EPAA l The European Partnership for Alternative Approaches to Animal TestingSecretariat: 45 Avenue d’Auderghem l 1040 Brussels l Tel: +32 2 295 66 00 l e-mail: entr-epaa@ec.europa.eu

ANNUAL REPORT2010

Foreword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

Overview.of.the.EPAA.activities.in.2010. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

Workshop.on.2Rs.-.Reduction.and.Refinement,.combining.excellence.in.science..and.animal.welfare . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

Computational.Chemistry.&.Systems.Biology.-.Workshop.on.“Harnessing.the.Chemistry.of.Life”. . . . . . . . . . . . . . .5

Workshop.on.acute.toxicity.testing.-.reviewing.the.drivers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

Workshop.on.vaccines.-.the.consistency.approach. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

Thematic.review.on.Reproductive.Toxicity.supported.by.the.EPAA. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

The.extended.one-generation.study. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

The.EPAA.awards .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. ..8

The.next.the.EPAA.Action.Programme . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

A.look.back.over.the.first.five.years.(2006-2010). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

The.EPAA.partners. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .10

The.EPAA.projects.underway. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

Governance. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

CONTENT

Annual Report 2010

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“The mission of the EPAA is fully consistent with the objective of the EU to secure more competitiveness through innovative research, which would deliver better and safer products to EU in-dustries, consumers and patients… We need to explore the full potential of the virtuous circle of innovation resulting in better animal welfare, and animal welfare resulting in better science”.

Antonio Tajani, European.Commissioner.for.Enterprise.and.Industry

FOREwORdThe.EPAA’s.aim.is.to.accelerate.the.development,.validation.and.acceptance.and.use.of.alternative.approaches.to.animal.testing ..For.five.years.now,.the.EPAA.has.initiated.and.recommended.many.actions.regarding.3Rs.methods.and.strategies ..The.EPAA.work.adapts.to.evolving.scientific.progress.and.policy.changes .

Crucial. legislative.initiatives.with.implications.for.the.concept.of.3Rs.have.been.taken.on.over.the.past.two.years ..This.has.led.to.some.major.changes,.which.are.now.being.implemented,.including.a.definition.of.3Rs.methods.under.the.new.rules.on.the.protection.of.animals.used.for.scientific.purposes,.and.the.mandatory.provisions.on.3Rs.for.regulatory.tests,.notably.under.REACH ..These.offer.possibilities.for.constructive.dialogue.on.how.best.to.move.from.principle.to.practice ..The.EPAA.is.determined.to.play.its.role,.through.its.unique.pooling.of.expertise.and.its.ambition.to.see.the.widest.applica-tion.of.the.3Rs .

Georgette Lalis Gerd Ries. European.Commission. Johnson.&.Johnson. Commission.Co-chair.Steering.Committee. Industry.Co-chair.Steering.Committee

whAT is ThE EPAA?The.European.Partnership.for.Alternative.Approaches.to.Animal.Testing.(EPAA).is.an.unprecedented.collaboration.between.the. European. Commission. and. major. companies. from. seven. industry. sectors .. It. is. a. partnership. in. which. knowledge,.research.and.resources.are.pooled.to.accelerate.the.development,.validation.and.acceptance.of.modern.alternative.ap-proaches.for.regulatory.use,.and.in.which.best.practice.is.shared.to.promote.the.use.of.3Rs.methods .

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OVERViEw OF ThE EPAA ACTiViTiEs iN 2010

wORkshOP ON 2Rs - REdUCTiON ANd REFiNEmENT, COmBiNiNg ExCELLENCE iN sCiENCE ANd ANimAL wELFARE

Opening.a.specifically.dedicated.workshop.on.the.2Rs,.on.4.-.5.October.2010,.Gustaaf.Borchardt,.Director.for.Water,.Chemi-cals.and.Biotechnology.in.the.European.Commission’s.DG.Environment,.said.that.“whilst.emphasis.should.not.be.diverted.from.the.importance.of.replacement.methods,.oftentimes.considerable.and.more.immediate.animal.welfare.benefits.can.be.achieved.through.the.application.of.reduction.and.refinement.methods” ..He.welcomed.the.EPAA.spotlight.on.the.“hith-erto.veiled.potential.of.the.2Rs” ..A.structured.discussion.among.the.participating.test.method.developers,.test.method.users,.regulators.and.policy.makers.then.made.it.possible.to.reach.concrete.views.on.the.next.steps.to.be.taken.towards.the.use.of.“non-replacement”.methods.and.strategies ..These.recommendations.on.implementing.“reduction”.and.“refine-ment”.methods.and.strategies. focused.on.how.to. include.opportunities. for. research. in.the.area.of. refinement.and.re-duction,.as.well.as.on.coordination.actions.-.through.consortia.-.that.could.be.supported.through.public.and/or.private.financing.schemes .

