Alfamed Fipronil 402 mg Spot-On Solution for Very Large Dogs

Main information

  • Trade name:
  • Alfamed Fipronil 402 mg Spot-On Solution for Very Large Dogs
  • Pharmaceutical form:
  • Spot-on solution
  • Medicine domain:
  • Animals
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • Alfamed Fipronil 402 mg Spot-On Solution for Very Large Dogs
    United Kingdom
  • Language:
  • English

Therapeutic information

  • Therapeutic group:
  • fipronil
  • Therapeutic area:
  • Dogs

Other information

Status

  • Source:
  • HMA - Europe
  • Authorization number:
  • UK/V/0397/005
  • Authorization date:
  • 21-03-2012
  • EU code:
  • UK/V/0397/005
  • Last update:
  • 09-08-2016

Patient Information leaflet: composition, indications, side effects, dosage, interactions, adverse reactions, pregnancy, lactation

Vetflea67mgSpot-OnSolutionforSmallDogs UK/V/0397/002/DC

Vetflea134mgSpot-OnSolutionforMediumDogs UK/V/0397/003/DC

Vetflea268mgSpot-OnSolutionforLargeDogs UK/V/0397/004/DC

Vetflea402mgSpot-OnSolutionforVeryLargeDogs UK/V/0397/005/DC

Alfamed ApplicationforDecentralised

PubliclyAvailableAssessmentReport

UnitedKingdom

VeterinaryMedicinesDirectorate

WoodhamLane

NewHaw

Addlestone

SurreyKT153LS

MUTUALRECOGNITION

PUBLICLYAVAILABLEASSESSMENTREPORTFORAVETERINARY

MEDICINALPRODUCT

Vetflea67mgSpot-OnSolutionforSmallDogs

Vetflea134mgSpot-OnSolutionforMediumDogs

Vetflea268mgSpot-OnSolutionforLargeDogs

Vetflea402mgSpot-OnSolutionforVeryLargeDogs

Vetflea67mgSpot-OnSolutionforSmallDogs UK/V/0397/002/DC

Vetflea134mgSpot-OnSolutionforMediumDogs UK/V/0397/003/DC

Vetflea268mgSpot-OnSolutionforLargeDogs UK/V/0397/004/DC

Vetflea402mgSpot-OnSolutionforVeryLargeDogs UK/V/0397/005/DC

Alfamed ApplicationforDecentralised

PubliclyAvailableAssessmentReport

MODULE1

PRODUCTSUMMARY

EUProcedurenumber UK/V/0397/002/DC

UK/V/0397/003/DC

UK/V/0397/004/DC

UK/V/0397/005/DC

Name,strengthand

pharmaceuticalform Vetflea67mgSpot-OnSolutionforSmallDogs UK/V/0397/002/DC

Vetflea134mgSpot-OnSolutionforMedium

Dogs

Vetflea268mgSpot-OnSolutionforLarge

Dogs

Vetflea402mgSpot-OnSolutionforVeryLarge

Dogs

Applicant ALFAMED

13èmeRue –L.I.D.

06517CARROSCEDEX

FRANCE

Activesubstance Fipronil

ATCVetcode QP53AX15

Targetspecies Dogs

Indicationsforuse Treatmentofflea(Ctenocephalidesspp.)and

tick(Dermacentorreticulatus)infestations.

Insecticidalefficacyagainstnewinfestations

withadultfleaspersistsforupto8weeks.

Theproducthasapersistentacaricidalefficacy

forupto4weeksagainstticks(Rhipicephalus

sanguineus, Ixodes ricinus, Dermacentor

reticulatus). If ticks of some species

(RhipicephalussanguineusandIxodesricinus)

arepresentwhentheproductisapplied,allthe

ticksmaynotbekilledwithinthefirst48hours

buttheymaybekilledwithinaweek.

Theproductcanbeusedaspartofatreatment

strategyforthecontrolofFleaAllergy

Dermatitis(FAD)wherethishasbeen

previouslydiagnosedbyaveterinarysurgeon.

Vetflea67mgSpot-OnSolutionforSmallDogs UK/V/0397/002/DC

Vetflea134mgSpot-OnSolutionforMediumDogs UK/V/0397/003/DC

Vetflea268mgSpot-OnSolutionforLargeDogs UK/V/0397/004/DC

Vetflea402mgSpot-OnSolutionforVeryLargeDogs UK/V/0397/005/DC

Alfamed ApplicationforDecentralised

PubliclyAvailableAssessmentReport

MODULE2

TheSummaryofProductCharacteristics(SPC)forthisproductisavailableon

theHeadsofMedicinesAgencies(veterinary)(HMA(v))website( www.hma.eu ).

