Cevac

Main information

  • Trade name:
  • Cevac IBird
  • Pharmaceutical form:
  • Oral lyophilisate
  • Medicine domain:
  • Animals
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • Cevac IBird
    Ireland
  • Language:
  • English

Therapeutic information

  • Therapeutic group:
  • IMMUNOLOGICALS
  • Therapeutic area:
  • Chicken Broilers, Chicken Layers

Other information

Status

  • Source:
  • HMA - Europe
  • Authorization number:
  • FR/V/0245/001
  • Authorization date:
  • 29-05-2013
  • EU code:
  • FR/V/0245/001
  • Last update:
  • 09-08-2016

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

Frenchagencyforfood,environnementalandoccupationalhealthsafety –FrenchAgencyforVeterinaryMedicinalProducts

LaHauteMarche –JavenéBP90203-35302FougèresCédex-Téléphone:+33(0)299947878-Télécopie:+33(0)299947899- www.anses.fr

FRENCHAGENCYFORVETERINARYMEDICINALPRODUCTS

8rueClaudeBourgelat

Parcd'activitésdelaGrandeMarche-Javené

CS70611

35306Fougères

France

DECENTRALISEDPROCEDURE

PUBLICLYAVAILABLEASSESSMENTREPORTFORAVETERINARYMEDICINALPRODUCT

CevacIBird FR/V/0245/001/DC

Ceva ApplicationforDecentralisedProcedure

PUBLICLYAVAILABLEASSESSMENTREPORT

MODULE1

PRODUCTSUMMARY

EUProcedurenumber FR/V/0245/001/DC

Name,strengthand

pharmaceuticalform CevacIBird

Lyophilisateforsuspensionforreconstitutionin

water

Applicant

CEVA-PhylaxiaveterinaryBiologicalsCo.Ltd

Activesubstance(s) LiveInfectiousBronchitisVirus,strain1/96

ATCvetcode QI01AD07

Targetspecies Chickens

Indicationforuse Fortheactiveimmunizationofbroilerchickens,

andfuturelayerchickensinordertoreducethe

impactontheciliaryactivityoftheinfection,

whichmaybemanifestedinrespiratoryclinical

signscausedbyvariantstrainsofinfectious

bronchitisvirusbelongingtothe793/Bgroup

MODULE2

TheSummaryofProductCharacteristics(SPC)forthisproductisavailableonthewebsite

http://www.anmv.anses.fr/

MODULE3

PUBLICASSESSMENTREPORT

Legalbasisoforiginal

application Decentralisedapplicationinaccordancewith

Article31ofDirective2001/82/ECasamended.

Dateofcompletionofthe

originalmutualrecognition

procedure 29/05/2013

Dateproductfirstauthorised

intheReferenceMember

State(MRPonly) 29/05/2013

ConcernedMemberStatesfor

originalprocedure AT,BE,BG,CY,CZ,DE,DK,EE,EL,ES,HU,

IE,IT,LT,LU,LV,MT,NL,PL,PT,RO,SI,SK,

UK

CevacIBird FR/V/0245/001/DC

Ceva ApplicationforDecentralisedProcedure

PUBLICLYAVAILABLEASSESSMENTREPORT

I.SCIENTIFICOVERVIEW

Theproductisproducedandcontrolledusingvalidatedmethodsandtests,whichensurethe

consistencyoftheproductreleasedonthemarket.

Ithasbeenshownthattheproductcanbesafelyusedinthetargetspecies;thereactions

observedareindicatedintheSPC.

Theproductissafefortheuser,theconsumeroffoodstuffsfromtreatedanimalsandforthe

environment,whenusedasrecommended.Suitablewarningsandprecautionsareindicated

intheSPC.

TheefficacyoftheproductwasdemonstratedaccordingtotheclaimsmadeintheSPC.

Theoverallrisk/benefitanalysisisinfavourofgrantingamarketingauthorisation.

II. QUALITYASPECTS

A. Composition

Composition:

Activesubstance:

LiveattenuatedAvianInfectiousBronchitisvirus,10 2.8 –10 4.3 EID

/dose

strain1/96

Listofexcipients:

Gelatine

Hydroxypropylbetadex

Sucrose

Monosodiumglutamate

Potassiumdihydrogenephosphate

Dipotassiumhydrogenephosphate

Purifiedwater

ThevaccineisfilledinvialsofhydrolyticglasstypeIpresentedincardboardboxwith1,10or

20vials/box.The500dosespresentationisfilledin3mLvials.The1000dosespresentation

isfilledin3mLor10mLvials.The2500and5000dosespresentationsarefilledin10mL

vials.