The. conclusions. recommended. promoting. reduction. and. refinement. whilst. keeping. replacement. as. the. ultimate. goal ..They.also.urged.the.use.of.existing.data.to.validate.the.2Rs,.replacing.prescriptive.regulatory.standards.with.perform-ance.standards,.and.improving.perception.and.raising.awareness.of.their.value ..This,.the.conclusions.noted,.will.increase.understanding.of.refinement,.bring.greater.coherence.and.specific.objectives.to.research.funding.relating.to.reduction.and.refinement,.and.facilitate.consultation.with.regulators.and. legal. risk.assessors.on.requirements.for. reduction.and.refinement.to.be.validated.and.accepted .

Examples.of.2R.approaches.submitted.by.industry,.regulators,.academia.and.animal.protection.organisations.were.selected.for.presentation.based.on.their.potential.to.improve.the.quality.of.science.and.animal.welfare,.interest.for.further.dissemination.and.wider.use.both.within.and.across.industry.sectors ..Some.of.these.approaches.-.including.good.practice.-.could.be.used.across.the.range.of.safety.testing,.from.screening.to.methods.accepted.by.regulators ..The.submissions.received.were.presented.in.the.poster.session.and.competition.at.the.EPAA.2010.annual.confer-ence.on.30.November.and.will.appear.in.an.EPAA.on-line.publication.soon.after ..The.flash.report.of.the.2RS.workshop.is.available.on.the.EPAA.website .

The.EPAA.chose.this.theme.for.2010.because,.while.significant.efforts.are.being.made.in.developing.and.validating.new.alterna-tive.methods.that.can.completely.replace.the.use.of.animals,.im-portant.progress.has.also.been.made.in.the.other.two.Rs ..As.said.Commission’s.Vice.President.Antonio.Tajani,.“Science progresses at a much slower pace than policy makers would sometimes wish”,.and.“the choice of reduction and refinement as the EPAA lead theme for 2010 will make it possible not only to qualify but also to quantify certain achievements” ..Conditions.are.being.im-proved.for.animals.still.used.in.procedures,.and.their.numbers.are.being.reduced.at.the.same.time.as.the.scientific.validity.of.animal. models. still. required. in. risk. assessment. is. constantly.being.improved ..Reduction.and.refinement.methods.are.capable.of.producing.immediate,.tangible.and.significant.results.in.terms.of.numbers.of.animals.saved,.scientific.output.and.animal.wel-fare ..They.are.easily.disseminated.among.scientists,.and.merit.recognition.and.encouragement ..Drawing.the.attention.of.policy.makers. to. the. enormous. potential. of. these. approaches. and.building. trust. in. these. methods. with. regulators. are. tasks. that.the.EPAA.has.taken.on .

Replacement remains the final objective of the EPAA, but this year the EPAA decided to highlight the significant opportunities that Reduction and Refinement offer, for both animal welfare and science. so as its lead theme for 2010, EPAA selected “harnessing the untapped Reduction and Refinement potential (2Rs) in the regulatory context”, to highlight its work on reduction and refinement strategies.

The workshop recommendations:

1 ...Promote.reduction.and.refinement.whilst.keeping.replacement.as.the.ultimate.goal

2 ..Use.existing.data.to.validate.reduction.and.refinement

3 ...Replace.prescriptive.regulatory.standards.with.performance.standards

4 ...Improve.perception.and.raise.awareness.of.the.value.of.reduc-tion.and.refinement

5 ..Increase.understanding.of.refinement

6 ...Bring.coherence.and.specific.objectives.to.research.funding.relating.to.reduction.and.refinement

7 ...Consult.with.regulators.and.legal.risk.assessors.on.requirements.for.reduction.and.refinement.to.be.validated.and.accepted .

8 ...The.EPAA.to.maintain.a.focus.on.reduction.and.increase.refine-ment.in.its.second.five.year.programme

More.information:.Flash.report.available.on.the.EPAA.website .

