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© 2007-2015Accell Clinical Research, LLC
New Russian Drug Law: Changes Concerning Clinical Studies and
Marketing Authorization and Their Implications
Dr. Natalia NayanovaDirector, Clinical Operations
Accell Clinical Research
ClinicalTrialsInnovationProgrammeOctober22-23,2015Frankfurt,Germany
© 2007-2015Accell Clinical Research, LLC
Russian Pharmaceutical Market Turnover, Dynamics & Forecast
7,2 9,5 11,8 12,6 14,6 16,1 17,4 18,3 19,7 21,3 23,3 25,7
0
5
10
15
20
25
30
2007 2008 2009 2010 2011 2012 2013 2014(forecast)
2015(forecast)
2016(forecast)
2017(forecast)
2018(forecast)
blnUSD
2
Source: DSMGroupandIMSHealthviaDeloitte
© 2007-2015Accell Clinical Research, LLC
Russia in the List of Countries by Pharmaceutical Market Size
2008 2013 20171 USA USA USA2 Japan China China3 China Japan Japan4 France Germany Brazil5 Germany France Germany6 Italy Brazil France7 Canada Italy Italy8 United Kingdom UnitedKingdom Russia9 Spain Canada UnitedKingdom10 Brazil Spain Canada11 Mexico Russia India12 Australia India Spain13 Russia Mexico Mexico
3
(Source:IMSHealthviaDeloitte)
© 2007-2015Accell Clinical Research, LLC
Russian Clinical Trial Market: Facts and Figures
4
Clinicaltrialsapprovedin3months
Centralizedhealthcare,specializedhospitals
Lowmigrationrates,thushighretention
Loweraccesstostate-of-the-arttreatmentprotocols
Treatment-naïvepatientsinmanyindications
Experiencedandhighlyqualifiedinvestigators
Fasterrecruitment
HighqualityofdataGCPincorporatedinlegislation
Inourrecent7clinicalstudies,enrollmentratesatAccell’ssiteswere
1,4to7timeshigherthanintherestoftheworld
© 2007-2015Accell Clinical Research, LLC
Russian Clinical Trial Market: No. of Clinical Trials by Phase
25 43 64 39 34 37
129 86 87 111 91 84
289232
327396
373 338
47
38
7548
2824
2009 2010 2011 2012 2013 2014
PhaseI PhaseII PhaseIII PhaseIV
Total:490
399
553594
526483
5
Source:OrangePaper— clinicaltrialsinRussiabySynergy
© 2007-2015Accell Clinical Research, LLC
Russian Clinical Trial Market: FDA & EMEA Acknowledgement
6
2008 2009 2010 2011 2012 2013 2014
8197 101 102 102
114 111
34
820
3421
53 45
Total ofthem:usingRussiandata
2008 2009 2010 2011 2012 2013 2014
85
142
5167
87101 104
35 27 2232
48
8664
Total ofthem:usingRussiandata
Source:OrangePaper— clinicaltrialsinRussiabySynergy
NewDrugsApprovedbyFDA
NewDrugApplicationsApprovedbyEMEA
Year FDAaudits
NAI VAI OAI
2008 20 13 7 0
2009 15 11 4 0
2010 10 9 1 0
2011 3 2 1 0
2012 7 6 1 0
2013 4 2 2 0
Total 36 24 12 0
*NAI=noactionindicatedVAI=voluntaryactionindicatedOAI=officialactionindicatedSource:FDA
ClinicalInvestigatorInspectionsbyFDAinRussia
© 2007-2015Accell Clinical Research, LLC
Regulatory Framework in Russia
7
3months
MinistryofHealthand
CentralEthicsCommittee
parallelsubmissions40workdays(2months)
LocalEthicsCommittee• Presentatmostsites• LECapprovalrequired
werepresent2-4weeks
Import/exportlicense• RequiredforanyIMP,
materialsoriginatingfromoutsideRussia
• Requiredforexportofallmaterials,samplesoutsideRussia5workdays
1month 1month
Feasibilityanddossier
preparation
IMPimport
Siteinitiation
Firstpatientin
5monthstotal
© 2007-2015Accell Clinical Research, LLC
Legislative Framework for Medicinal Products in Russia
Ø FederalLaw# 61-FZ dated April12,2010 “Oncirculationofmedicinalproducts”Ø FederalLaw#429-FZamendsLaw#61-FZØ Majorityofchangesto#61-FZlawtookeffectonJuly1,2015;
certainprovisionswilltakeeffectJanuary1,2017Ø NationalStandardofRussianFederation«GoodClinical
Practice» GOST-R 52379-200 (effectiveSeptember27,2005)