Vetflea67mgSpot-OnSolutionforSmallDogs UK/V/0397/002/DC

Vetflea134mgSpot-OnSolutionforMediumDogs UK/V/0397/003/DC

Vetflea268mgSpot-OnSolutionforLargeDogs UK/V/0397/004/DC

Vetflea402mgSpot-OnSolutionforVeryLargeDogs UK/V/0397/005/DC

Alfamed ApplicationforDecentralised

PubliclyAvailableAssessmentReport

MODULE3

PUBLICASSESSMENTREPORT

Legalbasisoforiginal

application ‘Hybrid’applicationsinaccordancewithArticle

13(3)ofDirective2001/82/ECasamendedby

Directive2004/28/BC.

Dateofcompletionofthe

originalDecentralised

Procedure 21March2012.

Dateproductfirstauthorised

intheReferenceMember

State(MRPonly) Notapplicable.

ConcernedMemberStatesfor

originalprocedure Belgium,Hungary,Romania.

I.SCIENTIFICOVERVIEW

TheseapplicationsweresubmittedusingtheDecentralisedProcedure,in

accordancewithArticle13(3 )asamended,as‘hybrid’applications,where

bioequivalencecouldnotbedemonstratedviabioavailabilitystudies,butwas

demonstratedbyclinicalequivalence.ThereferenceproductwasFrontlineSpot

OnDog10%w/vSpot-OnSolution,firstauthorisedintheUKin1996.The

productsarespot-onsolutionsintendedforuseindogs,forthetreatmentofflea

andtickinfestationscausedbyCtenocephalidesspp.andthetickspecies

Dermacentorreticulatus,RhipicephalussanguineusandIxodesricinus.

Insecticidalactivitymaybeseenagainstnewinfestationsofadultfleas,

persistentforupto8weeks.Thereispersistentactivityofupto4weeksagainst

thespecifiedtickspecies,howeverifRhipicephalussanguineusandIxodes

ricinusarealreadypresentpriortotreatment,allticksmaynotbekilledwithin

thefirst48hours,butwillbekilledwithinaweek.Theproductsarepresentedin

arangeofpacksizes.

Theproductsareproducedandcontrolledusingvalidatedmethodsandtests

whichensuretheconsistencyoftheproductsreleasedonthemarket.Ithas

beenshownthattheproductscanbesafelyusedinthetargetspecies,theslight

reactionsobservedareindicatedintheSPC 1 .Theproductsaresafefortheuser,

andfortheenvironment,whenusedasrecommended.Suitablewarningsand

precautionsareindicatedintheSPCs.Theefficacyoftheproductswas

demonstratedaccordingtotheclaimsmadeintheSPCs.Theoverallbenefit/risk

analysisisinfavourofgrantingamarketingauthorisation.

SPC –SummaryofProductCharacteristics.

Vetflea67mgSpot-OnSolutionforSmallDogs UK/V/0397/002/DC

Vetflea134mgSpot-OnSolutionforMediumDogs UK/V/0397/003/DC

Vetflea268mgSpot-OnSolutionforLargeDogs UK/V/0397/004/DC

Vetflea402mgSpot-OnSolutionforVeryLargeDogs UK/V/0397/005/DC

Alfamed ApplicationforDecentralised

PubliclyAvailableAssessmentReport

II. QUALITYASPECTS

A. Composition

Theproductsconsistoftheactivesubstancefipronilat67mg,134mg,268mg

or402mgperpipette,preparedtoman ufacturer’sspecification,andthe

excipientsbutylhydroxyanisoleE320,butylhydroxytolueneE321,benzylalcohol

anddiethyleneglycolmonoethylether,allofwhicharemonographedinthe

EuropeanPharmacopoeia.Thepackagingconsistsofpipettesofvarying

colours,onecolourforeachpresentation,deliveringadifferentamountof

solutionforeachproduct:0.67ml,1.34ml,2.68mlor4.02ml,formedfrom

polyacrylonitrile-methacrylate and polypropylene/cyclic olefin

copolymer/polypropylene.Pipettesarepresentedin1,2,3,4,6,8,12,24,30,

60,90or150;notallpresentationsmaybemarketed.Theparticularsofthe

containersandcontrolsperformedareprovidedandconformtotheregulation.

Theproductisanestablishedpharmaceuticalformanditsdevelopmentis

adequatelydescribedinaccordancewiththerelevantEuropeanguidelines.

B. MethodofPreparationoftheProduct

Theproductsaremanufacturedfullyinaccordancewiththeprinciplesofgood

manufacturingpracticefromalicensedmanufacturingsite.Processvalidation

dataontheproductshavebeenpresentedinaccordancewiththerelevant

Europeanguidelines.Themethodofpreparationisessentiallyamixingprocess:

twoexcipientsareaddedtoavesselandmixed,followedbytheactive

substanceandthentheremainderoftheexcipients.

C. ControlofStartingMaterials

FipronilisanestablishedactivesubstancedescribedintheEuropean

Pharmacopoeia.Theactivesubstanceismanufacturedinaccordancewiththe

principlesofgoodmanufacturingpractice.