Theparticularsofthecontainersandcontrolsperformedareprovidedandconformtothe

regulationofmonographs3.2.1and3.2.9oftheEuropeanPharmacopoeia.

Thechoiceofthevaccinestrain,ofthevaccinecomposition,ofthedosevolumeand

vaccinationschedulearejustified.

Theproductisanestablishedpharmaceuticalformanditsdevelopmentisadequately

describedinaccordancewiththerelevantEuropeanguidelines.

CevacIBird FR/V/0245/001/DC

Ceva ApplicationforDecentralisedProcedure

PUBLICLYAVAILABLEASSESSMENTREPORT

B. MethodofPreparationoftheProduct

Theproductismanufacturedfullyinaccordancewiththeprinciplesofgoodmanufacturing

practicefromalicensedmanufacturingsite.Acorrespondingmanufacturinglicenceand

GMPcertificatesareprovided.

Processvalidationdataontheproducthavebeenpresentedinaccordancewiththerelevant

Europeanguidelines.

TheproductismanufacturedinaccordancewiththeEuropeanPharmacopoeiaandrelevant

Europeanguidelines.

C. ControlofStartingMaterials

Startingmaterialsofnon-biologicaloriginusedinproductioncomplywithindicated

pharmacopoeiamonographs.

BiologicalstartingmaterialsusedareincompliancewiththerelevantPh.Eur.Monographs

andguidelinesandareappropriatelyscreenedfortheabsenceofextraneousagents

accordingtothePh.Eurmonographs.

ThemasterandworkingseedshavebeenproducedaccordingtotheSeedLotSystemas

describedintherelevantguideline.

D. SpecificMeasuresconcerningthePreventionoftheTransmissionofAnimal

SpongiformEncephalopathies

Scientificdataand/orcertificatesofsuitabilityissuedbytheEDQMhavebeenprovidedand

compliancewiththeNoteforGuidanceonMinimisingtheRiskofTransmittingAnimal

SpongiformEncephalopathyAgentsviaHumanandVeterinaryMedicinalProductshasbeen

satisfactorilydemonstrated.

E. Controltestsduringproduction

Thetestsperformedduringproduction(candling,microbiologicalpuritytest,filledvolume)

aredescribedindetail.

F. ControlTestsontheFinishedProduct

Thetestsperformedonthefinalproductconformtotherelevantrequirements;anydeviation

fromtheserequirementsisjustified.Relevantvalidationsareprovided.

Thetestsincludeinparticular:

-appearance

-residualhumidity

-virusidentity

-virustitration

CevacIBird FR/V/0245/001/DC

Ceva ApplicationforDecentralisedProcedure

PUBLICLYAVAILABLEASSESSMENTREPORT

-purity

-Mycoplasma

-absenceofextraneousagentsaccordingtoPhEur2.6.25

Thedemonstrationofthebatchtobatchconsistencyisbasedontheresultsof3batches

producedaccordingtothemethoddescribedinthedossier.

G. Stability

Stabilitydataonthefinishedproducthavebeenprovidedinaccordancewithapplicable

Europeanguidelines,demonstratingthestabilityoftheproductthroughoutitsshelflife(12

months)whenstoredundertheapprovedconditions(2-8°C).Accordingtothestabilitydata,

anoverageintitreisperformedtoensuretheminimalguaranteeddoseattheendofthe

shelf-life.

Thein-useshelf-life(2h)ofthereconstitutedvaccineissupportedbythedata.

III. SAFETYASSESSMENT

Thevaccineissuppliedinamulti-dose,lyophilizedcakewhichisreconstitutedbytheend

userformassapplicationthroughcoarsesprayordrinkingwater.Vaccinationis

recommendedonbroilerschickensfromonedayofageandforfuturelayersfrom10daysof

age.

Safetystudieshavebeenperformedwithvaccinebatchesproducedaccordingthedescribed

productionprocess.

Laboratorytrials

Thesafetyoftheadministrationofonedose,anoverdoseandtherepeatedadministrationof

onedoseinthetargetanimalisdemonstratedincontrolledlaboratorystudieswhichintotal

included400vaccinatesand292controlanimals(SPFbirds,commercialbroilersandfuture

layers).TheinvestigationwasperformedaccordingtotherecommendationsofDirective

2001/82/ECasamendedandtherelevantguidelines

Thesafetystudiesdemonstratethattheadministrationofonedose,anoverdose,andthe

repeatedadministrationofadosecanbeconsideredtobesafe,whenusedinaccordance

withtherecommendedvaccinationschedule.Someminor,transientadversereactionswere

observedfollowingvaccination(slighttrachealraleswhichmaypersistforatleast10days).