Ø December23,2014— anAgreementonCommonPrinciplesandRulesofDrugCirculationintheEurasianEconomicUnionwassigned,andwillbeineffectfollowingratificationbyallpartiesbutnoearlierthanJanuary1,2016
8
© 2007-2015Accell Clinical Research, LLC
General Regulatory Approach to Changes to 61-FZ Drug Law
Ø “OldLaw”hadsomeinherentflawsintheareasof:Ø DefinitionsØ CorrelationwithglobalbestpracticesØ LegalframeworkforgenericdrugsØ Inconsistencywiththecurrentstateofthepharmaceuticalmarketanditsdevelopment
Ø “NewLaw”approvedafterconsultationsandreviewbytheindustryandaimstooptimizethequalityofregulatoryprocessesandenhancetheexperienceofcompaniesapplyingforMarketingAuthorizationinRussia
9
© 2007-2015Accell Clinical Research, LLC
Improvements to Existing Definitions
PreviouslyØ Pharmaceuticalsubstance
Ø Withlimiteddefinitionoforigin
Ø Originalmedicinalproduct
Ø Reproduced(generic)medicinalproduct
CurrentlyØ Pharmaceuticalsubstance
Ø Anysubstancewithpharmacologicalactivityregardlessoforigin
Ø Referencemedicinalproduct
Ø Reproduced(generic)medicinalproductØ Includesbiologicaland
therapeuticequivalenceconfirmation
10
© 2007-2015Accell Clinical Research, LLC
New Definitions in 2015 LawØ NewLawaddsdefinitionsfor:
Ø OrphanmedicinalproductØ BiologicalmedicinalproductØ Biotechnology-basedmedicinalproductØ Immunobiological drugsØ GenetherapymedicinalproductØ HomeopathicdrugsØ Biosimilar drugsØ Therapeuticequivalency
Ø Additionofnewdefinitionscreatesnewregulatorypathwaysforcertaincategoriesofdrugs
Ø Formerlawdidnotdefinethesecategoriesofdrugseparately
11
© 2007-2015Accell Clinical Research, LLC
Biosimilars VS. Generic
ØNewlawforthefirsttimeintroducesthedifferencebetween“generic”and“biosimilar”medicinalproducts
ØDifferenceinhandlingmarketingauthorizationbytheregulator
12
© 2007-2015Accell Clinical Research, LLC
Interchangeable Medicinal Products
Ø DefinitioninitiatedbyFederalAntimonopolyService(FAS)toimprovecompetitionforfederalprocurementofdrugs
Ø StartingJanuary1,2018informationaboutinterchangeabilityofdrugsissubjecttoinclusiontotheFederalDrugRegistry
Ø Interchangeabilityisdeterminedbythepanelofexpertsduringthemarketingauthorizationdossierreview
Ø FordrugsregisteredpriorDecember22,2014interchangeabilitymustbedefinedbyDecember31,2017
13
© 2007-2015Accell Clinical Research, LLC
GxP
ØMinistryofHealthnowresponsibleforapprovalandimplementationofØGLPØGCPØGMPØGoodStorageandTransportPracticeØGoodDistributionPracticeØGoodPharmacyPracticeØGoodPharmacovigilancePractice
14
© 2007-2015Accell Clinical Research, LLC
Clinical Trials for Medicinal Products
Ø Previously,clinicaltrialsweresubjecttoreviewintheframeworkoftheMarketingAuthorizationsubmission
Ø Keychange:clinicaltrialapplicationreviewprocess(ECandMOH)isexcludedfromthemarketingauthorizationprocess
Ø Standaloneapproachtoclinicaltrialdossierreviewsimplifiesandstreamlinestheapplicationandreviewprocess
Ø ClinicaltrialsconductedinpartorinwholeinRussiaarestillarequirementforMarketingAuthorizationapproval
15
© 2007-2015Accell Clinical Research, LLC
Scientific Advice: New Opportunity
PreviouslyØ Nomechanismforscientific
advicewaspresent;nofeedbackfromMinistryofHealth
CurrentlyØ Scientificadviceoptionis
availableunderthenewlawforØ PreclinicalstudiesØ ClinicaltrialsØ MarketingauthorizationØ Quality,efficacy,safetyreview
Ø ForfeeserviceofMinistryofHealth
Ø Writtenresponsetoinquiriesforscientificadvice
16
© 2007-2015Accell Clinical Research, LLC
Marketing Authorization Dossier Composition Changes
Ø DefinitionforMAHolderisaddedtotheLaw(previouslyabsent)