Theactivesubstancespecificationisconsideredadequatetocontrolthequality

ofthematerial.Batchanalyticaldatademonstratingcompliancewiththis

specificationhavebeenprovided.

D. SpecificMeasuresconcerningthePreventionoftheTransmission

ofAnimalSpongiformEncephalopathies

TherearenosubstanceswithinthescopeoftheTSEGuidelinepresentorused

inthemanufactureofthisproduct.

E. Controlonintermediateproducts

Therearenointermediateproducts.

Vetflea67mgSpot-OnSolutionforSmallDogs UK/V/0397/002/DC

Vetflea134mgSpot-OnSolutionforMediumDogs UK/V/0397/003/DC

Vetflea268mgSpot-OnSolutionforLargeDogs UK/V/0397/004/DC

Vetflea402mgSpot-OnSolutionforVeryLargeDogs UK/V/0397/005/DC

Alfamed ApplicationforDecentralised

PubliclyAvailableAssessmentReport

F. ControlTestsontheFinishedProduct

Thefinishedproductspecificationcontrolstherelevantparametersforthe

pharmaceuticalform.Thetestsinthespecification,andtheirlimits,havebeen

justifiedandareconsideredappropriatetoadequatelycontrolthequalityofthe

product.Satisfactoryvalidationdatafortheanalyticalmethodshavebeen

provided.Batchanalyticaldatafromtheproposedproductionsitehavebeen

provideddemonstratingcompliancewiththespecification.Testsperformed

includethoseforappearance,clarityofsolution,colour,density,uniformityof

dosageunits,relevantHPLC 2 testingandmicrobiologicalanalyses.

G. Stability

Stabilitydataontheactivesubstancesandthefinishedproducthavebeen

providedinaccordancewithapplicableEuropeanguidelines,demonstratingthe

stabilityoftheactivesubstancewhenstoredundertheapprovedconditions.

Threebatchesofactivesubstancewereanalysedunderavarietyofstorage

conditions,withsatisfactorydatabeingpresentedinordertosupportthe

proposedretestperiod.Storagedataonthefinishedproductsupportedthe

shelf-lifeasdefinedintheSPC.

H. GeneticallyModifiedOrganisms

Notapplicable.

J. OtherInformation

Theproducthasashelf-lifeaspackagedforsale:2years.

HPLC –HighPerformanceLiquidChromatography.

Vetflea67mgSpot-OnSolutionforSmallDogs UK/V/0397/002/DC

Vetflea134mgSpot-OnSolutionforMediumDogs UK/V/0397/003/DC

Vetflea268mgSpot-OnSolutionforLargeDogs UK/V/0397/004/DC

Vetflea402mgSpot-OnSolutionforVeryLargeDogs UK/V/0397/005/DC

Alfamed ApplicationforDecentralised

PubliclyAvailableAssessmentReport

III. SAFETY AND RESIDUES ASSESSMENT (PHARMACO-

TOXICOLOGICAL)

III.A SafetyTesting

PharmacologicalStudies

TheseapplicationsweresubmittedinaccordancewithArticle13(3)ofDirective

2001/82/EC,andthereforetheresultsofrelevantdatawererequired.

UserSafety

Theapplicantprovidedausersafetyassessmentincompliancewiththerelevant

guideline,suitablewarningsarecitedintheSPC:-

Thisproductcancausemucousmembraneandeyeirritation.Therefore,

contactbetweentheproductandthemouthoreyesshouldbeavoided.

Inthecaseofaccidentaleyecontact,immediatelyrinsetheeyeswith

cleanwater.Ifeyeirritationpersistsseekmedicaladviceandshowthe

packageleafletorthelabeltothephysician.

Donotsmoke,drinkoreatduringapplication.

Avoidcontentscomingintocontactwiththefingers.Ifthisoccurs,wash

handswithsoapandwater.Washhandsafteruse.

Peoplewithaknownhypersensitivitytofipronilorexcipients(seesection

6.1.oftheSPC)shouldavoidcontactwiththeveterinarymedicinal

product.

Treatedanimalsshouldnotbehandleduntiltheapplicationsiteisdry,

andchildrenshouldnotbeallowedtoplaywithtreatedanimalsuntilthe

applicationsiteisdry.Itisthereforerecommendedthatanimalsarenot

treatedduringtheday,butshouldbetreatedduringtheearlyevening,

andthatrecentlytreatedanimalsshouldnotbeallowedtosleepwith

owners,especiallychildren.

Ecotoxicity

TheapplicantprovidedaPhaseIenvironmentalriskassessmentincompliance

withtherelevantguidelinewhichshowedthatnofurtherassessmentwas

required.Warningsandprecautionsaslistedontheproductliteratureare

adequatetoensuresafetytotheenvironmentwhentheproductisusedas

directed.

