RegulationsRegulations andand TimelinesTimelinesin in BrazilBrazil

Eduardo Motti

RegulationsRegulations andand TimelinesTimelines in in BrazilBrazil

SummarySummary

�� DevelopmentDevelopment ofof regulationsregulations

�� CurrentCurrent requirementsrequirements

�� TimelinesTimelines: : pastpast andand presentpresent

�� WhereWhere are are wewe goinggoing to?to?

Content was partially presented at the 2005 DIA Annual Meeting,Washington, DC, session 447

EvolutionEvolution of of thethe clinicalclinical studystudyapprovalapproval processprocess in in BrazilBrazil

�� 1976 1976 –– LawLaw # 6360 # 6360 –– PublicPublic HealthHealth SystemSystem ActAct

�� 1988 1988 –– 1st 1st BylawBylaw (#01/88) (#01/88) �� requiredrequired Medical Medical EthicsEthics approvalapproval of of allall clinicalclinical studiesstudies

�� 1996 1996 –– NationalNational CouncilCouncil of of HealthHealth: : ResolResol. #196. #196�� CreatedCreated a new a new systemsystem for CS review for CS review andand approvalapproval

�� 1999 1999 –– CreationCreation of ANVISA: of ANVISA: independentindependent regulatoryregulatoryagencyagency

EvolutionEvolution of of thethe clinicalclinical studystudyapprovalapproval processprocess in in BrazilBrazil -- IIII

�� ResolutionsResolutions fromfrom thethe NationalNational CouncilCouncil of of HealthHealth::

�� #251/99 : #251/99 : DefinedDefined groupsgroups of of studiesstudies/review/review

�� #292/99 : #292/99 : InternationalInternational studiesstudies mustmust go to CONEPgo to CONEP

�� #301/00 : #301/00 : BestBest comparatorcomparator shouldshould bebe usedused

�� #346/05 : “#346/05 : “UmbrellaUmbrella approvalapproval” for ” for multicentricmulticentric studiesstudies

�� ResolutionsResolutions fromfrom ANVISAANVISA

�� # 911/98, # 219/05 : # 911/98, # 219/05 : CompositionComposition of of dossierdossier

http://www.anvisa.gov.br/medicamentos/pesquisa/legis.htm

CEP (CEP (BrazilianBrazilian IRB)IRB)

�� At At leastleast 7 7 membersmembers

�� AccreditedAccredited byby CONEP CONEP afterafter review of review of writtenwritten proceduresprocedures

�� CompositionComposition of of dossierdossier::

�� ProtocolProtocol, IC, IB...(in , IC, IB...(in PortuguesePortuguese), ), CVsCVs, , plusplus::

�� StudyStudy budget, budget, insuranceinsurance, , listlist of of participatingparticipating

countriescountries andand BrazilianBrazilian sitessites

�� CopyCopy of IRB of IRB approvalapproval in in otherother countriescountries

�� DeclarationsDeclarations of of responsibilityresponsibility

CONEP CONEP -- ““NationalNational EthicsEthics CommitteeCommittee””

�� 13 + 13 13 + 13 membersmembers, 3, 3--yryr mandatemandate

�� ExecutiveExecutive staff is staff is permanentpermanent

�� MonthlyMonthly meetingsmeetings (2 (2 daysdays))

�� StrongStrong politicalpolitical hueshues (social (social controlcontrol organismorganism))

�� Short of Short of resourcesresources

�� DifficultDifficult communicationcommunication

CONEP CONEP –– ModusModus operandioperandi

�� CEPCEP submitssubmits studystudy dossierdossier, , plusplus::

�� ApprovalApproval letterletter andand a a detaileddetailed reportreport

�� CONEP CONEP willwill sendsend to 1to 1-- 2 2 refereesreferees

�� ReportReport issuedissued afterafter monthlymonthly meetingmeeting

�� CommunicationCommunication onlyonly withwith CEPsCEPs

�� InquiriesInquiries oror pendingpending issuesissues restartrestart thethe

processprocess

CONEP CONEP –– ModusModus operandioperandi

�� ResolutionResolution 346 (346 (MarchMarch 05) 05) ononinternationalinternational multicentricmulticentric studiesstudies::

�� OnlyOnly 1st site1st site willwill bebe reviewedreviewed

�� ApprovalApproval willwill bebe goodgood for for allall sitessites(if (if acceptedaccepted byby local local ethicsethics committeescommittees))

�� CommunicationCommunication betweenbetween CONEP/1st site CONEP/1st site duringduring thethe wholewhole studystudy

((periodicperiodic reportsreports, SAE, etc), SAE, etc)

ANVISAANVISAWhatWhat does it does it approveapprove in in clinicalclinical studiesstudies ??