EffectsonlayingperformancewereexaminedinafieldtrialinHungary:21000layerswere

vaccinatedwithCevacIBirdat11and101daysofageandcomparedwith42000controls

vaccinatedwithothervaccines.Thevaccinationhadnoimpactontheeggproductionrate.

TheSPCindicatesthatthevaccineisnotrecommendedforuseduringlayandshouldnotbe

donewithin4weeksbeforethelayingperiod.

Therearenodatasuggestingthatthisproductmightadverselyaffecttheimmunesystemof

thevaccinatedanimaloritsprogenythereforeaspecificstudywasnotcarriedout.

Theapplicanthassatisfactorilyaddressedspecialrequirementstobetakenintoaccountfor

livevaccines:

CevacIBird FR/V/0245/001/DC

Ceva ApplicationforDecentralisedProcedure

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-Thevaccinevirusdisseminatestobursa,caecaltonsil,kidney,liver,lung,spleen,trachea

andoviduct/testis.RapidvaccinevirusdisseminationhasbeendemonstratedbyRT-PCR.

Viruscolonizedmosttissuestested,within3daysofvaccination,andpersistedinuntilthe

endofthestudy(28days),thecolonisationofthereproductiveorganswaslessfrequent.

-Thevaccinestrainiscapableofhorizontaltransmissionfromvaccinatedtargetanimalsto

non-vaccinatedtargetanimals,followingadministrationofanoverdosetoSPFanimals.The

spreadingatleastupto28dayswasdemonstratedbyPCRtestingperformedonbursa,

caecaltonsil,kidney,liver,lung,spleen,tracheaandoviduct/testis.Noinvestigationof

horizontaltransmissionundertherecommendedconditionsofusewasconductedinother

species,intheabsenceofthisdatatheSPCindicatesthatcareshouldbetakentoavoid

spreadtopheasantsandturkeys.

-Theconclusionofthereversiontovirulencestudy,thatthevaccinestraindoesnotrevertto

avirulentformfollowing5invivoserialpassagesingroupsof7SPFchicks,isacceptable.

-TheriskofrecombinationbetweenthevaccinestrainandotherIBVstrainspresentinthe

field(fieldstrainsorvaccinestrains)cannotbeexcludedandtheprobabilitytoobtainanew

virulentstrainisnotnil.Nevertheless,othervaccinescontainingthesametypeofIBVstrain

arealreadyusedinthefieldanduntilnownonegativeeffectslinkedtothesevaccineswas

observed.

Gentamicinsulphateandhydroxyproplybetadexpresentasexcipientsinthevaccinearenot

coveredbytheMRLsregulation.Thegentamicinsulphateusedduringtheproduction

processisnotrecommendedforuseinchickensandisnotlistedintableIoftheannexto

regulation37/2010forchickens.Asitisaddedonlytothevirusharvestandvaccinatedbirds

ingestgentamicinbelowtheMIC,itcannotbeconsideredaspharmacologicallyactive.

Hydroxyproplybetadexinthedoseappliedtothetargetspeciesisnotcapableofany

pharmacologicalactivity,Theuseoflowlevelofthesecomponentswouldhavea

negligibleeffectontheconsumersafety.FurthermorethevaccineCevacTransmunethat

containsalsohydroxypropylbetadexasexcipientiscurrentlyauthorisedindifferentMember

States.

Nospecificassessmentoftheinteractionofthisproductwithothermedicinalproductwas

made.Therefore,anappropriatewarningintheSPCisincluded.

Fieldstudies

Theapplicanthaspresentedthreefieldtrialswhichwereconductedincommercialfarmsin

Hungary.

Thefirsttrialwasperformedinbroilerchickens(20000vaccinatesand22800controls)

vaccinatedatonedayofagebycoarsespray.

Twootherfieldtrialswereperformedinfuturelayers(totalof34680vaccinatesand30480

controls)usingavaccinationbydrinkingwater.Inonestudytheanimalswerevaccinatedat

11dayofageandintheotherstudytheyreceivedarepeatedadministrationofvaccineat11

and101daysofage.

Theresultsobtainedreflectedthoseobservedinthelaboratorysafetystudies,noadverse

effectsattributabletovaccinationwereobservedandtheparametersofanimalsvaccinated

withCevacIBirdwerenotdifferenttoparametersofanimalsinthepositivecontrolgroup.

Ecotoxicity

Theapplicantprovidedafirstphaseenvironmentalriskassessmentincompliancewiththe

relevantguidelinewhichshowedthatnofurtherassessmentisrequired.

CevacIBird FR/V/0245/001/DC

Ceva ApplicationforDecentralisedProcedure

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Theconclusionsoftheenvironmentalriskassessmentaspresentedbytheapplicant,that

thereisaverylowrisktotheenvironmentassociatedwithuseofthevaccine,areaccepted.