Vetflea67mgSpot-OnSolutionforSmallDogs UK/V/0397/002/DC

Vetflea134mgSpot-OnSolutionforMediumDogs UK/V/0397/003/DC

Vetflea268mgSpot-OnSolutionforLargeDogs UK/V/0397/004/DC

Vetflea402mgSpot-OnSolutionforVeryLargeDogs UK/V/0397/005/DC

Alfamed ApplicationforDecentralised

PubliclyAvailableAssessmentReport

III.B Residuesdocumentation

Notapplicable.

IV CLINICALASSESSMENT(EFFICACY)

Asthisiswasageneric ‘hybrid’applicationaccordingtoArticle13(3),and

bioequivalencewithareferenceproducthasbeendemonstrated,efficacy

studiesarenotrequired. Dissolutiontestswereperformedasappropriateforthe

originalapplication.

IV.APre-ClinicalStudies

Pharmacology

Pharmacodynamics

Noadditionaldatawerepresentedasthepharmacodynamicpropertiesofthese

productswereconsideredidenticaltothoseofthereferenceproduct,Frontline

SpotOnDog10%w/vSpot-OnSolution.

Pharmacokinetics

Noadditionaldatawerepresentedasthepharmacokineticpropertiesofthese

productswereconsideredidenticaltothoseofthereferenceproduct,Frontline

SpotOnDog10%w/vSpot-OnSolution.

ToleranceintheTargetSpeciesofAnimals

TheapplicantconductedaGLP 3 -complianttargetanimalsafetystudy.A

suitablenumberofyoungdogsreceivedtheproductinasuitablycontrolled

study.Theanimalsweredividedintogroups,andreceivednotreatment,orthe

recommendeddose,threetimestherecommendeddose,orfivetimesthe

recommendeddose.Noadversereactionstothetreatmentwereobserved,in

thedifferentgroups,orbetweenmaleandfemaleanimals.

Resistance

Asthesewereapplicationsfora‘genericantiparasiticproduct’assubmitted

underArticle13(3),thepotentialforresistancewasconsideredtobethesame

asthatofthereferenceproducts,andnofurtherdatawererequired.

GLP –GoodLaboratoryPractise.

Vetflea67mgSpot-OnSolutionforSmallDogs UK/V/0397/002/DC

Vetflea134mgSpot-OnSolutionforMediumDogs UK/V/0397/003/DC

Vetflea268mgSpot-OnSolutionforLargeDogs UK/V/0397/004/DC

Vetflea402mgSpot-OnSolutionforVeryLargeDogs UK/V/0397/005/DC

Alfamed ApplicationforDecentralised

PubliclyAvailableAssessmentReport

IV.B ClinicalStudies

LaboratoryTrials

Theapplicantprovidedappropriateinformationondosedeterminationstudies.

Dosedeterminationstudies:

Anumberofdoseconfirmationstudieswerepresented:-

Study1

Studytitle Comparativestudyontheefficacyofagenericfipronil

spot-onformulationandFrontlineSpotOnDog10%w/v

Spot-OnSolution 4 againstfleas(Ctenocephalidesfelis)

ondogs.

Objectives Toevaluatetheefficacyofatopicallyappliedspot-on

formulationoffipronilagainstfleas(Ctenocephalides

felis)ondogsunderlaboratoryconditions.

Testsite(s) Laboratoryenvironment.Singlecentre.

Compliancewith

Regulatoryguidelines GoodClinicalPractice(GCP)

TestProduct Formulation104.7(10%fipronil),synonymouswiththe

producttobeauthorised.Productdeliveredateither

0.67mlor1.34ml.(Dependingonsizeofdog).

Control

product/placebo Controlproduct,FrontlineSpotOnDog10%w/vtopical

solution,at0.67mlor1.34ml.(Dependingondog

size).

Negativecontrolgroup(notreatment).

Animals Healthydogs,8animalseachgroup.

Outcomes/endpoints Determinetheefficacyofagenericspot-onformulation

againstfleasondogs.Efficacyofthetestproductwas

comparedtothenegativecontrolandreferenceproduct

uponweeklyinfestationoffleas,uptoDay90.

Randomisation Randomised.

Blinding Blinded.

Method Thiswasaparallel-groupedstudy.Afteracclimatisation,

animalswereinfestedasappropriate(approximately

100fleasperdog,atvarioustimepoints,andgiven

treatmentaccordingtotheirrespectivegroups.Flea

countswereperformedonseveraloccasionsafter

treatment.

Statisticalmethod Alltestsweretwo-sided.Statisticalanalysiswas

performedusingappropriatesoftware.Levelof

significancewassetat5%(p<0.05).Primary

CitedasFrontlineTopSpotinthetrials.

