Cost/BenefitIssues: AnalyzethecostoftheexistingEPAGLPprogramtothe  privatesectorandcomparethesecoststothatoftheoptionsdevelopedbyTeam1.Thebenefitsofalternativeswillbeassessed.Thisbenefitassessmentshouldinclude,butnotbelimitedtopossibleregulatoryreliefthroughreducedindustryinvestmentinqualityassurance,reducednumberofsponsorinspection/auditsofcontractfacilities,greaterfreedomtooperateeithernationallyorinternationallybysponsorsandcontractfacilities.%L__݌̌ ;;  ! X` X!  X;?+ ` hp x (#X?  <   NX NN  B.` hp x (#XB  b  TheSubcommitteeconcludedthatthischarterwasveryambitiousandthattodoaneffectivejobaconsiderableamountoftimewouldberequired.Evenwithanaggressivescheduleitwasconcludedthatafinalproductwasextremelyunlikelyuntilthemiddleof1997attheearliest.However,thetaskwasacceptedtomakethisapriorityandtomovetheworkforwardasrapidlyaspossible.buc݌̌ NN  ! XX!  NB.` hp x (#XB   B.` hp x (#XB .%& ..   e   2  C  .3    NewDirectiveef݌ @%$ Ќ ! XX! &%..  &%&   N NN  B.` hp x (#XB  #h  OnJune3,1996theELABGLPSubcommitteewasgivenanexpandeddirectivefromthe [' !& EnvironmentalMonitoringManagementCouncil(EMMC),ahighlevelEPAmanagementcouncilwithauthorityoveraccreditationissuesandotherAgencylaboratoryanddataqualityissues.TheϢGLPSubcommitteecharterwasexpandedtoincludetheauthorityandresponsibilitytoconductanindepthanalysisoftheFIFRAandTSCAGLPprograms,toanalyzeallalternatives,andmakeappropriaterecommendations.TherecommendationsweretoensurethatdataofappropriatequalityaregeneratedinacosteffectivemannerandthattheycontinuetosupportestablishedGLPprograms.TheSubcommitteesanalysisshouldinclude:#hh݌ _-'- Ќ NN  ! XX!  NB.` hp x (#XB ;% ;;  ?+ ` hp x (#X?  %pl  CharacterizingthelaboratoryneedsofOPPTSandOECAprograms,includingmeetingOECDinternationalrequirements.%pll݌̌ ;;  ! X` X!  X;?+ ` hp x (#X?     ;X% ;;  ?+ ` hp x (#X?  %en  Evaluatingfeasibleprogramdesignalternativesand/orphysicalinspections.%enn݌̌ ;;  ! X` X!  X;?+ ` hp x (#X?   L   ;X% ;;  ?+ ` hp x (#X?  %0p  Examiningprogramimplementationoptions;and%0pp݌̌ ;;  ! X` X!  ;B.` hp x (#XB ;% ;;  ?+ ` hp x (#X?  %q  DeterminingthebenefitsofaccreditationtoEPAandothers.%q#r݌̌ ;;  ! X` X!  ;B.` hp x (#XB   S *t SE1X` hp x (#XE .%&.. #bbdd   >s  (2  II  .3    GROUP1REPORT >sct݌ t  Ќ J ' H# AJ XXX (&%..&%& #ddbb  C  H CB.` hp x (#XB N NN B.` hp x (#XB .%& ..   v   2  A  .3    SummaryReportOfTeam1OfTheELABGLPSubcommittee,   December29,1996vw݌̌ NN! XX! &%..  &%&    NN  B.` hp x (#XB  y  OnApril23,1996thenewlyappointedELABGLPsubcommitteemetbyteleconference.During , thismeetingitwasdecidedthatthesubcommitteeshoulddivideintothreegroupsinordertomoreefficientlyhandlethetaskithadbeenassigned.ThistaskincludedstudyingtheneedsoftheGLPcommunityanditsregulatorswithrespecttotheproposalthatGLPcompliancebehandledwithintheauspicesofNELAP,andreportingitsfindingstotheELAB.Theyweredesignatedasfollows:yy݌̌ NN  ! XX!  N   E1X` hp x (#XE#bbdd  !|  !||݌̌    XXX#ddbb   N  B.` hp x (#XB  I}  Group1:AlternativeProgramsI}}݌ T Ќ N  ! XX!   N  B.` hp x (#XB  q~  Group2:International/InteragencyIssuesq~~݌̌ N  ! XX!   N  B.` hp x (#XB    Group3:Cost/BenefitIssues݌̌ N  ! XX!  N NN  B.` hp x (#XB    )݌̌ NN  ! XX!   NN  B.` hp x (#XB    ThefollowingisasummaryoftheactivitiesofGroup1,fromitsinceptioninApril,throughitsfinalreporttotheoverallGLPSubCommitteeonOctober13,1996.݌̌ NN  ! XX!  N   E1X` hp x (#XE#bbdd  R  Rރ݌̌    XXX#ddbb  N NN  B.` hp x (#XB  z  Group1,alsoreferredtoasTeam1,wasassignedtostudytheeffectivenessoftheexistingGLP X  programandthentoattempttodefineanddevelopthestructureofalternativeapproaches.ThirteenofthetwentytwomembersoftheGLPSubcommitteejoinedtogethertoformTeam1.TheyincludedrepresentativesfromboththeregulatedindustryandtheEnvironmentalProtectionAgency.IndividualsinvolvedrepresentedtheEnvironmentalProtectionAgency'sOfficeofComplianceandtheOfficeofPesticidePrograms,AmericanCropProtectionAssociation(ACPA),ChemicalSpecialtiesManufacturersAssociation(CSMA),NationalAllianceofIndependentCropConsultants(NAICC),SocietyofQualityAssurance(SQA),AmericanAssociationforLaboratoryAccreditation(A2LA),aswellasnumerouschemicalcompaniesandcontractlaboratories.Alistisprovidedasanappendixtothisreport(AppendixA),givingthenamesandaffiliationsofthemembersofTeam1.z݌̌ NN  ! XX!  N   E1X` hp x (#XE#bbdd  _  _݌̌    XXX#ddbb  N NN  B.` hp x (#XB    Atateleconferencecallonthe21stofMay,thisgroupsetouttoplanthebeststrategyto *X$) accomplishitsgoals.SeveralparticipantsgavereportsabouttheactivitiesofothergroupssuchasϢACPAandSQAwhoalsohavecommitteesthathaveworkedonthefeasibilityofaccreditationforlaboratories.AlsodiscussedwasthecurrentstatusoftheGLPsintheNELACQualitySystems <-&, Committee.ThesepresentationsspawneddiscussionsaboutotherworkthathasbeendonetostudyϢGLPsandaccreditation.Itbecameclearthattherewasalargereservoirofbackgroundinformationthatexistedthatcouldhelpthegroupinitsefforts.Inorderforeveryonetomakeuseofthisinformation,andforallparticipantstounderstandeachother'sdiscussions,itwasdecidedthatusefuldocumentsshouldbeidentifiedandassembledfordistributiontoall.Approximately1200pagesofpertinentdocumentswerecollectedanddistributedforreview.Thatinformation,coupledwithanewlyissueddirectivefromtheEMMCformedthebasisfordiscussionsatasecondteleconferencemeetingofthisgrouponJune4,1996.Thisextensivereferencebaseisincludedasanattatchmenttothisreport.݌̌ NN  ! XX!  N   E1X` hp x (#XE#bbdd  o  o݌̌    XXX#ddbb  N NN  B.` hp x (#XB    ThechargeofTeam1includednotonlydefinitionandanalysisofalternativeprograms,butalso   studyoftheexistingGLPComplianceMonitoringProgramandconsiderationoftheneedsofϢOPPTSandOECA.Tofacilitatetheseobjectives,Team1wasdividedintotwosmallerworkgroups.Team1AwaschargedwithstudyingtheexistingGLPprogramanddefiningtheneedsofOPPTSandOECA,whileTeam1B'sdirectivewastodefineandanalyzeallfeasibleoptionsthatcansatisfytheseneeds,aswellastheneedsofindustryandtheinternationalcommunity.݌̌ NN  ! XX!  N   E1X` hp x (#XE#bbdd    u݌̌    XXX#ddbb  N NN  B.` hp x (#XB    AworkshopwasscheduledinconjunctionwiththeNELACSecondAnnualMeeting,July2224,  1996,inWashingtonD.C.OnJuly23,1996,Teams1Aand1Bassembledforaworkingsessiontoexchangeprogressreportsandtoworktogethertodevelopanexpandedlistofalternativeprogramsor"options".Thisbrainstormingsessionresultedinthecreationofalistof35options.Whilemostnewoptionswerecloselyrelatedtoothersthathadalreadybeendiscussed,eachrepresentedsomedifferencethatcouldpotentiallychangetheadvantagesanddisadvantagesassociatedwithit.Also,thegrouprecognizedthatcertainterminologywasnotbeingdefinedconsistently,andthisresultedinconfusionduringdiscussions.Forthepurposesofunderstandingthemeaningbehindeachoftheoptions,alistofdefinitionswascreatedanddistributedtoallTeammembers.Itisincludedasanappendixtothisreport(AppendixB)andismeantonlytobeusedforclarificationofthisteam'sworkingdocuments.Finally,asetofcriteriawasdiscussedandagreeduponforallteammemberstoconsiderintheiranalysisoftheadvantagesanddisadvantagesoftheoptions.Thissetofcriteriaisalsoprovided.(seeAppendixC).݌̌ NN  ! XX!  N   E1X` hp x (#XE#bbdd    ݌̌    XXX#ddbb  N NN  B.` hp x (#XB    AtthissamemeetingofJuly23,1996,Team1Apresentedareportofitsfindingsthatincludedthe   needsofOECAandOPP.(seeAppendixD)OneoftheissuesthatwasdiscussedattheworkshopwastheconcernthatthetruescopeoftheuniverseoflaboratorieswasstillanunknowntobothindustryandtheEPA.Asofthisdate,thequestionstillremainsofwhetherthe2000laboratoriesthattheEPAhasidentifiedisarealisticnumberforuseinthedevelopmentofacompliancemonitoringprogram.݌̌ NN  ! XX!  N   E1X` hp x (#XE#bbdd  4  4݌̌    XXX#ddbb  N NN  B.` hp x (#XB  \  Aftertheworkshop,eachoftheparticipantswasassignedseveraloptionsforindepthstudy.A & & matrixwascreatedthatincludedall35options,andaskeletonsetofadvantages,disadvantagesandconstraintsforeach.ThismatrixwasdistributednotonlytothemembersofTeam1,butalsotoTeams2and3forthemtoaddtheircomments.AfinalversionofthismatrixisincludedasAppendixE.\ӡ݌̌ NN  ! XX!  N   E1X` hp x (#XE#bbdd    ݌̌    XXX#ddbb  N NN  B.` hp x (#XB  ,  AtameetingoftheoverallELABGLPSubCommitteeinBaltimore,MDonOctober13,1996,  ,%, Team1presentedtheresultsoftheirstudytotheentiresubcommittee.Thegroupasawholediscussedthesimilarityofmanyoftheoptionsandagreedthatthelistcouldbecollapsedintofour -'. basicprogramtypes,underwhichallofthevariousalternativeswouldfall.Oncethesefourprogramtypesweredefinedandlisted,ananonymousvotewastakenwherebyeachparticipantwasgiventenpointstodivideupamongthefouroptions.Anindividualwouldassignmorepointstotheprogramtypehe/shefavored,andlesstoonehe/shedidnot.Thisvoteresultedinapreliminaryrankingofthealternativeprogramtypes.Atthispoint,Team1wasdisbanded,itsobjectiveshavingbeenmet.Thedevelopmentoffeasiblealternativesunderthefourbasicprogramtypeswasassignedtonewteams,composedofthesamesubcommitteemembers,andisinprogressatthistime.,݌̌ NN  ! XX!  NB.` hp x (#XB N NN B.` hp x (#XB .%& ..   t   2  B  .3    ELABGLPSubcommitteeGroup1ADraftSummaryReporttX݌    Ќ NN! XX! &%..  &%&   NB.` hp x (#XB%& ; ;; ?+ ` hp x (#X? XBX XBXXXB   \  &%XB2  1  .3    Goals\:݌   Ќ ;;! X` X! & h   &%% ;;  ?+ ` hp x (#X?  %ů  Studyexistingcomplianceinspectionprogram%ů9݌ W  Ќ ;;  ! X` X!  % ;;  ?+ ` hp x (#X?  %  Gatheradditionalstatisticstodefineprogram%l݌̌ ;;  ! X` X!  % ;;  ?+ ` hp x (#X?  %  CharacterizelabevaluationneedsofOPPandOECA%݌̌ ;;  ! X` X!  % ;;  ?+ ` hp x (#X?  %A  %A݌̌ ;;  ! X` X!   ;; ?+ ` hp x (#X? XBX%& XBXXXB   &%XB4   2  2  .3    ExistingComplianceInspectionProgram41݌  Ќ ;;! X` X! &%& &%&   ;'   ?+M M ` hp x (#X?   '  a). M Objective:ForalldatageneratedandsubmittedtoEPAunderFIFRAsections3,4,5,8,18  and24andundersections4and5ofTSCA,'=݌̌   ! XM M ` X!   '   ?+M M ` hp x (#X?   'w  'w݌ K Ќ   ! XM M ` X!   (   ?+9 M ` hp x (#X?   (  1)assurethatfacilitiesconductingstudiesareincompliancewithEPAGLPregulations;(*݌̌   ! X9 M ` X!   (   ?+9 M ` hp x (#X?   (  2)assurethatdatasubmittedtoEPAhavebeenconductedincompliancewithEPAGLPregulations;(݌̌   ! X9 M ` X!   (   ?+9 M ` hp x (#X?   (  3)assuretheintegrity,qualityandvalidityofdatathathavebeensubmitted.(݌̌   ! X9 M ` X!   '   ?+M M ` hp x (#X?   '  's݌  Ќ   ! XM M ` X!   '   ?+M M ` hp x (#X?   '  b). M CurrentProgramDescription1995Data'݌ s Ќ   ! XM M ` X!   '   ?+M M ` hp x (#X?   's  's݌ O Ќ   ! XM M ` X!   (   ?+9 M ` hp x (#X?   (  1)Staffing17fulltimeequivalents(FTE),10whichconductinspectionsandaudits.(DoesnotincludeFDAinspections.)(&݌̌   ! X9 M ` X!   (   ?+9 M ` hp x (#X?   (2  (2݌ 3"  Ќ   ! X9 M ` X!   (   ?+9 M ` hp x (#X?   (U  2)Numberofinspectionsperformed82(4byFDA).(U݌̌   ! X9 M ` X!   (   ?+9 M ` hp x (#X?   (  (݌ #" Ќ   ! X9 M ` X!   (   ?+9 M ` hp x (#X?   (  3)Travelbudget$100,000.(>݌̌   ! X9 M ` X!   (   ?+9 M ` hp x (#X?   (  (k݌ %S$ Ќ   ! X9 M ` X!   (   ?+9 M ` hp x (#X?   (   4)Outsidecontractorsarenotused.( ݌̌   ! X9 M ` X!   (   ?+9 M ` hp x (#X?   (A  (A݌ [' !& Ќ   ! X9 M ` X!   (   ?+9 M ` hp x (#X?   (d  5)OECAhasdeterminedthatthereare2,000facilitiesinvolvedindatadevelopmentforsubmissiontoEPAunderGLP.StatisticsprovidedforFiscalYears19931995showed3,040facilitiessubmitteddata(Table1).2,261(74.4%)ofthe3,040facilitiessubmitted5orfewerstudiesduringthat3yearperiod(Table2).1,703(56%ofthe3,040facilitiessubmitted2,orfewerstudiesduringthat3yearperiod.(d݌̌   ! X9 M ` X!   (   ?+9 M ` hp x (#X?   (  (݌ ,3&, Ќ   ! X9 M ` X!   (   ?+9 M ` hp x (#X?   (:  6)Eachtestsiteinastudyiscountedasafacility.Facilitieswhichareontimefieldsites _-'- areincluded.During19931995,1,195or39.3%ofthefacilitieswereinvolvedinonly1submittedstudy.(:݌̌   ! X9 M ` X!   (   ?+9 M ` hp x (#X?   (*  (*݌  Ќ   ! X9 M ` X!   (   ?+9 M ` hp x (#X?   (M  7)OECAdoesnothavethestafforbudgettoinspectall2,000facilities.Table3showprojectionsofbudgetandstaffrequirementstoachieveinspectionfrequenciesof2,3,or5yearintervals.Eventhelongestinterval(5years)wouldrquirestaffingandabudgetatgreaterthan4timesthe1995level.(M݌̌   ! X9 M ` X!   (   ?+9 M ` hp x (#X?   (  (݌ T  Ќ   ! X9 M ` X!   (   ?+9 M ` hp x (#X?   (  8)AsanoutcomeofcriticisminanearlierreportfromtheOfficeoftheInspectorGeneral,thecurrentsystemdoesnottargetlabswhosubmitmostofthestudies.Thisshouldbereevaluatedinviewofthecurrentsituationandtheneedtomaximizeeffectivenessofresources.(;݌̌   ! X9 M ` X!   (   ?+9 M ` hp x (#X?   (  (a݌ P  Ќ   ! X9 M ` X!   (   ?+9 M ` hp x (#X?   (  9)Thereisnomandateforinspectionof100%offacilities.(݌̌   ! X9 M ` X!   (   ?+9 M ` hp x (#X?   (O  (O݌ X  Ќ   ! X9 M ` X!   (   ?+9 M ` hp x (#X?   (r  10)OECAusesOPPsdatabasefordeterminelabstobeinspected.Thereisnoregistrationprogramforlabs.Theresultisthelagtimefromwhenthelaboratorystartsdevelopingdataforsubmissiontothetimewhenstudiesareactuallysubmitted.(r݌̌   ! X9 M ` X!   (   ?+9 M ` hp x (#X?   (  (݌ x Ќ   ! X9 M ` X!   (   ?+9 M ` hp x (#X?   (  11)TheOECAcomplianceinspectionprogramissupplementedbyinspection/monitoringdonebyQAUnitsofsponsorcompanies.Thistypicallyincludesonsiteinspectionofeachfacilitiy,protocolreview,reportreviewand,insomecases,datareview.ThisisallinadditiontothefacilityQAUmonitoringspecifiedinGLPs.(%݌̌   ! X9 M ` X!   (   ?+9 M ` hp x (#X?   (  (݌  Ќ   ! X9 M ` X!   ; ;; ?+ ` hp x (#X? XBX%& XBXXXB   &%XB2  2  3  .3    LabEvaluationNeedsofOECA,OPPandIndustry2/݌  Ќ ;;! X` X! &%& &%&   ;'   ?+M M ` hp x (#X?   '  a). M OECA'9݌ l Ќ   ! XM M ` X!   '   ?+M M ` hp x (#X?   '  'w݌ H Ќ   ! XM M ` X!   (   ?+9 M ` hp x (#X?   (&  1)Toinspect2,000labsaccordingtothecurrentprogramdefinition,additionresourcesarerequiredaslistedinTable3.(&݌̌   ! X9 M ` X!   (   ?+9 M ` hp x (#X?   (  (4݌ ,  Ќ   ! X9 M ` X!   (   ?+9 M ` hp x (#X?   (  2)AmeanstoaccuratelyidentifyallfacilitiescurrentlygeneratingdataforsubmissiontoEPA.(W݌̌   ! X9 M ` X!   (   ?+9 M ` hp x (#X?   (G  (G݌ "p! Ќ   ! X9 M ` X!   '   ?+M M ` hp x (#X?   'x  b). M OPPPrioritiesforComplianceInspections'x݌ #L" Ќ   ! XM M ` X!   (   ?+9 M ` hp x (#X?   (  (k݌ x$(# Ќ   ! X9 M ` X!   (   ?+9 M ` hp x (#X?   (   1)Studiesunderwayonchemicalsforwhichregulatorydecisionsarepending.( ݌̌   ! X9 M ` X!   (   ?+9 M ` hp x (#X?   (i  (i݌ 0&% Ќ   ! X9 M ` X!   (   ?+9 M ` hp x (#X?   (  2)Longtermandfieldstudies.(݌̌   ! X9 M ` X!   (   ?+9 M ` hp x (#X?   (  (>݌ '!' Ќ   ! X9 M ` X!   (   ?+9 M ` hp x (#X?   (  3)FacilitieswithlargenumbersofFIFRA/FFDCAstudiesunderway.(a݌̌   ! X9 M ` X!   (   ?+9 M ` hp x (#X?   (5  (5݌ )P#) Ќ   ! X9 M ` X!   (   ?+9 M ` hp x (#X?   (X  4)InspectorstrainedinconductingstudiesofthetypetheyinspecttoallowthemtofocusonmeaningfulviolationsandpermitthemtoprovideOPPinformationregardingtheimportanceofproblemsobserved.(X݌̌   ! X9 M ` X!   (   ?+9 M ` hp x (#X?   (9  (9݌ -&- Ќ   ! X9 M ` X!   ;% ;;  ?+ ` hp x (#X?  %j  c). ` IndustryPrioritiesforaComplianceInspectionProgram%j݌ -'. Ќ ;;  ! X` X!  ;(   ?+9 M ` hp x (#X?   (  (M݌ P Ќ   ! X9 M ` X!   (   ?+9 M ` hp x (#X?   (  1)Effectivemonitoringtoassuredataintegrity.(p݌̌   ! X9 M ` X!   (   ?+9 M ` hp x (#X?   (0  (0݌  Ќ   ! X9 M ` X!   (   ?+9 M ` hp x (#X?   (S  2)Addedvalueforanyprogramchangeswhichresultinincreasedcoststoindustry.(S݌̌   ! X9 M ` X!   (   ?+9 M ` hp x (#X?   (  (9݌  p Ќ   ! X9 M ` X!   (   ?+9 M ` hp x (#X?   (  3)MaintainGLPsasaneffectivequalitymanagementprogramandQAU.(\݌̌   ! X9 M ` X!   (   ?+9 M ` hp x (#X?   (3  (3݌ x ( Ќ   ! X9 M ` X!   (   ?+9 M ` hp x (#X?   (V  4)Providecreditforindustrymonitoringofcontractfacilities.(V݌̌   ! X9 M ` X!   (   ?+9 M ` hp x (#X?   (  (*݌ 0  Ќ   ! X9 M ` X!   (   ?+9 M ` hp x (#X?   (  5)Reevaluatenumberandtypesoflabsthatneedinspectiontomaximizeutilizationofresources.Justifydecisionsasbusinessesmusttotodayseconomy.(M݌̌   ! X9 M ` X!   (   ?+9 M ` hp x (#X?   (z  (z݌ t  Ќ   ! X9 M ` X!   (   ?+9 M ` hp x (#X?   (  6)Avoidexcessiveburdensonsmallbusinessbyavoidingduplicativeprograms.( ݌̌   ! X9 M ` X!   B.` hp x (#XB#XBX%&k#   B.` hp x (#XB .XXB ..      &  2  C  .3    Group1bReportAlternativePrograms e ݌ \  Ќ ! XX! XBX.. XBXXB   B.` hp x (#XB&%XXB ; ;; ?+ ` hp x (#X? XBX%& XBXXXB   b    2  1  .3    Option1ExistingEPAFIFRAAndTSCAGLPComplianceMonitoring 2 ProgramWithAugmentationAndIncreasedFundingb @݌̌ ;;! X` X! &%XB  &%&    ;; ?+ ` hp x (#X?      INTRODUCTION:~݌ @ Ќ ;;! X` X!    % ;;  ?+ ` hp x (#X?  %<  ThecurrentEPAFIFRAandTSCAGoodLaboratoryPractice(GLP)compliancemonitoring  programisawellestablished,effective,nationallyandinternationallyrecognizedprogramfor' \ monitoringscientificresearch.ItisdesignedtoassurethequalityandintegrityofGLPstudiesdoneinthelaboratoryorintheenvironmenttosupportthesafetyand,insomecases,theefficacyofproducts.StrongelementsoftheGLPprogramforverifiabilityandϢreconstructabilityare:%<݌̌ ;;  ! X` X!  ;   ?+u u` hp x (#X?  L  L݌̌   ! Xuu` X!  '   ?+M M ` hp x (#X?   'M  ݄ M EPAOfficeofEnforcementandComplianceAssurance(OECA)/OfficeofCompliance   (OC)conductperiodiconsiteinspectionsanddataauditsoffacilitiesforcompliance'M݌̌   ! XM M ` X!   '   ?+M M ` hp x (#X?   '$  ݄ M ArchiveandretentionrequirementsareincludedforallcompletedGLPstudies'$݌ "S  Ќ   ! XM M ` X!   '   ?+M M ` hp x (#X?   '  ݄ M AnindependentQualityAssuranceUnit(QAU)isrequiredtocontinuallymonitorforGLP #/! complianceandkeepGLPstudymanagementinformedofcorrectiveaction,ifneeded.[Note:ThisincludesareviewofeachGLPstudyprotocol,data,andthefinalreport,aswellasmonitoring/inspectingatleastoneandoftenmanycriticalphases].QAUmonitoring/inspectingsupplementstheEPAOECA/OCGLPcomplianceprogram.'%݌̌   ! XM M ` X!      ?+u u` hp x (#X?    ݌̌   ! Xuu` X!  ;% ;;  ?+ ` hp x (#X?  %  Over13yearsofexperiencesincetheinceptionoftheEPAFIFRAandTSCAGLPfederalregulationshavedemonstratedthatthequalityandconsistencyoffinalreportssubmittedtoEPAhasimproved.%݌̌ ;;  ! X` X!  ;   ?+u u` hp x (#X?  [  [݌̌   ! Xuu` X!  ;% ;;  ?+ ` hp x (#X?  %\  Withtheinclusion,over8yearsago,offieldstudiesintherevisedEPAGLPprogram,thenumberofGLPlaboratories/facilitiesidentifiedbyEPAforonsiteinspectionsanddataauditsincreasedtoover2000.%\݌ -'- Ќ ;;  ! X` X!  ;   ?+u u` hp x (#X?  I!  I!!݌̌   ! Xuu` X!  ;% ;;  ?+ ` hp x (#X?  %J"  EPAOECA/OCGLPonsiteinspectionsdonotcurrentlyfocusonlyontheprimary/majordatageneratingfacilities.%J""݌̌ ;;  ! X` X!  ;   ?+u u` hp x (#X?  #  #5$݌̌   ! Xuu` X!  ;% ;;  ?+ ` hp x (#X?  %$  OneofthedifficultiesnotedbytheEPA'sOfficeoftheInspectorGeneral(OIG)wasthatthefrequencyofEPAonsiteGLPmonitoringofthelargenumberoffacilitieswasnotsufficient.EPAGLPmonitoringinspectors(initially20fulltimeequivalents,currently11fulltimeequivalents)aswellasresourcesarenotsufficienttoallowonsiteGLPinspectionfrequenciestosatisfyallconstituencies,includingthosewithinternationalrequirements.%$6%݌ ;;  ! X` X!  ,;B.` hp x (#XB       ;, ;; B+ ` hp x (#XB   (   &  DESCRIPTIONOFOPTION:((݌ P Ќ ;;$ X` X$    % ;;  B+ ` hp x (#XB  %x)  Thisoptionwillpreservetheintegrityandstructureoftheexisting,nationallyand  internationallyrecognizedEPAGLPcomplianceprogram.ThisoptionmaximizestheeffectivenessofthecurrentEPAGLPcomplianceprogramthroughaugmentationproceduresandfundstoincreasethenumberoffacilitiesinspectedonsitebyEPAinspectors.UnderthisOption,facilitieswouldbeabletorequestanauditasneededtoremainincompliancewithgovernmentprogramsaroundtheworld.Iftheyexercisethisoption,theywouldbeexpectedtopayallcostsassociatedwiththeinspectionandaccompanyingreport.%x))݌̌ ;;  $ X` X$  ;   B+u u` hp x (#XB  ,  ,n-݌̌   $ Xuu` X$  ;% ;;  B+ ` hp x (#XB  %-  TheexistingEPAOECA/OCGLPcompliancemonitoringprogramiscontinuedbutinitiallyaugmentedbyredefiningthescopeofthefacilities.Subsequently,theoptioncouldbeexpandedbyobtainingtargetedfundsfroma"DirectedEPAOECA/OCInspectionFee."Theseadditionalfundscouldbeusedinsupportingthecurrentfocusontheprimary/majordatageneratingfacilities,whilestillprovidingasufficientincreaseintargetedresourcesformonitoringsmallerdatagenerators.%-u.݌̌ ;;  $ X` X$  ;E.` hp x (#XE ; ;; ?+ ` hp x (#X?   @1   IMPLEMENTATIONSTRATEGY:@11݌  Ќ ;;! X` X!    % ;;  ?+ ` hp x (#X?  %2  ThecurrentEPAGLPcompliancemonitoringprogramofonsiteEPAinspectionsanddata 2 auditsaswellasindependentQAUmonitoringandinspectingforGLPcompliancewouldcontinuetobeinplace.ToinitiallyaugmentthecurrentEPAGLPcompliancemonitoringprogram,thescopeandfocusoftheEPAonsiteinspectionsisredefined.Theapproximately2000GLPlaboratories/facilities,asdefinedbyinformationfromFranciscaLiem,EPA,includeseachfacilityandeachsubcontractedtestsitenotedintheSponsor'sfinalreport.Thefacilitycouldberedefinedasafacilitywithstudydirector(s).Byredefiningthefacility,thetotalnumberofGLPfacilitiesforinspectiononsitebyEPAisreduced,althoughtheoptiontovisittestsitesaspartofthefacilityismaintained.%22݌̌ ;;  ! X` X!  ;   ?+u u` hp x (#X?  6  697݌̌   ! Xuu` X!  ;% ;;  ?+ ` hp x (#X?  %7  InformationprovidedbyFranciscaLiem,EPA,notedthatforfiscalyears1993throughl995,74percentofthelistedfacilities/sitessubmitted5orfewerGLPstudies,56percentsubmitted2orfewerGLPstudies,and39percentsubmittedonly1GLPstudy.ThefocusofEPAonsiteGLPinspectionsshouldbecontinuedonthefacilitiesthataretheprimary/majordatageneratingfacilities,althoughtheoptiontovisitotherdatageneratingfacilitiesismaintained.ThecombinationoftheGLPfacilitydefinition,asnotedabove,andthebroadeningoftheonsiteEPAGLPinspectionfocus,asnotedhere,couldbeimplementedbyEPAwithareasonableeffortandwithinareasonableperiodoftime.Theseinitialaugmentationprocedureswill maximizetheeffectivenessofthecurrentEPAGLPcomplianceprogram.%7:8݌̌ ;;  ! X` X!  ;   ?+u u` hp x (#X?  <  <<݌̌   ! Xuu` X!  ;% ;;  ?+ ` hp x (#X?  %=  Subsequently,theoptionexpansioncallsfora"DirectedEPAOECA/OCInspectionFee."TheincreasedfundscouldbeobtainedasanallocationofEPA'sOECAbudget.ThisallocationwouldrecognizethatthecurrentOECA/OCMresourcesarenotsufficientforonsiteGLPinspectionfrequenciestosatisfyallconstituencies.AnalternativefundingsourcecouldbethroughanadditiontotheregistrationfeeforFIFRAorTSCApetitions.AnappropriatefeecouldbedeterminedbyEPAindiscussionswiththeregistrantsandagreeduponbeforeimplementation.AthirdalternativefundingsourcecouldbethroughaGLPinspectionfeepaidbytheGLPfacility.ThisapproachissimilartotheGLPinspectionschemeimplementedin -f'. МGermany,SwitzerlandandtheUnitedKingdom.Thefeestructuremighttakeintoaccountthecomplexityoftheinspectionandthusbeadjustedaccordingly.This"directed"fee,fromanyofthealternativesourcesnotedhere,wouldrequirecongressionalauthorizationandmaythereforerequiresometimeforimplementation.This"directed"feeneedstobefullydedicatedanddirectlychanneledtotheEPAOECA/OC.ItwouldbestrictlyusedtoallowanincreaseinthenumberofEPAGLPinspectorsinOECA/OCtoincreasethenumberoffacilitiesinspectedonsitebyEPAinspectors.Theamountofthedirectedfeeshouldbesufficientandreasonable.%==݌̌ ;;  ! X` X!  ;B.` hp x (#XB ; ;; ?+ ` hp x (#X?   C   STRENGTHS:CtD݌ 0  Ќ ;;! X` X!    % ;;  ?+ ` hp x (#X?  %1E  Thisoptionwaschosenasthemostfavorableovertheotherproposedoptionsbecauseitwould   preservetheintegrityandstructureofthecurrentEPAOECA/OCGLPcompliancemonitoringprogramandbetheleastdisruptive.ThisapproachmaintainstheharmonizationoftheGLPstandardsbothnationallyandinternationally.Thisapproachremovesthejurisdictionalconcernofincludingafederallymandated,wellrecognized(nationallyandinternationally),programunderavoluntarystateparticipatoryNELACprogram.Withareasonableeffort,EPAcouldinitiallyaugmentthecurrentOECA/OCGLPcomplianceprogrambyredefiningtheGLPfacilities,andfocusingonsiteEPAGLPinspectionsontheprimary/majordatageneratingfacilities.ThiswouldenhancetheeffectivenessandresourceutilizationofthecurrentEPAGLPcomplianceprogram.ItwouldalsoaugmenttheharmonizationeffortsoftheinternationalGLPcommunityandprovideconsistencywiththeircurrentrevisioneffortsunderconsideration.%1EE݌̌ ;;  ! X` X!  ;   ?+u u` hp x (#X?  ;J  ;JJ݌̌   ! Xuu` X!  ;% ;;  ?+ ` hp x (#X?  %݌̌   -` XM M ` X-      K+u u` hp x (#` XK    @݌ t-$'. Ќ   -` Xuu` X-  '   K+M M ` hp x (#` XK   '   M Thereisaneedtomaintainconfidentialityandavoidconflictorinterests.HoweverwiththisprogramthelaboratoryhastherighttorequesttheassignmentofanotherassessorifaconflictofinterestexistsandOECAapprovaldependsonacceptableaccreditorconfidentialityprocedures.'{݌̌   -` XM M ` X-      K+u u` hp x (#` XK  P  P݌̌   -` Xuu` X-  '   K+M M ` hp x (#` XK   'i   M Issuessurroundingsponsorliabilityundertheenforcementpolicy,andtheresponsibilityoftheaccreditingbodiestoreportfindingstotheaccreditingauthorityarebeyondthescopeofthisdiscussionandstillremainunresolved.'i݌̌   -` XM M ` X-      K+u u` hp x (#` XK    ݌̌   -` Xuu` X-  '   K+M M ` hp x (#` XK   '   M Theissueofwhetherthisprogramshouldbemandatoryorvoluntaryneedsfurtherdiscussion.Asavoluntaryprogram,thedecisiontoparticipterestswiththelaboratoryandonlythoselaboratoriesinterestedintheinternationalbenefitsofthisprogrammaywanttoparticipate.HoweveravoluntaryprogramwouldnotassistindefiningtheuniverseofGLPlaboratoriesorensureanadequateauditfrequencyfornonparticipatinglaboratories.TheEPAwouldhavetomaintaintheircompliancemonitoringprogramandacquirethenecessaryresourcestomeettheexpectedauditfrequency.';݌̌   -` XM M ` X-   T4` hp x (#` XT '   K+M M ` hp x (#` XK   '  5. M Conclusion'8݌  Ќ   -` XM M ` X-   T4` hp x (#` XT '   K+M M ` hp x (#` XK   '   M ThedevelopmentofathirdpartyaccreditationprogramforGLPspromotestheuseoftheGLPstandardswhichensurescontinuedOECDharmonizationandinternationalacceptanceoftestdata.RelianceonthirdpartyaccreditorsfostersincreasedinspectionfrequencyandaddressestheconcernsoftheInspectorGeneralandtheinternationalcommunity.AfederalagencyremainsastheAccreditingAuthorityandEnforcementEntity.Thisprogramwouldbeacceptedinternationally.Theaccreditationcostsappearreasonableandthetimetoimplementtheprogramminimal.'݌̌   -` XM M ` X-   N.` hp x (#` XN ; ;; ?+ ` hp x (#X? XBX%& XBXXXB   m   2  3  .3    OPTION3SPONSORMONITORINGPROGRAMmK݌ R Ќ ;;! X` X! &%XB  &%&    ;; ?+ ` hp x (#X?      Introduction8݌   Ќ ;;! X` X!    % ;;  ?+ ` hp x (#X?  %  ThecurrentEPAlistoffacilitiesgeneratingGLPdataisover2000facilities,andtheEPAdoes  w nothaveadequatestaffandresourcestoinspectthemallonaregularschedule.Thislistisgeneratedbylistingstudytestingfacilitiesplusallsubcontractedtestsitesidentifiedinthefinalreports.BasedoninformationfromFranciscaLiemoftheEPA,themajorityofthesetestsitesgenerateonlyasmallamountofthedata.Currently,theEPAdoesnotprioritizetheirinspectionscheduletofocusonfacilitiesthatgeneratethemajorityoftheGLPdata.%i݌̌ ;;  ! X` X!  ;   ?+u u` hp x (#X?  A  A݌̌   ! Xuu` X!  ;% ;;  ?+ ` hp x (#X?  %B  ThisOptionutilizesexistingEPAandSponsorinspectionprogramsbyaddinganinspectionsharingpartnershipbetweenEPAandSponsors.EPAwouldprioritizetheirinspectionschedulestofocusonregularinspectionsofSponsors,testingfacilitieswithstudydirectorsandfacilitiesthatgeneratethemajorityoftheGLPdata.EPAwouldestablishadatabaseofSponsorsGLPinspectionschedulestotrackthenumberofSponsorsinspectionsatcontractfacilities.ThisinformationwouldsupplementEPAsinspectionsandhelptoprioritizetheneedforEPAinspectionsattheremainingtestsites.%B݌̌ ;;  ! X` X!  ;   ?+u u` hp x (#X?    ݌̌   ! Xuu` X!  ;% ;;  ?+ ` hp x (#X?  %  EPAwouldretainfullauthorityforGLPComplianceMonitoringandtheoptiontoinspectall -['. testsitesgeneratingGLPdata.ByprioritizingandutilizinganinspectionsharingpartnershipwithSponsors,theEPAwouldbemuchmoreeffectiveinadequatelyinspectingtestingfacilitiesthatgeneratethemajorityoftheGLPdata.%݌̌ ;;  ! X` X!  ;   ?+u u` hp x (#X?    o݌̌   ! Xuu` X!  ;% ;;  ?+ ` hp x (#X?  %  CostsassociatedwiththisOptionwouldbeminimalforbothEPAandSponsors.%p݌̌ ;;  ! X` X!  ;   ?+u u` hp x (#X?  J  J݌̌   ! Xuu` X!  ;% ;;  ?+ ` hp x (#X?  %K  Withthisfocusontheirinspectionschedule,EPAsGLPmonitoringprogramwouldbecomparabletocurrentpracticesinusebyFDAandInternationalAgencies.%K݌̌ ;;  ! X` X!  ;B.` hp x (#XB ; ;; ?+ ` hp x (#X?   =   DescriptionofOption3SponsorMonitoringProgram=݌    Ќ ;;! X` X!    % ;;  ?+ ` hp x (#X?  %  TheexistingEPAGLPComplianceMonitoringProgramiscontinuedwiththeadditionofan c  inspectionsharingpartnershipbetweenEPAandSponsors.%݌̌ ;;  ! X` X!  ;   ?+u u` hp x (#X?  