�� StudiesStudies withwith new new drugsdrugs//devicesdevices

�� ImportationImportation of of suppliessupplies

�� ExportationExportation of of biologicalbiological samplessamples

ANVISAANVISAApprovalApproval of of ClinicalClinical StudiesStudies

�� SponsorSponsor oror investigatorinvestigator submitsubmit new new dossierdossier::

�� CopyCopy of of dossierdossier submittedsubmitted to CEPto CEP

�� CopyCopy of of approvalapproval letterletter fromfrom CONEPCONEP

�� PaymentPayment of feeof fee

�� ANVISA ANVISA authorizesauthorizes importationimportation of of suppliessupplies andand

studystudy initiationinitiation

(CE=(CE=““SpecialSpecial CommunicationCommunication”)”)

ANVISAANVISAApprovalApproval of of importationimportation of of suppliessupplies

�� ImporterImporter files files anan importimport licenselicense (on(on--line), line),

basedbased onon exporter´sexporter´s proformaproforma invoiceinvoice

�� HardcopyHardcopy of IL of IL sentsent to ANVISA, to ANVISA, togethertogether

withwith importationimportation planplan

�� ANVISA ANVISA approvesapproves IL onIL on--lineline

�� SuppliesSupplies maymay bebe shippedshipped

RegulatoryRegulatory TimelinesTimelinesHowHow longlong does it does it taketake ??

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RegulatoryRegulatory TimelinesTimelines

HowHow longlong does it REALLY does it REALLY taketake ??

�� 4 4 monthsmonths

�� 6 6 monthsmonths

�� 99--12 12 monthsmonths

AlertAlert signssigns

�� StudiesStudies approvedapproved byby ANVISAANVISA•• 2003: 1922003: 192

•• 2004: 2142004: 214

•• 2005: 1262005: 126

�� InterfarmaInterfarma, 2006: , 2006:

�� 98% 98% ofof projectsprojects sentsent to CONEP in 2004to CONEP in 2004--5 5 hadhadpendingpending issuesissues (n= 145)(n= 145)

MostMost commoncommon pendingpending issuesissues

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A.A. ConsentConsent FormForm

B.B. Country Country ofof OriginOrigin

C.C. MissingMissing documentsdocuments

D.D. ReasonReason for central for central lablab..

E.E. Access to Access to drugdrug atat thetheendend ofof studystudy

F.F. InsuranceInsurance

G.G. PlaceboPlacebo

H.H. OthersOthersSource: Interfarma, 2006

CurrentCurrent TimelinesTimelines

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Source: Interfarma, 2006

CurrentCurrent TimelinesTimelines

Time from question responseto approval by CONEP

Time from CONEP approvalto ANVISA approval

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Source: Interfarma, 2006

SPEED - study start-up duration

� source: IMPACT� phase 2, 3 studies� DE-projects� years 2004 - today

protocol submission

protocol approval

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WhereWhere are are wewe goinggoing to?to?

�� FromFrom 1996 to 2005, 1996 to 2005, thethe numbernumber ofof clinicalclinical

studiesstudies rose rose byby 30 times !30 times !

�� NowNow, , approvalapproval timelinestimelines are are goinggoing in in thethe

samesame directiondirection......

WhereWhere are are wewe goinggoing to ?to ?

�� BrazilBrazil is is notnot takingtaking advantageadvantage ofof favorablefavorableinternationalinternational environmentenvironment

�� IncreasingIncreasing numbernumber ofof studiesstudies

�� MigrationMigration ofof projectsprojects to to lessless traditionaltraditional areasareas

�� PrivatePrivate sector sector investmentsinvestments are flat are flat oror decreasingdecreasingsincesince 20032003

�� BothBoth CONEP CONEP andand ANVISA:ANVISA:�� havehave contributedcontributed to more to more bureaucracybureaucracy andand delaysdelays, ,

withoutwithout qualityquality gainsgains..

�� havehave similar similar problemsproblems, , butbut theythey won´twon´t talktalk to to eacheachotherother..

ThankThank youyou

emotti@uol.com.bremotti@uol.com.br