Vetflea67mgSpot-OnSolutionforSmallDogs UK/V/0397/002/DC

Vetflea134mgSpot-OnSolutionforMediumDogs UK/V/0397/003/DC

Vetflea268mgSpot-OnSolutionforLargeDogs UK/V/0397/004/DC

Vetflea402mgSpot-OnSolutionforVeryLargeDogs UK/V/0397/005/DC

Alfamed ApplicationforDecentralised

PubliclyAvailableAssessmentReport

calculationsforefficacywerebasedonmeanflea

counts.ComparisonsweremadebyANOVA.

RESULTS Theproductwasseentobeeffective,andnoadverse

eventswereobservedduringthestudy

Outcomesfor

endpoints After48hours,thetherapeuticefficaciesoftheproducts

werecomparable.Efficacywasdemonstratedasbeing

morethen95%fortheappropriatetimespans.

DISCUSSION Theproductwasshowntobeeffectiveagainstthe

targetparasites.

Study2

Studytitle Comparativestudyontheefficacyofagenericfipronil

spot-onformulationandFrontlineSpotOnDog10%

w/vSpot-OnSolutionagainstticks(Rhipicephalus

sanguineus)ondogs.

Objectives Toevaluatetheefficacyofatopicallyappliedspot-on

formulationoffipronilagainstagainstticks

(Rhipicephalussanguineus)ondogsunderlaboratory

conditions.

Testsite(s) Laboratoryenvironment.Singlecentre.

Compliancewith

Regulatoryguidelines GoodClinicalPractice(GCP)

TestProduct Formulation104.7(10%fipronil),synonymouswiththe

producttobeauthorised.Productdeliveredateither

0.67mlor1.34ml.(Dependingonsizeofdog).

Control

product/placebo Controlproduct,FrontlineSpotOnDog10%w/vtopical

solution,at0.67mlor1.34ml.(Dependingondog

size).

Negativecontrolgroup(notreatment).

Animals Healthydogs,8animalseachgroup.

Outcomes/endpoints Determinetheefficacyofagenericspot-onformulation

againstticksondogs.Efficacyofthetestproductwas

comparedtothenegativecontrolandreferenceproduct

uponweeklyinfestationoffleas,uptoDay37.

Randomisation Randomised.

Blinding Blinded.

Method Thiswasaparallel-groupedstudy.Afteracclimatisation,

animalswereinfestedasappropriate(approximately50

ticksperdog,atvarioustimepoints,andgiven

treatmentaccordingtotheirrespectivegroups.Tick

countswereperformedonseveraloccasionsafter

treatment.

Statisticalmethod Alltestsweretwo-sided.Statisticalanalysiswas

performedusingappropriatesoftware.Levelof

significancewassetat5%(p<0.05).Primary

calculationsforefficacywerebasedonmeanflea

Vetflea67mgSpot-OnSolutionforSmallDogs UK/V/0397/002/DC

Vetflea134mgSpot-OnSolutionforMediumDogs UK/V/0397/003/DC

Vetflea268mgSpot-OnSolutionforLargeDogs UK/V/0397/004/DC

Vetflea402mgSpot-OnSolutionforVeryLargeDogs UK/V/0397/005/DC

Alfamed ApplicationforDecentralised

PubliclyAvailableAssessmentReport

counts.ComparisonsweremadebyANOVA.

RESULTS Theproductwasseentobeeffective,andnoadverse

eventswereobservedduringthestudy

Outcomesfor

endpoints After48hours,thetherapeuticefficaciesofthe

productswerecomparable.Efficacywasdemonstrated

asbeingmorethen90%fortheappropriatetimespans.

DISCUSSION Theproductwasshowntobeeffectiveagainstthe

targetparasites.

Study3

Studytitle Comparativestudyontheefficacyofasingle

applicationofagenericfipronilspot-onformulationand

FrontlineSpotOnDog10%w/vSpot-OnSolution

againstticks(Dermacentorreticulatus)ondogs.

Objectives Toevaluatetheefficacyofatopicallyappliedspot-on

formulationoffipronilagainstfleas(Dermacentor

reticulatus)ondogsunderlaboratoryconditions.

Testsite(s) Laboratoryenvironment.Singlecentre.

Compliancewith

Regulatoryguidelines GoodClinicalPractice(GCP)

TestProduct Formulation104.7(10%fipronil),synonymouswiththe

producttobeauthorised.Productdeliveredateither

0.67mlor1.34ml.(Dependingonsizeofdog).

Control

product/placebo Controlproduct,FrontlineSpotOnDog10%w/vtopical

solution,at0.67mlor1.34ml.(Dependingondog

size).

Negativecontrolgroup(notreatment).

Animals Healthydogs,6animalseachgroup.

Outcomes/endpoints Determinetheefficacyofagenericspot-onformulation

againstfleasondogs.Efficacyofthetestproductwas

comparedtothenegativecontrolandreferenceproduct

uponweeklyinfestationoffleas,uptoDay65.

Randomisation Randomised.

Blinding Blinded.