M  M݌̌   ! Xuu` X!  '   ?+M M ` hp x (#X?   'N  ݄ M Sponsorscontinuetoinspecttheirsubcontractedtestsitesascurrentlyisdone.Underboth G  FDAandEPAGLPregulations,SponsorsareassignedresponsibilityforGLPcomplianceregardlessofwherethestudyisconducted.Inresponsetothisrequirement,Sponsorsdevelopedinspectionprogramsfortheircontractfacilities,andtheymustattesttotheGLPcomplianceofstudywhenitissubmittedtotheAgency.'N݌̌   ! XM M ` X!   &   <(9 9 hp x (#X< K  &*  &*݌ C Ќ   ! X9 9 X! K  '   ?+M M ` hp x (#X?   'X  ݄ M EPAwouldcontinuetheirinspection/auditprogramingenerallythesamemanner,buttheir o targetingschemefromthelistof2000plusfacilitieswouldbealtered.EPAwouldprioritizetheirinspectionscheduletofocusoninspectionsofSponsorsandtestingfacilitieswithstudydirectors,butwouldretaintheoptiontoinspectanytestsite.'X݌̌   ! XM M ` X!   &   <(9 9 hp x (#X< K  &  &n݌  Ќ   ! X9 9 X! K  '   ?+M M ` hp x (#X?   '  ݄ M Asanewresponsibilityundertheinspectionsharingpartnership,registrantswouldbe k requiredtoreporttotheAgencyeachtimetheyvisitedandevaluatedacontractfacility,preferablyinanestablishedelectronicformat.EPAwouldthenincorporatethisinformationintoadatabase.Presumingalaboratory/testsitewasevaluatedwithsomeregularity,thetestsitewouldnotgenerallybeinspectedbyEPA,thoughitwouldhavetheoptiontodosoatanytime.Ifatestsitewerenotvisitedregularlybymultiplesponsors,presumablythattestsitewouldbetargetedforinspectionsoonerthanonethathasbeenthoroughlyevaluatedbyseveralregistrants.'݌̌   ! XM M ` X!   &   <(9 9 hp x (#X< K  &  &s݌ "K! Ќ   ! X9 9 X! K  '   ?+M M ` hp x (#X?   '"  ݄ M EPAsinspectionsaretheprimaryenforcementtypeinspections.EPAretainsfull w#'" responsibilityforallaspectsofcompliancemonitoringandisnotdependentonthequalityoftheinspectionsofanyonesponsor.IndustrysinspectionsservetosupplementtheEPAsinspections,notreplacethem.'"݌̌   ! XM M ` X!   B.` hp x (#XB ; ;; ?+ ` hp x (#X?      ImplementationStrategy[݌ 's!' Ќ ;;! X` X!    % ;;  ?+ ` hp x (#X?  %#  SponsorswouldreporttheirGLPcomplianceinspectionschedulesofcontractfacilitiestothe j)#) EPA,preferablyinaestablishedelectronicformat.Informationreportedwouldbestandardizedandincludethedate(s)ofvisit(s),lengthofvisit,systemsandtypesofoperationsobserved,andpertinentinformationotherthaninspectionfindings.Asdescribedunder@Inspectionofa +%, testingfacility:intheGLPStandards,the@qualityassuranceunitrecordsoffindingsandproblems,ortoactionsrecommendedandtaken,:wouldnotbeprovided.%#݌ -f'. Ќ ;;  ! X` X!  ;   ?+u u` hp x (#X?    ݌̌   ! Xuu` X!  ;% ;;  ?+ ` hp x (#X?  %  EPAwouldthenincorporatethisinformationintoadatabase.EPAwouldfocustheirinspection/auditresourcesfirstonSponsorsandtestingfacilitieswithstudydirectors.Asresourcespermit,routineinspectionswouldbedirectedatfacilitiesthatgeneratethemajorityofGLPdata.Presumingalaboratory/testsitewasevaluatedwithsomeregularitybymultiplesponsors,thetestsitewouldnotgenerallybeinspectedbyEPA,thoughtheyhavetheoptiontodosoatanytime.Ifatestsitewerenotvisitedregularly,presumablythattestsitewouldbetargetedforinspectionsoonerthanonethathasbeenthoroughlyevaluatedbyseveralregistrants. %݌ T  Ќ ;;  ! X` X!  ;B.` hp x (#XB ; ;; ?+ ` hp x (#X?      Strengths  ݌    Ќ ;;! X` X!   % ;;  ?+ ` hp x (#X?  %   ThisOptiontakesintoconsiderationthenumerousevaluationsofcontractlaboratoriesand c  facilitiesbystudysponsors,sothattheAgencymightnothavetoexpendlimitedresourcesonlaboratorieswhichhavebeenthoroughlyevaluated. Byrecognizingsponsorsinspectionsas k  asupplementalpartoftheirprogram,inspection/auditingscheduleisgreatlyenhanced.EPAcanprioritizetheirinspectionstofocusontestingfacilities(withstudydirectors),analyticallaboratories(involvedwithmanysponsors),andtestsiteswheretherearesuspectedorobviousproblems. % @ ݌  Ќ ;;  ! X` X!  ;   ?+u u` hp x (#X?  Q  Q݌̌   ! Xuu` X!  ;% ;;  ?+ ` hp x (#X?  %U  ThereportingprocesswillresultinaminorincreaseincosttoGLPregulatedcommunityandpotentialcostbenefit.SponsorcompaniescurrentlymonitorthetestsitesinvolvedintheirstudiesbecausetheyhavetheprimaryresponsibilityforGLPcomplianceofastudyeveniftheworkisconductedbyacontractfacility.ExistingGLPregulations(FDAsandEPAsFIFRA,TSCA)assignedthisresponsibilitytoSponsors,andindustryrespondedbymonitoringcontractfacilitiesthatgenerateGLPdata.ItwasreinforcedbyEPAsEnforcementResponsePolicy,wheremonetaryfinesandpenaltiesaremuchgreaterforSponsorsthanforcontractfacilities. %U݌ k Ќ ;;  ! X` X!  ;   ?+u u` hp x (#X?    r݌̌   ! Xuu` X!  ;% ;;  ?+ ` hp x (#X?  %  QualityofGLPdataremainshighbecauseexistingprogramsdonotreallychange.(Undertheexistingprogram,thequalityofdatahasbeenconsideredgood.TheconcernhasbeenwiththenumberoffacilitiesandnotbeingabletoscheduleAgencyinspectionsonaregularbasis.) %v݌ + Ќ ;;  ! X` X!  ;   ?+u u` hp x (#X?  1  1݌̌   ! Xuu` X!  ;% ;;  ?+ ` hp x (#X?  %5  EPAsinspectionsaretheprimaryenforcementtypeinspectionsandoverallcontrolofGLPcomplianceresideswithEPA.ItisanimportantadvantagebecauseGLPsareafederalregulationandprimaryresponsibilityformonitoringcompliancemustresidewithEPAsOfficeofCompliance(OC).EPAsinspectorshavethenecessarybackgroundandexperiencewithGLPstoprovideindustrywithfairenforcementpracticesandcomplianceassistance. %5݌ S$# Ќ ;;  ! X` X!  ;   ?+u u` hp x (#X?    {݌̌   ! Xuu` X!  ;% ;;  ?+ ` hp x (#X?  %   TheinformationrequiredforEPAtoeffectivelymonitorthepartnershipisavailabletothemunderthecurrentGLPregulation[160.35(c)].AtestingfacilityswrittenproceduresforconductinginspectionsandauditsareevaluatedduringEPAinspections,aswellastrainingrecordsforQAUpersonnel.UnderexistingGLPregulations,recordsofinspectionsconductedbyaQAUareavailabletorepresentativesoftheEPAorFDA.IftheEPAfindsthatatestingfacilitysQAUproceduresarenotadequateduringaninspection,theywouldcitethemasfindingsintheirinspectionreport. % ݌ 3+$+ Ќ ;;  ! X` X!  ;B.FF` hp x (#XB ;% ;;  B+ ` hp x (#FFXB  %  EPAisnotdependentonthequalityoftheinspectionsofanyonesponsor.ByestablishingadatabaseforSponsorsinspections,theEPAwouldknowhowmanySponsorshaveinspected -w'. atestingfacilityandhowfrequentlythefacilityhadbeeninspected.TheInspectorGeneralsreportstatedthatGLPfacilitieswerenotadequatelyinspectedandOCdidnothavetheresourcestomonitorsomanytestsites.IftheIGhadconsideredSponsorsprograms,U.S.testingfacilitieslikelyhaveundergonemoreGLPinspectionsthananyplaceintheworld. %;݌  Ќ ;;  $ FFX` X$  ;   B+u u` hp x (#FFXB  "  ""݌̌   $ FFXuu` X$  ;% ;;  B+ ` hp x (#FFXB  %(#  WithadatabaseofSponsorsinspections,theEPAwouldknowtheidentityoffacilitiesactivelyconductingGLPwork.Currently,thisinformationbecomesavailableaftertheworkhasbeencompletedandthefinalreporthasbeensubmitted. %(##݌ T  Ќ ;;  $ FFX` X$  ;   B+u u` hp x (#FFXB  6%  6%%݌̌   $ FFXuu` X$  ;% ;;  B+ ` hp x (#FFXB  %@&  Option3couldbecombinedwitharegistrationlistprogramtofacilitatetrackingoffacilitiesandtestsitesconductingGLPstudies.SeeOption5forFIFRA/TSCAGLPTestingFacilityRegistration. %@&&݌ t  Ќ ;;  $ FFX` X$  ;E.` hp x (#FFXE ; ;; ?+ ` hp x (#X?  y(   Weaknessesy((݌ |,  Ќ ;;! X` X!   % ;;  ?+ ` hp x (#X?  %)  Thereisapotentialconflictofinterestbyallowingindustrytowatchoverthecontracttestsites #  whoareconductingthestudiesforthem.Somesponsorsmaynotbediligentintheirassessmentofthetestsites,andmayjustdoacursoryevaluation.Eveniftheprogramwasconductedproperly,thepublic'sperceptionofthisprogrammaybenegative. %)+*݌ g Ќ ;;  ! X` X!  ;   ?+u u` hp x (#X?  F,  F,,݌̌   ! Xuu` X!  ;% ;;  ?+ ` hp x (#X?  %J-  IfacontractlabthoughtthatitwouldbeunlikelythattheAgencywouldinspectit(becauseitwasvisitedbyitsclients),itmayonlymeettheminimumstandardsrequiredtokeepitsclients.%J--݌̌ ;;  ! X` X!  ;   ?+u u` hp x (#X?  /  //݌̌   ! Xuu` X!  ;% ;;  ?+ ` hp x (#X?  %0  Internationalconcernsabouta Certificateofcompliancearenotaddressed.%00݌  Ќ ;;  ! X` X!  ;B.` hp x (#XB ; ;; ?+ ` hp x (#X?   1   Conclusion1H2݌ k Ќ ;;! X` X!    % ;;  ?+ ` hp x (#X?  %3  Option3SponsorMonitoringProgramdependsonthecontinuationofEPAsGLP b ComplianceMonitoringProgram.ImplementationwouldbesimpleandcosteffectivebecauseitutilizestheexistinginspectionprogramsofEPAandindustry.EPAwouldprioritizetheirinspectionscheduletofocusonSponsorsandtestingfacilitieswithstudydirectors.TheEPAinspectionprogramwouldbesupplementedwithadatabaseofSponsorsGLPinspectionsofcontractfacilities.Sponsorswouldonlyhaveaddedreportingresponsibilities.TheAgencystartupandmaintenancecostsforadatabasecouldbeminimizedbyprioritizingtheirinspectionschedules.%3w3݌̌ ;;  ! X` X!  ;   ?+u u` hp x (#X?  6  67݌̌   ! Xuu` X!  ;% ;;  ?+ ` hp x (#X?  %7  TheOptionisinconformancewithexistingGLPregulationssotherearenolegalramifications.SponsorshaveprimaryresponsibilityforGLPcompliancewhenstudiesorphasesofstudiesareperformedatcontractedfacilities.ThisOptionshouldnotpresentaconflictwithFDAregulationsorInternationalAgencies.UnderFDAGLPs,Sponsorsalsohaveresponsibilitytomonitortheircontractfacilities.InternationalAgencyinspectionsseemtobeprimarilydirectedattestingfacilitieswithstudydirectors,andtestsites(withoutstudydirectors)arenotroutinelyinspectedbygovernmentinspectors.%78݌̌ ;;  ! X` X!  ;B.` hp x (#XB ; ;; ?+ ` hp x (#X? XBX%& XBXXXB   Z;   2  4  .3    Option4InclusionOfGLPProgramUnderTheUmbrellaOfNelapZ;8<݌ ,&- Ќ ;;! X` X! &%XB  &%&    ;; ?+ ` hp x (#X?   =   Introduction:=?>݌ P Ќ ;;! X` X!    % ;;  ?+ ` hp x (#X?  %>  DuringthedevelopmentoftheNationalEnvironmentalLaboratoryAccreditationProgram  (NELAP),therehasbeenindecisionwithintheNationalEnvironmentalLaboratoryAccreditationConference(NELAC)andEPAastowhethertheEPAGoodLaboratoryPractice(GLP)ProgramshouldbeincludedinNELAPorremainasaseparateprogram.AnELABSubcommitteeconsistingofrepresentativesfromEPA,thestates,theGLPregulatedcommunity,consultantsandGLPtestinglaboratorieswasestablishedbyEPA/NELAPtodevelopandevaluateotheroptionstoplacingtheGLPunderNELAP.%>q?݌̌ ;;  ! X` X!  ;B.` hp x (#XB ;% ;;  ?+ ` hp x (#X?  %B  Inthisoption,theEPAGLPProgramwouldbeplacedundertheumbrellaofNELAPasaparallelprogramandwouldoperateindependentlyoftheotherNELAPprograms.AdditionalsupporttotheEPAGLPProgramwouldbeprovidedbyEPAapprovedthirdpartyassessmentgroups.%BC݌̌ ;;  ! X` X!  ;B.` hp x (#XB ; ;; ?+ ` hp x (#X?   E   DescriptionOfOption:EE݌ #  Ќ ;;! X` X!    % ;;  ?+ ` hp x (#X?  %GF  TheadministrationoftheEPAGLPProgramwouldremainundertheFederalEPAcontrol. z FederalEPAinspectorswouldbeusedtoconductpriorityGLPcomplianceinspectionsanddataauditsandtomonitortheactivitiesofNELACandtheapprovedthirdpartyassessorsinvolvedintheprogram.EPAwouldalsomaintainthedatafileandarchivesrelatingtoGLPstudyandlaboratoryevaluations.EPAwouldcontinuetoharmonizetheirregulationsandprogramswithFDAandothercountries.InternationalcomplianceissueswouldstillbeaddressedbyEPA.%GFF݌̌ ;;  ! X` X!  ;B.` hp x (#XB ;% ;;  ?+ ` hp x (#X?  %I  NELACwouldprovidethelogisticaladministrationfortheaccreditationprogram.FundingwouldbelargelyderivedfromtheinspectionfeesthatwouldbeleviedbyNELACand/orthirdpartyaccreditinggroup(s)foraccreditationinspections/assessments.TheadditionalmanpowerresourceswouldbesuppliedbyEPAapprovedcontractedthirdpartyaccreditingbody(s).ThisadditionalmanpowerwouldbeavailabletoEPAtoassistEPAtoretainoversightresponsibilitiesfortheGLPProgram.NELACwouldrestrictitsresponsibilitiestofacilityaccreditationandwouldallowtheEPAtoretainoversightresponsibilitiesfortheGLPProgram.%IGJ݌̌ ;;  ! X` X!  ;B.` hp x (#XB ;% ;;  ?+ ` hp x (#X?  %M  NochangesshouldbemadetotheexistingGLPStandardsunlesstheyareconsistentwithotherinternalestablishedGLPProgramsorexistingFederalInsecticideFungicideandRodenticideAct(FIFRA)andToxicSubstanceControlAct(TSCA)regulations,orexternallywithotherinternationalGLPprograms,suchasOECD.%MN݌̌ ;;  ! X` X!  ;B.` hp x (#XB ; ;; ?+ ` hp x (#X?   4P   ImplementationStrategy:4PP݌ & & Ќ ;;! X` X!    % ;;  ?+ ` hp x (#X?  %}Q  TheELABSubcommitteebelievesthatthereshouldbenochangesmadeinthecurrentEPA }(-"( GLPStandardstoaccommodatetheinclusionoftheGLPProgramundertheNELACumbrella.ThisrecommendationismadebecauseofthelongsuccessoftheGLPProgram,thesimilaritiestotheFDAGLPs,theconsistencywiththeexistingstudyguidelinesofbothFIFRAandTSCA,andtheuseoftheUSGLPstodraftinternationalGLPs.ChangesintheGLPStandardsatthistime,toaccommodateNELACrequirements,woulddisrupttheharmonizationofGLPProgramsthathaveoccurredbothnationallyandinternationally.%}QQ݌ -U'. Ќ ;;  ! X` X!  ݛ ;B.` hp x (#XB ;% ;;  ?+ ` hp x (#X?  %OU  Toimplementthisoption,changeswouldneedtobemadeinthestructureandconstitutionofNELACtoaccommodatethespecialrequirements/nuancesoftheGLPStandards,andtoallowtheEPAGLPInspectionProgramtoproceed.ThisoptionconsidersplacingtheEPAGLPProgramunderNELAC,butnotthatpartoftheEPAComplianceMonitoringProgramcurrentlyinvolvedinGLPcomplianceactivities.OnlyasmallpartoftheEPAComplianceMonitoringProgramisresponsiblefortheGLPProgram.Totakepartoftheenforcement,legalresourcesandexpertiseinoravailabletotheOfficeofEnforcementandComplianceAssurance(OECA),andplacetheminanotherprogram,woulddisrupttheactivitiesofOECAandcouldcreateanotherenforcementprogramthatmaynotbeconsistentwithexistingenforcementactions.Also,theexistingprogrammakesuseofawiderangeofexperienceintheOfficeofPesticidePrograms(OPP),OfficeofToxicSubstances(OTS),OECAandthelegaloffices,whichmaynotbeasreadilyavailabletotheprogramsinNELAC,ifpartoftheEPAprogramwasmovedintoNELAC.%OUU݌̌ ;;  ! X` X!  ;B.` hp x (#XB ;% ;;  ?+ ` hp x (#X?  %Z  NELACsroleintheEPAGLPprogramwouldlargelybeadministrative.TheywoulddesignanequitablelaboratoryaccreditationprogramthatwouldaddresstheuniquenessoftheGLPStandard.Theywouldalsoestablishasuitablefeestructureforinspections,establishanappealprocess,wouldprioritizeandscheduleroutinethirdpartyassessments,andchannelinspectionreportstoOECAforprocessing.%Zr[݌̌ ;;  ! X` X!  ;B.` hp x (#XB ;% ;;  ?+ ` hp x (#X?  %]  TheadditionalresourcesneededbyEPA,toconductmoretimelyevaluationsofEPAGLPtestingfacilitiestoaddressthecriticismsoftheInspectorGenerals(IG)Officeandinternationalcommunity,wouldbeprovidedbythecontractedEPAapprovedthirdpartyaccreditingbodies.Thefeescollectedwouldbepaiddirectlytotheaccreditingbody(s),ortoNELAC,toavoidlegislativeactiontoallowOECAtoreceivefundsdirectlyfromtheregulatedcommunity.%]_^݌̌ ;;  ! X` X!  ;B.` hp x (#XB ;% ;;  ?+ ` hp x (#X?  %a  ݢOECAwouldcontinuetomanageanddirecttheactivitiesoftheAgencysGLPprogram.Theirinspectorswouldconductthepriorityinspectionsanddataaudits,andtheywouldmonitortheinspection/assessmentactivitiesofthethirdpartyassessmentbody(s)andNELAC,whichrelatetoGLPtestingfacilities.OECAwouldcontinuetoharmonizetheEPAGLPactivitiesandregulationswithFDAandothercountriesinvolvedinGLPs.EPAwouldalsomonitortheGLPrelatedactivitiesofNELAP,assistinthetrainingthirdpartyassessors,andwouldretainoversightresponsibilities,particularlyintheareasofdirectingassessments/inspectionsandensuringthatapprovedGLPtypetrainingisavailabletothethirdpartyaccreditors.Last,EPAwouldmaintainthedatabaseandarchivesrelatingtoGLPinspections/assessmentsandwouldprocessadverseinspectionfindings.%aa݌̌ ;;  ! X` X!  ;B.` hp x (#XB ; ;; ?+ ` hp x (#X?   e   Strengths:edf݌ & & Ќ ;;! X` X!    % ;;  ?+ ` hp x (#X?  %g  Inprinciple,thisoptionshouldallowforadequateresourcestobecomeavailabletoOECA,both (O"( intermsofmanpowerandfunding.FundingwouldbelargelyderivedfromtheinspectionfeesthatwouldbeleviedbyNELACorthethirdparty(s)foraccreditinginspections.AdditionalmanpowerresourceswouldbeavailabletoEPAfromthecontractedthirdpartyaccreditingbody(s).%gg݌̌ ;;  ! X` X!  ;B.` hp x (#XB ;% ;;  ?+ ` hp x (#X?  %j  Nationally,aslongasnochangesaremadeintheGLPStandardstoaccommodatetheNELAP, -w'. theharmonizationeffortswithFDAwillremainintact,therebypreservingasinglenationalGLPstandard.ChangesthatonlyimpactenforcementandlabaccreditationelementsshouldnotadverselyaffecttheharmonizationagreementsbetweenFDAandEPA.Theseelementsmay,however,impactthesharingofinspectionsbetweenthetwoAgencies.%jxj݌̌ ;;  ! X` X!  ;B.` hp x (#XB ;% ;;  ?+ ` hp x (#X?  % m  Internationally,aslongastheNELACframeworkdoesnothindertheabilityofEPAtomodify/harmonizethecurrentGLPstandardswithOECD,oradverselyaffecttheexistingformalstatutorymechanismsinplacetocoverthechangingofGLPstandards,thisoptionshouldbeacceptabletotheinternationalcommunity.Infact,withtheanticipatedincreaseinfacilityinspections,plusthepossibleissuanceofacertificateofaccreditation/compliance,thisoptionshouldbeviewedveryfavorablybytheinternationalcommunity.% mm݌̌ ;;  ! X` X!  ;B.` hp x (#XB ;% ;;  ?+ ` hp x (#X?  %p  ThedevelopmentofanadequatelyGLPtrainedthirdpartyassessmentgroup(s)toassistEPAinlaboratoryevaluationsandthepotentialincreaseinonsiteinspections/assessmentsshouldupgradethequalityofdatabeingsuppliedtotheAgencyandregulatedcommunity.%pp݌̌ ;;  ! X` X!  ;B.` hp x (#XB ;% ;;  ?+ ` hp x (#X?  %r  PlacingtheEPAGLPProgramundertheumbrellaofNELACwouldprovideaprocessbywhichEPAcouldmakeuseofapprovedforfeethirdpartygroup(s)withouttheirbeinginvolvedinreceivingfundsdirectlyfromtheregulatedcommunity%rYs݌̌ ;;  ! X` X!  ;B.` hp x (#XB ; ;; ?+ ` hp x (#X?   #u   Weaknesses:#uu݌ 0 Ќ ;;! X` X!    % ;;  ?+ ` hp x (#X?  %_v  ThisoptionwouldnotnecessarilybenefitoraddresstheneedsofOPPtohaveappropriatetimed ' auditinformation(i.e.,duringevaluationofaregistrationpetition),nordoesthisoptionaddresstheneedtooptimizethecomplianceprogramtoallowscientificjudgmenttobeincludedinthecomplianceassessmentdecisions(s).Bywayofanexplanation,itisanticipatedthattheprimaryfocusofNELACwillbeontheaccreditationprocess,ofwhichthefacilityinspectionwouldconstitutetheprimaryelement.ThiswouldleavetheexistingOECAstafftocontinuetoperformdataauditsand/orundertakeoversightdutieswithrespecttothirdpartyaccreditationactivitiesandNELAPinvolvementintheprogram.Assuch,norealchangesinthecurrentdatareviewprocessisanticipated.%_vv݌̌ ;;  ! X` X!  ;B.` hp x (#XB ;% ;;  ?+ ` hp x (#X?  %z  ThisoptionprovideslittleincentiveforOECAtostreamline/improveupontheexistingcomplianceprogramprocess.Explicitly,theNELACoptionsimplyaddressestheresourcelimitationswithoutprovidingincentivestoimproveupontheeffectivenessoftheexistingprogram.Italsoaddsanotherlayerofbureaucracythatprovidesno valueaddedadvantages. S$# Theexpectationis,andshouldbe,thattheEPAwouldevaluatetheirexistingcomplianceprogram(whetherthisoptionisselectedornot)toensuremorejudicious/effectivemeansofutilizingthecomplianceresources.%zW{݌̌ ;;  ! X` X!  ;B.` hp x (#XB ;% ;;  ?+ ` hp x (#X?  %~  Secondly,unlesstheNELACconstitutionismodifiedtoallowformalinputbytheregulatedcommunity(e.g,proposedrulemakingstructure,commentingperiods,etc.)thisoptionwilllikelycomeunderintensecriticismandchallengesbytheregulatedcommunity.Inadditiontothisconcern,thereareseveralotheranticipateddisadvantagesofthisoptiontotheregulatedcommunity.First,thelaboratoryaccreditationprogramwouldprovideminimal valueadded ,%, impacttothequalityofdataproducedinGLPlaboratoriesfortheincreasedcostofaccreditation.Somecontractlaboratoriesmay,however,gainabusinessbenefitfrombecoming -w'. Мaccredited.Secondarily,unlessEPAimplementssomeadjustmentstotheirexistingcompliancemonitoringprogramtomakeallowancesforfacilitiesinspected,frequencyofinspections,timelinessofreporting,andqualityofscientificreviews,stakeholderswouldattainlittlebenefitfromtheincreasednumberoffacilityinspections.And,thirdly,smallspecialtylaboratorieswouldbeimpactedmostfromtheimpositionoffacilityinspectionsfees.Thiscouldresultinareductionofavailabletestingfacilitiesinthesmallspecialtylaboratoryareas,anoutcomethatcouldbeviewedaseithergoodorbaddependingontheviewpoint.Also,dependinguponthecostofaccreditation,somebusinessmaypotentiallybedrivenoutofthecountry.%~݌̌ ;;  ! X` X!  ;B.` hp x (#XB ;% ;;  ?+ ` hp x (#X?  %  OriginallythefocusoftheNELAPwastoensurethequalityofdatabeingsuppliedtoandregulatedbytheStates,andtostandardize(withreciprocity)theexpectationsbytheStatesforthesedata.ByincludingtheGLPlaboratoriesundertheNELACumbrella,itcouldpotentiallyrequiresomeinvolvementbytheStatesinthesharingoftheoversightworkload,whichoriginallywasfullyinthedomainoftheFederalEPA.ThismightincludetheGLPtrainingofstateorthirdpartyinspectors/assessorsorthedevelopmentoffederalenforcementcases.ItisanticipatedthattheStatesareundersimilarresourceconstraintsastheFederalEPA.Underthesecircumstances,theremaynotbemuchincentiveforsomeStatestoadoptthisoption.%݌̌ ;;  ! X` X!  ;B.` hp x (#XB ;% ;;  ?+ ` hp x (#X?  %Ɖ  Forthisoptiontobeworkable,severalotherimportantareaswillhavetobeaddressedandreasonablesolutionsdeveloped:%Ɖ:݌̌ ;;  ! X` X!  ;B.` hp x (#XB ;% ;;  ?+ ` hp x (#X?  %  WillplacingtheGLPprogramundertheNELAPumbrella,plusthe exclusionarystructureof \  theNELACconstitution,givetheregulatedcommunitydueprocess(rulemaking,commentperiods,etc.,)inhandlingdisagreementswiththedevelopmentandchangingofregulationsrelatingtothem?%݌̌ ;;  ! X` X!  ;B.` hp x (#XB ;% ;;  ?+ ` hp x (#X?  %"  IftheparticipationintheNELAPprogramisvoluntaryfortheStatesbutmandatoryforGLPtestingfacilities,howwillthelegalityofsuchanarrangementfortheGLPprograms,relativetothestatutoryconstraintsofEPA,behandled?%"݌̌ ;;  ! X` X!  ;B.` hp x (#XB ;% ;;  ?+ ` hp x (#X?  %`  IssuesinvolvingEPAsdelegationofspecificGLPComplianceProgramresponsibilitiestothestateswillhavetobeexamined.%`Ԑ݌̌ ;;  ! X` X!  ;B.` hp x (#XB ;% ;;  ?+ ` hp x (#X?  %2  Procedureforprocessingenforcementactionsresultingfromfindingsbythestatesorthirdpartygroups(particularlyiftheycrossstatelines)willhavetobeworkedout.%2݌̌ ;;  ! X` X!  ;B.` hp x (#XB ;% ;;  ?+ ` hp x (#X?  %0  ProceduresforEPAtodirectthirdpartyforfeeinspections/assessmentsoftestingfacilitieswillneedtobeaddressed.%0݌̌ ;;  ! X` X!  ;B.` hp x (#XB ;% ;;  ?+ ` hp x (#X?  %  Appropriateandreasonablefeestructureswillneedtobeestablished.%o݌̌ ;;  ! X` X!  ;B.` hp x (#XB ;% ;;  ?+ ` hp x (#X?  %  AdditionalresourcesmayneedtobemadetoOECAtosupporttheirexistingcomplianceinspectionprogram,aswellastheirincreaseinresponsibilities;suchasmonitoringtheactivitiesofNELACandthethirdpartygroups;providingtrainingtoassessors;trackingandschedulinginspections/assessmentsbythirdpartiesandthearchivingandprocessinginspectionfindings.%݌̌ ;;  ! X` X!  ;B.` hp x (#XB ; ;; ?+ ` hp x (#X?   \   Conclusion:\ܚ݌ -'. Ќ ;;! X` X!   ݛ  % ;;  ?+ ` hp x (#X?  %  TheEPAGLPprogramcouldbeplacedundertheumbrellaofNELACifitweretreatedasa P separateandindependentprogramsoastonotinterferewiththesuccessofthecurrentprogram.TheadditionalresourcesthatcouldbeprovidedtotheEPAGLPprogrambythestatesorthirdpartyassessmentgroup(s)couldbeusedveryeffectivelytoincreasetheresponsivenessoftheAgencysGLPprogram.BynotchangingtheGLPregulationstoaccommodateNELAPrequirements,thereshouldbelittleadverseaffectontheharmonizationofseveralregulationswithinEPA,withFDAortheinternationalGLPcommunity.DueconsiderationwouldhavetobegiventoallowtheGLPregulatedcommunitytorespondtochangesmadeintheregulationsordirectionofenforcementactions(rulemaking,commentperiods,etc.).SuchproblemareasastheconcernsoftheregulatedGLPcommunity;thelegalityofdelegationofEPAGLPresponsibilitiestoStates;theuseofforfeethirdpartyassessors;theestablishmentofareasonablefeestructure;thearchiving,trackingandprocessingofinspection/assessmentdata,etc.,allneedtobeaddressedbeforethisoptioncanbeseriouslyconsidered.% ݌̌ ;;  ! X` X!  ;B.` hp x (#XB ; ;; ?+ ` hp x (#X? XBX%& XBXXXB      2  5  .3    OPTION5FIFRA/TSCAGLPTESTINGFACILITYREGISTRATION݌ X  Ќ ;;! X` X! &%XB  &%&    ;; ?+ ` hp x (#X?      Background݌ &  Ќ ;;! X` X!    % ;;  ?+ ` hp x (#X?  %M  OneofthedifficultiesfacedbyOECA,inadditiontonothavingthestaffresourcesorbudgetto } inspecttheestimated2000facilitiesidentifiedasdevelopingdataforsubmissiontoEPAunderϢGLPs,isthatitcannotidentifythefulluniverseoftestinglaboratories.OECAusesOPPandOTSdatabasesforthelaboratorylistwhichisgeneratedfrominformationprovidedinthefinalreportbythesponsor.TheresultisalagtimefromwhenthelaboratorybeginsdevelopingdataforsubmissiontothetimewhenstudiesareactuallysubmittedandbecomeknowntoEPAandtowhentheselabsareinspected.Eachtestsiteinastudyiscountedasafacilitybasedoninformationprovidedinthefinalreportbythesponsor.EPAhasdataontestfacilitiesbutitisincomplete.%M݌̌ ;;  ! X` X!  ;B.` hp x (#XB ;% ;;  ?+ ` hp x (#X?  %ǩ  OnesolutionEPAhasbeenlookingat,toimplementtheEPAsOfficeoftheInspectorGenerals(OIG)recommendations,isthemandatoryregistrationofallfacilitiesparticipatinginϢGLPregulatedstudies,basedondocumentsubmissionandassessment.%ǩ;݌̌ ;;  ! X` X!  ;B.` hp x (#XB ; ;; ?+ ` hp x (#X?      DescriptionofOption݌ !  Ќ ;;! X` X!    % ;;  ?+ ` hp x (#X?  %c  FacilitieswhichintendtoperformFIFRAandTSCAGLPstudiesforsubmissiontoEPAwould |#," berequiredtoregistertheirfacilitywithEPA.Facilityregistrationwouldinvolveaninitialsubmissionofinformationanddocumentsfromthefacilityforreviewtoestablishthebasicprofileforthefacility.Documentationcouldpossiblyinclude:descriptionofsize,organization,andcapabilitiesofthefacility;theorganization,functions,andproceduresofthequalityassuranceunit;generaldescriptionofinstrumentsandequipmentusedatthesite,andthenumberandareasofexpertiseofstaff.Itmightalsoincludecurrentlistofstandardoperatingprocedures,resumes,CVsandtrainingrecordsofkeypersonnel,floorplansoffacility,andacurrentmasterschedule.Onaperiodicschedule,facilitieswouldberequiredtoresubmitcertaindocumentsandinformation.%c׭݌̌ ;;  ! X` X!  ;B.` hp x (#XB ;% ;;  ?+ ` hp x (#X?  %D  TheAgencyoradesignatedthirdpartycontractorwouldauditthesubmitteddocuments.Registrationwouldnotconferapproval.Facilitieswithcorrectedminordeficiencieswouldbe -|'. provisionallyregistered,whilefacilitieswithmajordeficiencieswouldbetargetsforinspection.PeriodicsubmissionofthefacilitysmasterschedulewouldberequiredandwouldprovideameansofmonitoringworkintendedforsubmissiontotheAgency.ThiswouldallowOECAtoprioritizeitsinspectionsandbeabletoconductinlifeauditreviewsofongoingstudies.Toremainontheregistrationlist,asubmitterwouldneedtocontinuetoremaininGLPcomplianceverifiedbyanEPAfacilityinspectionaudit.%D݌̌ ;;  ! X` X!  ;B.` hp x (#XB ; ;; ?+ ` hp x (#X?   s   & A ImplementationStrategys݌ T  Ќ ;;! X` X!    % ;;  ?+ ` hp x (#X?  %Ƿ  Aregistrationfeewouldbechargedwhichwouldcoverallparticipantsinastudy,andwouldbe    byfacility(sitesactuallyconductingworkaspartofthestudy),notbycompanyorcorporation.Theregistrationfee,whichwouldrequirecongressionalauthorization,wouldbelargeenoughtoadministerandmaintaintheregistrationlistandreviewofdocumentsubmissions.EPAwouldhavetoidentifyanddevelopfaircriteriastandards.Afterareasonableperiodforregistrationtobeimplemented,theAgencycouldrejectanystudiesutilizingunregisteredfacilities,iftheregistrationsystemistosucceed.%Ƿ;݌̌ ;;  ! X` X!  ;B.` hp x (#XB ; ;; ?+ ` hp x (#X?      Strengths݌  Ќ ;;! X` X!    % ;;  ?+ ` hp x (#X?  %̼  Withlittleeffort,amandatoryregistrationlistwouldprovideEPAwithacompletedatabaseor 2  knownpopulationofGLPtestingfacilities.ThiswouldmeettheIGsrecommendationsthat ^ theAgencyhaveassuranceofalaboratorysawarenessofandabilitytomeetGLPrequirementsandtheprovisionofanindustrywidelaboratoryenvironmentmoreconducivetoGLPcompliancewiththequalityofthedataremaininghigh.%̼@݌̌ ;;  ! X` X!  ;B.` hp x (#XB ;% ;;  ?+ ` hp x (#X?  %  Inaddition,aregistrationlistwouldprovidetheAgencywithascreeningcapabilityandwouldpermitmoreefficienttargetinganduseofresources.ItwouldalsopermittheAgencytomakeapreliminaryassessmentofpreviouslyuninspectedfacilities,andutilizelimitedresourcestoinspectfacilitieswhichappeartohavethemostseriousdeficiencies.AssessmentofGLPcompliancecontinuestoremainwithEPA.IfEPAweretoimplementthisprogram,concernsforconflictsofinterestandconfidentialitywouldbeminimized.%q݌̌ ;;  ! X` X!  ;B.` hp x (#XB ;% ;;  ?+ ` hp x (#X?  %e  EPAcouldprovidethelistofregisteredGLPlaboratoriestointernationalgovernments,whichmayaddressinternationalconcerns.Additionally,theregistrationlistcouldbeannotatedwiththedatesofEPAfacilityinspections.%e݌̌ ;;  ! X` X!  ;B.` hp x (#XB ; ;; ?+ ` hp x (#X?      Weaknesses݌ %$ Ќ ;;! X` X!    % ;;  ?+ ` hp x (#X?  %  TherewillbeanadditionalminimalregistrationcosttotheGLPtestingfacilitiestocover &u & administrationoftheregistrationlist.RegistrationcoststoGLPcommunitymaybegreaterforsmallcompaniesandcompanieswithmultipletestingfacilities.Inaddition,EPAwouldincuraninitialadministrativecosttostarttheprogramandmaintainit.Therewouldbeno value Y) #) addedtocurrentGLPcompliancefordataquality.%M݌ 5*#* Ќ ;;  ! X` X!  ;B.` hp x (#XB ;% ;;  ?+ ` hp x (#X?  %!  Onsiteevaluationswouldstillberequired,andasnotedbeforeEPAlackssufficientresourcestoadequatelyinspectallGLPlaboratories,butitwouldbebetterinformedofwhichlabsandwhichstudieswerebeingconductedsoitcouldprioritizeitsinspections.A voluntary -U'. registrationlistwouldbecounterproductivebecauseitwouldnotprovidetheAgencywithan P  approveduniverseoflabs.%!݌ , Ќ ;;  ! X` X!  ;B.` hp x (#XB ; ;; ?+ ` hp x (#X?   O   ConclusionO݌  Ќ ;;! X` X!    % ;;  ?+ ` hp x (#X?  %  ThealternativeprogramsbeingproposedtohelpaugmentthecurrentEPAGLPcompliance  ; monitoringsystemrepresentaprogressivelistofoptionsthatcanbeimplementedbythemselvesorincombinationwitheachother.TheregistrationlistwasnotincludedintheoptionforthereevaluationofexistingEPAGLPcompliancemonitoringprogramwithfundingconsiderations,becausethegroupfelt,byitself,itwouldnotsolvetheEPAsproblemswithfundingandresourcesforconductingfacilitysiteinspections.However,theregistrationlistcouldproveusefulinconjunctionwithotherproposedoptions.%݌̌ ;;  ! X` X!  ;B.` hp x (#XB#bbdd  JU *G UE1X` hp x (#XE .%&.. #bbbb  l  >& A 2  III  .3    Group2AINTERAGENCYANDInternationalIssuesPertaining G  toU.S.EPAGoodLaboratoryPracticePrograml݌̌ JJ ' H#hAJ XXX >&%..&%& #bbbb  C  HhC  E1X` hp x (#XE N NN B.` hp x (#XXB .%& ..   F     2  A  .3    #ddbbGROUP2AREPORTU.S.InteragencyIssuesPertainingtoU.S. D EPALabAccreditationFDAPositionStatementF*݌ \ Ќ NN! XXX! &%..  &%&    NN  B.` hp x (#XXB    Aspartofthisassignment,aninvestigationofDepartments,AgenciesandAdministrationsoutside w ofU.S.EPAwasmadetodeterminetheirpositionondevelopingaNationalGLPAccreditationprogram.ThetwogroupspotentiallyaffectedbyanaccreditationprogramareUSDAandFDA.݌̌ NN  ! XXX!   NN  B.` hp x (#XXB  9  9݌̌ NN  ! XXX!   NN  B.` hp x (#XXB  /  TheUSDAprogramfundsseveralprogramsthatpotentiallywouldbeaffectedbythedevelopmentofaNationalGLPAccreditationprogram.TheseprogramsincludeIR4MinorUseprogram,NationalAgriculturePesticideImpactAssessmentProgram,andtheAnimalPlantHealthInspectionService(onbehalfoftheDenverWorklifeResearchCenter.Internally,USDAdoesnothaveGLPrequirements.However,thoseprograms,wheredataaresubmittedtoEPAinsupportofregistrationofapesticide,dorequireGLPaspartofUSDAfundingrequirements.ImplementationofaNationalAccreditationprogramforGLPspotentiallywouldstraintheseprogramsalreadywithlimitedfunds./݌̌ NN  ! XXX!   NN  B.` hp x (#XXB    F݌̌ NN  ! XXX!   NN  B.` hp x (#XXB    TheU.S.FDAmanagesasimilarGLPprogramtothatoftheEPA.TheoutcomeofthedebateondevelopingaNationalGLPAccreditationprogramhasgreatestimpactonthisprogram.FDAGLPProgramDirector,Dr.StanWollenhaswrittenthefollowingpositiononLaboratoryAccreditationofGLPLaboratories.<݌̌ NN  ! XXX!  NE1X` hp x (#XXE#bbdd ; ;; ?+ ` hp x (#XX? XBX%& XBXXXB   i   2  1  .3    #ddbbBackgroundiG݌ ?(!& Ќ ;;! XX` X! &%XB  &%&   % ;;  ?+ ` hp x (#XX?  %  Since1978,theFDAhashadaprogramforinspectingthoselaboratoriesconductingnonclinical  *#( safetystudiessubmittedtotheagencyorintendedforsubmissiontosupportapplicationsforresearchormarketingpermitsforallproductsthatitregulates.SuchstudiesaretobeconductedandreportedinaccordancewiththeGoodLaboratoryPractice(GLP)regulationsfoundin21ϢCFR58.%݌ }--', Ќ ;;  ! XX` X!  N; NN  B.` hp x (#XXB  ]  ]݌̌ NN  ! XXX!  ;N% ;;  ?+ ` hp x (#XX?  %a  BoththeFDAsGLPregulationsanditsprogramtoensureindustryscompliancewiththemarosefromthepracticalexperienceoftheagencyinthemidtolate1970s.AsurveyofthesafetytestingindustrybytheFDAfoundseriousandwidespreadproblemswithboththeconductandreportingofsafetystudiesuponwhichtheagencyhadreliedtomakeapprovaldecisionsofbroadpublichealthsignificance.Nonclinicaltestinglaboratorieswereunregulatedatthistimeandrecognizedstandardsforthesetypesoflaboratorieswereessentiallynonexistent.TheFDAscurrentGLPsanditsbioresearchmonitoringinspectionprogramresultedfromaCongressionalmandatetoaddresstheseproblems.%a݌̌ ;;  ! XX` X!  N; NN  B.` hp x (#XXB  /  /݌̌ NN  ! XXX!  ;N% ;;  ?+ ` hp x (#XX?  %3  Indevelopingitsapproachforregulatingtheselaboratories,theFDAconsideredseveraloptions,includingathirdpartyaccreditationprogram.TheFDAconcluededthataprogramofregularlaboratoryinspectionsanddataaudits,conductedbyFDApersonnel,wasthemostcosteffectiveandefficientmeanstoensurethequalityandintegrityofdatasubmittedtotheagency.TheFDAreachedthisconclusioninpartbaseduponitsdecisiontoincludeintheproposednewregulationsarequirementthateachlaboratoryappointanindependentqualityassuranceunit(QAU).TheQAUswouldmonitoralaboratoryscompliancewiththeregulations,auditfinalreports,andkeepmanagementapprisedofneededcorrectiveaction.Additionally,thedatarecordingandretentionprovisionsoftheGLPregulationswouldpermitreconstructionofcompletedstudiesbyFDAinspectorsduringanaudit,permittingtheFDAtodirectlyvalidatethequalityandintegrityofstudyspecificdata.%3݌̌ ;;  ! XX` X!  N; NN  B.` hp x (#XXB    ݌̌ NN  ! XXX!  ;N% ;;  ?+ ` hp x (#XX?  %  ThisselfregulationapproachwasfavoredbytheFDAastheleastburdensometoindustryandmostefficientforFDAoversight.TheFDAwouldneedonlytoconductperiodicinspectionsofthelaboratoriestoensurethattherequiredGLPqualitysystemswereinplaceandoperational.TheseinspectionswouldalsoincludedataauditsofspecificstudiestovalidatestudydataandmeettheFDAsCongressionallymandatedresponsibilityofensuringthequalityandintegrityofdataitreliesupontomakeimportantpublichealthdecisionsregardingtheapprovalofnewϢproucts.%݌̌ ;;  ! XX` X!  N; NN  B.` hp x (#XXB  _  _݌̌ NN  ! XXX!  ;N% ;;  ?+ ` hp x (#XX?  %c  TheadvantagesoftheFDAsapproachtoregulatenonclinicalsafetytestinglaboratorieswererecognizeddomesticallybyotheragenciesoftheU.S.governmentandinternationally.Domestically,theEPApromulgatedGLPregulationsvirtuallyidenticaltotheFDAsandimplementedaprogramofinspections.Toleverageresources,theagenciessignedanInteragencyAgreementthroughwhichtheFDAprovidesinspectionsupporttotheEPAprogram.SincenearlyhalfofthelaboratoriesinspectedbytheFDAalsoconductEPAtests,theFDAcoordinateswiththeEPAonaquarterlybasistoauditEPAstudiesatthesefacilitiesduringitsowninspections.%c݌̌ ;;  ! XX` X!  N; NN  B.` hp x (#XXB    p݌̌ NN  ! XXX!  ;N% ;;  ?+ ` hp x (#XX?  %  Internationally,theFDAsGLPshaveheavilyinfluencedtherestofourmajortradingpartnerstoadoptGLPprinciplesandinspectionprogramssimilartothoseoftheFDAandtheEPA.In1981theOECDservedasamajorharmonizingforceinternationallybyadopting,throughitschemicalsprogram,the MutualAcceptanceofDataDecision.Thedecisionbasically h*$* establishedtheOECDGLPsasaninternationalstandardforOECDmembercountriesdefinedtheelementsofanacceptablenationalmonitoringprogram.BoththeGLPprinciplesandmonitoringprogramsproposedbytheOECDcloselyresemblethoseoftheU.S.FDAandtheEPA.%q݌ -'. Ќ ;;  ! XX` X!  N; NN  B.` hp x (#XXB    '݌̌ NN  ! XXX!  ;N ;; ?+ ` hp x (#XX? XBX%& XBXXXB      2  2  .3    CurrentPositiononLabAccreditationSystemforGLPLabs݌ , Ќ ;;! XX` X! &%XB  &%&   % ;;  ?+ ` hp x (#XX?  %  TherearecurrentlynoplansbytheFDAtoadoptanaccreditationapproachtoregulationof  ТGLPlaboratories.TheprogramofinspectionsanddataauditscurrentlyinplaceattheFDAprovidesthenecessarylevelofdataqualityandintegritywithaminimaloutlayofresources.TheuseofFDApersonneltoauditdataandperforminspectionspermitsdirectinteractionwiththereviewdivisionsandallowsquickandefficientdecisionmakingregardingtheacceptabilityofdatasupportingtheapprovalofnewproducts.%݌̌ ;;  ! XX` X!  N; NN  B.` hp x (#XXB  3  3݌̌ NN  ! XXX!  ;N% ;;  ?+ ` hp x (#XX?  %7  Implementationofanaccreditationprogrambyathirdparty,wouldentailtheaddedexpenditureofresourcestoestablishaninfrastructureoftraining,oversightandadditionalregulation.TherehasbeennoinformationpresentedtotheFDAatthispointtosuggestanyjustificationforthisaddedexpense,nordoestheFDAhaveanyindicationthatitscurrentprogramhasbeenineffective.%7݌̌ ;;  ! XX` X!  ;E1X` hp x (#XXE#bbdd N NN B.` hp x (#XXB .%& ..   '    2  B  .3    #ddbbGROUP2BInternationalIssuesPertainingtoU.S.EPAGood  LaboratoryPracticeProgram'  ݌̌ NN! XXX! &%..  &%&   NB.` hp x (#XXB'P ; ;; ?+ ` hp x (#X? XBX%& XBXXXB   3   2  1  .3    OriginoftheOrganizationforEconomicCooperationandDevelopment  (OECD)GoodLaboratoryPractice(GLP)Program3݌̌ ;;! X` X! &%XB  &%&   % ;;  ?+ ` hp x (#X?  %  TheOECDGLPprogramhasitsprovenanceinthesameeventastheU.S.FDAandEPA  programstheIBTdatafraudscandalofthe1970's.IBTconductedstudiesforsubmissioninnumerousOECDMembercountries,andforeigncompaniesthatwereattemptingtoregisterpharmaceuticalandpesticideproductsintheUnitedStates.ThedevelopmentofaUnitedStatesϢGLPrequirementbytheFDAinthelate1970'spromptedinterestinGLPonthepartofotherOECDMembercountriesinordertoensurecontinuedacceptanceoftheirdatainthelargeU.S.market.OECD'sinvolvementflowedlogicallyfromaprinciplepurposeofallofitsprogramstheavoidanceofnontarifftradebarriersbetweenOECDMembercountriesasaconsequenceofnationalregulatoryprograms.%@݌̌ ;;  ! X` X!  ;B.` hp x (#XB ;% ;;  ?+ ` hp x (#X?  %9  OECDGLPprogram,datingfromitsfirstexpertgroupin1978,hashadthreephases.ThefirstinvolvedworkofanexpertgroupthatresultedintheOECDPrinciplesofGLP,[1]publishedin1981asanannextotheOECDCouncilDecisiononMutualAcceptanceofData.[2]ThesecondinvolvedanefforttoaddressactualMembercountrycompliancewithGLP,andtheinternationalacceptabilityofnationalGLPcomplianceprograms.Thiseffortresultedinthe1989CouncilDecisionRecommendationsonCompliancewithPrinciplesofGoodLaboratoryPractices.[3]AttachedtothisCouncilActweretwoimportantdocumentsdevelopedbyearlierexpertgroups:"GuidesforComplianceMonitoringProceduresforGoodLaboratoryPractices"and"GuidancefortheConductofLaboratoryInspectionsandStudyAudits."Thesetwodocumentswererevisedin1995.[4][5]Thethird,andcurrentphase,hasinvolvedvariousactivitiesoftheOECDPanelonGoodLaboratoryPracticetoensureaforumforinformationexchangeandevaluationofeachothersprograms,andincludesanongoingeffortforthecontinuedgrowthoftheOECD -'- МPrinciplesofGLP.%9݌̌ ;;  ! X` X!  ; B.` hp x (#XB &%%&&%%&  "  &%%&&%%&  v݌ , Ќ ! XX!   ; ;; ?+ ` hp x (#X? XBX%& XBXXXB   h   2  2  .3    DescriptionoftheQualitySystems,TradeIssuesandRegulatory  RequirementshF݌̌ ;;! X` X! &%XB  &%&   % ;;  ?+ ` hp x (#X?  %  Asnotedabove,amajorpurposeoftheOECDProgramonGLPsistheavoidanceofnontariff  R tradebarriersthatcouldresultasaconsequenceofOECDMembercountriesestablishingregulatoryprogramsthatwereinconsistentwitheachother.Thus,itisfrequentlystatedthatthegoaloftheOECDprogramisthe"internationalharmonization"ofGLPrequirements.Ingeneral,theOECDMembercountrieswithnationalGLPprogramshaveadoptedtheOECDPrincipleofGLPastheirbasicstandard,asrequiredbythe1981CouncilAct.Thisisespeciallytrueforthe15memberstatesoftheEuropeanUnion,(whosestandardistheOECDPrinciplesverbatim),Japan(MHW,MAFF,MITI),theUnitedStates(FDAandEPA),andSwitzerland.Ingeneral,thereisaveryhighdegreeofharmonizationamongstthesecountries.NewerprogramsbasedonGLParebeingdevelopedinCanada,MexicoandBrazil.%N݌̌ ;;  ! X` X!  ;B.` hp x (#XB ;% ;;  ?+ ` hp x (#X?  %#  Anunresolvedfactorandmajorissueexistsinthedifferencesbetween internationaltrade  standardssanctionedbytheWorldTradeOrganization,verses regulatorystandards  implementedthroughcountryspecificregulationsforhealthandenvironmentaltestingprogramsofregulatedproducts(i.e.pesticides,pharmaceuticals,veterinaryproducts,andmedicaldevices).ThesedifferencesaregivensignificanceintheGATTagreementwhichreferencetheISOStandardsastheinternationaltradestandardsandnottheGLPs,whichareimplementedascountryspecificregulatorystandardsfortestingtheseaffectedproducts.Interestinglyenough,theNAFTAagreementdoesindeedreferencetheGLPregulatorystandardasonetobesupported.ISOGuide25isusedtoevaluatelaboratoriesundertheISOsystem.%#-$݌̌ ;;  ! X` X!  ;B.` hp x (#XB#bbdd ;% ;;  ?+ ` hp x (#X?  %{(  InAugust,1996,apublicationbytheU.S.DepartmentofCommercestatesthat Mexicoallowsthe ^ certificationofaqualitysystem#ddbbto#bbddԀserveasthebasisforproductcertification...Thequalitysystem : certificationsarebaseduponISO9000requirements.[6]Areviewoftradeincentivescan f concludethatindevelopingcountrieswhereenvironmentalandhealthregulationshavenotyetbeenimplementedandgovernmentfundsarelimited,thequalitystandardsareoftenprivatizedanddrivenbyvoluntaryeconomicmarkets,ratherthanregulatorymandates.TheoutfallofthesedifferencesalongwiththeprominenceofISOhaspromotedthedevelopmentofnumerousAccreditationprograms,includingNELACandaneweronecalledTheNationalCouncilforLaboratoryAccreditation.ThesuccessfulapplicationoftheseprogramstoGLPregulatedprogramsisstillquestionable.%{((݌̌ ;;  ! X` X!  ;B.` hp x (#XB ; ;; ?+ ` hp x (#X? XBX%& XBXXXB   -   2  3  .3    #ddbbDescriptionoftheOECDProgramonGLP-z.݌ "' & Ќ ;;! X` X! &%XB  &%&   % ;;  ?+ ` hp x (#X?  %/  #bbddInmanyofthenationalprogramsinEurope,primaryemphasisisplacedonthesiteevaluation, ("( ratherthanthedataauditindeterminingGLPCompliance.InseveralEuropeancountries,apreliminaryGLPsiteinspectionisconductedattherequestofthelaboratory.Aftersuccessfullycompletingthisinspection,thelaboratoryisplacedonanationallistofGLPfacilities,andreinspected#ddbbapproximately#bbddԀeverytwoyearsthereafter.Thisprocessproducesaregistryofactive `,&, GLPlaboratories.IntheU.S.program,ontheotherhand,emphasisisplacedonthestudyaudit <-&- andtheaccuracyofthecompliancestatementthatmustaccompanystudies#ddbbsubmitted#bbddԀtoFDAand P EPA.InspectionsaretargetedbyEPAbasedonthenumberandstudytypesubmittedbythelaboratorytotheAgency;therefore,prequalificationinspectionsarenotpartoftheU.S.system.Rather,intheU.S.program,administrativepenaltyactionsforfalsecomplianceisonemethodofachievingcompliance.ThepossibilityofstudyrejectionfornoncompliancewithGLPalsoplaysaroleinachievingGLPcompliance.%/n0݌̌ ;;  ! X` X!  ;E1X` hp x (#XE ;% ;;  ?+ ` hp x (#XX?  %;6  EquallyrelevanttoanalyzingtheimpactandconditionsofaU.S.GLPAccreditationprogramistheevaluationofexistingbilateralagreementsandMOUbetweentheU.S.andOECDMembercountries.[6]TheseagreementsreiterateprovisionsformeetingtheMutualAcceptanceofDataAgreementandgoals,includingpromotionofdataacceptanceandreciprocityamongstparticipatingcountries,andcontinuedcooperativerelationshipbetweencountries.Requirementscanbesummarizedintofourgeneral#ddbbconditions#bbdd;1)AdherencetostandardsofGLPbasedon P  nationalGLPprogramsandtheOECDCouncilRecommendationsandDecisions;2)Mutuallyconsistentnationalprograms,includingperiodic(approximatelyeverytwoyears)inspectionsbytrainedgovernmentinspectors(orgovernmentsanctionedprograms);3)Nationalcomplianceprocedures,includingnotifyinglaboratoriesofobserveddeficienciesandrequirementsforcorrectiveaction;and4)#ddbbPeriodically#bbdd,providingthesignatorieswithnamesandaddressesofnon  clinicalHealth,Safety&Environmentallaboratoriesoperatingwithinthecountryandthedatesofinspection,andcurrentcompliancestatus,andhonoringappropriaterequestsbyothersignatoriestoconductGLPinspectionsdataauditsofitsnonclinicallaboratories.%;66݌̌ ;;  ! XX` X!  ;E1X` hp x (#XXE ;% ;;  ?+ ` hp x (#XX?  %=  NoneoftheserequirementseithernegateorpromotetheconceptofdevelopingaU.S.GLPLaboratoryAccreditationprogram.Criticalhowever,toevaluatingtheimpactofaccreditationontheU.S.EPAGLPprogramisthepreambleto#ddbbthe#bbddԀdocumententitled"RevisedGuidefor  ComplianceMonitoringProceduresforGoodLaboratoryPractices".[4]Thepreambleofthisdocumentrecognizesthat..."MembercountrieswilladoptGLPPrinciplesandestablishcompliancemonitoringproceduresaccordingtonationallegalandadministrativepractices..."Thus,itwould#ddbbappear#bbddԀevidentthatEPAcouldestablishathirdpartyaccreditationprogramwhere ` actualfacilityinspectionswereconductedbyanongovernmentalthirdpartyorganization,aslongasEPAplayedanappropriateroleinestablishingandoverseeingtheprogram.ConsistentwiththisconclusionistheactualpracticeofanumberofOECDMembercountriesthatparticipateintheactivitiesoftheOECDPanelonGLP.Thus,intheUnitedKingdom,France,Australia,Norway,andSwedenGLPassessmentofatleastsometestfacilitiesiscarriedoutbynongovernmentalaccreditationbodies.%=v=݌̌ ;;  ! XX` X!  ;E1X` hp x (#XXE ;% ;;  ?+ ` hp x (#XX?  %?C  InSwitzerland,France,Germany,Australia,Ireland,andtheU.K.,CertificatesofGLPCompliancearegiventolaboratories#ddbbafter#bbddԀsuccessfullycompletingthenationalGLPmonitoringprocess.In &% Japan,thepesticideGLPprogramisregulatedunderTheMinistryforAgriculture,ForestryandFisheries(MAFF).MAFFalsoissuesaCertificateforGLPcomplianceformammaliantoxicologylaboratories,butnotforenvironmentallaboratories.These#ddbbprograms#bbddԀhavebeenreferred (`"( toas"quasiaccreditation"forGLPcompliance.InEurope,approvedlaboratoriesareplacedonalistwhichispublishedeachyear;thus,successfulcompletionoftheGLPassessmentprogramdirectlyaffectsthereputationandmarketofthelaboratory.TheUnitedStateshasnosuchapprovalsystemorGLPCertificate,makingitdifficultforinternationalregulatorsandcorporationstoascertaintheGLPcompliancestatusofmanyU.S.laboratories.%?CC݌̌ ;;  ! XX` X!  ;E1X` hp x (#XXE -'.  ;% ;;  ?+ ` hp x (#XX?  %H  Asignificantconsequenceofthesedifferences(i.e.someinspectionsconductedbynongovernmentpersonnelandissuingaGLPCertificate)isthatmostlaboratoriesfromEuropeandJapanparticipatinginGLPprograms#ddbbareinspected#bbddԀapproximately#ddbbevery#bbddԀtwoyears,andare  generallyprequalifiedbeforeconductinganyGLPworkorsubmittinganystudiestoregulatoryauthority.ProponentsofdevelopinganinternationalGLPLaboratoryAccreditationStandardseethisasasignificantadvantageinevaluatingGLPcomplianceanddatausedforregulatorypurposes.[7]%H(I݌̌ ;;  ! XX` X!  ;E1X` hp x (#XXE : ;: ?+ ` hp x (#XX? XBX%& XBXXXB   L   &  2  4  .3    #ddbbOECDPositionofLaboratoryAccreditationLzM݌ 0  Ќ :;! XX` X! &%XB  &%&   % ;:  ?+ ` hp x (#XX?  % O  & A #bbddAsnotedabove,OECDtestfacilitycompliancewithGLPhasbeenassessedbyprivate   accreditationbodies,inthecaseofIreland,Australia,France,andSweden,orbynongovernmentinspectorscontractedbynationalities,withoutformalobjectionbytheOECDCouncil.However,theOECDhastakenafirmpositionregardingprogrammaticrequirementsandscopeoftheaccreditationprocess.In1994,anOECDworkinggrouppreparedadocument#ddbbentitled#bbddԀ"TheUse n  ofLaboratoryAccreditationwithReferencetoGLPComplianceMonitoring:PositionoftheOECDPanelonGoodLaboratoryPractices",whichwaslateradoptedbytheOECDPanelonGLPandratifiedbyhigherlevelbodiesinOECD.ThisdocumentexpresslyrejectstheideathatISO/IECGuide25isequivalenttotheOECDPrinciplesofGLP,andgoesontogivethefollowingguidelines:% O}O݌̌ :;  ! XX` X!  :E1X` hp x (#XXE' 0 O ;% ;;  ?+ ` hp x (#XX?  % T  "Requirements,whilecalledforinlaboratoryaccreditation,aremorestringentunderGLP...ThereforedatageneratedsolelyunderISO/#ddbbIEC#bbddԀGuide25orequivalentstandardsisunlikelytobe N acceptedbyregulatoryauthoritiesforpurposesofassessmentofchemicalsrelatedtoprotectionofhealthandtheenvironment."[8]% TT݌̌ ;;  ! XX` X!  ;E1X` hp x (#XXE ;% ;;  ?+ ` hp x (#XX?  %V  Forthisreason,thedevelopmentofanyU.S.GLPLaboratoryAccreditationprogrammustbebasedupontheOECDGLPStandardoritsrecognizednationalequivalentratherthanontheISO/IECGuide25program.%VcW݌̌ ;;  ! XX` X!  ;E1X` hp x (#XXE ; ;; ?+ ` hp x (#XX? XBX%& XBXXXB   Y   2  5  .3    #ddbbGeneralConclusionYY݌ .  Ќ ;;! XX` X! &%XB  &%&   % ;;  ?+ ` hp x (#XX?  %[[  #bbddTheGLPistheprimaryinternationalstandardusedtoregulatedataintegrityandpracticesin !  laboratoriesconductinghealthand#ddbbenvironmental#bbddԀpreclinicalstudiesonpesticides, "! pharmaceutical/veterinaryproducts,andchemicals.Studiesareconductedproactivelytoassesstheriskoftheseproductstohumanhealthandtheenvironment.ApplicationoftheinternationalGLPprogramisdevelopedbyconsensusthroughtheOECDGLPPanelandMembercountries.Thisconsensusisadoptedbygovernmentsintonationalprograms.ThereisnothinginherentintheOECDGoodLaboratoryPracticeCouncilActs(1981;1989),ortheOECDGLPprogramestablishedasaconsequenceoftheseCouncilActs,thatwouldpreventtheU.S.EPAfromestablishingathirdparty,orothertypeofaccreditationprogram.However,CouncilActsdoputcertainrestrictionsonthedevelopmentandimplementationofsuchanaccreditationprogram;1)thatthestandardforaccreditationistheOECDPrinciplesofGoodLaboratoryPractices,oritsequivalent,2)thatgovernmentauthoritiesstandbehindtheaccreditationprogram,and3)periodicinspectionsbeconductedapproximatelyevery2years.%[[[݌̌ ;;  ! XX` X!  ;E1X` hp x (#XXE .'.    U *PUE1X` hp x (#XXE .%&.. #bbbb   a  2  IV  .3    Group3SurveytoEstimatecostofepaglpcompliance P monitoringprogram ab݌̌ J ' H#qAJ XXXX &%..&%& #bbbb  C  Hq C  E1X` hp x (#XXE    E1X` hp x (#XXE#bbbb  Ze  TheEnvironmentalLaboratoryAccreditationBoard(ELAB)GLPsubcommittee,whichiscomposed  M ofrepresentativesfromindustry,sponsors,laboratories,contractors,Agency(EPAandFDA),andconsultants,hasbeenworkingveryhardatidentifyingalternativesandoptionstothecurrentEPAGLPComplianceMonitoringProgramtatmaybeconsideredundertheNationalEnvironmentalLaboratoryAccreditationProgram(NELAP)umbrella.Thissubcommitteeestablishedthreeworkingteamswiththefollowingtasks:Team1Evaluatealternativeprogramoptions;Team2Examinetheinternationalimplicationsandinteragencyaspectsofthevariousprogramoptions;and,Team3Developcostestimatesandbenefitsforthevariousoptions.Zee݌̌    XXXX#bbbb     E1X` hp x (#XXE#bbbb  di  dii݌̌    XXXX#bbbb     E1X` hp x (#XXE#bbbb  ~j  InanefforttodeterminethecurrentEPAGLPprogramcost,Team3hasputtogetherthesurvey(see Y  below).WeareinterestedininformationoncurrentGLPprogram(s)includingthecostofmaintaininganactivequalityassuranceprogram,conductingGLPstudies,andallancillaryactivitiesassociatedwithacompliancemonitoringprogram,suchasSOPs,archive,training(externalandinternal),inspections(preparation,audit,andresponsetofindings),etc.Alldatawillbetreatedconfidentiallybythesubcommittee.ThecompletedsurveyshouldbesenttotheSocietyofQualityAssurance.~j k݌̌    XXXX#bbbb     E1X` hp x (#XXE#bbbb  n  nn݌̌    XXXX#bbbb     E1X` hp x (#XXE#bbbb  o  Theinformationprovidedwillbeusedasabaselineforcomparingthecostandbenefitofimplementing ]  recommendationsfromTeam1.Onlystatisticalaverageswillbeusedwithnomentionofindividualentities.However,pleaseindicatewhetheryouareasponsor,contractlaboratory,fieldresearchcontractor,independentconsultantorother.ThecompositeinformationwillbeavailabletoallparticipatingcompaniesatthenextSQAmeetinganduponrequest.oo݌̌    XXXX#bbbb     E1X` hp x (#XXE#bbbb  r  rr݌̌    XXXX#bbbb     E1X` hp x (#XXE#bbbb  3s  Yourinputisveryimportant.RecommendationsfromtheELABGLPsubcommitteewillaffecthow 5 wewillconductourbusinessinthefutureaswellasthecostofdoingbusiness.Ifyouarenotthepersonwithinyourorganizationwhocanprovidetheinformationrequested,pleaseforwardthislettertotheproperindividual.3ss݌̌    XXXX#bbbb     E1X` hp x (#XXE#bbbb  u  u0v݌̌    XXXX#bbbb     E1X` hp x (#XXE#bbbb  v  TheELABGLPsubcommitteeverymuchappreciatesyourtimeandhelp.vJw݌   Ќ    XXXX#bbbb     E1X` hp x (#XXE#bbbb  /x  /xx݌̌    XXXX#bbbb     E1X` hp x (#XXE#bbbb  Iy  Sincerely,Iyy݌ "9  Ќ    XXXX#bbbb     E1X` hp x (#XXE#bbbb  z  z {݌̌    XXXX#bbbb     E1X` hp x (#XXE#bbbb  {  {'|݌̌    XXXX#bbbb     E1X` hp x (#XXE#bbbb  |  6" X` x (#XX6JimFlowers,DowElanco `   Team3|A}݌ %# Ќ   - XXX`X-#bbbb     E1X` hp x (#XXE#bbbb  \~  3 X` x (#XX3Team3Chair ` FredSiegelman,EPA  DebiGarvin,PacificRimConsulting\~~݌ %$ Ќ   * XXX`X*#bbbb     E1X` hp x (#XXE#bbbb  #  3 X` x (#XX3(317)3373554 ` TammyWhite,RutgersUniv.  RayMcAllister,ACPA#݌ & % Ќ   * XXX`X*#bbbb     E1X` hp x (#XXE#bbbb    p݌̌    XXXX#bbbb     E1X` hp x (#XXE#bbbb    ݌̌    XXXX#bbbb     E1X` hp x (#XXE#bbbb    %& SURVEYTOESTIMATECOSTOFEPAGLPCOMPLIANCEMONITORINGPROGRAM1996݌ i)#( Ќ    XXXX#bbbb     E1X` hp x (#XXE#bbbb    <݌̌    XXXX#bbbb     E1X` hp x (#XXE#bbbb  І  1.Pleaseprovideyourcompanys1996costindollarstoexecuteyourEPAGLPcomplianceprogram.І\݌ *$* Ќ    XXXX#bbbb     E1X` hp x (#XXE#bbbb  c  c݌̌    XXXX#bbbb     E1X` hp x (#XXE#bbbb  }  -Xu$#(#XX-a) u QAUannualbudgetindollars   $# } ݌ ,A&, Ќ   - XXXu$#-#bbbb     E1X` hp x (#XXE#bbbb  /  -Xu$#(#XX- u NumberofQAauditors   $# /݌ [- '- Ќ   - XXXu$#-#bbbb  ݛ   E1X` hp x (#XXE#bbbb  ٌ  -Xu$#(#XX-ٌe݌̌   - XXXu$#-#bbbb     E1X` hp x (#XXE#bbbb  /  -Xu$#(#XX- u   Ifnotincludedintheabove:/݌  Ќ   - XXXu$#-#bbbb     E1X` hp x (#XXE#bbbb  Ώ  -Xu$#(#XX- u   QAUsalaries/benefits/bonuses   $# ΏZ݌  Ќ   - XXXu$#-#bbbb     E1X` hp x (#XXE#bbbb    -Xu$#(#XX- u   Proportionalsalariesandexpensesforpersonsdevotingaportionof   $# ݌ ^ Ќ   - XXXu$#-#bbbb     E1X` hp x (#XXE#bbbb  q  -Xu$#(#XX- u   theirtimetoGLPactivities(e.g.,archivist,training,etc.)q݌ x ( Ќ   - XXXu$#-#bbbb     E1X` hp x (#XXE#bbbb  3  -Xu$#(#XX- u   QAUtravelexpense(inspections,audits)   $# 3݌ B  Ќ   - XXXu$#-#bbbb     E1X` hp x (#XXE#bbbb    -Xu$#(#XX- u   GLPtrainingexpensecontractedorreceivedatmeetingssuchasSQA   $# ݌   Ќ   - XXXu$#-#bbbb     E1X` hp x (#XXE#bbbb    -Xu$#(#XX- u   Outsidecontractorcostsfortraining   $# p݌   Ќ   - XXXu$#-#bbbb     E1X` hp x (#XXE#bbbb    -Xu$#(#XX- u   Outsidecontractorcostsforauditing/inspecting   $# 5݌  P Ќ   - XXXu$#-#bbbb     E1X` hp x (#XXE#bbbb  y  -Xu$#(#XX- u   Othercost(pleasespecify)   $# y݌ j   Ќ   - XXXu$#-#bbbb     E1X` hp x (#XXE#bbbb  4  -Xu$#(#XX-4݌̌   - XXXu$#-#bbbb     E1X` hp x (#XXE#bbbb    -Xu$#(#XX-b) u R&DdollarsspentforGLPs.   $# ݌   Ќ   - XXXu$#-#bbbb     E1X` hp x (#XXE#bbbb  =  -Xu$#(#XX- u   IncludeexpensesofSOPs,archives,protocolpreparation,preparationfor=ɡ݌ x  Ќ   - XXXu$#-#bbbb     E1X` hp x (#XXE#bbbb     -Xu$#(#XX- u   audit,audit,responsestoaudits,correctionofauditfindings,labeling,special ݌ B  Ќ   - XXXu$#-#bbbb     E1X` hp x (#XXE#bbbb  ޤ  -Xu$#(#XX- u   documentationnotexpectedifworkwasnotconductedundertheGLPs(ifnotޤj݌ \  Ќ   - XXXu$#-#bbbb     E1X` hp x (#XXE#bbbb    -Xu$#(#XX- u   includedabove).9݌ &  Ќ   - XXXu$#-#bbbb     E1X` hp x (#XXE#bbbb  ?  -Xu$#(#XX-?˨݌̌   - XXXu$#-#bbbb     E1X` hp x (#XXE#bbbb    -Xu$#(#XX-2. u Pleaseprovideyour1996audit/inspectionhistoryforEPA/GLPcompliance.!݌ j  Ќ   - XXXu$#-#bbbb     E1X` hp x (#XXE#bbbb  X  -Xu$#(#XX-X݌̌   - XXXu$#-#bbbb     E1X` hp x (#XXE#bbbb    -Xu$#(#XX- u NumberofGLPstudiesinitiated   $# :݌ N Ќ   - XXXu$#-#bbbb     E1X` hp x (#XXE#bbbb  c  -Xu$#(#XX- u Numberofprotocolauditsconducted   $# c݌  Ќ   - XXXu$#-#bbbb     E1X` hp x (#XXE#bbbb    -Xu$#(#XX- u Numberofinprogressinspectionsconducted   $# ݌  Ќ   - XXXu$#-#bbbb     E1X` hp x (#XXE#bbbb  ٱ  -Xu$#(#XX- u Numberofdataauditsconducted   $# ٱe݌ \ Ќ   - XXXu$#-#bbbb     E1X` hp x (#XXE#bbbb    -Xu$#(#XX- u Percentageofstudiescontractedtooutsidefacilities   $# ݌ v& Ќ   - XXXu$#-#bbbb     E1X` hp x (#XXE#bbbb  V  -Xu$#(#XX- u Numberinternal(company)facilityinspectionsconducted   $# V݌ @ Ќ   - XXXu$#-#bbbb     E1X` hp x (#XXE#bbbb  "  -Xu$#(#XX- u Numberexternalfacilityinspectionsconducted   $# "݌   Ќ   - XXXu$#-#bbbb     E1X` hp x (#XXE#bbbb    -Xu$#(#XX- u Numberexternal(contract)facilityinspectionshosted   $# p݌  Ќ   - XXXu$#-#bbbb     E1X` hp x (#XXE#bbbb    -Xu$#(#XX- u NumberofEPAfacilityinspectionshosted   $# :݌ N Ќ   - XXXu$#-#bbbb     E1X` hp x (#XXE#bbbb  k  -Xu$#(#XX-k݌̌   - XXXu$#-#bbbb     E1X` hp x (#XXE#bbbb    -Xu$#(#XX-3. u Pleaseprovideatelephonenumberandcontactnameshouldquestionsconcerningthissurveyarise.M݌ 2 Ќ   - XXXu$#-#bbbb     E1X` hp x (#XXE#bbbb    -Xu$#(#XX-&݌̌   - XXXu$#-#bbbb     E1X` hp x (#XXE#bbbb    0XuL9`$#(#XX0 u Name: L  9 Pleasecheckonebox:|݌ v Ќ   0 XXXuL9`$#0#bbbb     E1X` hp x (#XXE#bbbb    0XuL9`$#(#XX0 u Company: L  9 .&%.Sponsor ` .%&&%.FieldResearchContractor1݌ @  Ќ   0 XXXuL9`$#0#bbbb     E1X` hp x (#XXE#bbbb    0XuL9`$#(#XX0 u Phone: L  9 .%&&%.Contract ` .%&&%.IndependentConsultant݌  X! Ќ   0 XXXuL9`$#0#bbbb     E1X` hp x (#XXE#bbbb  I  0XuL9`$#(#XX0 u Fax: L  9 Laboratory ` I݌ !p" Ќ   0 XXXuL9`$#0#bbbb     E1X` hp x (#XXE#bbbb    0XuL9`$#(#XX0 u Email: L  9 .