Theapplicanthasincludedthestandarddisposalstatementforlivevaccinesontheproduct

literatureandthisisconsideredacceptable.

IV.EFFICACY

Theefficacyoftheproducthasbeendemonstratedinlaboratorychallengestudiesin

accordancewiththePh.Eur.monograph0442:AvianInfectiousBronchitisVaccine(Live).

TheefficacyonthetargetspecieschickenswasdemonstratedinSPFanimals,broilersand

futurelayersattheminimumagerecommendedforvaccination.

Minimumandstandarddoseswereusedintheefficacystudies.

Efficacystudieshavebeenperformedwithvaccinebatchesproducedaccordingthe

describedproductionprocess.

Thechallengestrainusedintheefficacystudiesisa793/BstrainwhichisaUKisolate

correspondingtothesecondeggpassageofastrainisolatedfromaffectedchickensin

1991inScotland.

LaboratoryTrials

TheefficacystudiesprovidedinsupportoftheclaimedindicationsforCevacIBirdare

supportedbyninelaboratorystudies,whichincludedeitherchickensvaccinatedinlaboratory

conditionswiththeminimumdose(10 2.8 EID

/doseinsixstudies),orchickensvaccinatedin

fieldconditionswithstandardbatches(10 3.1 EID

/doseinthreestudies).Challengeofstudy

animalswasconductedwitha793/BstrainwhichisaUKisolatecorrespondingtothe

secondeggpassageofastrainisolatedfromaffectedchickensin1991inScotland.

TheanimalsusedinthedifferentchallengestudiesareSPFchickens(totalof57vaccinates

and33controls),broilers(totalof80vaccinatesand75controls)andfuturelayers(totalof85

vaccinatesand70controls).

TheefficacyofthevaccineisdemonstratedinSPFbirdsaccordingtotherequirementsof

thePh.Eur.Monograph0442,section2.4.3.1.Immunogenicity –Ciliaryactivityoftracheal

explants.

Theefficacyincommercialchickenswasdemonstratedafterachallengeperformedeitherat

21daysorat42daysafterthevaccination.Afterthechallenge,therewasasignificant

reductionoftheimpactonciliaryactivityoftheinfectioninducedbythechallengestrainin

thevaccinatescomparedtothecontrols.Intwostudies,asignificantreductionofrespiratory

signswasobservedinvaccinatesbycomparisonwithcontrolanimals.

ThefollowingclaimedindicationsforCevacIBirdareconsideredtobesupportedbythenine

laboratorystudies:

Fortheactiveimmunizationofbroilerchickens,andfuturelayerchickensinordertoreduce

theimpactontheciliaryactivityoftheinfection,whichmaybemanifestedinrespiratory

clinicalsignscausedbyvariantstrainsofinfectiousbronchitisvirusbelongingtothe793/B

group.

Onsetofimmunityis3weeksafteroneadministrationofthevaccine.

Durationofimmunityis6weeksafterthefirstvaccination.

CevacIBird FR/V/0245/001/DC

Ceva ApplicationforDecentralisedProcedure

PUBLICLYAVAILABLEASSESSMENTREPORT

Fieldstudies

Theapplicanthaspresentedthreefieldtrialswhichwereconductedincommercialfarmsin

Hungary.

Thefirsttrialwasperformedinbroilerchickens(20000vaccinatesand22800controls)

vaccinatedatonedayofagebycoarsespray.

Twootherfieldtrialswereperformedinfuturelayers(totalof34680vaccinatesand30480

controls)usingavaccinationbydrinkingwater.Inonestudytheanimalswerevaccinatedat

11dayofageandintheotherstudytheyreceivedarepeatedadministrationofvaccineat11

and101daysofage.Theanimalswerevaccinatedwithstandardbatchesofvaccine(10 3.1

/dose).

Basedonthedailymonitoringoftheflockhealthstatusandtheserologymonitoringthere

wasnoindicationofanIBVfieldinfectioninthesestudies.Nevertheless50vaccinatedand

60controlanimalsweretakenfromthefieldandwerechallengedinlaboratoryconditions.

Afterthechallenge,therewasasignificantreductionoftheimpactonciliaryactivityofthe

infectioninducedbythechallengestraininthevaccinatescomparedtothecontrols.

V.OVERALLCONCLUSIONANDBENEFIT –RISKASSESSMENT

Thedatasubmittedinthedossierdemonstratethatwhentheproductisusedinaccordance

withtheSummaryofProductCharacteristics,theriskbenefitprofileforthetargetspeciesis

favourableandthequalityandsafetyoftheproductforhumansandtheenvironmentis

acceptable.