Method Thiswasaparallel-groupedstudy.Afteracclimatisation,

animalswereinfestedasappropriate(approximately

100fleasperdog,atvarioustimepoints,andgiven

treatmentaccordingtotheirrespectivegroups.Flea

countswereperformedonseveraloccasionsafter

treatment.

Statisticalmethod Alltestsweretwo-sided.Statisticalanalysiswas

performedusingappropriatesoftware.Levelof

significancewassetat5%(p<0.05).Primary

calculationsforefficacywerebasedonmeanflea

counts.ComparisonsweremadebyANOVA.

RESULTS Theproductwasseentobeeffective,andnoadverse

Vetflea67mgSpot-OnSolutionforSmallDogs UK/V/0397/002/DC

Vetflea134mgSpot-OnSolutionforMediumDogs UK/V/0397/003/DC

Vetflea268mgSpot-OnSolutionforLargeDogs UK/V/0397/004/DC

Vetflea402mgSpot-OnSolutionforVeryLargeDogs UK/V/0397/005/DC

Alfamed ApplicationforDecentralised

PubliclyAvailableAssessmentReport

eventswereobservedduringthestudy

Outcomesfor

endpoints After48hours,thetherapeuticefficaciesoftheproducts

werecomparable.Efficacywasdemonstratedasbeing

morethen95%fortheappropriatetimespans.

DISCUSSION Theproductwasshowntobeeffectiveagainstthe

targetparasites.

Study4

Studytitle Comparativestudyontheefficacyofasingle

applicationofagenericfipronilspot-onformulationand

FrontlineSpotOnDog10%w/vSpot-OnSolution

againstfleas(Ixodesricinus)ondogs.

Objectives Toevaluatetheefficacyofatopicallyappliedspot-on

formulationoffipronilagainstticks(Ixodesricinus)on

dogsunderlaboratoryconditions.

Testsite(s) Laboratoryenvironment.Singlecentre.

Compliancewith

Regulatoryguidelines GoodClinicalPractice(GCP)

TestProduct Formulation104.7(10%fipronil),synonymouswiththe

producttobeauthorised.Productdeliveredateither

0.67mlor1.34ml.(Dependingonsizeofdog).

Control

product/placebo Controlproduct,FrontlineSpotOnDog10%w/vtopical

solution,at0.67mlor1.34ml.(Dependingondog

size).

Negativecontrolgroup(notreatment).

Animals Healthydogs,6animalseachgroup.

Outcomes/endpoints Determinetheefficacyofagenericspot-onformulation

againstticksondogs.Efficacyofthetestproductwas

comparedtothenegativecontrolandreferenceproduct

uponweeklyinfestationoffleas,uptoDay37.

Randomisation Randomised.

Blinding Blinded.

Method Thiswasaparallel-groupedstudy.Afteracclimatisation,

animalswereinfestedasappropriate(approximately50

ticksperdog,atvarioustimepoints,andgiven

treatmentaccordingtotheirrespectivegroups.Tick

countswereperformedonseveraloccasionsafter

treatment.

Statisticalmethod Alltestsweretwo-sided.Statisticalanalysiswas

performedusingappropriatesoftware.Levelof

significancewassetat5%(p<0.05).Primary

calculationsforefficacywerebasedonmeanflea

counts.ComparisonsweremadebyANOVA.

RESULTS Theproductwasseentobeeffective,andnoadverse

eventswereobservedduringthestudy

Outcomesfor After48hours,thetherapeuticefficaciesoftheproducts

Vetflea67mgSpot-OnSolutionforSmallDogs UK/V/0397/002/DC

Vetflea134mgSpot-OnSolutionforMediumDogs UK/V/0397/003/DC

Vetflea268mgSpot-OnSolutionforLargeDogs UK/V/0397/004/DC

Vetflea402mgSpot-OnSolutionforVeryLargeDogs UK/V/0397/005/DC

Alfamed ApplicationforDecentralised

PubliclyAvailableAssessmentReport

endpoints werecomparable.Efficacywasdemonstratedasbeing

morethen90%fortheappropriatetimespans.

DISCUSSION Theproductwasshowntobesuitablyeffectiveagainst

thetargetparasites.TheSPCclarifiestheefficacyof

theproduct.

Study5

Studytitle Theeffectofshampooingontheefficacyofageneric

fipronilspot-onformulation(104.07)againstflea

(Ctenocephalidesfelis)ondogs.

Objectives Toevaluatetheefficacyofatopicallyappliedspot-on

formulationoffipronilagainstfleas(Ctenocephalides

felis)ondogsunderlaboratoryconditions.

Testsite(s) Laboratoryenvironment.Singlecentre.

Compliancewith

Regulatoryguidelines GoodClinicalPractice(GCP)

TestProduct Formulation104.7(10%fipronil),synonymouswiththe

producttobeauthorised.Productdeliveredateither

0.67mlor1.34ml.(Dependingonsizeofdog).