%&&%.Other___________________________݌ "L# Ќ   0 XXXuL9`$#0#bbbb     E1X` hp x (#XXE#bbbb    0XuL9`$#(#XX0݌̌   0 XXXuL9`$#0#bbbb     E1X` hp x (#XXE#bbbb  c  0XuL9`$#(#XX0Thankyouforyourassistanceinthisimportantproject.Thisdatawillbeusedforcomparingcostfor $@% theimplementationofaGLPcompliancemonitoringprogram.Ifyoureceivemorethanonesurvey,pleasecompleteonlyone.ReturnsurveybyJanuary15,1997.c݌̌   0 XXXuL9`$#0#bbbb     E1X` hp x (#XXE#bbbb    0XuL9`$#(#XX0g݌̌   0 XXXuL9`$#0#bbbb     E1X` hp x (#XXE#bbbb  7  0XuL9`$#(#XX0Returnsurveyto:SocietyofQualityAssurance,515KingSt.,Suite420,Alexandria,VA22314.7݌ (!) Ќ   0 XXXuL9`$#0#bbbb     E1X` hp x (#XXE#bbbb    0XuL9`$#(#XX0݌̌   0 XXXuL9`$#0#bbbb     E1X` hp x (#XXE#bbbb  b  0XuL9`$#(#XX0Allinformationprovidedisconfidential;noindividualcompanynamesorrespondeeswillbementioned )h#+ inthesurveyresults.Statisticalaveragesonly.%&b݌ *D$, Ќ   0 XXXuL9`$#0#bbbb  E1X` hp x (#XXE&% C  H(-& CE1X` hp x (#XXE (-&/  N NN B.` hp x (#XXB .%& ..        2  A  .3    #ddbbAPPENDIXAGLPSUBCOMITTEE݌ P  NN! XXX! &%..  &%&     E1X` hp x (#XXE#bbddMailingAddresses: k  NE1X` hp x (#XXE 3a XaLp x (#XX3RayMcAllister L JohnHenshaw #  ТACPA,Suite400 L Monsanto   1156FifteenthStreet,NW L 800N.LindberghBlvd.   Washington,DC20005 L St.Louis,MO63167  g Phone:2028723874 L Phone:3146948830  C Fax:2024630474 L Fax:3146945500 o  email:ray@acpa.org L email:jlhens@ccmail.monsanto.com K  MaureenBarge L FranDillon   ТFMC L StewartPesticideRegistrationAssociates   POBox8 L 1901NorthMooreSt.,Suite603 k  Princeton,NJ08543 L Arlington,VA22209 G  Phone:6099513479 L Phone:7035273601ext.3003 s# Fax:6099513670 L Fax:7035273602 O JimmyFlowers L DebiGarvin  DowElanco L PacificRimConsulting  9410ZionsvilleRd.,Bldg.306 L 4730LondonDrive o POBox68955 L Mt.Hood,OR97041 K Indianapolis,IN462681053 L Phone:5413527120 w' Phone:3173373554 L Fax:5413527121 S Fax:3173373237 L email:prcwcqti@gorge.net / CliveHalder L LouiseHess  8400HawthorneRoad L LancasterLaboratories s KansasCity,MO64120 L 2425NewHollandPike O Phone:8162422110 L POBox12425 { + Fax:8162422753 L Lancaster,PA176052425 W! Phone:8162422110 L Phone:7176562301 3"  Fax:9134335125 L Fax:7176562681 #! email:clive.halder.b@bayer.comWynnJohn L RobertKiefer %S$ ТDuPontAgProducts L ChemicalSpecialtiesMfrs.Assoc.Inc. &/ % POBox80038 L 1913EyeStreet,NW [' !& ТRts.141&48 L Washington,DE200062106 7(!' Wilmington,DE198800038 L Phone:2028728110 )"( Phone:3029926029 L Fax:2028728114 )#) Fax:3029922276email:johnww@csag1.dnet.dupont.com  ,3&,  <d XdLp x (#aXaLpX<& P  JohnD.Kobland L DorisMason P AmericanCyanamideCompany L RhonePoulencAg , AgriculturalProductsRes.Div. L 2T.W.AlexanderDrive  POBox400 L ResearchTrianglePark,NC27709  101GroversMillRoad(shipping) L Phone:9195492731  p ТLaurenceville,NJ08648(shipping) L Fax:9195492387  L Princeton,NJ085430400Phone:6097162477Fax:6092753580Internet:kobland@pt.cyanamid.com <a XaLp x (#dXdLpX<'P P~JohnMcCann L MickQualls t  ABCLaboratories L QuallsAgLaboratory P  348RiversideRoad L 3579DodsonRoad |,  Edgewater,MD21307 L Ephrata,WA98823 X  Phone:4109566221 L Phone:5097874210 4  Fax:4109566221 L Fax:5097874966   RoxanneRobinson L PatriciaOBrienPomerleau x ТA2LA L CIIT T 656QuinceOrchardRd.,Suite620 L 6DavisDrive 0 Gaithersburg,MD30878 L ResearchTrianglePark,NC27709 \  Phone:3016701377 L Phone:9195581341 8 Fax:3018691495 L Fax:9195581300  email:a21a@aol.comGaryRoy L PatriciaRoyal X AlliedSignal,Toxicology L QualitySystemsConsultant 4 POBox1139 L 24ProspectCourt ` 101ColumbiaRoad L Kingston,MA02364 < ТMorristown,NJ079621139 L Phone:6175859370   Phone:2014554994 L Fax:5082958107   Fax:2014555405email:royg@mtomp003.allied.comPaulSwidersky L LeeWest d$# QualityAssociates,Inc. L RDA&NAICC @%$ 10310BBaltimoreNationalPkwy. L 2345East16thStreet &% ТEllicottCity,MD21042 L Yuma,AZ85365 & & Phone:4104652511or2725 L Phone:5207833552 '!' Fax:4104652728 L Fax:5207833877 (`"( email:7541,633@compuserve.com L email:WestYuma@aol.com )<#)   h*$*  <d XdLp x (#aXaLpX<&   TammyWhite L StanWoollen P USDA/IR4,NJAgExp.Station L U.S.FDA,DivisionofCompliancePolicy , CookCollege L 7520StandishPlace  POBox231 L Rockville,MD20855  NewBrunswick,NJ089030231 L Phone:3015940020  p Phone:9089329575 L Fax:3015941204  L Fax:9089328481 L email:swoollen@FDAem.ssw.dhhs.gov x ( email:white@aesop.rutgers.edu <a XaLp x (#dXdLpX<'PDavidAlexander L DavidDull    U.S.EPA(7501C) L U.S.EPA(2225A)   401MStreetSW L 401MStreetSW t  Washington,DC20460 L Washington,DC20460 P  Phone:7033057678 L Phone:2025642320 |,  Fax:7033081850 L Fax:2025640028 X  email:Alexander.david@epamail.epa.gov L email:dull.david@epamail.epa.gov 4  ̢FranciscaLiem L JeanneMourrain  U.S.EPA(2225A), L EPAAREAL x 401MStreet,SW L U.S.EPA(MD75) T Washington,DC20460 L ResearchTrianglePark,NC27711 0 Phone:2025642365 L Phone:9195411120 \  Fax:2025640029 L Fax:9195414101 8 email:liem.francisca@epamail.epa.govChrisOlinger L FredSiegelman | U.S.EPA(7509C),Room816 L U.S.EPA(2225A) X 401M.Street,SW L 401M.Street,SW 4 Washington,DC20460 L Washington,DC20460 ` Phone:7033055406 L Phone:2025644159 < Fax:7033055147 L Fax:2025640029   email:olinger.christine@epamail.epa.gov L email:siegelman.frederic@epamail.epa.gov   GeorgeFongFloridaEnvironmentalAdmin.̢FDACS,ChemicalResidueLab3125ConnerBlvd.Tallahassee,FL323991650Phone:9044889670Fax:9049229110 N NN K.` hp x (#aXaLpXK .%& ..   `     2  B  .3    `M݌  )<#) Ќ NN*aXaLpXX* &%..  &%&    NN K.` hp x (#aXaLpXK .%& ..      #ddbbAPPENDIXBGLOSSARYOFTERMS݌ P Ќ NN*aXaLpXX* &%..  &%&    NN  K.` hp x (#aXaLpXK    S݌̌ NN  *aXaLpXX*   NN  K.` hp x (#aXaLpXK    InPreparation...[݌̌ NN  *aXaLpXX*  N  K.` hp x (#aXaLpXK .%& ..      2  C  .3    ݌  #  Ќ *aXaLpXX* &%..  &%&     K.` hp x (#aXaLpXK .%& ..   C   APPENDIXCCRITERIAFORLISTOFOPTIONSC0݌ P Ќ *aXaLpXX* &%..  &%&   N NN  K.` hp x (#aXaLpXK  p  p݌̌ NN  *aXaLpXX*   NN  K.` hp x (#aXaLpXK  x  InPreparation...x݌̌ NN  *aXaLpXX*  N  K.` hp x (#aXaLpXK .%& ..      2  D  .3    ݌  #  Ќ *aXaLpXX* &%..  &%&     K.` hp x (#aXaLpXK .%& ..      APPENDIXDDRAFTSUMMARYREPORT݌ P Ќ *aXaLpXX* &%..  &%&   N NN  K.` hp x (#aXaLpXK       ݌̌ NN  *aXaLpXX*   NN  K.` hp x (#aXaLpXK     InPreparation...  ݌̌ NN  *aXaLpXX*  N   K.` hp x (#aXaLpXK .%& ..    4    2  E  .3     4 ! ݌  #  Ќ *aXaLpXX* &%..  &%&      K.` hp x (#aXaLpXK .%& ..    u   APPENDIXEMATRIX ub݌ P Ќ *aXaLpXX* &%..  &%&     K.` hp x (#aXaLpXK .%& ..   ~   2  F  .3    ~k݌  k Ќ *aXaLpXX* &%..  &%&     K.` hp x (#aXaLpXK .%& ..      APPENDIXF݌ P Ќ *aXaLpXX* &%..  &%&   N NN  K.` hp x (#aXaLpXK    N݌̌ NN  *aXaLpXX*   NN  K.` hp x (#aXaLpXK    InPreparation...V݌̌ NN  *aXaLpXX*  N*  K.` hp x (#aXaLpXK .%& ..   *   2  G  .3    *݌  #  Ќ *aXaLpXX* &%..  &%&   *  K.` hp x (#aXaLpXK .%& ..   *>   ӀReferences:*>+݌  Ќ *aXaLpXX* &%..  &%&   K.` hp x (#aXaLpXK     ..E1uX` hp x (#XE #bbdd     2  1  .3   ` OECD[C(89)87(Final)]PrinciplesofGoodLaboratoryPracticed݌  Ќ    XuXX #ddbb       ..E1uX` hp x (#XE #bbdd     2  2  .3   ` OECD[C(81)30(Final)]CouncilDecisionconcerningMutualAcceptanceofDatainthe ^ AssessmentofChemicals.{݌̌    XuXX #ddbb       ..E1uX` hp x (#XE #bbdd      2  3  .3   ` OECD[C(89)87(Final)]CouncilDecisionRecommendationsofCompliancewithPrinciples  ! ofGoodLaboratoryPractices.  ݌̌    XuXX #ddbb       ..E1uX` hp x (#XE #bbdd  R"   2  4  .3   ` OECDGD(95)66GuidanceforGLPMonitoringAuthorities;RevisedGuideforCompliance d  MonitoringProceduresforGoodLaboratoryPracticeR"#݌̌    XuXX #ddbb       ..E1uX` hp x (#XE #bbdd  $   2  5  .3   ` OECDGD(95)67GuidanceforGLPMonitoringAuthorities:RevisedfortheConductof '  LaboratoryInspectionsandStudyAudits.$s%݌̌    XuXX #ddbb       ..E1uX` hp x (#XE #bbdd  '   2  6  .3   ` U.S.BilateralAgreements;(MOU)variousdates.Switzerland,1985;Japan,1983;Canada, j 1980;Sweden,1980;Italy,1988;U.K.,1988(exp1993);Germany,1988;TheNetherlands,1988''݌̌    XuXX #ddbb       ..E1uX` hp x (#XE #bbdd  )   2  7  .3   ` JohnGilmore;1995GoodLaboratoryPracticeandLaboratoryAccreditation(presentation; - noreference))^*݌̌    XuXX #ddbb       ..E1uX` hp x (#XE #bbdd  +   2  8  .3   ` OECD1994(22JointMeeting)TheUseofLaboratoryAccreditationwithReferencetoGLP p ComplianceMonitoring;PositionoftheOECDPanelonGoodLaboratoryPractice.+,݌̌    XuXX #ddbb    E1X` hp x (#XEC  $$C--.XX/Z,Z    .-/- .  TRO'33''3 Letter Landscape3'T /.;N /  -YX0,XYe*q23 Xddd Xdd Xdd XX81X81q,"/JJ+  [ ;4444( ; 8d;[e[ ;4444( ; 8d;[d 4.%&C&[%%&  da ELABGLPSUBCOMMITTEECOMBINEDCOMMENTS s8 FOURTHDRAFT(11/22/96)OPTIONSFOREPAGLPCOMPLIANCEMONITORINGPROGRAMS ad#&%[%C&V3##&%.73#de7-+s8 8  4444d 7edv3d*q67 Xddd Xdd Xdd XX81X81q,,m , , ,` +  _`f ?4444, ; 8d?ff :4444' ; 8d:f`` 64444#  8d6`_`_ I44446%"4444d dI__ I44446%"4444d dI__ I44446%"4444d dI__ I44446%"4444d dI_`b.%&C'.ELABGLPSUBCOMMITTEECOMBINEDCOMMENTS s8 FOURTHDRAFT(11/22/96)OPTIONSFOREPAGLPCOMPLIANCEMONITORINGPROGRAMS#.'C7##&%.7#bf d4444Q3h" 8  4444d 8ddМff _4444L3h" 8  4444d 8d_fF&*%%&IgTEMghtemh# I44446%"4444d dIProgramDescription I44446%"4444d dIAdvantages I44446%"4444d dIDisadvantages I44446%"4444d dIConstraints W4444D0" 8  4444d 8dW! XXX!FG,*%F& V.APPENDIX   ZC` hp x (#%'0*,.81XZE.Matrix #F&*%,FG;# u4444b%+   8 4444d  ?18d?ud 4dZCXX` hp x (#%'0*,.81XZ1. _4444L; l&  ?1 ?4444d d_From2ndDraft(08/02/96)  F' CurrentEPAGLPComplianceMonitoringProgramNochange @4444-% )4444d d@From2ndDraft(08/02/96)  F* a)NoincreaseincosttoGLPregulatedcommunityb)QualityofGLPdataremainshighc)AssessmentofGLPcomplianceresideswithEPAd)GLPstudiesInternationallyacceptableLouiseHess  2 e)[added]Complianceiswell 3 understoodbytheregulatedcommunityf)[added]Thereareprofessionalgroups(e.g.SQA)setuptofacilitatecomplianceg)[added]Industryhasinvestedheavilyincompliancetocurrentrequirementsh)[added]Nolegislativechangeneeded @4444-=4444d d@From2ndDraft(08/02/96)  F> a)InsufficientcurrentEPAresourcestoadequatelyvisitallϢGLPlaboratoriesb)TotallistofGLPlaboratoriesunknownc)InternationalcommunityrequestsforCompliance"Certificate"notaddressedd)MaynotaddressIGreportconcernse)DoesnotaddressnewGLPlabsLouiseHess YJ f)[added]Compliancelevelsat +K differentfacilitiesmaynotbeequalg)[added]Currentregulationsarevagueinsomeareas.Certificationchangeswouldprovideamechanismtoclarify @4444-E P4444d d@ 4RoxanneRobinson  FQ a)[added]NationalTechnologyTransb  ԍbferAct(bbNTTAbb)signedbyPresidentin03/96,directsgovernmentagenciestonolongerperformdutiesandserviceswhichareavailableintheprivatesector.Thirdpartyaccreditingbodiescanperformaccreditation(compliancemonitoring)presentlydonebyEPAb  b S4444@"_ 8 4444d 8dS 41.Cont. @4444-C^4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringProgramNochange @4444- 4444d d@CliveHalder 8  b)[modified]QualityofGLPdata  ! remainshigh,i.e.currentstandard̢i)[added]CurrentprogramisacceptabletoFDAj)[added]Nodisadvantagetocontractfacilitiesisperceivedk)[added]Noneofthelegal/legislativeissuesconcerningNELACareofconcernherel)[added]CurrentprogramdoesnotjeopardizeOECDharmonizationeffortsm)[added]Problemsassociatedwithlevyingafeewouldbeobviated @4444- .4444d d@CliveHaldere)[modified]NewGLPlabsare  0 overlookeduntildataarealreadysubmitted̢i)[added]ResourcesinsufficienttoallowEPAtostreamlinecomplianceprogramtoallowfordatatobeauditedpriortoproductassessmentbyOPPBranchj)[added]Currentreviewscheduleinappropriateforinstitutingaprogramofaccreditationorforissuingcertificatesofcompliancek)[added]Currentresourcefocusisinappropriate,i.e.,coveringlabswhichcontributeaminorshareofstudies @4444-=X ?4444d d@ 4 S4444@"8@ 8 4444d 8dS 42. @4444-C^4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPCompliance   MonitoringProgram,plusscopeofϢGLP@community:isreevaluated,andGLPcompliancemonitoringisadjustedaccordingly(i.e.,priority/focusredefinedtoenhancethecoverageoftheprimarydatageneratingfacilities) @4444-%4444d d@From2ndDraft(08/02/96) 8& a)NoincreaseincosttoGLPregulatedcommunityb)QualityofGLPdataremainshighc)AssessmentofGLPcomplianceresideswithEPAd)GLPstudiesInternationallyacceptablee)RemovesperceptionofMonitoringgapsforentireGLP@Community:f)TotallistofentireGLPϢ@Community:isknowng)QualityofentireGLPϢ@Community:ispotentiallyknownLouiseHess  4 f)[added]Withoutalistorsometypeofregistrations,howcanthisbeassumed?h)[added]Currentregulationsarevagueinsomeareas.Certificationchangeswouldprovideamechanismtoclarify @4444-Wr;4444d d@From2ndDraft(08/02/96) 8< a)InsufficientcurrentEPA  = resourcestoadequatelyvisitallϢGLPlaboratoriesb)InternationalcommunityrequestsforCompliance"Certificate"notaddressedLouiseHess  C c)[added]Requireschangestobemadethroughlegislativeprocess @4444-E4444d d@ 4RoxanneRobinson 8F a)[added]NationalTechnologyTransferAct(NTTA)signedbyPresidentin03/96,directsgovernmentagenciestonolongerperformdutiesandserviceswhichareavailableintheprivatesector.Thirdpartyaccreditingbodiescanperformaccreditation(compliancemonitoring)presentlydonebyEPA S4444@" T 8 4444d 8dSМ 42.Cont. @4444-C^4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPCompliance   MonitoringProgram,plusscopeofϢGLP@community:isreevaluated,andGLPcompliancemonitoringisadjustedaccordingly(i.e.,priority/focusredefinedtoenhancethecoverageoftheprimarydatageneratingfacilities) @4444-%4444d d@CliveHalderb)[modified]QualityofGLPdata  ' remainshigh,i.e.currentstandarde)[modified]Streamliningofcompliancemonitoringprogramwouldbettersatisfyinternationalconcerns̢i)[added]CurrentprogramisacceptabletoFDAj)[added]Nodisadvantagetocontractfacilitiesisperceivedk)Noneofthelegal/legislativeissuesconcerningNELACareofconcernherel)[added]CurrentprogramdoesnotjeopardizeOECDharmonizationeffortsm)[added]Potentially,streamliningofresourcesmayallowEPAtoauditdatafromprimarydatageneratingfacilitiespriortoproductassessmentbyOPPBranchn)[added]Problemsassociatedwithlevyingafeewouldbeobviated @4444-=4444d d@CliveHalderd)[added]Currentreviewschedule  ? inappropriateforinstitutingaprogramofaccreditationorforissuingcertificatesofcompliancee)[added]SomesmalllaboratorieswillescapeGLPmonitoringcomplianceoverviewf)[added]GLPenforcementincentivewouldbelackingforsmallfacilitieswhich,ingeneral,havethehighestprobabilityofhaving"gaps"incompliance @4444- J4444d d@ 4 S4444@"8K 8 4444d 8dS 43. @4444-C^4444d d@From2ndDraft(08/02/96) 8 CurrentGLPCompliance   MonitoringProgramplusincreasedfundingforadditionalEPAinspectorsfromEPAbudget @4444-e !4444d d@From2ndDraft(08/02/96) 8" a)SufficientresourcestoadequatelyvisitallGLPlaboratoriesb)AssessmentofGLPcomplianceresideswithEPAc)NoincreaseincosttoGLPregulatedcommunityd)WiderInternationalacceptancee)AddressesIGsdataqualityconcernsf)QualityofGLPdataremainshighCliveHalder #> - g)[added]CurrentprogramisacceptabletoFDAh)[added]Nodisadvantagetocontractfacilitiesisperceivedi)[added]Noneofthelegal/legislativeissuesconcerningNELACareofconcernherej)[added]CurrentprogramdoesnotjeopardizeOECDharmonizationefforts @4444-)D84444d d@From2ndDraft(08/02/96) 89 a)CurrentEPAandgovernmentfundingdifficultiesmayhinderdevelopmentofthisoptionb)InternationalcommunityrequestsforCompliance"Certificate"notaddressedc)No@valueadded:tocurrentGLPcompliancefordataqualityLouiseHess B d)[added]Eveniffundingcouldbeobtainednow,thereisnoguaranteethatthefundinglevelwillremainsufficientintothefuture.Therefore,thismaynotbealongtermoptionevenifitwerepossiblenowe)[added]WithoutaregistrationcomponentthetotallistofGLPlaboratorieswouldremainunknown @4444-K4444d d@ 4RoxanneRobinson 8L a)[added]NationalTechnologyTransferAct(NTTA)signedbyPresidentin03/96,directsgovernmentagenciestonolongerperformdutiesandserviceswhichareavailableintheprivatesector.Thirdpartyaccreditingbodiescanperformaccreditation(compliancemonitoring)presentlydonebyEPA S4444@" Z 8 4444d 8dS 43.Cont.  @4444-C^4444d d@From2ndDraft(08/02/96) 8 CurrentGLPCompliance   MonitoringProgramplusincreasedfundingforadditionalEPAinspectorsfromEPAbudget @4444-e !4444d d@CliveHalder(Continued) 8" k)[added]Problemsassociated  # withlevyingafeewouldbeobviatedl)[added]TheaddedresourceswouldallowforEPAtostreamlinecomplianceprogramtoallowfordatatobeauditedpriortoproductassessmentbyOPPBranch @4444- )4444d d@ @4444-8*4444d d@ 4ӛ S4444@"8+ 8 4444d 8dS 44. @4444-C^4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPCompliance   MonitoringProgram,plustheconstructionofaRegistrationListforwhichtheGLP"community"mustsupplyEPAwithdocumentationoftheirGLPprogram.Documentationreviewis  $ performedbyEPAandtoremain % ontheregistrationlistsubmittermustmeetEPAestablishedcriteria @4444-Ql'4444d d@From2ndDraft(08/02/96) 8( a)TotallistofGLPlaboratoriescouldbepreparedb)RegistrationcosttoGLPregulatedcommunitywouldbeminimalc)EPAwouldincuraminimaladministrativecostd)CouldaideEPAinstreamliningonsiteComplianceMonitoringe)EPAwouldprovidelistofRegisteredGLPlaboratoriestoInternationalgovernmentsf)Registration@Certificate:mayaddressInternationalcommunityconcernshgToremainonGLPRegistrationListwouldencourageGLPcomplianceh)QualityofGLPdataremainshigh̢i)AssessmentofGLPcomplianceresideswithEPA @4444-)D>4444d d@From2ndDraft(08/02/96) 8? a)InsufficientcurrentEPAresourcestoadequatelyvisitallϢGLPlaboratoriesb)EPAwouldincuranadministrativecosttomaintainGLPRegistrationListc)No@valueadded:tocurrentϢGLPcompliancefordataqualityd)InternationalcommunityrequestsforCompliance"Certificate"maynotbesatisfiede)EPAwouldhavetodevelopfaircriteriastandards @4444- L4444d d@ 4RoxanneRobinson 8M a)[added]NationalTechnologyTransferAct(NTTA)signedbyPresidentin03/96,directsgovernmentagenciestonolongerperformdutiesandserviceswhichareavailableintheprivatesector.Thirdpartyaccreditingbodiescanperformaccreditation(compliancemonitoring)presentlydonebyEPA.Listingofanykinddoesnotsatisfythe"accreditation"definitionassociatedwithNELACeffortsandinternationalefforts.Accreditation:Procedurebywhichanauthoritativebody S4444@")Dc 8 4444d 8dS 44.Cont. @4444-C^4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPCompliance   MonitoringProgram,plustheconstructionofaRegistrationListforwhichtheGLP"community"mustsupplyEPAwithdocumentationoftheirGLPprogram.Documentationreviewis  $ performedbyEPAandtoremain % ontheregistrationlistsubmittermustmeetEPAestablishedcriteria @4444-Ql'4444d d@CliveHalder 8( h)[modified]QualityofGLPdata  ) remainshigh,i.e.currentstandardj)[added]CurrentprogramisacceptabletoFDAk)[added]Nodisadvantagetocontractfacilitiesisperceivedl)[added]Noneofthelegal/legislativeissuesconcerningNELACareofconcernherem)[added]CurrentprogramdoesnotjeopardizeOECDharmonizationeffortsn)[added]WithEPAcontinuingtoimplementtheprogram,concernsforissuessuchasconflictsofinterest,confidentiality,etc.,wouldbeminimized @4444-*94444d d@CliveHalderf)[added]Resourcesinsufficientto  ; allowEPAtostreamlinecomplianceprogramtoallowfordatatobeauditedpriortoproductassessmentbyOPPBranchg)[added]Notmuchofacomplianceincentivefornoninternationallaboratoriesh)[added]Coverageofsmalllabs(thatcontributeonlyafewstudies/data)woulddilutetheeffectivenessoftheprogram @4444- F4444d d@ 4RoxanneRobinsona)[added](Cont.)  H givesformalrecognition  I thatabodyorpersoniscompetenttocarryoutspecifictasks S4444@" $M 8 4444d 8dS 44.Cont. @4444-C^4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPCompliance   MonitoringProgram,plustheconstructionofaRegistrationListforwhichtheGLP"community"mustsupplyEPAwithdocumentationoftheirGLPprogram.Documentationreviewis  $ performedbyEPAandtoremain % ontheregistrationlistsubmittermustmeetEPAestablishedcriteria @4444-Ql'4444d d@JackMcCann 8( o)[added]Ifacentralizedgroup  ) wererecordingtheactivities,itcouldresultinatypeofregistrationlistthatwouldgivethecurrentstatusofallparticipatingtestingfacilitiesinvolvedinthevoluntaryormandatoryprogramp)[added]AvoluntaryprogramcouldhelptheAgencyevaluatemoretestingfacilitiesthantheyarecurrentlyabletocover.Arandomschedulingofinspectionsmayormaynotbemoreinformativethanonesetupusinganextensivedatabasesuppliedbyavoluntaryprogramq)[added]Wouldprovideincreasecoverage/evaluationofmorefacilitiesinareasonabletimeframe @4444-;4444d d@JackMcCann 8< i)[added]Avoluntaryprogram  = mightnotbeasbeneficialtotheAgencyifenoughlabsoptedtonotparticipateinvoluntaryprogramswhetheritbealabaccreditationprogramoraregistrationlistj)[added]Avoluntaryprograminvolvingasmallnumberofparticipatingfacilitiesmightbemoretimeconsumingthantheeffortisworthk)[added]AvoluntaryprogramwouldnotprovideEPAwithacompletelistoftestingfacilitiesuponwhichtheycouldestablishtheirinclusiveprogram(reasonϢIGswantinglabaccreditation)l)[added]MightnotreducesizeoreffortofEPA @4444-P4444d d@ 4 S4444@"8Q 8 4444d 8dSМ 44.Cont.  @4444-04444d d@DavidAlexander&PatriciaO'Brien 8 Pomerleau   [reworded]    CurrentEPAGLPCompliance  ! MonitoringProgram,plustheconstructionofaRegistrationListforwhichtheGLP@community:suppliesEPAwithdocumentationoftheirGLPprogram[suchasfieldsitedescriptionandcapabilities,keypersonnel(includingQAU)resumesorCVs,masterschedulesheet,currentlistofstandardoperatingprocedures,QAUdescriptionandprocedures,generaldescriptionofinstrumentationandequipmentused,bytypeandageandarchives];documentationreviewisperformedbyEPA;toremainontheregistrationlistsubmittermustmeetEPAcriteriatoestablishappropriateGLPcapabilities;foraSponsor,StudyDirector,etc.tocertifycompliancewithGLPs[notmandatoryunderGLPregulations],atestsitemustbeincludedontheGLPRegistrationList @4444-C^94444d d@DavidAlexander&PatriciaO'Brien 8: Pomerleau  ; a)[modified]MorecompletelistofGLPlaboratoriescouldbepreparedb)[modified]GrossregistrationcosttoGLPregulatedcommunityincreaseswithsizec)[modified]CosttoEPAexpectedtodecreaseafterinitialqualificationd)[modified]CouldaidEPAinstreamliningonsiteGLPComplianceMonitoringe)andf)[combinedandmodified]EPAwouldprovidelistofRegisteredGLPlaboratoriesand"Certificate"toInternationalgovernmentswhichmayaddressInternationalcommunityconcernsr)[added]EPAcouldgainscreeningcapability @4444-WrO4444d d@DavidAlexander&PatriciaO'Brien 8P Pomerleau  Q b)[modified]EPAwouldincuraninitialqualificationcost,likelytobesubstantialunless"phasedin"andanadministrativecosttomaintainGLPRegistrationListd)[modified]InternationalcommunityrequestsforCompliance"Certificate"maynotbesatisfiedunlessonsiteinspectionsbyEPAoccurm)[added]NetregistrationcosttoGLPregulatedcommunitymaybegreaterforsmallcompaniesofGLPlaboratories @4444-k _4444d d@ 4DavidAlexander& 8` PatriciaO'BrienPomerleau  b b)[added]Interagencyacceptanceunknown S4444@"e d 8 4444d 8dS 45. @4444-C^4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPCompliance   MonitoringProgram,plustheconstructionofaRegistrationListforwhichtheGLP"community"mustsupplyEPAwithdocumentationoftheirGLPprogram.Documentationreviewis  $ performedbyathirdpartysubcontractortoEPAandtoremain & ontheregistrationlistsubmittermustmeetEPAestablishedcriteria @4444-#> (4444d d@From2ndDraft(08/02/96) 8) a)TotallistofGLPlaboratoriescouldbepreparedb)RegistrationcosttoGLPregulatedcommunitywouldbeminimalc)EPAwouldincuraminimaladministrativecostd)CouldaideEPAinstreamliningonsiteComplianceMonitoringe)EPAwouldprovidelistofRegisteredGLPlaboratoriestoInternationalgovernmentsf)Registration@Certificate:mayaddressInternationalcommunityconcernsg)ToremainonGLPRegistrationListwouldencourageGLPcomplianceh)QualityofGLPdataremainshigh̢i)AssessmentofGLPcomplianceresideswithEPA @4444-)D?4444d d@From2ndDraft(08/02/96) 8@ a)InsufficientcurrentEPAresourcestoadequatelyvisitallϢGLPlaboratoriesb)EPAwouldincuranadministrativecosttomaintainGLPRegistrationListc)No@valueadded:tocurrentϢGLPcompliancefordataqualityd)InternationalcommunityrequestsforCompliance"Certificate"maynotbesatisfiede)EPAwouldhavetodevelopfaircriteriastandards @4444- M4444d d@ 4RoxanneRobinson 8N a)[added]NationalTechnologyTransferAct(NTTA)signedbyPresidentin03/96,directsgovernmentagenciestonolongerperformdutiesandserviceswhichareavailableintheprivatesector.Thirdpartyaccreditingbodiescanperformaccreditation(compliancemonitoring)presentlydonebyEPA.Listingofanykinddoesnotsatisfythe"accreditation"definitionassociatedwithNELACeffortsandinternationalefforts.Accreditation:Procedurebywhichanauthoritativebody S4444@")Dd 8 4444d 8dS 45.Cont. @4444-C^4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPCompliance   MonitoringProgram,plustheconstructionofaRegistrationListforwhichtheGLP"community"mustsupplyEPAwithdocumentationoftheirGLPprogram.Documentationreviewis  $ performedbyathirdpartysubcontractortoEPAandtoremain & ontheregistrationlistsubmittermustmeetEPAestablishedcriteria @4444-#> (4444d d@CliveHalder 8) h)[modified]QualityofGLPdata  * remainshigh,i.e.currentstandardj)[added]CurrentprogramisacceptabletoFDAk)[added]Nodisadvantagetocontractfacilitiesisperceivedl)[added]Noneofthelegal/legislativeissuesconcerningNELACareofconcernherem)[added]CurrentprogramdoesnotjeopardizeOECDharmonizationeffortsn)[added]WithEPAcontinuingtoimplementtheprogram,concernsforissuessuchasconflictsofinterest,confidentiality,etc.,wouldbeminimized @4444-*:4444d d@CliveHalderf)[added]Resourcesinsufficientto  < allowEPAtostreamlinecomplianceprogramtoallowfordatatobeauditedpriortoproductassessmentbyOPPBranchg)[added]Notmuchofacomplianceincentivefornoninternationallaboratoriesh)[added]Coverageofsmalllabs(thatcontributeonlyafewstudies/data)woulddilutetheeffectivenessoftheprogram̢i)[added]Conflictofinterestandconfidentialityissueswillneedtobeaddressed @4444-k J4444d d@ 4RoxanneRobinsona)[added](Cont.)  