Ø Effective01.01.2016;Format:StandardTechnicalDocumentØ AdministrativesectionØ Chemical,pharmaceutical,biologicalsectionØ PharmacologyandtoxicologysectionØ Clinicalsection
Ø FormatshouldbeestablishedbytheMinistryofHealthØ Lawstipulatesadetailedlistofrequireddocumentsgenerallyaswellasallowedexceptions
17
© 2007-2015Accell Clinical Research, LLC
Marketing Authorization Timelines
PreviouslyØ GeneralMApathway— 210
businessdays;clockstopsforQ&A
Ø ExpeditedMApathway—60businessdaysØ Reproduced(generic)drugs
Ø Confirmationoffederalregistration— 90businessdays
CurrentlyØ GeneralMApathway— 160
businessdays;clockstopsforQ&A
Ø ExpeditedMApathway—80businessdaysØ OrphanindicationsØ FirstthreegenericdrugsØ Exclusivelypediatricdrugs
Ø Confirmationoffederalregistration— 60businessdays(asof01.01.17)
18
© 2007-2015Accell Clinical Research, LLC
Marketing Authorization: New Exception Examples, Generics
ØGenericdrugs:Ø AllowstoprovidescientificliteraturereviewofpreclinicalstudiesofthereferencedrugINLIEUoftheSponsor’sownpreclinicalstudiesofthegenericdrug
Ø ClinicalStudyReportforBioequivalencystudiesonlyinlieuofthefullclinicaltrialprogram(previouslyfullprogramofclinicalstudieswasrequired)
Ø Effective01.01.2016:drugmakerscanapplyforgenericmarketingauthorizationin§ 4yearsfromreferenceproductregistration— forbiosimilardrugs
§ 6yearsfromreferenceproductregistrationforgenericdrugs
19
© 2007-2015Accell Clinical Research, LLC
Marketing Authorization: New Exception Examples, Orphan DrugsØOrphandrugs:
Ø NewMAapplicationpathwayfororphandrugsØ AllowstheSponsortoprovidereportsofpreclinicalandclinicalstudiesperformedoutsideofRussianFederationinaccordancewithGCPandGLP
ØOrphanandbiotechnology-baseddrugs:Ø MAholdersarenowrequiredtoprovideforafeetheirreferenceproductforthepurposeofclinicaltrials,atcostnotinexcessofregisteredpriceinthecountry(effective01.01.2016)
20
© 2007-2015Accell Clinical Research, LLC
New Additional Provisions for MA Cancellation
ØLackofregistereddrugonthemarketforover3yearsfromregistrationdate
ØLackofPVreportingØRefusalofMAholdertoamendMAwithnewlydiscoveredinformationonrisksoutweighingthebenefits
ØVoluntaryMAcancellationbytheMAholder
21
© 2007-2015Accell Clinical Research, LLC
PharmacovigilanceØ DefinitionsaddedtothenewLawfor
Ø PharmacovigilanceØ RiskManagementPlan
Ø Regulatorwillanalyzeallmonitoredinformation(safety,efficacy,risks)notonlyinRussiabutglobally
Ø MAholdersarerequiredto:Ø Collect,analyze,retainandreporttotheRegulatoryAuthorities
informationonsideeffects,SAE,SUSAR,drug-druginteraction,tolerabilityandotherfactorsposingpotentialhealththreats
Ø Effective01.01.16frequencyofPVGreportingchangesto:§ Onceevery6monthsforthefirsttwoyearspost-registration§ Annuallyforthesubsequentthreeyears§ Onceevery5yearsthereafter
22
© 2007-2015Accell Clinical Research, LLC
Implications of Changes to Drug Law for Foreign Sponsors
Ø DruglawcorrelateswithlatestinternationalstandardsØ TransparencyØ RobustdefinitionsØ MinistryofHealthScientificAdvisoryoption.
Ø Expandeddefinitionsofbiological,biosimilar,immunobiological,andotherdrugscreatednewregulatorypathways.
Ø Reductionofoveralltimetomarketforthedrugs.Ø Streamlinedclinicaltrialapplicationprocess.Ø Competitivelandscapeforparticipationinthefederalprocurement
processfordrugmakers.Ø OpensuptheRussianmarketforeasieraccessforpharmaceutical
companiesspecializedingeneric,orphanandpediatricdrugdevelopment.
23
© 2007-2015Accell Clinical Research, LLC
Thank you for attention!
Dr.NataliaNayanovaDirector,ClinicalOperations
[email protected]:+7-812-332-1420Mobile:+7-921-864-2517