Control

product/placebo Noadditionalpositivecontrolproduct.

Negativecontrolgroup(notreatment).

Animals Healthydogs,8animalseachgroup.

Outcomes/endpoints Determinetheefficacyofagenericspot-onformulation

againstfleasondogs.Efficacyofthetestproductwas

comparedtothenegativecontroluponweekly

infestationoffleas,uptoDay65.

Randomisation Randomised.

Blinding Blinded.

Method Thiswasaparallel-groupedstudy.Afteracclimatisation,

animalswereinfestedasappropriate(approximately

100fleasperdog,atvarioustimepoints,andgiven

treatmentaccordingtotheirrespectivegroups.Flea

countswereperformedonseveraloccasionsafter

treatment.

Statisticalmethod Alltestsweretwo-sided.Statisticalanalysiswas

performedusingappropriatesoftware.Levelof

significancewassetat5%(p<0.05).Primary

calculationsforefficacywerebasedonmeanflea

counts.ComparisonsweremadebyANOVA.

RESULTS Theproductwasseentobeeffective,andnoadverse

eventswereobservedduringthestudy

Outcomesfor

endpoints After48hours,thetherapeuticefficaciesoftheproducts

werecomparable.Efficacywasdemonstratedasbeing

morethen95%fortheappropriatetimespans.

DISCUSSION Theproductwasshowntobeeffectiveagainstthe

targetparasites.Noeffectontheproductwasobserved

afterrepeatedshampooingwith3%chlorhexidine,on

Vetflea67mgSpot-OnSolutionforSmallDogs UK/V/0397/002/DC

Vetflea134mgSpot-OnSolutionforMediumDogs UK/V/0397/003/DC

Vetflea268mgSpot-OnSolutionforLargeDogs UK/V/0397/004/DC

Vetflea402mgSpot-OnSolutionforVeryLargeDogs UK/V/0397/005/DC

Alfamed ApplicationforDecentralised

PubliclyAvailableAssessmentReport

weeklyinfestationoffleas,withshampooingoccurring

withinanhourofapplication.

Study6

Studytitle 'Theeffectofweeklywaterimmersionsontheefficacy

ofagenericfipronilspot-onformulation(104.07)against

flea(Ctenocephalidesfelis)ondogs

Objectives Toevaluatetheefficacyofatopicallyappliedspot-on

formulationoffipronilagainstfleas(Ctenocephalides

felis)ondogsunderlaboratoryconditions.

Testsite(s) Laboratoryenvironment.Singlecentre.

Compliancewith

Regulatoryguidelines GoodClinicalPractice(GCP)

TestProduct Formulation104.7(10%fipronil),synonymouswiththe

producttobeauthorised.Productdeliveredateither

0.67mlor1.34ml.(Dependingonsizeofdog).

Control

product/placebo Controlproduct,FrontlineSpotOnDog10%w/vtopical

solution,at0.67mlor1.34ml.(Dependingondog

size).

Negativecontrolgroup(notreatment).

Animals Healthydogs,8animalseachgroup.

Outcomes/endpoints Determinetheefficacyofagenericspot-onformulation

againstfleasondogs.Efficacyofthetestproductwas

comparedtothenegativecontrolandreferenceproduct

uponweeklyinfestationoffleas,uptoDay65.

Randomisation Randomised.

Blinding Blinded.

Method Thiswasaparallel-groupedstudy.Afteracclimatisation,

animalswereinfestedasappropriate(approximately

100fleasperdog,atvarioustimepoints,andgiven

treatmentaccordingtotheirrespectivegroups.Flea

countswereperformedonseveraloccasionsafter

treatment.

Statisticalmethod Alltestsweretwo-sided.Statisticalanalysiswas

performedusingappropriatesoftware.Levelof

significancewassetat5%(p<0.05).Primary

calculationsforefficacywerebasedonmeanflea

counts.ComparisonsweremadebyANOVA.

RESULTS Theproductwasseentobeeffective,andnoadverse

eventswereobservedduringthestudy

Outcomesfor

endpoints After48hours,thetherapeuticefficaciesoftheproducts

werecomparable.Efficacywasdemonstratedasbeing

morethen95%fortheappropriatetimespans.

DISCUSSION Theproductwasshowntobeeffectiveagainstthe

targetparasites,indogsimmersedonaweeklybasisin

water.TheSPCcarriesappropriateefficacy

Vetflea67mgSpot-OnSolutionforSmallDogs UK/V/0397/002/DC

Vetflea134mgSpot-OnSolutionforMediumDogs UK/V/0397/003/DC

Vetflea268mgSpot-OnSolutionforLargeDogs UK/V/0397/004/DC

Vetflea402mgSpot-OnSolutionforVeryLargeDogs UK/V/0397/005/DC

Alfamed ApplicationforDecentralised

PubliclyAvailableAssessmentReport

information.