L givesformalrecognitionthatabodyorpersoniscompetenttocarryoutspecifictasks S4444@"7 RP 8 4444d 8dS 45.Cont. @4444-C^4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPCompliance   MonitoringProgram,plustheconstructionofaRegistrationListforwhichtheGLP"community"mustsupplyEPAwithdocumentationoftheirGLPprogram.Documentationreviewis  $ performedbyathirdpartysubcontractortoEPAandtoremain & ontheregistrationlistsubmittermustmeetEPAestablishedcriteria @4444-#> (4444d d@JackMcCann 8) o)[added]Ifacentralizedgroup  * wererecordingtheactivities,itcouldresultinatypeofregistrationlistthatwouldgivethecurrentstatusofallparticipatingtestingfacilitiesinvolvedinthevoluntaryormandatoryprogramp)[added]AvoluntaryprogramcouldhelptheAgencyevaluatemoretestingfacilitiesthantheyarecurrentlyabletocover.Arandomschedulingofinspectionsmayormaynotbemoreinformativethanonesetupusinganextensivedatabasesuppliedbyavoluntaryprogramq)[added]Wouldprovideincreasecoverage/evaluationofmorefacilitiesinareasonabletimeframe @4444-<4444d d@JackMcCann 8= j)[added]Avoluntaryprogram  > mightnotbeasbeneficialtotheAgencyifenoughlabsoptedtonotparticipateinvoluntaryprogramswhetheritbealabaccreditationprogramoraregistrationlistk)[added]Avoluntaryprograminvolvingasmallnumberofparticipatingfacilitiesmightbemoretimeconsumingthantheeffortisworthl)[added]CouldbedetrimentaltotheAgency,ifthetradegroupand/or3rdpartyfindingswerefoundtobeinconsistentwithonsiteEPAevaluationsm)[added]AvoluntaryprogramwouldnotprovideEPAwithacompletelistoftestingfacilitiesuponwhichtheycouldestablishtheirinclusiveprogram(reasonϢIGswantinglabaccreditation) @4444-T4444d d@ 4 S4444@"8U 8 4444d 8dS 45.Cont. @4444-C^4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPCompliance   MonitoringProgram,plustheconstructionofaRegistrationListforwhichtheGLP"community"mustsupplyEPAwithdocumentationoftheirGLPprogram.Documentationreviewis  $ performedbyathirdpartysubcontractortoEPAandtoremain & ontheregistrationlistsubmittermustmeetEPAestablishedcriteria @4444- )4444d d@ @4444-8*4444d d@JackMcCann(Continued) 8+ n)[added](Cont.)Atrade  , associationor3rdpartymightnothavetheinterestortheexpertisetoevaluatealldisciplinesthatcouldbeinvolvedintheprogramo)[added]Ifmorethanonegroup(TA)or3rdpartyisrequiredtomaketheevaluationsconsistencyinevaluationscouldbeanissuep)[added]MightnotreducesizeoreffortofEPA @4444-#> 64444d d@ 4 S4444@"87 8 4444d 8dS 45.Cont. @4444-C^4444d d@DavidAlexander&PatriciaO'Brien 8 ТPomerleau[reworded]   CurrentEPAGLPComplianceMonitoringProgram,plustheconstructionofaRegistrationListforwhichtheGLP@community:mustsupplyEPAwithdocumentationoftheirGLPprogram[suchasfieldsitedescriptionandcapabilities,keypersonnel(includingQAU)resumesorCVs,masterschedulesheet,currentlistofstandardoperatingprocedures,QAUdescriptionandprocedures,generaldescriptionofinstrumentationandequipmentused,bytypeandageandarchives];documentationreviewisperformedbyathirdpartysubcontractortoEPA;toremainon 1 theregistrationlistsubmittermustmeetEPAcriteriatoestablishappropriateGLPcapabilities;foraSponsor,StudyDirector,etc.tocertifycompliancewithGLPs[notmandatoryunderGLPregulations],atestsitemustbeincludedontheϢGLPRegistrationList @4444-094444d d@DavidAlexander&PatriciaO'Brien 8: ТPomerleau  ; a)[modified]MorecompletelistofϢGLPlaboratoriescouldbepreparedb)[modified]GrossregistrationcosttoGLPregulatedcommunitywouldbeminimald)[modified]CouldaidEPAinstreamliningonsiteGLPComplianceMonitoringe)andf)[combinedandmodified]EPAwouldprovidelistofRegisteredϢGLPlaboratoriesand"Certificate"toInternationalgovernmentswhichmayaddressInternationalcommunityconcernsr)[added]EPAcouldgainscreeningcapability @4444-N4444d d@DavidAlexander&PatriciaO'Brien 8O ТPomerleau  P a)[modified]InsufficientcurrentEPAresourcestoadequatelycoverthecostsofathirdpartysubcontractorb)[modified]EPAwouldincuraninitialqualificationcost,likelytobesubstantialunless"phasedin"andanadministrativecosttomaintainϢGLPRegistrationListd)[modified]InternationalcommunityrequestsforCompliance"Certificate"maynotbesatisfiedunlessonsiteinspectionsbyEPAoccursq)[added]NetregistrationcosttoϢGLPregulatedcommunitymaybegreaterforsmallcompaniesofGLPlaboratories @4444-b4444d d@DavidAlexander&Patricia 8c O'BrienPomerleau  d  4b)[added]Interagencyacceptanceunknownc)[added]RoutineEPAprocedurestoensurethatcontractorsprotectConfidentialBusinessInformationagainstdisclosuremustbefollowed S4444@"Qlm 8 4444d 8dS 46. @4444-C^4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPCompliance   MonitoringexceptconstructionofaϢGLPRegistrationListthatwouldsimplylistallexistingGLPlaboratories.ToremainontheRegistrationList,laboratorieswouldhavetosuccessfullycompletesubsequentGLPinspectionsbyEPA @4444-&4444d d@From2ndDraft(08/02/96) 8' a)TotallistofGLPlaboratoriescouldbepreparedb)RegistrationcosttoGLPregulatedcommunitywouldbeminimalc)EPAwouldincuraminimaladministrativecostd)CouldaideEPAinstreamliningonsiteComplianceMonitoringe)EPAwouldprovidelistofRegisteredGLPlaboratoriestoInternationalgovernmentsf)Registration@Certificate:mayaddressInternationalcommunityconcernsg)ToremainonGLPRegistrationListwouldencourageGLPcomplianceh)QualityofGLPdataremainshigh̢i)AssessmentofGLPcomplianceresideswithEPA @4444-Wr<4444d d@From2ndDraft(08/02/96) 8= a)DoesnotaddressnewGLPlaboratoriesb)InsufficientcurrentEPAresourcestoadequatelyvisitallϢGLPlaboratoriesc)EPAwouldincuranadministrativecosttomaintainGLPRegistrationListd)No@valueadded:tocurrentϢGLPcompliancefordataqualitye)InternationalcommunityrequestsforCompliance"Certificate"maynotbesatisfiedf)EPAwouldhavetodevelopfaircriteriastandards @4444-k L4444d d@ 4RoxanneRobinson 8M a)[added]NationalTechnologyTransferAct(NTTA)signedbyPresidentin03/96,directsgovernmentagenciestonolongerperformdutiesandserviceswhichareavailableintheprivatesector.Thirdpartyaccreditingbodiescanperformaccreditation(compliancemonitoring)presentlydonebyEPA.Listingofanykinddoesnotsatisfythe"accreditation"definitionassociatedwithNELACeffortsandinternationalefforts.Accreditation:Procedurebywhichanauthoritativebody S4444@")Dc 8 4444d 8dS 46.Cont. @4444-C^4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPCompliance   MonitoringexceptconstructionofaϢGLPRegistrationListthatwouldsimplylistallexistingGLPlaboratories.ToremainontheRegistrationList,laboratorieswouldhavetosuccessfullycompletesubsequentGLPinspectionsbyEPA @4444-&4444d d@CliveHalder 8' h)[modified]QualityofGLPdata  ( remainshigh,i.e.currentstandardj)[added]CurrentprogramisacceptabletoFDAk)[added]Nodisadvantagetocontractfacilitiesisperceivedl)[added]Noneofthelegal/legislativeissuesconcerningNELACareofconcernherem)[added]CurrentprogramdoesnotjeopardizeOECDharmonizationeffortsn)[added]WithEPAcontinuingtoimplementtheprogram,concernsforissuessuchasconflictsofinterest,confidentiality,etc.,wouldbeminimized @4444-*84444d d@CliveHalderg)[added]Resourcesinsufficientto  : allowEPAtostreamlinecomplianceprogramtoallowfordatatobeauditedpriortoproductassessmentbyOPPBranchh)[added]Notmuchofacomplianceincentivefornoninternationallaboratories̢i)[added]Coverageofsmalllabs(thatcontributeonlyafewstudies/data)woulddilutetheeffectivenessoftheprogramj)[added]Thecurrentfrequencyofsite/facilityauditsmightnotsatisfyIGOfficeandinternationalconcerns @4444-k H4444d d@ 4RoxanneRobinson 8I a)[added](Cont.)givesformalrecognitionthatabodyorpersoniscompetenttocarryoutspecifictasks S4444@"7 RN 8 4444d 8dSМ 46.Cont. @4444-C^4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPCompliance   MonitoringexceptconstructionofaGLPRegistrationListthatwouldsimplylistallexistingGLPlaboratories.ToremainontheRegistrationList,laboratorieswouldhavetosuccessfullycompletesubsequentGLPinspectionsbyEPA @4444-&4444d d@JackMcCann 8' o)[added]Avoluntaryprogram  ( couldhelptheAgencyevaluatemoretestingfacilitiesthantheyarecurrentlyabletocoverp)[added]Wouldprovideincreasecoverage/evaluationofmorefacilitiesinareasonabletimeframe @4444- .4444d d@JackMcCann 8/ k)[added]Avoluntaryprogram  0 mightnotbeasbeneficialtotheAgencyifenoughlabsoptedtonotparticipateinvoluntaryprogramswhetheritbealabaccreditationprogramoraregistrationlistl)[added]Avoluntaryprograminvolvingasmallnumberofparticipatingfacilitiesmightbemoretimeconsumingthantheeffortisworthm)[added]CouldbedetrimentaltotheAgency,ifthetradegroupand/or3rdpartyfindingswerefoundtobeinconsistentwithonsiteEPAevaluationsn)[added]AvoluntaryprogramwouldnotprovideEPAwithacompletelistoftestingfacilitiesuponwhichtheycouldestablishtheirinclusiveprogram(AreasonIGswantinglabaccreditation) @4444-F4444d d@ 4 S4444@"8G 8 4444d 8dS 46.Cont. @4444-C^4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPCompliance   MonitoringexceptconstructionofaGLPRegistrationListthatwouldsimplylistallexistingGLPlaboratories.ToremainontheRegistrationList,laboratorieswouldhavetosuccessfullycompletesubsequentGLPinspectionsbyEPA @4444-&4444d d@ @4444-8'4444d d@JackMcCann(Continued) 8( o)[added](Cont.)Atrade  ) associationor3rdpartymightnothavetheinterestortheexpertisetoevaluatealldisciplinesthatcouldbeinvolvedintheprogramp)[added]Ifmorethanonegroup(TA)or3rdpartyisrequiredtomaketheevaluationsconsistencyinevaluationscouldbeanissueq)[added]MightnotreducesizeoreffortofEPA @4444-#> 34444d d@ 4 S4444@"84 8 4444d 8dS 46.Cont. @4444-C^4444d d@DavidAlexander&PatriciaO'Brien 8 Pomerleau[reworded]Eliminatethisoptionbecause    appropriateGLPcapabilitynecessarilyincludesminimallyacceptableEPAGLPComplianceMonitoringinspectionresults,ifundertaken.Therefore,aseparateoptionisnotnecessaryunlessthe & intentisthatalltestsitesmustundergoaGLPEPAComplianceMonitoringinspection,and,ifso,thisiscurrentlynotfeasibleunderthecurrentEPAComplianceMonitoringProgram.Andthisdisadvantagemustnecessarilyeliminatethisasanoption @4444-*.4444d d@ @4444-8/4444d d@ @4444-804444d d@ 4 S4444@"81 8 4444d 8dS 47. @4444-C^4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringProgramplusonsitetestingfacilities,paidforby    participantwithaperdiemandexpensescharge.(e.g.,likeGerman,Swiss) @4444- $#4444d d@From2ndDraft(08/02/96) 8$ a)FundingforsitevisitswouldhelpEPAresourcerestrictionsandallowEPAtoadequatelyvisitalllaboratoriesb)AssessmentofGLPcomplianceresideswithEPAc)Issuanceof@Certificate:ofcompliancebyEPAwouldaddressInternationalconcernsd)Costofprogramwouldinherentlypenalizenoncomplianceandrewardcompliancee)ProgramshouldnotinterferewithharmonizationagreementswithFDAf)TheComplianceMonitoringProgramwouldremainfamiliar,i.e.,unchangedexceptforfrequencyofauditsg)QualityofGLPdataremainshigh @4444-74444d d@From2ndDraft(08/02/96) 88 a)Highercost,novalueaddedotherthanissuanceof@Certificate:ofcomplianceb)MonetaryreimbursementforEPAwouldhavetobeaddressedatfederallevelc)TherewillbeastartupcostforEPA @4444-A4444d d@ 4RoxanneRobinson 8B a)[added]NationalTechnologyTransferAct(NTTA)signedbyPresidentin03/96,directsgovernmentagenciestonolongerperformdutiesandserviceswhichareavailableintheprivatesector.Thirdpartyaccreditingbodiescanperformaccreditation(compliancemonitoring)presentlydonebyEPA.LegislationneededtoallowEPAtoacceptpayment S4444@"*S 8 4444d 8dS 47.Cont. @4444-4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringProgramplusonsitetestingfacilities,paidforby   participantwithaperdiemandexpensescharge.(e.g.,likeGerman,Swiss) @4444- $ 4444d d@CliveHalder 8! g)[modified]QualityofGLPdata  " remainshigh,i.e.currentstandardh)[added]WithEPAcontinuingtoimplementtheprogram,concernsforissuessuchasconflictsofinterest,confidentiality,etc.,wouldbeminimizedi)[added]Threatoflossofcertificateofcompliancewouldserveasanincentivetosustainqualityoflaboratoriesj)[added]TheaddedresourceswouldallowforEPAtostreamlinecomplianceprogramtoallowfordatatobeauditedpriortoproductassessmentbyOPPBranchk)[added]Nodisadvantagetocontractfacilitiesisperceivedl)[added]EnhancedprogramshouldbeperceivedtobecrediblebyIGOfficeandothersm)[added]CurrentprogramdoesnotjeopardizeOECDharmonizationefforts @4444-94444d d@CliveHalderd)[added]Anequitable  ; assessmentprogramwouldneedtobeestablishedtoallowforfair/uniformissuanceofcertificateofcompliancee)[added]Thecompliancestatusoflaboratoriesnotdefinedasa@testingfacility:wouldnotbeaddressedf)[added]Testingfacilitieswithnointernationalneedswouldbepenalizedbytheimposeduserfeeg)[added]Afair/equitablefeestructurewouldneedtobeestablishedh)[added]Feeswillhaveasignificantnegativeimpactonsmall,specialtytestingfacilities @4444-L4444d d@ 4 S4444@"8M 8 4444d 8dS 47.Cont. @4444-C^4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringProgramplusonsitetestingfacilities,paidforby    participantwithaperdiemandexpensescharge.(e.g.,likeGerman,Swiss) @4444- $#4444d d@FranciscaLiem 8$ n)[added]Allowsassessmentof  % facilitiespriortousebyEPAo)[added]EPAhastotalcontrolandenforcementdiscretionp)[added]Adequateinspectioncoverageq)[added]Uniformityofinspectionprocessr)[added]Noanticompetitiveeffects @4444-Ql.4444d d@FranciscaLiem 8/ i)[added]Highercosttotesting  0 facility,novalueaddedotherthanissuance...j)[added]MonetaryreimbursementforEPAwouldhavetobeaddressedatfederallevel(Congress)k)[added]TherewillbeaminimalstartupcostforEPAl)[added]ItdoesnotallowassessmentofstudiespriortousebytheEPAm)[added]Notalltestingfacilitiesgeneratedata @4444- =4444d d@FranciscaLiem 8>  4b)[added]OPPpolicyto  ? acceptonlystudiesfrom@incompliance:testingfacilitiesshouldbedetermined S4444@"7 RC 8 4444d 8dS 47.Cont. @4444-C^4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringProgramplusonsitetestingfacilities,paidforby    participantwithaperdiemandexpensescharge.(e.g.,likeGerman,Swiss) @4444- $#4444d d@DorisMason 8$ a)[additionalcomment]Itwouldbe  % anadvantageiffundingforsitevisitsresultedinincreasedEPAstaffforcompliancereviews.Itwouldnottakealargeincreaseinstafftoregularlyinspecttestingfacilitiesasdefinedabove.BecausetheEPAhasbeenattemptingtoinspectalltestsites,theinspectionschedulefortestingfacilitiesisaffected.ThisoptionwouldlikelyallowassessmentoffacilitiespriortousebyEPAb)[additionalcomment]ItisanimportantadvantagetoretainEPAsGLPcompliancemonitoringprogram.GLPsareafederalregulationandprimaryresponsibilityformonitoringcompliancemustresidewithEPAsOfficeofCompliance(OC).EPAsinspectorshavethenecessarybackgroundandexperiencewithGLPstoprovideindustrywithfairenforcement @4444-<4444d d@DorisMason 8= a)[additionalcomment]Themost  > importantdisadvantagefromindustriesperspectiveishighercostsofdoingbusinesswithnoaddedvalueintheintegrityandqualityofdata.FeesandcostsofinspectionsisoneoftheprimaryreasonsindustryisopposedtoincludingGLPsunderthescopeofNELAC.QualityofdatasupportingregistrationshasgenerallybeenrecognizedasgoodbytheAgencyandindustry.Dataqualitywasnottargetedastheproblem,butratherthefactthatnotallfacilitieshavebeeninspectedorvisitedonaregularbasisbytheEPA. @4444-O4444d d@DorisMason 8P c)[added]OPPpolicyto  Q acceptonlystudiesfrom@incompliance:testingfacilitiesshouldbedetermined S4444@"7 RU 8 4444d 8dS7.Cont. @4444-C^4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringProgramplusonsitetestingfacilities,paidforby    participantwithaperdiemandexpensescharge.(e.g.,likeGerman,Swiss) @4444- $#4444d d@DorisMason(Continued) 8$ practicesandcomplianceassistance  % c)[additionalcomment]AssumestheEPAwouldissue@CertificatesofCompliance:whichwouldbeachangefromtheircurrentpolicy.Iftheywereabletoincreasethefrequencyofinspectionsandissuedcertificates,internationalconcernswouldbeaddressed.Internationally(atleastinsomecountries)certificatesforGLPcomplianceareissuedtothetestingfacility.Theydonotgototheindividualtestsites.d)[additionalcomment]No.Idonotunderstandhowthisisanadvantage.Costsarehighforthosefacilitiesthatareincompliancetoo.Sponsorcompanieswouldhavethehighestcostsbecauseofthenumberoffacilitiestheyuse @4444-Wr94444d d@ @4444-8:4444d d@ S4444@"8; 8 4444d 8dS7.Cont. @4444-C^4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringProgramplusonsitetestingfacilities,paidforby    participantwithaperdiemandexpensescharge.(e.g.,likeGerman,Swiss) @4444- $#4444d d@DorisMason(Continued) 8$ e)[additionalcomment]Aslongas  % EPAsGLPcompliancemonitoringprogramisretained,itshouldnotinterferewithFDAharmonizationagreementsf)[additionalcomment]ItisanimportantadvantagetoretainEPAsGLPcompliancemonitoringprogram.GLPsareafederalregulationandprimaryresponsibilityformonitoringcompliancemustresidewithEPAsOfficeofCompliance(OC).EPAsinspectorshavethenecessarybackgroundandexperiencewithGLPstoprovideindustrywithfairenforcementpracticesandcomplianceassistanceg)[additionalcomment]ItshouldremainhighaslongasEPAsGLPcompliancemonitoringprogramisretained @4444-;4444d d@ @4444-8<4444d d@ S4444@"8= 8 4444d 8dS8. @4444-C^4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPCompliance   MonitoringProgramplusonsiteinspectionsofalltestsites,paidfor    byparticipantwithaperdiemandexpensescharge @4444-7 R"4444d d@From2ndDraft(08/02/96) 8# a)FundingforsitevisitswouldhelpEPAresourcerestrictionsandallowEPAtoadequatelyvisitalllaboratoriesb)AssessmentofGLPcomplianceresideswithEPAc)Issuanceof@Certificate:ofcompliancebyEPAwouldaddressInternationalconcernsd)Costofprogramwouldinherentlypenalizenoncomplianceandrewardcompliancee)ProgramshouldnotinterferewithharmonizationagreementswithFDAf)TheComplianceMonitoringProgramwouldremainfamiliar,i.e.,unchangedexceptforfrequencyofauditsg)QualityofGLPdataremainshigh @4444-64444d d@From2ndDraft(08/02/96) 87 a)Highercost,novalueaddedotherthanissuanceof@Certificate:ofcomplianceb)MonetaryreimbursementforEPAwouldhavetobeaddressedatfederallevelc)TherewillbeastartupcostforEPA @4444-@4444d d@ 4RoxanneRobinson 8A a)[added]NationalTechnologyTransferAct(NTTA)signedbyPresidentin03/96,directsgovernmentagenciestonolongerperformdutiesandserviceswhichareavailableintheprivatesector.Thirdpartyaccreditingbodiescanperformaccreditation(compliancemonitoring)presentlydonebyEPA.LegislationneededtoallowEPAtoacceptpayment S4444@"*R 8 4444d 8dS 48.Cont. @4444-C^4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPCompliance   MonitoringProgramplusonsiteinspectionsofalltestsites,paidfor    byparticipantwithaperdiemandexpensescharge @4444-7 R"4444d d@FranciscaLiem 8# h)[added]Allowsassessmentof  $ facilitiespriortousebyEPAi)[added]EPAhastotalcontrolandenforcementdiscretionj)[added]Adequateinspectioncoveragek)[added]Uniformityofinspectionprocessl)[added]Noanticompetitiveeffects @4444-Ql-4444d d@FranciscaLiem 8. a)[modified]Highercosttotestsite,  / novalueaddedotherthanissuance...b)[modified]MonetaryreimbursementforEPAwouldhavetobeaddressedatfederallevel(Congress)c)[modified]TherewillbeaminimalstartupcostforEPAd)[added]ItdoesnotallowassessmentofstudiespriortousebytheEPA @4444- ;4444d d@FranciscaLiem 8<  4b)[added]OPPpolicyto  = acceptonlystudiesfrom@incompliance:testingfacilitiesshouldbedetermined S4444@"7 RA 8 4444d 8dS 48.Cont. @4444-C^4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPCompliance   MonitoringProgramplusonsiteinspectionsofalltestsites,paidfor    byparticipantwithaperdiemandexpensescharge @4444-7 R"4444d d@DorisMason 8# a)[additionalcomment]Itwouldbe  $ anadvantageiffundingforsitevisitsresultedinincreasedEPAstaffforcompliancereviews.However,itwouldtakeaverylargeincreaseinEPAsresourcestoinspectallGLPtestsiteswithanyfrequency.ThisoptionwouldlikelyallowassessmentoffacilitiespriortousebyEPAb)[additionalcomment]ItisanimportantadvantagetoretainEPAsGLPcompliancemonitoringprogram.GLPsareafederalregulationandprimaryresponsibilityformonitoringcompliancemustresidewithEPAsOfficeofCompliance @4444-*44444d d@DorisMason 85 a)[additionalcomment]Themost  6 importantdisadvantagefromindustriesperspectiveishighercostsofdoingbusinesswithnoaddedvalueintheintegrityandqualityofdata.FeesandcostsofinspectionsisoneoftheprimaryreasonsindustryisopposedtoincludingGLPsunderthescopeofNELAC.QualityofdatasupportingregistrationshasgenerallybeenrecognizedasgoodbytheAgencyandindustry.Dataqualitywasnottargetedastheproblem,butratherthefactthatnotallfacilitieshavebeeninspectedorvisitedonaregularbasisbytheEPA.e)[added]Internationally(atleastinsomeofthecountries),certificatesforGLPcomplianceareissuedtothetestingfacilityafterafeebasedinspectionby @4444-)DK4444d d@DorisMason 8L c)[added]OPPpolicyto  M acceptonlystudiesfrom@incompliance:testingfacilitiesshouldbedetermined.Aspartofthatpolicy,howwouldtheyevaluateatestsite(notthetestingfacility)thatwasnotinfullcompliance,butonlygeneratedsupplementaldataforthestudy;e.g.,NOAAweather,specialanalyticalinstrumentationnotroutinelyusedorrequiredunderGLPs,etc.? S4444@"k [ 8 4444d 8dS8.Cont. @4444-C^4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPCompliance   MonitoringProgramplusonsiteinspectionsofalltestsites,paidfor    byparticipantwithaperdiemandexpensescharge @4444-7 R"4444d d@DorisMason(Continued) 8# (OC).EPAsinspectorshavethe  $ necessarybackgroundandexperiencewithGLPstoprovideindustrywithfairenforcementpracticesandcomplianceassistancec)[additionalcomment]AssumestheEPAwouldissue@CertificatesofCompliance:whichwouldbeachangefromtheircurrentpolicy.Iftheywereabletoincreasethefrequencyofinspectionsandissuedcertificates,internationalconcernswouldbeaddressedd)[additionalcomment]No.Idonotunderstandhowthisisanadvantage.Costsarehighforthosefacilitiesthatareincompliancetoo.Sponsorcompanieswouldhavethehighestcostsbecauseofthenumberoffacilitiestheyuse @4444-Wr84444d d@DorisMason(Continued) 89 e)[added](Cont.)  : anaccreditingauthority.Theydonotaccreditindividualtestsites.IfintheUSalltestsitesmustbeofficiallyaccreditedorissued@CertificatesofCompliance:afterafeebasedinspectionbytheEPA,thecoststosponsorcompanieswouldbeverysignificant.ForinternationalcompanieswithlocationsintheU.S.andabroad,thecostsforconductingstudiesintheirU.S.researchcenterswouldnotbecompetitivewiththecompaniesEuropeanresearchcenters.WhentherearetoomanycostsassociatedwithgovernmentregulationsforUSlocations,morestudieswillbeconductedoutsideofthecountry. @4444-WrN4444d d@ 4 S4444@"8O 8 4444d 8dS 48.Cont. @4444-C^4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPCompliance   MonitoringProgramplusonsiteinspectionsofalltestsites,paidfor    byparticipantwithaperdiemandexpensescharge @4444-7 R"4444d d@DorisMason(Continued) 8# e)[additionalcomment]Aslongas  $ EPAsGLPcompliancemonitoringprogramisretained,itshouldnotinterferewithFDAharmonizationagreementsf)[additionalcomment]ItisanimportantadvantagetoretainEPAsGLPcompliancemonitoringprogram.GLPsareafederalregulationandprimaryresponsibilityformonitoringcompliancemustresidewithEPAsOfficeofCompliance(OC).EPAsinspectorshavethenecessarybackgroundandexperiencewithGLPstoprovideindustrywithfairenforcementpracticesandcomplianceassistanceg)[additionalcomment]ItshouldremainhighaslongasEPAsGLPcompliancemonitoringprogramisretained @4444-:4444d d@ @4444-8;4444d d@ 4 S4444@"8< 8 4444d 8dS 49. @4444-C^4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPCompliance   MonitoringProgramplusonsiteinspectionsofalltestingfacilities,    paidforbyparticipantwithausers e ! fee @4444-7 R"4444d d@From2ndDraft(08/02/96) 8# a)FundingforsitevisitswouldhelpEPAresourcerestrictionsandallowEPAtoadequatelyvisitalllaboratoriesb)AssessmentofGLPcomplianceresideswithEPAc)Issuanceof@Certificate:ofcompliancebyEPAwouldaddressInternationalconcernsd)Costofprogramwouldinherentlypenalizenoncomplianceandrewardcompliancee)ProgramshouldnotinterferewithharmonizationagreementswithFDAf)TheComplianceMonitoringProgramwouldremainfamiliar,i.e.,unchangedexceptforfrequencyofauditsg)QualityofGLPdataremainshigh @4444-64444d d@From2ndDraft(08/02/96) 87 a)Highercost,novalueaddedotherthanissuanceof@Certificate:ofcomplianceb)MonetaryreimbursementforEPAwouldhavetobeaddressedatfederallevelc)TherewillbeastartupcostforEPAChristineOlinger @ d)[added]OECAwouldnotbeable QlA todisregardcontractlabsandfieldstationswhicharetestsites,butnotfacilities.Testingfacilitieswouldthenbesubsidizingtheinspectionprogramfortestsites @4444-k F4444d d@ 4RoxanneRobinson 8G a)[added]NationalTechnologyTransferAct(NTTA)signedbyPresidentin03/96,directsgovernmentagenciestonolongerperformdutiesandserviceswhichareavailableintheprivatesector.Thirdpartyaccreditingbodiescanperformaccreditation(compliancemonitoring)presentlydonebyEPA.LegislationneededtoallowEPAtoacceptpayment. S4444@"*X 8 4444d 8dS 49.Cont. @4444-C^4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPCompliance   MonitoringProgramplusonsiteinspectionsoftestingfacilities,    paidforbyparticipantwithausers e ! fee @4444-7 R"4444d d@CliveHalder 8# a)[modified]FundingforsitevisitswouldhelpEPAresourcerestrictionsandallowEPAtoadequatelyimplementtheircomplianceprogramc)[modified]Issuanceofcertificateofcomplianceplusincreasedfrequencyofauditingwouldaddressinternationalconcernsd)[modified]Costofprogramwouldinherentlypenalizenoncomplianceandrewardcompliance,i.e.,certificateonlyissueduponsuccessfulinspectionrecordg)[modified]QualityofGLPdataremainshigh,i.e.,currentstandardh)[added]Itisamoreeffectiveuseofresourcestolimitfocustotestingfacilitiesratherthanalltestsites @4444-64444d d@CliveHalder 87 b)[modified]Legal/legislative  8 feasibilityofinvolvingadditionaluserfees,aswellaschannelingthefundsdirectlytotheOCwillhavetobeaddressede)[added]Anequitableassessmentprogramwouldneedtobeestablishedtoallowforfair/uniformissuanceofcertificateofcompliancef)[added]Thecompliancestatusoflaboratoriesnotdefinedasa<testingfacilitywouldnotbeaddressedg)[added]Testingfacilitieswithnointernationalneedswouldbepenalizedbytheimposeduserfeeh)[added]Afair/equitablefeestructurewouldneedtobeestablishedi)[added]Feeswillhaveasignificantnegativeimpactonsmall,specialtytestingfacilities @4444-O4444d d@ 4 S4444@"8P 8 4444d 8dS 49.Cont. @4444-C^4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPCompliance   MonitoringProgramplusonsiteinspectionsofalltestingfacilities,    paidforbyparticipantwithausers e ! fee @4444-7 R"4444d d@CliveHalder(Continued) 8# i)[added]WithEPAcontinuingtoimplementtheprogram,concernsforissuessuchasconflictsofinterest,confidentiality,etc.,wouldbeminimizedj)[added]Threatoflossofcertificateofcompliancewouldserveasanincentivetosustainqualityoflaboratoriesk)[added]TheaddedresourceswouldallowforEPAtostreamlinecomplianceprogramtoallowfordatatobeauditedpriortoproductassessmentbyOPPBranchl)[added]Nodisadvantagetocontractfacilitiesisperceivedm)[added]EnhancedprogramshouldbeperceivedtobecrediblebyIGOfficeandothers @4444-64444d d@ @4444-874444d d@ 4 S4444@"88 8 4444d 8dS 410. @4444-C^4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPCompliance   MonitoringProgramplusonsiteinspectionsoftestsites,paidforby    participantwithausersfee @4444-e !4444d d@From2ndDraft(08/02/96) 8" a)FundingforsitevisitswouldhelpEPAresourcerestrictionsandallowEPAtoadequatelyvisitalllaboratoriesb)AssessmentofcomplianceresideswithEPAc)Issuanceof@Certificate:ofcompliancebyEPAwouldaddressInternationalconcernsd)Costofprogramwouldinherentlypenalizenoncomplianceandrewardcompliancee)ProgramshouldnotinterferewithharmonizationagreementswithFDAf)TheComplianceMonitoringProgramwouldremainfamiliar,i.e.,unchangedexceptforfrequencyofauditsg)QualityofGLPdataremainshighChristineOlinger 6 h)[added]Increasedfeestosmallerfacilitiesmayeliminatesomesmall,problematicfacilities @4444-94444d d@From2ndDraft(08/02/96) 8: a)Highercost,novalueadded  ; otherthanissuanceof@Certificate:ofcomplianceb)MonetaryreimbursementforEPAwouldhavetobeaddressedatfederallevelc)TherewillbeastartupcostforEPAd)AdditionalCostofGLPCompliancebornebyregulatedcommunitye)Financialimpactonsmallbusinesscouldeliminatevaluablesmallspecialtylabsf)Legislativeactionrequiredfor3rdpartyaccreditationprogramforGLPsg)IsthesponsorliableforGLPviolationsfoundatfullyaccreditedcontractlabs?h)QualityofGLPdatamaynotremainhigh @4444-Q4444d d@ 4RoxanneRobinson 8R a)[added]NationalTechnologyTransferAct(NTTA)signedbyPresidentin03/96,directsgovernmentagenciestonolongerperformdutiesandserviceswhichareavailableintheprivatesector.Thirdpartyaccreditingbodiescanperformaccreditation(compliancemonitoring)presentlydonebyEPA.LegislationneededtoallowEPAtoacceptpayment S4444@"*c 8 4444d 8dS 410.Cont. @4444-04444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPCompliance   MonitoringProgramplusonsiteinspectionsoftestsites,paidforby  ! participantwithausersfee @4444-e "4444d d@CliveHalder 8# a)[modified]FundingforsitevisitswouldhelpEPAresourcerestrictionsandallowEPAtoadequatelyimplementtheircomplianceprogramc)[modified]Issuanceofcertificateofcomplianceplusincreasedfrequencyofauditingwouldaddressinternationalconcernsd)[modified]Costofprogramwouldinherentlypenalizenoncomplianceandrewardcompliance,i.e.,certificateonlyissueduponsuccessfulinspectionrecordg)[modified]QualityofGLPdataremainshigh,i.e.,currentstandardi)[added]ThecompliancestatusoftheuniverseofGLPlocationswouldbecovered @4444-64444d d@CliveHalder 87 b)[modified]Legal/legislative  8 feasibilityofinvolvingadditionaluserfees,aswellaschannelingthefundsdirectlytotheOCwillhavetobeaddressedi)[added]Anequitableassessmentprogramwouldneedtobeestablishedtoallowforfair/uniformissuanceofcertificateofcompliancej)[added]Lesseffectiveuseofresourcestoinvestinauditingalltestsitesk)[added]Feeassessmentprocessmaybeproblematicfortestsitesthatmayonlybeusedonce,orinfrequentlyl)[added]Testingfacilitieswithnointernationalneedswouldbepenalizedbytheimposeduserfee @4444-K4444d d@ 4 S4444@"8L 8 4444d 8dS 410.Cont. @4444-C^4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPCompliance   MonitoringProgramplusonsiteinspectionsoftestsites,paidforby    participantwithausersfee @4444-e !4444d d@CliveHalder(Continued) 8" j)[added]WithEPAcontinuingtoimplementtheprogram,concernsforissuessuchasconflictsofinterest,confidentiality,etc.,wouldbeminimizedk)[added]Threatoflossofcertificateofcompliancewouldserveasanincentivetosustainqualityoflaboratoriesl)[added]TheaddedresourceswouldallowforEPAtostreamlinecomplianceprogramtoallowfordatatobeauditedpriortoproductassessmentbyOPPBranchm)[added]EnhancedprogramshouldbeperceivedtobecrediblebyIGOfficeandothersn)[added]Nodisadvantagetocontractfacilitiesisperceived @4444-54444d d@CliveHalder(Continued) 86 m)[added]Afair/equitablefee  7 structurewouldneedtobeestablishedn)[added]Feeswillhaveasignificantnegativeimpactonsmall,specialtytestingfacilities @4444- $<4444d d@ 4 S4444@"8= 8 4444d 8dS 411. @4444-C^4444d d@From2ndDraft(08/02/96) 8 EPAoversightofaGLPComplianceMonitoringProgramperformedbya3rdpartyaccreditingbodywithonsiteinspectionspaidforbyparticipantsdirectlytothe3rdpartyorganization(e.g.,EPAleadprogram) @4444-%4444d d@From2ndDraft(08/02/96) 8& a)Fundingforsitevisitswouldhelp  ' EPAresourcerestrictionsandallowEPAtoadequatelyvisitalllaboratoriesb)AssessmentofcomplianceresideswithEPAc)Issuanceof@Certificate:ofcompliancebyEPAwouldaddressInternationalconcernsd)Costofprogramwouldinherentlypenalizenoncomplianceandrewardcompliancee)ProgramshouldnotinterferewithharmonizationagreementswithFDAf)TheComplianceMonitoringProgramwouldremainfamiliar,i.e.,unchangedexceptforfrequencyofauditsRoxanneRobinson 9 g)[added]Universeoflabswouldbe : knownandcompetencyestablishedbeforesubmissionofdatah)[added]Federalauthorityandoversightismaintained @4444->4444d d@From2ndDraft(08/02/96) 8? F"K*%F&a)Highercost,novalueaddedother  @ thanissuanceof@Certificate:ofcomplianceb)AdditionalCostofGLPCompliancebornebyregulatedcommunityc)FinancialimpactonSmallBusinesscouldeliminatevaluablesmallspecialtylabsd)Legislativeactionrequiredfor3rdpartyaccreditationprogramforGLPse)Conflictbetween3rdpartyaccreditationofcontractlabsandsponsorliabilityissuesundertheEnforcementResponsePolicy(i.e.,differenceofinterpretationbetweenaccreditinginspectorandAgency)f)IsthesponsorliableforGLPviolationsfoundatfullyaccreditedcontractlabsg)ProgrammayinterferewithharmonizationagreementswithFDAh)PotentiallyunacceptabletointernationalcommunitywithoutdirectgovernmentinvolvementPerceptionofpotentialI)"ConflictOfInterest"andconfidentialityissuesremainj)QualityofGLPdatamaynotremainhighk)OverallassessmentofGLPaccreditationnolongerresidessolelywithEPA @4444-m _4444d d@ 4F&*%KF" S4444@"8` 8 4444d 8dS 411.Cont. @4444-C^4444d d@From2ndDraft(08/02/96) 8 EPAoversightofaGLPComplianceMonitoringProgramperformedbya3rdpartyaccreditingbodywithonsiteinspectionspaidforbyparticipantsdirectlytothe3rdpartyorganization(e.g.,EPAleadprogram) @4444-%4444d d@CliveHalder 8& a)[modified]Fundingforsitevisits  ' wouldhelpEPAresourcerestrictionsandallowEPAtoadequatelyimplementtheircomplianceprogram.c)[modified]Issuanceofcertificatesplusincreasedfrequencyofauditscouldaddressinternationalconcerns.d)[modified]Costofprogramwouldinherentlypenalizenoncomplianceandrewardcompliance,i.e.,certificateonlyissueduponsuccessfulrecord.f)[modified]Deletecurrentitemi)[added]QualityofGLPdataremainshighi.e.,currentstandardj)[added]Testingfacilitieswithnointernationalneedswouldnotneedtopetitionand,hence,wouldnotbepenalizedbytheprogramk)[added]EnhancedprogramshouldbeperceivedascrediblebyIGofficeandothers @4444-?4444d d@ChristineOlingerl)[added]Itisunclearwhowould  A beresponsibleforthecostsassociatedwithaforcauseaudit.Schedulingmaybedifficult.m)[added]Itislikelytobemoredifficultfortheprogramofficerstointeractwiththeauditorsandaccreditorsn)[added]EnforcementcasesmaybemoredifficulttodevelopCliveHalder #> K c)[modified]Feeswillhavea  L significantimpactonsmall,specialtytestingsfacilitiesf)[modified]Deletecurrentitemh)[modified]Potentiallyunacceptabletointernationalcommunitywithoutdirectgovernmentinvolvementi)[modified]Conflictofinterestandconfidentialityissueswillneedtobeaddressedj)[modified]Deletecurrentitem W  @4444-X4444d d@ 4 S4444@"8Y 8 4444d 8dS 411.Cont. @4444-C^4444d d@From2ndDraft(08/02/96) 8 EPAoversightofaGLPComplianceMonitoringProgramperformedbya3rdpartyaccreditingbodywithonsiteinspectionspaidforbyparticipantsdirectlytothe3rdpartyorganization(e.g.,EPAleadprogram) @4444-%4444d d@CliveHalder 8& l)[added]TheaddedresourceswouldallowforEPAtostreamlinecomplianceprogramtoallowfordatatobeauditedpriortoproductassessmentofOPPBranchm)[added]Nodisadvantagetocontractfacilitiesisperceivedn)[added]Itisamoreeffectiveuseofresourcestolimitfocustofacilitieswhichhaveaninterestinapplying,ratherthantotheuniverseofGLPlabso)[added]ThreatoflossofcertificatewouldserveasanincentivetosustainqualityoflabsRoxanneRobinson =X 6 p)[added]Ifthirdpartyaccreditors *7 adheretoISOGuide58,convexofinterestandconfidentialityisenforced @4444-:4444d d@CliveHalder 8; o)[added]Anequitableassessmentprogramisneededtoallowforfair/uniformissuanceofcertificatesofcompliancep)[added]ProgramwouldincorporateonlythatsegmentoftheregulatedcommunitywhoappliesF"K*%F&KF" @4444- B4444d d@ 4&%[ctionsof[ S4444@"8C 8 4444d 8dS 412. @4444-- H4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringProgramplusaseparatebutvoluntaryAccreditationProgramfortestsitecompliancemanagedbyaTradeAssociation.Onsiteinspectionsoftestsitesfacilities E `$ andsystemsonly,paidforby !<% participantsdirectlytotheTradeAssociation.(e.g.,variationofCSMAAntimicrobialQualityProgram) @4444- )4444d d@From2ndDraft(08/02/96) 8* a)CouldhelpEPAsresourcelimitationsb)Issuanceof@Certificate:ofaccreditationwouldaddressInternationalconcernsc)Providesstrongdrivingforce(economicincentive)forparticipationd)Voluntarynatureofprogramwouldeliminaterulemakingorlegislativeinterventione)MaynotinterferewithInteragencyGLPharmonizationf)ShouldenhancenumberofGLPlaboratoriesinspectedandfrequencyofaudits̀ @4444-;4444d d@From2ndDraft(08/02/96) 8< a)Potential@ConflictofInterest:issuestoberesolvedb)OverallassessmentofGLPaccreditationnolongerresidessolelywithEPAc)PotentiallyunacceptabletoInternationalcommunitywithoutdirectgovernmentinvolvementin@VoluntaryAccreditation:d)AdditionalcosttoGLPregulatedcommunityof@Voluntary:AccreditationPrograme)MayinterferewithInteragencyGLPharmonizationf)Highercost,novalueaddedotherthanissuanceof@Certificate:ofcomplianceg)QualityofGLPdatamaynotremainhighRoxanneRobinson MhP h)[added]TradeAssociationmayhaveverynarrowlyfocusedaccreditingprogramthatcouldnotmanagethebreadthofGLPtestingaccreditationi)[added]VoluntarynaturewouldnotdefineuniverseofGLPlabs @4444-uV4444d d@ 4 S4444@"8W 8 4444d 8dS 413. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringProgramplusaseparatebutvoluntaryAccreditationProgramfortestsitecompliancemanagedbyaTradeAssociation.Onsiteinspectionsoftestsitesfacilities E `# andsystemsincludinginlifeanddataaudits,paidforbyparticipantsdirectly % totheTradeAssociation.(e.g.,variationofCSMAAntimicrobialQualityProgram) @4444- (4444d d@From2ndDraft(08/02/96) 8) a)CouldhelpEPAsresourcelimitationsb)Issuanceof@Certificate:ofaccreditationwouldaddressInternationalconcernsc)Providesstrongdrivingforce(economicincentive)forparticipationd)Voluntarynatureofprogramwouldeliminaterulemakingorlegislativeinterventione)MaynotinterferewithInteragencyGLPharmonizationf)ShouldenhancenumberofGLPlaboratoriesinspectedandfrequencyofaudits̀ @4444-:4444d d@From2ndDraft(08/02/96) 8; a)Potential@ConflictofInterest:issuestoberesolvedb)OverallassessmentofGLPaccreditationnolongerresidessolelywithEPAc)PotentiallyunacceptabletoInternationalcommunitywithoutdirectgovernmentinvolvementin@VoluntaryAccreditation:d)AdditionalcosttoGLPregulatedcommunityof@Voluntary:AccreditationPrograme)MayinterferewithInteragencyGLPharmonizationf)Highercost,novalueaddedotherthanissuanceof@Certificate:ofcomplianceg)QualityofGLPdatamaynotremainhighRoxanneRobinson MhO h)[added]TradeAssociationmayhaveverynarrowlyfocusedaccreditingprogramthatcouldnotmanagethebreadthofGLPtestingaccreditationi)[added]VoluntarynaturewouldnotdefineuniverseofGLPlabs @4444-uU4444d d@ 4 S4444@"8V 8 4444d 8dS 414. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringProgramplusaseparatebutvoluntaryAccreditationProgramfortestsitecompliancemanagedbyaTradeAssociation.Onsiteinspectionsoftestsitesfacilities E `# andsystemsonly,paidforby !<$ participantsdirectlytotheTradeAssociation.(e.g.,variationofCSMAAntimicrobialQualityProgram) Plus   ( creationofaRegistrationList. @4444-m )4444d d@From2ndDraft(08/02/96) 8* a)CouldhelpEPAsresourcelimitationsb)Issuanceof@Certificate:ofaccreditationwouldaddressInternationalconcernsc)Providesstrongdrivingforce(economicincentive)forparticipationd)Voluntarynatureofprogramwouldeliminaterulemakingorlegislativeinterventione)MaynotinterferewithInteragencyGLPharmonizationf)ShouldenhancenumberofGLPlaboratoriesinspectedandfrequencyofaudits̀ @4444-;4444d d@From2ndDraft(08/02/96) 8< a)Potential@ConflictofInterest:issuestoberesolvedb)OverallassessmentofGLPaccreditationnolongerresidessolelywithEPAc)PotentiallyunacceptabletoInternationalcommunitywithoutdirectgovernmentinvolvementin@VoluntaryAccreditation:d)AdditionalcosttoGLPregulatedcommunityof@Voluntary:AccreditationPrograme)MayinterferewithInteragencyGLPharmonizationf)Highercost,novalueaddedotherthanissuanceof@Certificate:ofcomplianceg)QualityofGLPdatamaynotremainhighRoxanneRobinson MhP h)[added]TradeAssociationmayhaveverynarrowlyfocusedaccreditingprogramthatcouldnotmanagethebreadthofGLPtestingaccreditationI)[added]VoluntarynaturewouldnotdefineuniverseofGLPlabs @4444-QlW4444d d@ 4 S4444@"8X 8 4444d 8dS 415. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringProgramplusaseparatebutvoluntaryAccreditationProgramfortestsitecompliancemanagedbya3rdPartyAccreditingBody.Onsiteinspectionsoftestsitesfacilities E `# andsystemsonly,paidforby !<$ participantsdirectlytothe3rdParty % AccreditingBody. @4444-&4444d d@From2ndDraft(08/02/96) 8' a)CouldhelpEPAsresourcelimitationsb)Voluntarynatureofprogramwouldeliminaterulemakingorlegislativeinterventionc)MaynotinterferewithInteragencyGLPharmonizationd)ShouldenhancenumberofGLPlaboratoriesinspectedandfrequencyofauditsLouiseHess  2 e)[added]QualityofGLPdatawill m 3 remainhighf)[added]Ifindustrysupportedthisconcept,itcouldserveassteppingstonetoaformalizedaccreditationprocessinthefutureg)[added]Industryacceptanceof3rdpartyaccreditationsystemcoulddecreasecostsofsponsorsperformingauditsoftestsitesperformingstudiesforthem.Testsiteswouldalsobenefitfromreducednumberofclientaudits̀ @4444-?4444d d@From2ndDraft(08/02/96) 8@ a)Potential@ConflictofInterest:issuestoberesolvedb)OverallassessmentofGLPaccreditationnolongerresidessolelywithEPAc)PotentiallyunacceptabletoInternationalcommunitywithoutdirectgovernmentinvolvementin@VoluntaryAccreditation:d)AdditionalcosttoGLPregulatedcommunityof@Voluntary:AccreditationPrograme)MayinterferewithInteragencyGLPharmonizationf)Highercostg)QualityofGLPdatamaynotremainhighLouiseHess R h)[added]QualityofGLPdatamaynotremainhigh[disagreewiththisconclusionandhaveplacedthisitemintheadvantagescolumn] @4444-W4444d d@ 4 S4444@"8X 8 4444d 8dS 415.Cont. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringProgramplusaseparatebutvoluntaryAccreditationProgramfortestsitecompliancemanagedbya3rdPartyAccreditingBody.Onsiteinspectionsoftestsitesfacilities E `# andsystemsonly,paidforby !<$ participantsdirectlytothe3rdParty % AccreditingBody. @4444-&4444d d@ @4444-8'4444d d@LouiseHess 8( i)[added]Anyuseof3rdparty ) accreditingbodywouldrequireidentificationofrequirementsandacceptablepartiesbyEPA.Otherwise,theindustrysincentivetoparticipateislackingRoxanneRobinson !</ j)[added]Voluntarynaturewouldnot 0 allowuniverseoflabstobeknown @4444-14444d d@ 4 S4444@"82 8 4444d 8dS 416. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringProgramplusaseparatebutvoluntaryAccreditationProgramfortestsitecompliancemanagedbya3rdPartyAccreditingBody.Onsiteinspectionsoftestsitesfacilities E `# andsystemsincludinginlifeanddataaudits,paidforbyparticipantsdirectly % tothe3rdPartyAccreditingBody @4444-&4444d d@From2ndDraft(08/02/96) 8' a)CouldhelpEPAsresourcelimitationsb)Voluntarynatureofprogramwouldeliminaterulemakingorlegislativeinterventionc)MaynotinterferewithInteragencyGLPharmonizationd)ShouldenhancenumberofGLPlaboratoriesinspectedandfrequencyofauditsLouiseHess  2 e)[added]QualityofGLPdatawill m 3 remainhighf)[added]Ifindustrysupportedthisconcept,itcouldserveassteppingstonetoaformalizedaccreditationprocessinthefutureg)[added]Industryacceptanceof3rdpartyaccreditationsystemcoulddecreasecostsofsponsorsperformingauditsoftestsitesperformingstudiesforthem.Testsiteswouldalsobenefitfromreducednumberofclientaudits @4444->4444d d@From2ndDraft(08/02/96) 8? a)Potential@ConflictofInterest:issuestoberesolvedb)OverallassessmentofGLPaccreditationnolongerresidessolelywithEPAc)PotentiallyunacceptabletoInternationalcommunitywithoutdirectgovernmentinvolvementin@VoluntaryAccreditation:d)AdditionalcosttoGLPregulatedcommunityof@Voluntary:AccreditationPrograme)MayinterferewithInteragencyGLPharmonizationf)Highercostg)QualityofGLPdatamaynotremainhighLouiseHess Q h)[added]QualityofGLPdatamaynotremainhigh[disagreewiththisconclusionandhaveplacedthisitemintheadvantagescolumn] @4444-V4444d d@ 4 S4444@"8W 8 4444d 8dS 416.Cont. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringProgramplusaseparatebutvoluntaryAccreditationProgramfortestsitecompliancemanagedbya3rdPartyAccreditingBody.Onsiteinspectionsoftestsitesfacilities E `# andsystemsincludinginlifeanddataaudits,paidforbyparticipantsdirectly % tothe3rdPartyAccreditingBody @4444-&4444d d@ @4444-8'4444d d@LouiseHess 8( i)[added]Anyuseof3rdparty ) accreditingbodywouldrequireidentificationofrequirementsandacceptablepartiesbyEPA.Otherwise,theindustrysincentivetoparticipateislackingRoxanneRobinson !</ j)[added]Voluntarynaturewouldnot 0 allowuniverseoflabstobeknown @4444-14444d d@ 4 S4444@"82 8 4444d 8dS 417. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringplusinspectionsharingpartnershipbetweenEPAandSponsors @4444- !4444d d@From2ndDraft(08/02/96) 8" a)EPAsGLPcomplianceprogramwouldbeaugmentedinapartnershipwiththeGLPregulatedIndustryb)OverallburdenofGLPcompliancewouldbestreamlinedc)NoincreaseincosttoGLPregulatedcommunityandpotentialcostbenefitd)CouldhelpEPAsresourcelimitationse)FrequencyofGLPcomplianceauditingcoulddecreaseforsomefacilities,particularlycontractlaboratoriesf)QualityofGLPdataremainshighg)AssessmentofGLPcomplianceresideswithEPAFranciscaLiem 3 h)[added]AssessmentofGLP 4 complianceresideswithEPA.(Comment:ItisnotcleartoEPAhowtheGLPcomplianceresideswithEPA,ifthereisa @4444- 84444d d@From2ndDraft(08/02/96) 89 a)Potential@ConflictOfInterest:issuesb)AgreeduponinterpretationsofGLPsmaybeproblematicc)UniformityofGLPauditingstandardsmaybeproblematicd)Confidentialityissueswouldposeaprobleme)EPAandtheGLPregulatedIndustrywouldhavetodevelopfaircriteriastandardsf)SharingGLPauditresultswouldneedtoberesolvedlegallyg)InternationalcommunityrequestsforCompliance@Certificate:notaddressedh)InteragencyGLPharmonizationmaynotbesatisfiedFranciscaLiem qL i)[added]AcceptabilitybyFDAis MhM unknown.j)[added]Programcredibilityisunknown @4444-Q4444d d@ 4FranciscaLiem 8R a)[added]OPPpolicyto S acceptonlystudiesfrom@incompliance:testingfacilitiesshouldbedeterminedDorisMason E `X b)[added]Options17,18 !<Y and19weredevelopedundertheconstraintthattheyfollowedcurrentGLPStandards.Therefore,theinspectionsharingpartnershipdidnotinclude Id _ sharingresultsofinspectionreports.EPAwouldevaluateQAUproceduresandinspectionschedulesofthesponsor/testingfacility S4444@"Mhf 8 4444d 8dS 417.Cont. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringplusinspectionsharingpartnershipbetweenEPAandSponsors @4444- !4444d d@FranciscaLiem 8" h)(Cont.)sharedpartnershipbetween # EPAandSponsors)  $ DorisMasoni)[Noteadded]UndertheconstraintI  & havelisted,therewasnodifferencebetweenOption17andOption18.TheAdvantagesforOptions17arelistedunderOption18 @4444-*4444d d@FranciscaLiem 8+ k)[added]EPAhasnoadequate , controll)[added]Thereisnopotentialanticompetitiveeffect @4444- /4444d d@ 4RoxanneRobinson 80 c)[added]NTIA;NELAC; 1 accreditation(2ndpartyvs3rdparty) S4444@" 3 8 4444d 8dS 418. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringplusinspectionsharingpartnershipbetweenEPAandSponsors.Sponsorsinspecttheirsubcontractedtestsitesascurrentlyisdone,butEPAretainsoptiontoinspectanytestsite.EPAfocusesoninspectionsofSponsors,includingreviewofSponsorsQAUinspectionproceduresforcontractfacilitiesplusSponsor'sinspection/auditschedules[per160.35(c)]. @4444-m )4444d d@From2ndDraft(08/02/96) 8* a)EPAsGLPcomplianceprogramwouldbeaugmentedinapartnershipwiththeGLPregulatedindustryb)OverallburdenofGLPcompliancewouldbestreamlinedc)NoincreaseincosttoGLPregulatedcommunityandpotentialcostbenefitd)CouldhelpEPAsresourcelimitationse)FrequencyofGLPcomplianceauditingcoulddecreaseforsomefacilities,particularlycontractlaboratoriesf)QualityofGLPdataremainshighg)AssessmentofGLPcomplianceresideswithEPAFranciscaLiem ; h)[added]MinimalcosttoEPA < i)[added]Dataqualitymaybeacceptablej)[added]AllowsassessmentoffacilitiespriortousebyEPA @4444- @4444d d@From2ndDraft(08/02/96) 8A a)Potential@ConflictofInterest:issues   C   b)Agreeduponinterpretationsof  D GLPsmaybeproblematic c)UniformityofGLPauditingstandardsmaybeproblematicd)Confidentialityissueswouldposeaprobleme)EPAandtheGLPregulatedindustrywouldhavetodevelopfaircriteriastandardsf)SharingGLPauditresultswouldneedtoberesolvedlegallyg)InternationalcommunityrequestsforCompliance@Certificate:notaddressedh)InteragencyGLPharmonizationmaynotbesatisfiedFranciscaLiem qT i)[added]Sponsorsdon'talways MhU inspectcontractfacilitiesthemselves.Theyhireconsultants.Howdoesepa  W screentheconsultants? @4444-X4444d d@ 4FranciscaLiem 8Y   4WC``` hp x (#%'0*,.81XXXWa)[added]OPP'sacceptanceof Z thesharingofcomplianceevaluation/assessmentisunknown  4ZCXX` hp x (#%'0*,.81``XZDorisMason i ^ b)[added]Options17,18 E `_ and19weredevelopedundertheconstraintthattheyfollowedcurrentGLPStandards.Therefore,theinspectionsharingpartnershipdidnotinclude m e sharingresultsofinspectionreports.EPAwouldevaluateQAUproceduresandinspectionschedulesofthesponsor/testingfacility S4444@"k 8 4444d 8dS 418.Cont. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringplusinspectionsharingpartnershipbetweenEPAandSponsors.Sponsorsinspecttheirsubcontractedtestsitesascurrentlyisdone,butEPAretainsoptiontoinspectanytestsite.EPAfocusesoninspectionsofSponsors,includingreviewofSponsorsQAUinspectionproceduresforcontractfacilitiesplusSponsor'sinspection/auditschedules[per160.35(c)]. @4444-m )4444d d@FranciscaLiem 8* k)[added]Adequateinspection + coverageDorisMason  -  l)[added]EPAsGLPcompliance  . programwouldbeaugmentedinapartnershipwiththeGLPregulatedindustry.Byrecognizingsponsorsinspectionsasasupplementalpartoftheirprogram,inspection/auditingscheduleisgreatlyenhanced  WC``` hp x (#%'0*,.81XXXWm)[added]EPAretainsoverallcontrolofGLPcompliancemonitoringprogram.EPAcanprioritizetheirinspectionstofocusontestingfacilities(withstudydirectors),analyticallaboratories(involvedwithmanysponsors),andtestsiteswheretherearesuspectedorobviousproblems  <  ZCXX` hp x (#%'0*,.81``XZ @4444-q=4444d d@FranciscaLiem 8> j)[added]Nouniformityofinspectionsk)[added]Acceptanceinternationallyisunknownl)[added]AcceptancebyFDAisunknownm)[added]Legalfeasibilityhastobedeterminedn)[added]Programcredibilityisunknowno)[added]NocontrolbyEPAandenforcementauthorityisunknownp)[added]Problemswithanticompetitiveeffectsq)[added]WhowillbeissuingthecertificateofcomplianceDorisMason O r)[added]Internationalcommunity P requestsforCompliance@Certificate:arenotaddressed.ItwouldbelefttotheEPAtohandletheinternationalconcerns.Acceptanceofthistypeprograminternationallyisunknown @4444-U4444d d@ 4DorisMason 8V c)[added]Aspartofthe W partnershiparrangement,testingfacilitieswouldneedtoprovidetheEPAwithascheduleofcompletedinspectionsoftheircontractlabsortestsitessotheEPAwouldhaveamasterlistofinspections.ThesescheduleshavebeenavailabletotheEPAduringinspectionsasarequirementoftheGLPs[160.35(c)]andhavealsobeenreportedontheQAUStatementofInspectionsforsubmittedstudies,butthoseformatswerenotusefulfortheEPAtomonitorfrequency S4444@")Dk 8 4444d 8dS 418.Cont. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringplusinspectionsharingpartnershipbetweenEPAandSponsors.Sponsorsinspecttheirsubcontractedtestsitesascurrentlyisdone,butEPAretainsoptiontoinspectanytestsite.EPAfocusesoninspectionsofSponsors,includingreviewofSponsorsQAUinspectionproceduresforcontractfacilitiesplusSponsor'sinspection/auditschedules[per160.35(c)]. @4444-m )4444d d@DorisMason 8*  WC``` hp x (#%'0*,.81XXXWn)[added]NoincreaseincosttoGLP + regulatedcommunityandpotentialcostbenefit.SponsorcompaniescurrentlymonitorthetestsitesinvolvedintheirstudiesbecausetheyhavetheprimaryresponsibilityforGLPcomplianceofastudyeveniftheworkisconductedbyacontractfacility.ExistingGLPregulations(FDAsandEPAsFIFRA,TSCA)assignedthisresponsibilitytoSponsors,andindustryrespondedbymonitoringcontractfacilitiesthatgenerateGLPdata.ItwasreinforcedbyEPAsEnforcementResponsePolicy,wheremonetaryfinesandpenaltiesaremuchgreaterforSponsorsthanforcontractfacilities  ;  o)[added]QualityofGLPdataremains < highbecauseexistingprogramsdonotreallychange  Mh>  ,ZC` hp x (#%'0*,.81``XZ @4444-)D?4444d d@ ,ZCXX` hp x (#%'0*,.81XZDorisMason 8@ s)[added]InteragencyGLP A harmonizationhastobedetermined.FDAhasindicatedtheyaresatisfiedwiththecurrentGLPprogramsothisOptionmaybeacceptabletothemt)[added]Sponsorsdonotalwaysinspectcontractfacilitiesthemselves.Theyhireconsultants.HowdoesEPAscreentheconsultants? @4444-I4444d d@ 4DorisMason 8J c)(cont.)ofinspectionsatdifferentsitesbydifferentsponsorsRoxanneRobinson  N d)[added]NTIA; i O NELAC;accreditation̄doesntmeetdefinition S4444@"!<Q 8 4444d 8dS 418.Cont. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringplusinspectionsharingpartnershipbetweenEPAandSponsors.Sponsorsinspecttheirsubcontractedtestsitesascurrentlyisdone,butEPAretainsoptiontoinspectanytestsite.EPAfocusesoninspectionsofSponsors,includingreviewofSponsorsQAUinspectionproceduresforcontractfacilitiesplusSponsor'sinspection/auditschedules[per160.35(c)]. @4444-m )4444d d@DorisMason 8*  WC``` hp x (#%'0*,.81XXXWp)[added]AssessmentofGLP + complianceresideswithEPA.ItisanimportantadvantagebecauseGLPsareafederalregulationandprimaryresponsibilityformonitoringcompliancemustresidewithEPAsOfficeofCompliance(OC).EPAsinspectorshavethenecessarybackgroundandexperiencewithGLPstoprovideindustrywithfairenforcementpracticesandcomplianceassistance  m 6  q)[added]Theinformationrequiredfor Id 7 EPAtoeffectivelymonitorthepartnershipisavailabletothemunderexistingregulations.AtestingfacilityswrittenproceduresforconductinginspectionsandauditsareevaluatedduringEPAinspections,aswellastrainingrecordsforQAUpersonnel. @4444-)D?4444d d@ ZCXX` hp x (#%'0*,.81``XZ @4444-8@4444d d@ 4 S4444@"8A 8 4444d 8dS 418.Cont. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringplusinspectionsharingpartnershipbetweenEPAandSponsors.Sponsorsinspecttheirsubcontractedtestsitesascurrentlyisdone,butEPAretainsoptiontoinspectanytestsite.EPAfocusesoninspectionsofSponsors,includingreviewofSponsorsQAUinspectionproceduresforcontractfacilitiesplusSponsor'sinspection/auditschedules[per160.35(c)]. @4444-m )4444d d@DorisMason 8*  WC``` hp x (#%'0*,.81XXXWq)(cont.)UnderexistingGLP + regulations,recordsofinspectionsconductedbyaQAUareavailabletorepresentativesoftheEPAorFDA.IftheEPAfindsthatatestingfacilitysQAUproceduresarenotadequateduringaninspection,theywouldcitethemasfindingsintheirinspectionreportr)[added]EPAretainsfullresponsibilityforallaspectsofcompliancemonitoringandisnotdependentonthequalityoftheinspectionsofanyonesponsor.EPAsinspectionsaretheprimaryenforcementtypeinspections.IndustrysinspectionsonlysupplementtheEPAsinspections,notreplacethem. @4444-q=4444d d@ ZCXX` hp x (#%'0*,.81``XZ @4444-8>4444d d@ 4 S4444@"8? 8 4444d 8dS 418.Cont. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringplusinspectionsharingpartnershipbetweenEPAandSponsors.Sponsorsinspecttheirsubcontractedtestsitesascurrentlyisdone,butEPAretainsoptiontoinspectanytestsite.EPAfocusesoninspectionsofSponsors,includingreviewofSponsorsQAUinspectionproceduresforcontractfacilitiesplusSponsor'sinspection/auditschedules[per160.35(c)]. @4444-m )4444d d@DorisMason 8*  WC``` hp x (#%'0*,.81XXXWr)(cont.)Byestablishingadatabasefor + Sponsorsinspections,theEPAwouldknowhowmanySponsorshaveinspectedatestingfacilityandhowfrequentlythefacilityhadbeeninspected.TheInspectorGeneralsreportstatedthatGLPfacilitieswerenotadequatelyinspectedandOCdidnothavetheresourcestomonitorsomanytestsites.Intruth,ifSponsorsinspectionprogramswereconsidered,U.S.testingfacilitieslikelyhaveundergonemoreGLPinspectionsthananyplaceintheworld @4444-%@ 84444d d@ ZCXX` hp x (#%'0*,.81``XZ @4444-894444d d@ 4 S4444@"8: 8 4444d 8dS 419. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringplusinspectionsharingpartnershipbetweenEPAandSponsors.Sponsorsinspecttheirsubcontractedtestsitesascurrentlyisdone,butEPAretainsoptiontoinspectanytestsite.EPAfocusesoninspectionsofSponsors,includingreviewofSponsorsQAUinspectionproceduresforcontractfacilitiesplusSponsor'sinspection/auditschedules[per160.35(c)]... Plus creationofa m ) RegistrationList. @4444-Id *4444d d@ WC``` hp x (#%'0*,.81XXXW From2ndDraft(08/02/96) 8+ [ [ ZCXX` hp x (#%'0*,.81``XZ a)EPAsGLPcomplianceprogram , wouldbeaugmentedinapartnershipwiththeGLPregulatedindustry   . [ [ WC``` hp x (#%'0*,.81XXXW  b)OverallburdenofGLPcompliance  / wouldbestreamlined c)NoincreaseincosttoGLPregulatedcommunityandpotentialcostbenefit. ZCXX` hp x (#%'0*,.81``XZd)CouldhelpEPAsresourcelimitations e)FrequencyofGLPcomplianceauditingcoulddecreaseforsomefacilities,particularlycontractlaboratories  WC``` hp x (#%'0*,.81XXXWf)QualityofGLPdataremainshigh ZCXX` hp x (#%'0*,.81``XZg)AssessmentofGLPcomplianceresideswithEPAFranciscaLiem <  h)[added]Registrationisusefulto = EPA,becauseitwillgiveEPAtheinformationofalaboratoryandtheinitiationofastudy i)[added]MinimalcosttoEPA @4444- A4444d d@From2ndDraft(08/02/96)  8B   a)Potential@ConflictofInterest: C issues   D [  cl[ b)Agreeduponinterpretationsof  E GLPsmaybeproblematic[ [ WC``` hp x (#%'0*,.81XXXW c)UniformityofGLPauditingstandardsmaybeproblematic[  cl[d)Confidentialityissueswouldposeaproblem[  cl[e)EPAandtheGLPregulatedindustrywouldhavetodevelopfaircriteriastandards  ZCXX` hp x (#%'0*,.81``XZf)SharingGLPauditresultswouldneedtoberesolvedlegallyg)InternationalcommunityrequestsforCompliance@Certificate:notaddressed h)InteragencyGLPharmonizationmaynotbesatisfied FranciscaLiem qU i)[added]Sponsorsdon'talways MhV inspectcontractfacilitiesthemselves.Theyhireconsultants.Howdoesepa  X screentheconsultants? @4444-Z4444d d@ 4FranciscaLiem 8[  4a)[added]OPP'sacceptanceof \ thesharingofcomplianceevaluation/assessmentisunknown WC``` hp x (#%'0*,.81XXXWDorisMason i ` b)[added]Options17,18and19weredevelopedundertheconstraintthattheyfollowedcurrentGLPStandards.Therefore,theinspectionsharingpartnershipdidnot  f includesharingresultsof m g inspectionreports.EPAwouldevaluateQAUproceduresandinspectionschedulesofthesponsor/testingfacility  4ZCXX` hp x (#%'0*,.81``XZ S4444@"l 8 4444d 8dS 419.Cont. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringplusinspectionsharingpartnershipbetweenEPAandSponsors.Sponsorsinspecttheirsubcontractedtestsitesascurrentlyisdone,butEPAretainsoptiontoinspectanytestsite.EPAfocusesoninspectionsofSponsors,includingreviewofSponsorsQAUinspectionproceduresforcontractfacilitiesplusSponsor'sinspection/auditschedules[per160.35(c)]... Plus creationofa m ) RegistrationList. @4444-Id *4444d d@FranciscaLiem 8+ j)[added]Dataqualitymaybe , acceptable WC``` hp x (#%'0*,.81XXXW k)[added]AllowsassessmentoffacilitiespriortousebyEPA  ZCXX` hp x (#%'0*,.81``XZl)[added]AdequateinspectioncoverageDorisMason !<2  WC``` hp x (#%'0*,.81XXXWm)[added]EPAsGLPcompliance 3 programwouldbeaugmentedinapartnershipwiththeGLPregulatedindustry.Byrecognizingsponsorsinspectionsasasupplementalpartoftheirprogram,inspection/auditingscheduleisgreatlyenhanced ZCXX` hp x (#%'0*,.81``XZ n)[added]EPAretainsoverallcontrolofGLPcompliancemonitoringprogram.EPAcanprioritizetheirinspectionstofocusontestingfacilities(withstudydirectors),analyticallaboratories(involvedwithmanysponsors),andtestsiteswheretherearesuspectedorobviousproblems   A   @4444-B4444d d@FranciscaLiem 8C j)[added]Nouniformityof D inspections WC``` hp x (#%'0*,.81XXXWk)[added]Acceptanceinternationallyisunknown ZCXX` hp x (#%'0*,.81``XZl)[added]AcceptancebyFDAisunknown m)[added]Legalfeasibilityhastobedetermined n)[added]Programcredibilityisunknowno)[added]NocontrolbyEPAandenforcementauthorityisunknown p)[added]Problemswithanticompetitiveeffects q)[added]Whowillbeissuingthecertificateofcompliance?DorisMason T r)[added]Internationalcommunity U requestsforCompliance@Certificate:arenotaddressed.ItwouldbelefttotheEPAtohandletheinternationalconcerns.Acceptanceofthistypeprograminternationallyisunknown @4444-Z4444d d@ 4DorisMason 8[ c)[added]Aspartofthepartnershiparrangement,testingfacilitieswouldneedtoprovidetheEPAwithascheduleofcompletedinspectionsoftheircontractlabsortestsitessotheEPAwouldhaveamasterlistofinspections.ThesescheduleshavebeenavailabletotheEPAduringinspectionsasarequirementoftheGLPs[160.35(c)]andhavealsobeenreportedontheQAUStatementofInspectionsforsubmittedstudies,butthoseformatswerenotusefulfortheEPAtomonitorfrequencyofinspectionsatdifferentsitesbydifferentsponsors S4444@"r 8 4444d 8dS 419.Cont. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringplusinspectionsharingpartnershipbetweenEPAandSponsors.Sponsorsinspecttheirsubcontractedtestsitesascurrentlyisdone,butEPAretainsoptiontoinspectanytestsite.EPAfocusesoninspectionsofSponsors,includingreviewofSponsorsQAUinspectionproceduresforcontractfacilitiesplusSponsor'sinspection/auditschedules[per160.35(c)]... Plus creationofa m ) RegistrationList. @4444-Id *4444d d@DorisMason 8+  WC``` hp x (#%'0*,.81XXXW o)[added]NoincreaseincosttoGLP , regulatedcommunityandpotentialcostbenefit.SponsorcompaniescurrentlymonitorthetestsitesinvolvedintheirstudiesbecausetheyhavetheprimaryresponsibilityforGLPcomplianceofastudyeveniftheworkisconductedbyacontractfacility.ExistingGLPregulations(FDAsandEPAsFIFRA,TSCA)assignedthisresponsibilitytoSponsors,andindustryrespondedbymonitoringcontractfacilitiesthatgenerateGLPdata.ItwasreinforcedbyEPAsEnforcementResponsePolicy,wheremonetaryfinesandpenaltiesaremuchgreaterforSponsorsthanforcontractfacilities p)[added]QualityofGLPdataremainshighbecauseexistingprogramsdonotreallychange  Mh?  ZCXX` hp x (#%'0*,.81``XZ @4444-)D@4444d d@DorisMason 8A s)[added]InteragencyGLP B harmonizationhastobedetermined.FDAhasindicatedtheyaresatisfiedwiththecurrentGLPprogramsothisOptionmaybeacceptabletothem WC``` hp x (#%'0*,.81XXXWt)[added]Sponsorsdonotalwaysinspectcontractfacilitiesthemselves.Theyhireconsultants.HowdoesEPAscreentheconsultants?  J  ZCXX` hp x (#%'0*,.81``XZ @4444-K4444d d@ 4RoxanneRobinson 8L  4d)[added]NTIA;alsolisting M ofanykinddoesnotsatisfythe@accreditation:definitionassociatedwithNELACeffortsandinternationaleffortse)[added]Accreditation:Procedurebywhichanauthoritativebodygivesformalrecognitionthatabodyorpersoniscompetenttocarryoutspecifictasks. 4 S4444@"m X 8 4444d 8dS 419.Cont. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringplusinspectionsharingpartnershipbetweenEPAandSponsors.Sponsorsinspecttheirsubcontractedtestsitesascurrentlyisdone,butEPAretainsoptiontoinspectanytestsite.EPAfocusesoninspectionsofSponsors,includingreviewofSponsorsQAUinspectionproceduresforcontractfacilitiesplusSponsor'sinspection/auditschedules[per160.35(c)]... Plus creationofa m ) RegistrationList. @4444-Id *4444d d@DorisMason 8+  WC``` hp x (#%'0*,.81XXXWq)[added]AssessmentofGLP , complianceresideswithEPA.ItisanimportantadvantagebecauseGLPsareafederalregulationandprimaryresponsibilityformonitoringcompliancemustresidewithEPAsOfficeofCompliance(OC).EPAsinspectorshavethenecessarybackgroundandexperiencewithGLPstoprovideindustrywithfairenforcementpracticesandcomplianceassistance ZCXX` hp x (#%'0*,.81``XZr)[added]RegistrationwouldbeusefultotheEPAbecauseitprovidessomeinformationforevaluationofatestingfacilitysGLPprogrampriortoanactualinspection WC``` hp x (#%'0*,.81XXXW s)[added]CostsassociatedwithmaintainingaRegistrationListshouldbeminimaltoboththeEPAandtestingfacilities  )D@   ZCXX` hp x (#%'0*,.81``XZ WC``` hp x (#%'0*,.81XXXW ZCXX` hp x (#%'0*,.81``XZ @4444-C4444d d@ @4444-8D4444d d@ 4 S4444@"8E 8 4444d 8dS 419.Cont. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringplusinspectionsharingpartnershipbetweenEPAandSponsors.Sponsorsinspecttheirsubcontractedtestsitesascurrentlyisdone,butEPAretainsoptiontoinspectanytestsite.EPAfocusesoninspectionsofSponsors,includingreviewofSponsorsQAUinspectionproceduresforcontractfacilitiesplusSponsor'sinspection/auditschedules[per160.35(c)]... Plus creationofa m ) RegistrationList. @4444-Id *4444d d@DorisMason 8+  WC``` hp x (#%'0*,.81XXXWt)[added]Theinformationrequiredfor , EPAtoeffectivelymonitorthepartnershipisavailabletothemunderexistingregulations.AtestingfacilityswrittenproceduresforconductinginspectionsandauditsareevaluatedduringEPAinspections,aswellastrainingrecordsforQAUpersonnel.UnderexistingGLPregulations,recordsofinspectionsconductedbyaQAUareavailabletorepresentativesoftheEPAorFDA.IftheEPAfindsthatatestingfacilitysQAUproceduresarenotadequateduringaninspection,theywouldcitethemasfindingsintheirinspectionreport  <  ZCXX` hp x (#%'0*,.81``XZ @4444-=4444d d@ @4444-8>4444d d@ 4 S4444@"8? 8 4444d 8dS 419.Cont. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringplusinspectionsharingpartnershipbetweenEPAandSponsors.Sponsorsinspecttheirsubcontractedtestsitesascurrentlyisdone,butEPAretainsoptiontoinspectanytestsite.EPAfocusesoninspectionsofSponsors,includingreviewofSponsorsQAUinspectionproceduresforcontractfacilitiesplusSponsor'sinspection/auditschedules[per160.35(c)]... Plus creationofa m ) RegistrationList. @4444-Id *4444d d@DorisMason 8+  WC``` hp x (#%'0*,.81XXXWu)[added]EPAretainsfull , responsibilityforallaspectsofcompliancemonitoringandisnotdependentonthequalityoftheinspectionsofanyonesponsor.EPAsinspectionsaretheprimaryenforcementtypeinspections.IndustrysinspectionsonlysupplementtheEPAsinspections,notreplacethem.ByestablishingadatabaseforSponsorsinspections,theEPAwouldknowhowmanySponsorshaveinspectedatestingfacilityandhowfrequentlythefacilityhadbeeninspected.TheInspectorGeneralsreportstatedthatGLPfacilitieswerenotadequatelyinspectedandOCdidnothavetheresourcestomonitorsomanytestsites.Intruth,ifSponsorsinspectionprogramswereconsidered,U.S.testingfacilitieslikelyhaveundergonemoreGLPinspectionsthananyplaceintheworld @4444-B4444d d@ ZCXX` hp x (#%'0*,.81``XZ @4444-8C4444d d@ 4 S4444@"8D 8 4444d 8dS 420. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringplusinspectionsharingpartnershipbetweenEPAandSponsors.EPAfocusesoninspectionsofSponsors,butretainsoptiontoinspectanytestsite.Sponsorsinspecttheirsubcontractedtestsitesascurrentlyisdone,plusprovideEPAwithastatementofsponsorsQAinspectionsanddatesaswellasasponsorsdeclarationofGLPComplianceforthetestsites. @4444-m )4444d d@From2ndDraft(08/02/96) 8* a)EPAsGLPcomplianceprogram + wouldbeaugmentedinapartnershipwiththeGLPregulatedIndustryb)OverallburdenofGLPcompliancewouldbestreamlinedc)NoincreaseincosttoGLPregulatedcommunityandpotentialcostbenefitd)CouldhelpEPAsresourcelimitationse)FrequencyofGLPcomplianceauditingcoulddecreaseforsomefacilities,particularlycontractlaboratoriesf)QualityofGLPdataremainshighg)AssessmentofGLPcomplianceresideswithEPAFranDillonandLeeWest ;  h)[added]Utilizesskilled,trained < inspectorsforminimalstartuptime/costs  WC``` hp x (#%'0*,.81XXXWi)[added]Maximizesnumbersof(recognized)inspectionsoflabsforminimumcostincreasetoindustryandEPA ZCXX` hp x (#%'0*,.81``XZ @4444-C4444d d@From2ndDraft(08/02/96) 8D a)Potential@ConflictOfInterest: E issuesb)AgreeduponinterpretationsofGLPsmaybeproblematicc)UniformityofGLPauditingstandardsmaybeproblematicd)Confidentialityissueswouldposeaprobleme)EPAandtheGLPregulatedIndustrywouldhavetodevelopfaircriteriastandardsf)SharingGLPauditresultswouldneedtoberesolvedlegallyg)InternationalcommunityrequestsforCompliance@Certificate:notaddressedh)InteragencyGLPharmonizationmaynotbesatisfiedFranDillonandLeeWest qW i)[added]EPAdoesnotreallyhave MhX controloversharedportionofprogram.WithoutEPAsettingstandards,assessmentofcompliancedoesnotresidewithEPAj)[added]Withoutsharingfindings,assessmentofcompliancedoesnotresidewithEPA @4444-Ql_4444d d@ 4FranDillonandLeeWest 8`  4a)[added]Verycomplicated a toassureadequateschedulingb)[added]WouldSponsorsgiveEPAthelablistupfront?c)[added]Appealprocessneededclientrelationshipsmayinterfere 4RoxanneRobinson h d)[added]NTIA; i @accreditation:doesntmeetdefinition S4444@" k 8 4444d 8dS 420.Cont. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringplusinspectionsharingpartnershipbetweenEPAandSponsors.EPAfocusesoninspectionsofSponsors,butretainsoptiontoinspectanytestsite.Sponsorsinspecttheirsubcontractedtestsitesascurrentlyisdone,plusprovideEPAwithastatementofsponsorsQAinspectionsanddatesaswellasasponsorsdeclarationofGLPComplianceforthetestsites. @4444-m )4444d d@FranDillonandLeeWest 8*  WC``` hp x (#%'0*,.81XXXWj)[added]Utilizesskilled,trained + inspectorsforminimalstartuptime/costsk)[added]Maximizesnumbersof(recognized)inspectorsoflabsforminimumcostincreasetoindustryandEPA @4444-!<14444d d@ ZCXX` hp x (#%'0*,.81``XZFranDillonandLeeWest 82 k)[added]Lackofsinglepointof 3 controlforinspectorsandstandards,theinterpretationsofGLPcouldbecomeproblematicforcontractlaboratoriesl)[added]Schedulingcouldbecomplicatedandassuringfairnessamongsponsorscouldbeimpossiblem)[added]Industryinspectingindustryisunlikelytobeviewedbywatchdoggroupsasadequateregulatorymonitoringn)[added]Othercountriesareunlikelytobesatisfiedasabove  %@ @  o)[added]EPAdoesnotreallyhave  A controloversharedportionofprogramp)[added]WithoutEPAsettingstandards,assessmentofcompliancedoesnotresidewithEPAq)[added]Withoutsharingfindings,assessmentofcompliancedoesnotresidewithEPA @4444- H4444d d@ 4 S4444@"8I 8 4444d 8dS 420.Cont. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringplusinspectionsharingpartnershipbetweenEPAandSponsors.EPAfocusesoninspectionsofSponsors,butretainsoptiontoinspectanytestsite.Sponsorsinspecttheirsubcontractedtestsitesascurrentlyisdone,plusprovideEPAwithastatementofsponsorsQAinspectionsanddatesaswellasasponsorsdeclarationofGLPComplianceforthetestsites. @4444-m )4444d d@ WC``` hp x (#%'0*,.81XXXW @4444-8*4444d d@ ZCXX` hp x (#%'0*,.81``XZFranDillonandLeeWest 8+ r)[added]Lackofsinglepointof , controlforinspectorsandstandardstheinterpretationsofGLPcouldbecomeproblematicforcontractlaboratoriess)[added]Schedulingcouldbecomplicatedandassuringfairnessamongsponsorscouldbeimpossiblet)[added]Industryinspectingindustryisunlikelytobeviewedbywatchdoggroupsasadequateregulatorymonitorsu)[added]Othercountriesareunlikelytobesatisfiedasabove @4444-Id 84444d d@ 4 S4444@"89 8 4444d 8dS 421. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringplusinspectionsharingpartnershipbetweenEPAandSponsors.EPAfocusesoninspectionsofSponsors,butretainsoptiontoinspectanytestsite.Sponsorsinspecttheirsubcontractedtestsitesascurrentlyisdone,plusprovideEPAwithastatementofsponsorsQAinspectionsanddatesaswellasasponsorsdeclarationofGLPComplianceforthetestsites.Plus m ) EPAsetscriteriaforsponsorinspections. @4444-%@ +4444d d@From2ndDraft(08/02/96) 8, a)EPAsGLPcomplianceprogram - wouldbeaugmentedinapartnershipwiththeGLPregulatedIndustryb)OverallburdenofGLPcompliancewouldbestreamlinedc)NoincreaseincosttoGLPregulatedcommunityandpotentialcostbenefitd)CouldhelpEPAsresourcelimitationse)FrequencyofGLPcomplianceauditingcoulddecreaseforsomefacilities,particularlycontractlaboratoriesf)QualityofGLPdataremainshighg)AssessmentofGLPcomplianceresideswithEPA WC``` hp x (#%'0*,.81XXXWFranDillonandLeeWest = h)(added)Utilizesskilled,trainedinspectorsforminimalstartuptime/costs ZCXX` hp x (#%'0*,.81``XZi)(added)Maximizesnumbersof(recognized)inspectionsoflabsforminimumcostincreasetoindustryandEPA @4444-D4444d d@From2ndDraft(08/02/96) 8E a)Potential@ConflictOfInterest: F issuesb)AgreeduponinterpretationsofGLPsmaybeproblematicc)UniformityofGLPauditingstandardsmaybeproblematicd)Confidentialityissueswouldposeaprobleme)EPAandtheGLPregulatedIndustrywouldhavetodevelopfaircriteriastandardsf)SharingGLPauditresultswouldneedtoberesolvedlegallyg)InternationalcommunityrequestsforCompliance@Certificate:notaddressedh)InteragencyGLPharmonizationmaynotbesatisfiedFranDillonandLeeWest qX i)(added)EPAdoesnotreallyhave MhY controloversharedportionofprogram.WithoutEPAsettingstandards,assessmentofcompliancedoesnotresidewithEPA @4444-]4444d d@ 4FranDillonandLeeWest 8^  4a)[added]Verycomplicated _ toassureadequateschedulingb)[added]WouldSponsorsgiveEPAthelablistupfront?c)[added]Appealprocessneededclientrelationshipsmayinterfere 4RoxanneRobinson f d)(added)NTIA; g @accreditation:doesntmeetdefinition S4444@" i 8 4444d 8dS 421.Cont. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringplusinspectionsharingpartnershipbetweenEPAandSponsors.EPAfocusesoninspectionsofSponsors,butretainsoptiontoinspectanytestsite.Sponsorsinspecttheirsubcontractedtestsitesascurrentlyisdone,plusprovideEPAwithastatementofsponsorsQAinspectionsanddatesaswellasasponsorsdeclarationofGLPComplianceforthetestsites.Plus m ) EPAsetscriteriaforsponsorinspections. @4444-%@ +4444d d@ @4444-8,4444d d@FranDillonandLeeWest 8- j)(added)Withoutsharingfindings, . assessmentofcompliancedoesnotresidewithEPAk)(added)Schedulingcouldbecomplicatedandassuringfairnessamongsponsorscouldbeimpossiblel)(added)Industryinspectingindustryisunlikelytobeviewedbywatchdoggroupsasadequateregulatorymonitoringm)(added)Othercountriesareunlikelytobesatisfiedasabove  m 9  @4444-Id :4444d d@ 4 S4444@"8; 8 4444d 8dS 422. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringplusinspectionsharingpartnershipbetweenEPAandSponsors.EPAfocusesoninspectionsofSponsors,butretainsoptiontoinspectanytestsite.Sponsorsinspecttheirsubcontractedtestsitesascurrentlyisdone,plusprovideEPAwithastatementofsponsorsQAinspectionsanddatesaswellasasponsorsdeclarationofGLPComplianceforthetestsites.Plus m ) EPAsetscriteriaforsponsorinspectionsANDalsodirectsandcontrolsschedulingofsponsorinspections. @4444- -4444d d@From2ndDraft(08/02/96) 8. a)EPAsGLPcomplianceprogram / wouldbeaugmentedinapartnershipwiththeGLPregulatedIndustryb)OverallburdenofGLPcompliancewouldbestreamlinedc)NoincreaseincosttoGLPregulatedcommunityandpotentialcostbenefitd)CouldhelpEPAsresourcelimitationse)FrequencyofGLPcomplianceauditingcoulddecreaseforsomefacilities,particularlycontractlaboratoriesf)QualityofGLPdataremainshighg)AssessmentofGLPcomplianceresideswithEPA WC``` hp x (#%'0*,.81XXXWFranDillonandLeeWest ? h)[added]Utilizesskilled,trainedinspectorsforminimalstartuptime/costs ZCXX` hp x (#%'0*,.81``XZi)[added]Maximizesnumbersof(recognized)inspectionsoflabsforminimumcostincreasetoindustryandEPA @4444-F4444d d@From2ndDraft(08/02/96) 8G a)Potential@ConflictOfInterest: H issuesb)AgreeduponinterpretationsofGLPsmaybeproblematicc)UniformityofGLPauditingstandardsmaybeproblematicd)Confidentialityissueswouldposeaprobleme)EPAandtheGLPregulatedIndustrywouldhavetodevelopfaircriteriastandardsf)SharingGLPauditresultswouldneedtoberesolvedlegallyg)InternationalcommunityrequestsforCompliance@Certificate:notaddressedh)InteragencyGLPharmonizationmaynotbesatisfiedFranDillonandLeeWest qZ i)[added]EPAdoesnotreallyhave Mh[ controloversharedportionofprogram.WithoutEPAsettingstandards,assessmentofcompliancedoesnotresidewithEPA @4444-_4444d d@ 4FranDillonandLeeWest 8`  4a)[added]Verycomplicated a toassureadequateschedulingb)[added]WouldSponsorsgiveEPAthelablistupfront? 4c)[added]Appealprocessneededclientrelationshipsmayinterfere !<g RoxanneRobinsond)[added]NTIA; i @accreditation:doesntmeetdefinition S4444@" k 8 4444d 8dS 422.Cont. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringplusinspectionsharingpartnershipbetweenEPAandSponsors.EPAfocusesoninspectionsofSponsors,butretainsoptiontoinspectanytestsite.Sponsorsinspecttheirsubcontractedtestsitesascurrentlyisdone,plusprovideEPAwithastatementofsponsorsQAinspectionsanddatesaswellasasponsorsdeclarationofGLPComplianceforthetestsites.Plus m ) EPAsetscriteriaforsponsorinspectionsANDalsodirectsandcontrolsschedulingofsponsorinspections. @4444- -4444d d@ @4444-8.4444d d@FranDillonandLeeWest 8/ j)[added]Withoutsharingfindings, 0 assessmentofcompliancedoesnotresidewithEPAk)[added]Schedulingcouldbecomplicatedandassuringfairnessamongsponsorscouldbeimpossiblel)[added]Industryinspectingindustryisunlikelytobeviewedbywatchdoggroupsasadequateregulatorymonitoringm)(added)Othercountriesareunlikelytobesatisfiedasabove  m ;  @4444-Id <4444d d@ 4 S4444@"8= 8 4444d 8dS 423. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringplusinspectionsharingpartnershipbetweenEPAandSponsors.EPAfocusesoninspectionsofSponsors,butretainsoptiontoinspectanytestsite.Sponsorsinspecttheirsubcontractedtestsitesascurrentlyisdone,plusprovideEPAwithastatementofsponsorsQAinspectionsanddatesaswellasasponsorsdeclarationofGLPComplianceforthetestsites. Plus  m ) creationofaRegistrationList. @4444-Id *4444d d@From2ndDraft(08/02/96) 8+ a)EPAsGLPcomplianceprogram , wouldbeaugmentedinapartnershipwiththeGLPregulatedIndustryb)OverallburdenofGLPcompliancewouldbestreamlinedc)NoincreaseincosttoGLPregulatedcommunityandpotentialcostbenefitd)CouldhelpEPAsresourcelimitationse)FrequencyofGLPcomplianceauditingcoulddecreaseforsomefacilities,particularlycontractlaboratoriesf)QualityofGLPdataremainshighg)AssessmentofGLPcomplianceresideswithEPADavidAlexanderandPatriciaOBrien < Pomerleauh)[added]EPAsGLPcompliance q> programwouldbeaugmentedinapartnershipwiththeGLPSponsors @4444- A4444d d@From2ndDraft(08/02/96) 8B a)Potential@ConflictOfInterest: C issuesb)AgreeduponinterpretationsofGLPsmaybeproblematicc)UniformityofGLPauditingstandardsmaybeproblematicd)Confidentialityissueswouldposeaprobleme)EPAandtheGLPregulatedIndustrywouldhavetodevelopfaircriteriastandardsf)SharingGLPauditresultswouldneedtoberesolvedlegallyg)InternationalcommunityrequestsforCompliance@Certificate:notaddressedh)InteragencyGLPharmonizationmaynotbesatisfiedDavidAlexanderandPatriciaOBrien qU Pomerleaui)[added]EPAandtheGLPSponsors )DW wouldhavetodevelopstandardsforassuringconsistencyamongSponsorsforconductingassessorsandauditorstestsiteinspections @4444-[4444d d@ 4DavidAlexanderand 8\ PatriciaOBrienPomerleau 4a)[added]SharingGLPaudit  _ resultswouldneedtoberesolvedlegally;amnestyfordisclosuresisapossibilityb)[added]AgreeduponinterpretationsofGLPsmaybeproblematicc)[added]UniformityofGLPauditingstandardsmaybeproblematicd)[added]Interagencyacceptanceunknown e)[added]RoutineEPAprocedurestoensurethatSponsorsprotectConfidentialBusinessInformationagainstdisclosuremustbefollowed  4f)[added]AssumeSponsor'sQAUinspectionresultsreceivedbyEPAnolaterthansubmissionofstudyreporttoEPA S4444@"t 8 4444d 8dS 423.Cont. @4444-u4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringplusinspectionsharingpartnershipbetweenEPAandSponsors.EPAfocusesoninspectionsofSponsors,butretainsoptiontoinspectanytestsite.Sponsorsinspecttheirsubcontractedtestsitesascurrentlyisdone,plusprovideEPAwithastatementofsponsorsQAinspectionsanddatesaswellasasponsorsdeclarationofGLPComplianceforthetestsites. Plus  m ( creationofaRegistrationList. @4444-Id )4444d d@DavidAlexanderandPatriciaOBrien 8* Pomerleau WC``` hp x (#%'0*,.81XXXWi)[added]OverallburdenofEPAGLP  , ComplianceMonitoringwouldbestreamlined ZCXX` hp x (#%'0*,.81``XZj)[added]MinimalincreaseincosttoGLPregulatedcommunity(excludingSponsors) WC``` hp x (#%'0*,.81XXXWk)[added]CouldleverageEPAsresources ZCXX` hp x (#%'0*,.81``XZ l)[added]FrequencyofGLPcomplianceauditingcoulddecreaseforsometestsites,particularlycontractlaboratories,iftheSponsorssharedauditresultswitheachother  WC``` hp x (#%'0*,.81XXXWm)[added]QualityofGLPdataremainshigh n)[added]UltimateassessmentofGLPcomplianceresideswithEPA[ [ ZCXX` hp x (#%'0*,.81``XZ o)[added]MorecompletelistofGLPlaboratoriescouldbeprepared p)[added]ToremainonGLPRegistrationListwouldencourageGLPcompliance @4444-A4444d d@DavidAlexanderandPatriciaOBrien 8B Pomerleauj)[added]Internationalcommunity  D requestsforCompliance@Certificate:maynotbesatisfied @4444-E `H4444d d@ 4DavidAlexanderand 8I PatriciaOBrienPomerleau 4g)[added]EPAGLP  L ComplianceMonitoringProgramcredibilitywillbeatissue,asforanyother@selfcertification:programRoxanneRobinson Q  4h)[added]NTIA; R @accreditation:doesntmeetdefinition S4444@" T 8 4444d 8dS 423.Cont. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringplusinspectionsharingpartnershipbetweenEPAandSponsors.EPAfocusesoninspectionsofSponsors,butretainsoptiontoinspectanytestsite.Sponsorsinspecttheirsubcontractedtestsitesascurrentlyisdone,plusprovideEPAwithastatementofsponsorsQAinspectionsanddatesaswellasasponsorsdeclarationofGLPComplianceforthetestsites. Plus  m ) creationofaRegistrationList. @4444-Id *4444d d@D.AlexanderandP.OBrien 8+ Pomerleau WC``` hp x (#%'0*,.81XXXWq)[added]EPAcouldgainscreening  - capabilityr)[added]CouldaidEPAinstreamliningonsiteGLPComplianceMonitorings)[added]EPAwouldprovidelistofRegisteredGLPlaboratoriesand@Certificates:toInternationalgovernmentswhichmayaddressInternationalcommunityconcernst)[added]PotentialresourcesavingtoSponsorsfromreducednumberoftestsitetripsu)[added]PotentialresourcesavingstotestsitesfromreducednumberofSponsorvisits ZCXX` hp x (#%'0*,.81``XZ @4444-=4444d d@ @4444-8>4444d d@ 4 S4444@"8? 8 4444d 8dS 424. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringplusinspectionsharingpartnershipbetweenEPAandSponsors.EPAfocusesoninspectionsofSponsors,butretainsoptiontoinspectanytestsite.Sponsorsinspecttheirsubcontractedtestsitesascurrentlyisdone,plussharefindingswitheachotherandEPAfromthefacilityandsystemspartoftheinspection.(e.g.,variationofSCRIPSprogram) @4444-m )4444d d@From2ndDraft(08/02/96) 8* a)EPAsGLPcomplianceprogram + wouldbeaugmentedinapartnershipwiththeGLPregulatedIndustryb)OverallburdenofGLPcompliancewouldbestreamlinedc)NoincreaseincosttoGLPregulatedcommunityandpotentialcostbenefitd)CouldhelpEPAsresourcelimitationse)FrequencyofGLPcomplianceauditingcoulddecreaseforsomefacilities,particularlycontractlaboratoriesf)QualityofGLPdataremainshighg)AssessmentofGLPcomplianceresideswithEPA WC``` hp x (#%'0*,.81XXXWDavidAlexander&PatriciaOBrien ; Pomerleau < h)[added]EPAsGLPcomplianceprogramwouldbeaugmentedinapartnershipwiththeGLPSponsors ZCXX` hp x (#%'0*,.81``XZ @4444- @4444d d@From2ndDraft(08/02/96) 8A a)Potential@ConflictOfInterest: B issuesb)AgreeduponinterpretationsofGLPsmaybeproblematicc)UniformityofGLPauditingstandardsmaybeproblematicd)Confidentialityissueswouldposeaprobleme)EPAandtheGLPregulatedIndustrywouldhavetodevelopfaircriteriastandardsf)SharingGLPauditresultswouldneedtoberesolvedlegallyg)InternationalcommunityrequestsforCompliance@Certificate:notaddressed h)InteragencyGLPharmonizationmaynotbesatisfied[ [ WC``` hp x (#%'0*,.81XXXW DavidAlexander&PatriciaOBrien qT Pomerleau MhU [ [ ZCXX` hp x (#%'0*,.81``XZ i)[added]EPAandtheGLPSponsorswouldhavetodevelopstandardsforassuring @4444-X4444d d@DavidAlexander&Patricia 8Y OBrienPomerleau Z [  [a)[added]SharingGLPauditresultswouldneedtoberesolvedlegally;amnestyfordisclosuresisapossibility b)[added]AgreeduponinterpretationsofGLPsmaybeproblematicc)[added]UniformityofGLPauditingstandardsmaybeproblematicd)[added]Interagencyacceptanceunknowne)[added]RoutineEPAprocedurestoensurethatSponsorsprotectConfidentialBusinessInformationagainstdisclosuremustbefollowed 4f)[added]AssumeSponsor'sQAUinspectionresults S4444@")Dn 8 4444d 8dS 424.Cont. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringplusinspectionsharingpartnershipbetweenEPAandSponsors.EPAfocusesoninspectionsofSponsors,butretainsoptiontoinspectanytestsite.Sponsorsinspecttheirsubcontractedtestsitesascurrentlyisdone,plussharefindingswitheachotherandEPAfromthefacilityandsystemspartoftheinspection.(e.g.,variationofSCRIPSprogram) @4444-m )4444d d@ WC``` hp x (#%'0*,.81XXXWDavidAlexander&PatriciaOBrien 8* Pomerleau +  ZCXX` hp x (#%'0*,.81``XZi)[added]OverallburdenofGLPcompliancewouldbestreamlinedj)[added]MinimalincreaseincosttoGLPregulatedcommunity(excludingSponsors) WC``` hp x (#%'0*,.81XXXWk)(added)CouldleverageEPAsresourcesl)[added]FrequencyofGLPcomplianceauditingcoulddecreaseforsometestsites,particularlycontractlaboratoriesm)[added]QualityofGLPdataremainshighn)[added]UltimateassessmentofGLPcomplianceresideswithEPA ZCXX` hp x (#%'0*,.81``XZo)[added]EPAcouldgainscreeningcapabilitybyfollowingup,onanasneededbasis,withonsitefieldsiteGLPComplianceMonitoringafterexaminingQAUinspectionresultsfromthefacilityand @4444- @4444d d@DavidAlexander&PatriciaOBrien 8A Pomerleaui)(Cont.)consistencyamongSponsors  C forconductingassessorsandauditorstestsiteinspectionsj)[added]InternationalcommunityrequestsforCompliance@Certificate:maynotbesatisfiedJohnMcCann I k)[added]AdditionalworkforEPA J EPAwouldhavetoevaluatethecriteriaforeverysponsor(intheprogram)andthenassureconsistencyinfollowingstandards @4444-%@ O4444d d@DavidAlexander&Patricia 8P OBrienPomerleauf)(Cont.)receivedbyEPA  R wellinadvanceofsubmissionofstudyreporttoEPAg)[added]EPAGLPComplianceMonitoringProgramcredibilitywillbeatissue,asforanyother"selfcertification"program WC``` hp x (#%'0*,.81XXXWRoxanneRobinson Z  ZCXX` hp x (#%'0*,.81``XZh)[added]NTIA;@accreditation:doesntmeetdefinition 4 S4444@"%@ ^ 8 4444d 8dS 424.Cont. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringplusinspectionsharingpartnershipbetweenEPAandSponsors.EPAfocusesoninspectionsofSponsors,butretainsoptiontoinspectanytestsite.Sponsorsinspecttheirsubcontractedtestsitesascurrentlyisdone,plussharefindingswitheachotherandEPAfromthefacilityandsystemspartoftheinspection.(e.g.,variationofSCRIPSprogram) @4444-m )4444d d@ WC``` hp x (#%'0*,.81XXXWDavidAlexander&PatriciaOBrien 8* Pomerleau + o)(Cont.)systemspartoftheSponsorsinspectionp)[added]PotentialresourcesavingtoSponsorsfromreducednumberoftestsitetrips p)[added]PotentialresourcesavingstotestsitesfromreducednumberofSponsorvisits JohnMcCann 4  ZCXX` hp x (#%'0*,.81``XZq)[added]Couldworkbetweenreliable  5 andresponsiblesponsorswithadequateQAUsandmanagement WC``` hp x (#%'0*,.81XXXW @4444-%@ 84444d d@ ZCXX` hp x (#%'0*,.81``XZ @4444-894444d d@ 4 S4444@"8: 8 4444d 8dS 425. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringplusinspectionsharingpartnershipbetweenEPAandSponsors.EPAfocusesoninspectionsofSponsors,butretainsoptiontoinspectanytestsite.Sponsorsinspecttheirsubcontractedtestsitesascurrentlyisdone,plussharefindingswitheachotherandEPAfromthefacilityandsystemspartoftheinspection.PlusEPAsetscriteriaforinspections. @4444-m )4444d d@From2ndDraft(08/02/96) 8* a)EPAsGLPcomplianceprogramwouldbeaugmentedinapartnershipwiththeGLPregulatedIndustryb)OverallburdenofGLPcompliancewouldbestreamlinedc)NoincreaseincosttoGLPregulatedcommunityandpotentialcostbenefitd)CouldhelpEPAsresourcelimitationse)FrequencyofGLPcomplianceauditingcoulddecreaseforsomefacilities,particularlycontractlaboratoriesf)QualityofGLPdataremainshighg)AssessmentofGLPcomplianceresideswithEPAJohnMcCann ;  h)[added]EPAcouldcontrolqualityof < reportingbysettingcriteriatoensurecomplianceandreportingofresults @4444-Mh>4444d d@From2ndDraft(08/02/96) 8?  a)Potential@ConflictOfInterest:issuesb)AgreeduponinterpretationsofGLPsmaybeproblematicc)UniformityofGLPauditingstandardsmaybeproblematicd)Confidentialityissueswouldposeaprobleme)EPAandtheGLPregulatedIndustrywouldhavetodevelopfaircriteriastandardsf)SharingGLPauditresultswouldneedtoberesolvedlegallyg)InternationalcommunityrequestsforCompliance@Certificate:notaddressedh)InteragencyGLPharmonizationmaynotbesatisfiedJohnMcCann qR i)[added]Somesponsorsmightlack MhS theQAUcapabilitiestoparticipateinthisprogramcouldresultinpoorsupportof @4444-V4444d d@RoxanneRobinson 8W  a)[added]NTIA;@accreditation:doesntmeetdefinition.  4 S4444@" [ 8 4444d 8dS 425.Cont. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringplusinspectionsharingpartnershipbetweenEPAandSponsors.EPAfocusesoninspectionsofSponsors,butretainsoptiontoinspectanytestsite.Sponsorsinspecttheirsubcontractedtestsitesascurrentlyisdone,plussharefindingswitheachotherandEPAfromthefacilityandsystemspartoftheinspection.PlusEPAsetscriteriaforinspections. @4444-m )4444d d@ JohnMcCann 8* [  [i)[added]SponsorswithadequateQAUscouldaideEPAbyevaluatingtheirmultipletestsites  @4444- .4444d d@JohnMcCann 8/ i)(cont.)EPAifsponsorsstandardsarelow.MaynotbecosteffectiveifAgencyfoundsponsorstandardsunacceptableuponevaluationj)[added]Wouldrequireadditionalmonitoringandplanningtodirectparticipationofsponsorsk)[added]WouldrequireEPAreceivingpriorinformationontestsitesbeingcontractedbysponsors(mightrequiresomethinglikearegistrationlist)l)[added]WouldrequirerawinspectionreportsnotonesprovidedtoAgencyafterdeficiencieshavebeencorrected.Itsonethingtotellanothercompanythatafacilitymadeamajorbutcorrectableerror,butitsanotherthingtotelltheAgencysotheycanthrowthestudyout,orfinethesponsor @4444- E4444d d@ 4 S4444@"8F 8 4444d 8dS 425.Cont. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringplusinspectionsharingpartnershipbetweenEPAandSponsors.EPAfocusesoninspectionsofSponsors,butretainsoptiontoinspectanytestsite.Sponsorsinspecttheirsubcontractedtestsitesascurrentlyisdone,plussharefindingswitheachotherandEPAfromthefacilityandsystemspartoftheinspection.PlusEPAsetscriteriaforinspections. @4444-m )4444d d@  @4444-8*4444d d@JohnMcCann 8+  m)[added]Mightrequireregulationchangestomakesponsorliableforfaultyinspectionsandreportingn)[added]Couldinvolvethirdpartyparticipationwhenasponsorcannotconducttimelyinspections(whataretheresponsibilitiesandobligationsofthe3rdpartyorsponsorinthesecases?) @4444-44444d d@ 4 S4444@"85 8 4444d 8dS 426. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringplusinspectionsharingpartnershipbetweenEPAandSponsors.EPAfocusesoninspectionsofSponsors,butretainsoptiontoinspectanytestsite.Sponsorsinspecttheirsubcontractedtestsitesascurrentlyisdone,plussharefindingswitheachotherandEPAfromthefacilityandsystemspartoftheinspection.PlusEPAsetscriteriaforinspections m ) ANDalsodirectsandcontrolsschedulingofinspections @4444-%@ +4444d d@From2ndDraft(08/02/96) 8, a)EPAsGLPcomplianceprogramwouldbeaugmentedinapartnershipwiththeGLPregulatedIndustryb)OverallburdenofGLPcompliancewouldbestreamlinedc)NoincreaseincosttoGLPregulatedcommunityandpotentialcostbenefitd)CouldhelpEPAsresourcelimitationse)FrequencyofGLPcomplianceauditingcoulddecreaseforsomefacilities,particularlycontractlaboratoriesf)QualityofGLPdataremainshighg)AssessmentofGLPcomplianceresideswithEPA JohnMcCann =  h)[added]IfEPAknewofallthe > facilitiesbeingsubcontractedbysponsorsandthetimingofstudies,theycouldhelpscheduleinspectionsofall @4444-)DA4444d d@From2ndDraft(08/02/96) 8B a)Potential@ConflictOfInterest:issuesb)AgreeduponinterpretationsofGLPsmaybeproblematicc)UniformityofGLPauditingstandardsmaybeproblematicd)Confidentialityissueswouldposeaprobleme)EPAandtheGLPregulatedIndustrywouldhavetodevelopfaircriteriastandards f)SharingGLPauditresultswouldneedtoberesolvedlegally[  [g)InternationalcommunityrequestsforCompliance@Certificate:notaddressed[  [h)InteragencyGLPharmonizationmaynotbesatisfied JohnMcCann qU i)[added]Couldpermitsponsorsto MhV useEPAcriteria(conductinspection)atatimemostfavorabletothesubcontractedfacility.Pickand @4444-Y4444d d@RoxanneRobinson 8Z a)[added]NTIA;@accreditation:doesntmeetdefinition. 4 S4444@" ^ 8 4444d 8dS 426.Cont. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringplusinspectionsharingpartnershipbetweenEPAandSponsors.EPAfocusesoninspectionsofSponsors,butretainsoptiontoinspectanytestsite.Sponsorsinspecttheirsubcontractedtestsitesascurrentlyisdone,plussharefindingswitheachotherandEPAfromthefacilityandsystemspartoftheinspection.PlusEPAsetscriteriaforinspections m ) ANDalsodirectsandcontrolsschedulingofinspections. @4444-%@ +4444d d@JohnMcCann 8,  WC``` hp x (#%'0*,.81XXXWh)(Cont.)testingsitesusingthe - resourcesofthesponsors.EPAwouldhaveacompletelistofalltestingsites(forsponsorsparticipatingintheprogram)i)[added]Couldallowforunannouncedinspectionstoreallyevaluateafacility ZCXX` hp x (#%'0*,.81``XZ @4444-44444d d@JohnMcCann 85 i)(Cont.)inspectatatimewhena 6 studyisrunningsmoothly,notatatimewhenthefacilityishavingproblemsj)[added]OtherobligationsofthesponsorsQAUcoulddelaysponsorsresponsetoEPAsrequestforaninspection WC``` hp x (#%'0*,.81XXXW k)[added]WouldrequireadditionalEPAresourcestodocument,recordandscheduleinspectionsandrecordresults l)[added]Somesponsorswouldnotparticipateinavoluntaryprogram ZCXX` hp x (#%'0*,.81``XZm)[added]SomewouldprefertowaituntilEPAexpendedefforttoinspecttheirfieldsites @4444- E4444d d@ 4 S4444@"8F 8 4444d 8dS 427. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringplusinspectionsharingpartnershipbetweenEPAandSponsors.EPAfocusesoninspectionsofSponsors,butretainsoptiontoinspectanytestsite.Sponsorsinspecttheirsubcontractedtestsitesascurrentlyisdone,plusprovideEPAwithastatementofQAinspectionsanddatesaswellasasponsorsdeclarationofGLPcomplianceforthetestsites. Plus anyTestingFacility m ) canrequestanEPAaudit(andpayauserfee?)inordertomeetIntlneeds @4444-%@ +4444d d@From2ndDraft(08/02/96) 8, a)EPAsGLPcomplianceprogramwouldbeaugmentedinapartnershipwiththeGLPregulatedIndustryb)OverallburdenofGLPcompliancewouldbestreamlinedc)NoincreaseincosttoGLPregulatedcommunityandpotentialcostbenefitd)CouldhelpEPAsresourcelimitationse)FrequencyofGLPcomplianceauditingcoulddecreaseforsomefacilities,particularlycontractlaboratoriesf)QualityofGLPdataremainshighg)AssessmentofGLPcomplianceresideswithEPA WC``` hp x (#%'0*,.81XXXWFranDillonandLeeWest = h)[added]Utilizesskilled,trainedinspectorsforminimalstartuptime/costs ZCXX` hp x (#%'0*,.81``XZi)[added]Maximizesnumbersof(recognized)inspectionsoflabsforminimumcostincreasetoindustryandEPA @4444-D4444d d@From2ndDraft(08/02/96) 8E a)Potential@ConflictOfInterest:issuesb)AgreeduponinterpretationsofGLPsmaybeproblematicc)UniformityofGLPauditingstandardsmaybeproblematicd)Confidentialityissueswouldposeaprobleme)EPAandtheGLPregulatedIndustrywouldhavetodevelopfaircriteriastandardsf)SharingGLPauditresultswouldneedtoberesolvedlegallyg)InternationalcommunityrequestsforCompliance@Certificate:notaddressedh)InteragencyGLPharmonizationmaynotbesatisfiedFranDillonandLeeWest qX i)[added]EPAdoesnotreallyhave MhY controloversharedportionofprogram.WithoutEPAsettingstandards,assessmentofcompliancedoesnotresidewithEPA @4444-]4444d d@ WC``` hp x (#%'0*,.81XXXWRoxanneRobinson 8^  ZCXX` hp x (#%'0*,.81``XZ a)[added]NTIA;@accreditation:doesntmeetdefinition  4b)Userfeewouldrequirelegislation S4444@"i c 8 4444d 8dS 427.Cont. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPComplianceMonitoringplusinspectionsharingpartnershipbetweenEPAandSponsors.EPAfocusesoninspectionsofSponsors,butretainsoptiontoinspectanytestsite.Sponsorsinspecttheirsubcontractedtestsitesascurrentlyisdone,plusprovideEPAwithastatementofQAinspectionsanddatesaswellasasponsorsdeclarationofGLPcomplianceforthetestsites. Plus anyTestingFacility m ) canrequestanEPAaudit(andpayauserfee?)inordertomeetIntlneeds. @4444- ,4444d d@ @4444-8-4444d d@FranDillonandLeeWest 8. j)[added]Withoutsharingfindings, / assessmentofcompliancedoesnotresidewithEPAFranDillonandLeeWest  2 k)[added]Lackofsinglepointof i 3 controlforinspectorsandstandards,theinterpretationsofGLPcouldbecomeproblematicforcontractlaboratoriesl)[added]Schedulingcouldbecomplicatedandassuringfairnessamongsponsorscouldbeimpossiblem)[added]Industryinspectingindustryisunlikelytobeviewedbywatchdoggroupsasadequateregulatorymonitoring @4444-?4444d d@ 4 S4444@"8@ 8 4444d 8dS 428. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPCompliance  MonitoringProgramwithEPAdirectingtheStates(withEPA    criteria)toprovideonsiteinspectionsoftestsites @4444-E `#4444d d@LeeWest 8$ a)[added]Addsresourcesoffundsand % peopletocurrentprogramFranDillon  ' b)[added]SupplementsEPAresources  ( toaccomplishinspectionsbytransferringresponsibilityfromEPAtostates WC``` hp x (#%'0*,.81XXXWFranDillonandLeeWest , c)[added]Utilizesskilled,trainedinspectorsforminimalstartuptime/costs ZCXX` hp x (#%'0*,.81``XZd)[added]Maximizesnumbersof(recognized)inspectorsoflabsforminimumcostincreasetoindustryandEPAFranDillonandLeeWest  4  e)[added]Utilizesskilled,trained 5 inspectorsforminimalstartuptime/costs%&[%'0*[ q7   WC``` hp x (#%'0*,.81XXXW&%[ [f)[added]Maximizesnumbersof Mh8 (recognized)inspectionsoflabsforminimumcostincreasetoindustryandEPA ZCXX` hp x (#%'0*,.81``XZ @4444-<4444d d@LeeWest 8= a)[added]DoesnotmeetOPP'sneedforhavinginspectorsexperiencedinstudyconductb)[added]Mostlikelyproblemislackofproperlytrainedinspectors i B FranDillonc)[added]Statesarenotinterestedin !<D assumingthisresponsibilityd)[added]StateslackexperiencewiththeGLPprograme)[added]StartuptimewouldbelongbeforeEPAwouldbecomfortableacceptinginspectionsdoneby@new:inspectorsf)[added]Coordinationofinspectionsofmultiplesitestudieswillbedifficult.Whichstatewoulddoinspections?g)[added]Legality @4444-qP4444d d@LeeWest 8Q a)[added]Statesareunwilling R tobeinvolvedFranDillonandLeeWest  T b)[added]Verycomplicated  U toassureadequateschedulingc)[added]WouldsponsorsgiveEPAthelablistupfrontd)[added]Appealprocessneededclientrelationshipsmayinterfere [ FranDillone)[added]Overall m ] administrativeburdenlikelytobegreater S4444@"%@ _ 8 4444d 8dS28.Cont. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPCompliance  MonitoringProgramwithEPAdirectingtheStates(withEPA    criteria)toprovideonsiteinspectionsoftestsites @4444-E `#4444d d@ @4444-8$4444d d@RoxanneRobinson 8% h)[added]Statesdon'thaveexpertise & andtheydon'twanttodoit.Manycan'tdoregularNELACprogramforenvironmentalanalysisaccreditationandwillhavetorelyon3rdpartyaccreditorsinordertoparticipateFranDillonandLeeWest !<, i)[added]EPAdoesnotreallyhave - controloversharedportionofprogram.WithoutEPAsettingstandards,assessmentofcompliancedoesnotresidewithEPAj)[added]Withoutsharingfindings,assessmentofcompliancedoesnotresidewithEPAk)[added]Lackofsinglepointofcontrolforinspectorsandstandards,theinterpretationsofGLPcouldbecomeproblematicforcontractlaboratories @4444-)D:4444d d@ S4444@"8; 8 4444d 8dS28.Cont. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 CurrentEPAGLPCompliance  MonitoringProgramwithEPAdirectingtheStates(withEPA    criteria)toprovideonsiteinspectionsoftestsites @4444-E `#4444d d@ @4444-8$4444d d@FranDillonandLeeWest 8% l)[added]Schedulingcouldbe & complicatedandassuringfairnessamongsponsorscouldbeimpossiblem)[added]Industryinspectingindustryisunlikelytobeviewedbywatchdoggroupsasadequateregulatorymonitoringn)[added]Othercountriesareunlikelytobesatisfiedasabove @4444-.4444d d@ S4444@"8/ 8 4444d 8dS29. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 IncludedinNELACProgramwithGLPStandardsunchanged.StructureaccommodatesGLPsdirectlyundertheconstitution,bypassingtherestoftheNELAP.Assumesa3rdPartyAccreditingBodyandispaidforbyparticipantsdirectlytothe3rdpartyorganization.CliveHalder&ChristineOllinger & [Explanationadded]Thisscenario ' assumesthat,whilethestandardsoftheGLPsthemselvesareunchanged,theNELACconstitution/structureallowsforthegoverningofthe@peripheral:aspects,e.g.,accreditationprocess,feesetting,etc. @4444- -4444d d@From2ndDraft(08/02/96) 8. a)EPAsGLPComplianceMonitoringprogramwouldremainunchangedb)WouldfallundercommonNELAC@umbrella:c)ShouldenhancenumberofGLPlaboratoriesinspectedandfrequencyofauditsd)SufficientresourcestoadequatelyvisitallGLPlaboratoriese)Issuanceof@Certificate:ofcompliancebyEPAwouldaddressInternationalconcernsCliveHalder&ChristineOllinger Id ; a)[modified]TheEPAGLPstandards %@ < wouldremainunchangedd)[deleted]f)[added]EnhancedprogramshouldbeperceivedtobecrediblebyIGOfficeandothersg)[added]Nodisadvantagetocontractfacilitiesisperceived @4444- D4444d d@From2ndDraft(08/02/96) 8E a)Legalissuesconcerning@Voluntary:NELACstandardsversusGLPmandatorycompliancewillneedtobeaddressedb)FinancialburdenfortheGLPregulatedIndustry,especiallyhighlyspecializedsmallbusinesses(example:ContractPathologist,archive)c)Highercost,novalueaddedotherthanissuanceof@Certificate:ofcomplianced)Monetaryreimbursementwouldhavetobeaddressedatthefederallevele)Legislativeinterventionwouldbenecessarytoallowappropriatechannelingoffeesdespitethe@Voluntary:natureofNELACprogramf)QualityofGLPdatamaynotremainhighg)OverallassessmentofGLPaccreditationnolongerresidessolelywithEPA @4444-\4444d d@ 4From2ndDraft(08/02/96) 8] a)@Certificate:ofGLPComplianceforInternationalcommunityDorisMason  a b)[added]WillOPP/FDA, i b nationalcommunityrecognize3rdpartyaccreditivebody? S4444@"e 8 4444d 8dS 429.Cont. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 IncludedinNELACProgramwithGLPStandardsunchanged.StructureaccommodatesGLPsdirectlyundertheconstitution,bypassingtherestoftheNELAP.Assumesa3rdPartyAccreditingBodyandispaidforbyparticipantsdirectlytothe3rdpartyorganization. @4444-%4444d d@CliveHalder&ChristineOllinger 8& h)[added]Intheory,addedresourceswouldallowforEPAtostreamlinecomplianceprogramtoallowfordatatobeauditedpriortoproductassessmentbyOPPBranch @4444-i +4444d d@CliveHalder&ChristineOllinger 8, b)[modified]Feeswouldhavea - significantimpactonsmall,specialtytestingfacilitiesd)[modified]Legal/legislativefeasibilityofinvolvingadditionalfeeswillhavetobeaddressed E `2 h)[added]TheEPAGLPCompliance !<3 Programwouldbechangedi)[added]QuestionremainswhetherthissetupwouldprovidetheresourcestoenhancethecurrentGLPComplianceProgramj)[added]NeedtodetermineFDAsacceptanceofthissetupk)[added]TheNELACstructureisclosedtoformalinputbytheregulatedcommunity,preventingconstitutionalrightofregulatedcommunityl)[added]SinceNELAPis @4444-q?4444d d@ 4 S4444@"8@ 8 4444d 8dS 429.Cont. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 IncludedinNELACProgramwithGLPStandardsunchanged.StructureaccommodatesGLPsdirectlyundertheconstitution,bypassingtherestoftheNELAP.Assumesa3rdPartyAccreditingBodyandispaidforbyparticipantsdirectlytothe3rdpartyorganization. @4444-%4444d d@ @4444-8&4444d d@CliveHalder&ChristineOllinger 8' l)(Cont.)voluntarywithrespecttostateparticipation,programdoesnotassureasinglenationalaccreditationstandardorprogramm)[added]Afair/equitablefeestructurewouldneedtobeestablishedn)[added]Concernsaboutconfidentialityandfair/uniformimplementationwouldneedtobeaddressedo)[added]ConcernsaboutthequalityoftrainingforstatestoperformGLPinspectionswillneedtobeaddressedp)[added]TherewillbeasubstantialstartupandmaintenanceGLPtrainingprogramforEPAtooperateandfinanceCliveHalder 9 q)[added]Itisunclearwhowould q: inspectandauditinternationallabswhichsubmit @4444-)D<4444d d@ 4 S4444@"8= 8 4444d 8dS 429.Cont. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 IncludedinNELACProgramwithGLPStandardsunchanged.StructureaccommodatesGLPsdirectlyundertheconstitution,bypassingtherestoftheNELAP.Assumesa3rdPartyAccreditingBodyandispaidforbyparticipantsdirectlytothe3rdpartyorganization. @4444-%4444d d@ @4444-8&4444d d@DorisMason 8' q)(Cont.)studies ( r)[added]Itislikelytobemoredifficultfortheprogramofficestointeractwiththeauditorsandaccreditorss)[added]Itmaybemoredifficulttoscheduleforcauseauditst)[added]Enforcementcasesmaybemoredifficulttodevelopu)[added]IfGLPswereincludedunderNELAP,sponsorscouldnotstopmonitoringcontractfacilitiesunlesssponsorsliabilityfortheperformanceofcontractlaboratorieswaseliminated.SponsorcompaniescurrentlymonitoralltestsitesinvolvedintheirstudiesbecausetheyhaveprimaryresponsibilityforGLPcomplianceofastudyeveniftheworkisconductedbyacontractfacility.Thisresponsibilitytomonitorcontractfacilitiesisrecognized @4444- =4444d d@ 4 S4444@"8> 8 4444d 8dS 429.Cont. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 IncludedinNELACProgramwithGLPStandardsunchanged.StructureaccommodatesGLPsdirectlyundertheconstitution,bypassingtherestoftheNELAP.Assumesa3rdPartyAccreditingBodyandispaidforbyparticipantsdirectlytothe3rdpartyorganization. @4444-%4444d d@ @4444-8&4444d d@DorisMason 8' u)(Cont.)byindustryunderthe ( existingGLPregulations(FDAsandEPAsFIFRA,TSCA).SponsorresponsibilityisclearlyspelledoutintheEPAsEnforcementResponsePolicy,wherepenaltiesaremuchgreaterforthesponsorthanforthecontractfacilityv)[added]IfintheU.S.,alltestsitesmustbeofficiallyaccreditedunderNELAC,thecoststosponsorcompanieswouldbeverysignificant.ForinternationalcompanieswithlocationsintheU.S.andabroad,thecostsforconductingstudiesintheirU.S.researchcenterswouldnotbecompetitivewiththecompaniesEuropeanresearchcenters.WhentherearetoomanycostsassociatedwithgovernmentregulationsforU.S.locations,morestudieswillbeconductedoutsideofthecountryw)[added]TheprobabilityforinspectorstousetheinspectionopportunitytocovernonGLPissuessuchaspollutantair,OSHA,etc.Also,trainingofstateemployedinspectorswouldposeamajorproblem @4444-- HC4444d d@ 4 S4444@"8D 8 4444d 8dS 430. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 IncludedinNELACProgramwithGLPStandardsunchanged,butincorporatedintotheQualitySystemsChapterofNELAP.Assumesa3rdPartyAccreditingBodyandispaidforbyparticipantsdirectlytothe3rdpartyorganization.CliveHalder&ChristineOllinger % (explanation)Thisscenarioassumes & that,whilethestandardsoftheGLPsthemselvesareunchanged,theNELACconstitution/structureallowsforthegoverningofthe@peripheral:aspects,e.g.,accreditationprocess,feesetting,etc. @4444- ,4444d d@From2ndDraft(08/02/96) 8- a)EPAsGLPComplianceMonitoringprogramwouldremainunchangedb)WouldfallundercommonNELAC@umbrella:c)ShouldenhancenumberofGLPlaboratoriesinspectedandfrequencyofauditsd)SufficientresourcestoadequatelyvisitallGLPlaboratoriese)Issuanceof@Certificate:ofcompliancebyEPAwouldaddressInternationalconcernsCliveHalder&ChristineOllinger Id : a)[modified]TheEPAGLPstandards %@ ; wouldremainunchangedd)[deleted]  = f)[added]Enhancedprogramshouldbe > perceivedtobecrediblebyIGOfficeandothersg)[added]Nodisadvantagestocontractfacilitiesisperceived @4444-)DB4444d d@From2ndDraft(08/02/96) 8C a)Legalissuesconcerning@Voluntary:NELACstandardsversusGLPmandatorycompliancewillneedtobeaddressedb)FinancialburdenfortheGLPregulatedIndustry,especiallyhighlyspecializedsmallbusinesses(example:ContractPathologist,archive)c)Highercost,novalueaddedotherthanissuanceof@Certificate:ofcomplianced)Monetaryreimbursementwouldhavetobeaddressedatthefederallevele)Legislativeinterventionwouldbenecessarytoallowappropriatechannelingoffeesdespitethe@Voluntary:natureofNELACprogramf)QualityofGLPdatamaynotremainhighg)OverallassessmentofGLPaccreditationnolongerresidessolelywithEPA @4444-Z4444d d@ 4From2ndDraft(08/02/96) 8[ a)@Certificate:ofGLPComplianceforInternationalcommunity S4444@" ^ 8 4444d 8dS 430.Cont. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 IncludedinNELACProgramwithGLPStandardsunchanged,butincorporatedintotheQualitySystemsChapterofNELAP.Assumesa3rdPartyAccreditingBodyandispaidforbyparticipantsdirectlytothe3rdpartyorganization. @4444-!<$4444d d@CliveHalder&ChristineOllinger 8% h)[added]Intheory,addedresources & wouldallowforEPAtostreamlinecomplianceprogramtoallowfordatatobeauditedpriortoproductassessmentbyOPPBranch @4444-i *4444d d@CliveHalder&ChristineOllinger 8+ b)[modified]Feeswouldhavea , significantimpactonsmall,specialtytestingfacilitiesd)[modified]Legal/legislativefeasibilityofinvolvingadditionalfeeswillhavetobeaddressedh)[added]TheEPAGLPComplianceProgramwouldbechangedi)[added]QuestionremainswhetherthissetupwouldprovidetheresourcestoenhancethecurrentGLPComplianceProgramj)[added]NeedtodetermineFDAsacceptanceofthissetupk)[added]TheNELACstructureisclosedtoformalinputbytheregulatedcommunity,preventingconstitutionalrightofregulatedcommunity @4444-q>4444d d@ 4 S4444@"8? 8 4444d 8dS 430.Cont. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 IncludedinNELACProgramwithGLPStandardsunchanged,butincorporatedintotheQualitySystemsChapterofNELAP.Assumesa3rdPartyAccreditingBodyandispaidforbyparticipantsdirectlytothe3rdpartyorganization. @4444-!<$4444d d@ @4444-8%4444d d@CliveHalder&ChristineOllinger 8& l)[added]SinceNELAPisvoluntary ' withrespecttostateparticipation,programdoesnotassureasinglenationalaccreditationstandardorprogramm)[added]Afair/equitablefeestructurewouldneedtobeestablishedn)[added]Concernsaboutconfidentialityandfair/uniformimplementationwouldneedtobeaddressedo)[added]ConcernsaboutthequalityoftrainingforstatestoperformGLPinspectionswillneedtobeaddressedp)[added]TherewillbeasubstantialstartupandmaintenanceGLPtrainingprogramforEPAtooperateandfinance @4444-84444d d@ 4 S4444@"89 8 4444d 8dS 430.Cont. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 IncludedinNELACProgramwithGLPStandardsunchanged,butincorporatedintotheQualitySystemsChapterofNELAP.Assumesa3rdPartyAccreditingBodyandispaidforbyparticipantsdirectlytothe3rdpartyorganization. @4444-!<$4444d d@ @4444-8%4444d d@CliveHalder 8& q)[added]Itisunclearwhowould ' inspectandauditinternationallabswhichsubmitstudies̀r)[added]Itislikelytobemoredifficultfortheprogramofficestointeractwiththeauditorsandaccreditorss)[added]Itmaybemoredifficulttoscheduleforcauseauditst)[added]Enforcementcasesmaybemoredifficulttodevelop @4444- 14444d d@ 4 S4444@"82 8 4444d 8dS 430.Cont. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 IncludedinNELACProgramwithGLPStandardsunchanged,butincorporatedintotheQualitySystemsChapterofNELAP.Assumesa3rdPartyAccreditingBodyandispaidforbyparticipantsdirectlytothe3rdpartyorganization. @4444-!<$4444d d@ @4444-8%4444d d@DorisMason 8& u)[added]IfGLPswereincluded ' underNELAP,sponsorscouldnotstopmonitoringcontractfacilitiesunlesssponsorsliabilityfortheperformanceofcontractlaboratorieswaseliminated.SponsorcompaniescurrentlymonitoralltestsitesinvolvedintheirstudiesbecausetheyhaveprimaryresponsibilityforGLPcomplianceofastudyeveniftheworkisconductedbyacontractfacility.ThisresponsibilitytomonitorcontractfacilitiesisrecognizedbyindustryundertheexistingGLPregulations(FDAsandEPAsFIFRA,TSCA).SponsorresponsibilityisclearlyspelledoutintheEPAsEnforcementResponsePolicy,wherepenaltiesaremuchgreaterforthesponsorthanforthecontractfacility @4444-Mh:4444d d@ 4 S4444@"8; 8 4444d 8dS 430.Cont. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 IncludedinNELACProgramwithGLPStandardsunchanged,butincorporatedintotheQualitySystemsChapterofNELAP.Assumesa3rdPartyAccreditingBodyandispaidforbyparticipantsdirectlytothe3rdpartyorganization. @4444-!<$4444d d@ @4444-8%4444d d@DorisMason 8& v)[added]IfintheU.S.,alltestsites ' mustbeofficiallyaccreditedunderNELAC,thecoststosponsorcompanieswouldbeverysignificant.ForinternationalcompanieswithlocationsintheU.S.andabroad,thecostsforconductingstudiesintheirU.S.researchcenterswouldnotbecompetitivewiththecompaniesEuropeanresearchcenters.WhentherearetoomanycostsassociatedwithgovernmentregulationsforU.S.locations,morestudieswillbeconductedoutsideofthecountryw)[added]TheprobabilityforinspectorstousetheinspectionopportunitytocovernonGLPissuessuchaspollutantair,OSHA,etc.Also,trainingofstateemployedinspectorswouldposeamajorproblem @4444-Mh:4444d d@ 4 S4444@"8; 8 4444d 8dS 431. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 IncludedinNELACProgramwithchangesintheGLPStandardsmadetoaccommodatetheNELACstructure.Assumesa3rdPartyAccreditingBodyandispaidforbyparticipantsdirectlytothe3rdpartyorganization.CliveHalder&ChristineOllinger !<$ (explanation)Thisscenarioallowsfor % theGLPstandardstobemergedintothestructureoftheNELAP,therebyallowingtheexistingrequirementstobemodified @4444-m )4444d d@From2ndDraft(08/02/96) 8* a)WouldfallundercommonNELAC@umbrella:b)ShouldenhancenumberofGLPlaboratoriesinspectedandfrequencyofauditsc)SufficientresourcestoadequatelyvisitallGLPlaboratoriesd)Issuanceof@Certificate:ofcompliancebyEPAwouldaddressInternationalconcernsCliveHalder&ChristineOllinger  5 c)[deleted] m 6 e)[added]EnhancedprogramshouldbeperceivedtobecrediblebyIGOfficeandothersf)[added]Intheory,addedresourceswouldallowforEPAtostreamlinecomplianceprogramtoallowfordatatobeauditedpriortoproductassessmentbyOPPBranch @4444-Mh>4444d d@From2ndDraft(08/02/96)%&[)[added][ 8? a)EPAsGLPComplianceMonitoringprogramwouldchangeb)ChangesinGLPstandardswouldjeopardizetheInteragencyharmonizationc)Legalissuesconcerning@Voluntary:NELACstandardsversusGLPmandatorycompliancewillneedtobeaddressedd)FinancialburdenfortheGLPregulatedIndustry,especiallyhighlyspecializedsmallbusinesses(example:ContractPathologist,archive)e)Highercost,novalueaddedotherthanissuanceof@Certificate:ofcompliancef)Monetaryreimbursementwouldhavetobeaddressedatthefederallevelg)Legislativeinterventionwouldbenecessarytoallowappropriatechannelingoffeesdespitethe@Voluntary:natureofNELACprogramh)QualityofGLPdatamaynotremainhighi)OverallassessmentofGLPaccreditationnolongerresidessolelywithEPA @4444-UpV4444d d@ 4&%[)[added][ S4444@"8W 8 4444d 8dS 431.Cont. @4444-- H4444d d@From2ndDraft(08/02/96) 8 IncludedinNELACProgramwithchangesintheGLPStandardsmadetoaccommodatetheNELACstructure.Assumesa3rdPartyAccreditingBodyandispaidforbyparticipantsdirectlytothe3rdpartyorganization.CliveHalder&ChristineOllinger !<% (explanation)Thisscenarioallowsfor & theGLPstandardstobemergedintothestructureoftheNELAP,therebyallowingtheexistingrequirementstobemodified @4444-m *4444d d@ @4444-8+4444d d@CliveHalder&ChristineOllinger 8, d)[modified]Feeswouldhavea - significantimpactonsmall,specialtytestingfacilitiesf)[modified]Legal/legislativefeasibilityofinvolvingadditionalfeeswillhavetobeaddressed E `2 j)[added]Potentiallydamagesthe !<3 internationalharmonizationeffortswithOECDk)[added]Wouldrequirelegislativeapprovaltoallowsharingofcompliancemonitoringresponsibilitieswithstatesl)[added]SinceNELAPisvoluntarywithrespecttostateparticipation,programdoesnotassureasingleaccreditationstandardorprogramm)[added]Concernsaboutconfidentialityandfair/uniformimplementationwouldneedtobeaddressed%&[)[added][ @4444-)DA4444d d@&%[)[added][ S4444@"8B 8 4444d 8dS31.Cont. @4444-Ql4444d d@From2ndDraft(08/02/96) 8 IncludedinNELACProgramwithchangesintheGLPStandardsmadetoaccommodatetheNELACstructure.Assumesa3rdPartyAccreditingBodyandispaidforbyparticipantsdirectlytothe3rdpartyorganization.CliveHalder&ChristineOllinger !<$ (explanation)Thisscenarioallowsfor % theGLPstandardstobemergedintothestructureoftheNELAP,therebyallowingtheexistingrequirementstobemodified @4444-m )4444d d@ @4444-8*4444d d@CliveHalder&ChristineOllinger 8+ n)[added]WouldrequirerulemakinginordertoallowchangingofcurrentGLPstandardso)[added]QuestionremainswhetherthissetupwouldprovidetheresourcestoenhancethecurrentGLPComplianceProgramp)[added]NeedtodetermineFDAsacceptanceofthissetupq)[added]TheNELACstructureisclosedtoformalinputbytheregulatedcommunity,preventingconstitutionalrightsofregulatedcommunityCliveHalder %@ 9 q)[added]Itisunclearwhowould  : inspectandauditinternationallabswhichsubmitstudiesr)[added]Itislikelytobemoredifficultfortheprogramofficestointeractwiththeauditorsandaccreditorss)[added]Itmaybemoredifficulttoscheduleforcauseauditst)[added]Enforcementcasesmaybemoredifficulttodevelop @4444-D4444d d@ 4 S4444@"8E 8 4444d 8dS 432. @4444-4444d d@From2ndDraft(08/02/96) 8 GLPComplianceMonitoringProgramchangedtolookliketheNELAPandprovideaccreditation,butnotincludedunderNELAC.(fromJohnHenshaw)   Deletethisoption @4444-E ` 4444d d@Deletethisoption @4444-8!4444d d@Deletethisoption @4444-8"4444d d@ 4 S4444@"8# 8 4444d 8dS 433. @4444-4444d d@From2ndDraft(08/02/96) 8 EPAdirectedfeebasedinspectionprogram,whetherconducteddirectlybyEPA,orvia3rdPartycontractors,butusingGuide25asaCertificationStandard.(e.g.,France) @4444-i 4444d d@Pending @4444-8 4444d d@Pending @4444-8!4444d d@ 4 S4444@"8" 8 4444d 8dS 434. @4444-4444d d@From2ndDraft(08/02/96) 8 EPAdirectedfeebasedinspectionprogram,whetherconducteddirectlybyEPA,orvia3rdPartycontractors,butusingEN45001asaCertificationStandard.(e.g.,Netherlands,Denmark) @4444-E `!4444d d@Pending @4444-8"4444d d@Pending @4444-8#4444d d@ 4 S4444@"8$ 8 4444d 8dS 435. @4444-4444d d@From2ndDraft(08/02/96) 8 EPAdirectedfeebasedinspectionprogram,whetherconducteddirectlybyEPA,orvia3rdPartycontractors,butusingOECDGLPsasaCertificationStandard.(e.g.,UK,Swiss) @4444-E ` 4444d d@Pending @4444-8!4444d d@Pending @4444-8"4444d d@ 42(&8# 8 h 4444d 2 4  #bbdd