FieldTrials

Astheseweregeneric‘hybrid’applications,therewasnorequirementfordatain

thissection.

VOVERALLCONCLUSIONANDBENEFIT –RISKASSESSMENT

Thedatasubmittedinthedossierdemonstratethatwhentheproductisusedin

accordancewiththeSummaryofProductCharacteristics,thebenefit/riskprofile

forthetargetspeciesisfavourableandthequalityandsafetyoftheproductfor

humansandtheenvironmentisacceptable.

Vetflea67mgSpot-OnSolutionforSmallDogs UK/V/0397/002/DC

Vetflea134mgSpot-OnSolutionforMediumDogs UK/V/0397/003/DC

Vetflea268mgSpot-OnSolutionforLargeDogs UK/V/0397/004/DC

Vetflea402mgSpot-OnSolutionforVeryLargeDogs UK/V/0397/005/DC

Alfamed ApplicationforDecentralised

PubliclyAvailableAssessmentReport

MODULE4

POST-AUTHORISATIONASSESSMENTS

TheSPCandpackageleafletmaybeupdatedtoincludenewinformationonthe

quality,safetyandefficacyoftheveterinarymedicinalproduct.ThecurrentSPC

isavailableontheHeadsofMedicinesAgencies(veterinary)(HMA(v))website

( www.hma.eu ).

Thissectioncontainsinformationonsignificantchangeswhichhavebeenmade

aftertheoriginalprocedurewhichareimportantforthequality,safetyorefficacy

oftheproduct.

27September2012 Minorchangeinpurificationprocessofactive

substance,deletionofanon-significant

specification parameter from the

manufacturing,increaseinbatchsizerange

oftheactivesubstance.

31August2012 Changeintheprimarypackagingnotin

contactwiththefinishedproductformulation –

additionofanindividualblisterforeach

pipette.

14-12-2018

Risk to human health related to the presence of perfluorooctane sulfonic acid and perfluorooctanoic acid in food

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Europe - EFSA - European Food Safety Authority Publications

24-11-2018

The EFSA‐funded collection of dietary and related data in the general population aged 10‐74 years in Greece

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Europe - EFSA - European Food Safety Authority Publications

19-9-2018

National dietary survey in 2012‐2016 on the general population aged 1‐79 years in the Netherlands

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Published on: Tue, 18 Sep 2018 00:00:00 +0200 During the years 2012‐2016, the Dutch National Food Consumption survey was conducted in the Netherlands. For the survey, a random sample was drawn from consumer panels stratified by age and gender and maintained representative to the population with regard to region, address density and educational level. Complete results were obtained for 4,313 persons (response rate 65%); including toddlers, children, adolescents, adults and elderly. Pregnant or lactating ...

Europe - EFSA - European Food Safety Authority Publications

11-9-2018

Risk assessment of antimicrobial resistance along the food chain through culture‐independent methodologies

Risk assessment of antimicrobial resistance along the food chain through culture‐independent methodologies

Published on: Mon, 27 Aug 2018 00:00:00 +0200 Antimicrobial resistance (AMR) represents a major challenge for Public Health and the scientific community, and requires immediate and drastic solutions. Acquired resistance to certain antimicrobials is already widespread to such an extent that their efficacy in the treatment of certain life‐threatening infections is already compromised. To date, the emergence and spread of AMR has been attributed to the use, misuse or indiscriminate use of antibiotics as th...

Europe - EFSA - European Food Safety Authority Publications

25-6-2018

Commissie onderzoek fipronil in eieren: geef voedselveiligheid topprioriteit

Commissie onderzoek fipronil in eieren: geef voedselveiligheid topprioriteit

Bedrijven in de eierketen, de NVWA en de ministeries van VWS en LNV hebben onvoldoende voorrang gegeven aan voedselveiligheid. Bedrijven in de eierketen maken hun wettelijke verantwoordelijkheid niet waar. Bij de NVWA krijgt voedselveiligheid te weinig aandacht. Politiek en bestuur hebben een te beperkte opvatting over hun eigen rol ten aanzien van voedselveiligheid en komen pas in actie als zich een incident of crisis voordoet. Dat zijn de belangrijkste conclusies uit het rapport van de Commissie onderz...

Netherlands - Ministerie van Volksgezondheid, Welzijn en Sport

29-6-2018

BROADLINE (Merial)

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BROADLINE (Active substance: Fipronil/ S-methoprene/ Eprinomectin/ Praziquantel) - Centralised - Yearly update - Commission Decision (2018) 4164 of Fri, 29 Jun 2018

Europe -DG Health and Food Safety

30-4-2018

CERTIFECT (Merial)

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CERTIFECT (Active substance: (S)-Methoprene, Fipronil, Amitraz) - Withdrawal - Commission Decision (2018)2687 of Mon, 30 Apr 2018

Europe -DG Health and Food Safety