Annual Report 2010

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COmPUTATiONAL ChEmisTRy & sysTEms BiOLOgy - wORkshOP ON “hARNEssiNg ThE ChEmisTRy OF LiFE”In.2010.the.EPAA.followed.up.on.the.recommendations.of.the.2008.High.Level.Workshop.on.“New.Perspectives.on.Safety”.-.an.initiative.to.articulate.clearly.the.challenges.that.toxicologists.face.in.developing.approaches.for.safety.assessment.of.chemicals.and.medicines.without.the.use.of.animals ..Computational.chemistry.and.systems.biology.were.amongst.the.scientific.areas.that.were.suggested.for.further.investigation .

On.5-7.July.an.expert.workshop.brought.together.about.20.experts.from.different.disciplines.to.assess.recent.advances.in.compu-tational.chemistry.which,.taken.together.with.state-of-the-art.expertise.in.systems.and.synthetic.biology.and.in.biological.modelling,.could.lead.to.the.development.of.truly.novel.approaches.to.toxicity.testing.that.will.obviate.the.need.for.testing.on.animals .

The. EPAA. aimed. to. identify. the. needs. for. delivering. against. this. chal-lenge,. including. the. requirement. for. engagement. with. other. scientific.disciplines,.and.to.agree.on.a.strategic.plan.and.a.roadmap.for.progress .

The. EPAA. addressed. the. questions. of. whether. recent. advances. in.chemistry.and.effects.on.biological.systems.can.be.exploited.to.pre-dict.that.a.chemical.will.cause.damage.to.the.human.liver,.and.under.which.circumstances ..Requirements.to.drive.this.investigation.forward.were.studied,.as.well.as.which.information,.skills.and.disciplines.would.be.needed ..The.EPAA.considered.intrinsic.chemical.reactivity.(towards.proteins,. DNA. etc);. biologically-specific. chemical. interactions. (e .g ..receptor. and. enzyme. reactivity. and. mediation);. integration. of. these.chemical. interactions. with. initial. biological. consequences. (metabo-lism,.response.to. interference.with.macromolecules,.disturbed.cellu-lar. metabolism. etc);. integrative. bioinformatics. and. systems. effects;.quantitative.aspects.of.these.variables.(dose.responses,.kinetics.etc);.and.systems.and.synthetic.biology ..The.liver.was.used.as.a.case.study.for. this. workshop,. with. the. approach. extended. to. other. organs. if. it.proved.useful .

wORkshOP ON ACUTE TOxiCiTy TEsTiNg - REViEwiNg ThE dRiVERsIn.2010.the.EPAA.followed.up.a.project.-.initiated.in.2008.-.to.review.the.scientific.and.regulatory.drivers.for.acute.toxicity.test-ing.and.to.promote.the.use.of.3Rs.approaches.in.this.area ..This.year.it.published.a.paper.and.held.a.workshop.on.the.subject .

The.project.originated.from.the.recognition.in.the.pharmaceutical.sector.that.regulatory.testing.requirements.on.acute.toxicity.were.no.longer.relevant ..In.light.of.this.conclusion,.the.International.Conference.on.Harmonisation,.which.assures.cooperation.between.pharmaceutical.regulators.in.the.US,.Europe.and.Japan,.modified.the.testing.requirements.for.pharmaceuticals.accordingly .

Because.the.EPAA.brings.together.a.wide.range.of.industry.sectors,.it.can.offer.a.unique.overview.of.the.regulatory.and.scientific.issues.in.this.field,.and.can.recommend.approaches.that.could.be.adopted.widely.across.different.sectors .

Together.with.representatives.of.the.International.Humane.Society,.and.in.association.with.the.UK.NC3Rs,.the.EPAA.ana-lysed.these.testing.requirements.in.other.industrial.sectors ..Data.from.17.companies,.obtained.through.an.EPAA.survey,.led.to.the.conclusion.that.scope.existed.for.reviewing.requirements,.as.a.contribution.to.better.testing.and.better.animal.protection ..The.survey.revealed.that.the.key.driver.is.classification.and.labelling,.and.showed.that.certain.stated.reasons.for.testing.are.not.necessarily.supported.by.the.information.generated.from.the.studies ..Most.companies.also.confirmed.that.they.would.be.ready.to.skip.the.dermal.testing.route.if.a.robust.set.of.data.supported.the.possibility ..The.findings.were.published.in.the.paper.“Cross-Sector.Review.of.Drivers.and.Available.3Rs.Approaches.for.Acute.Systemic.Toxicity.Testing”,.T ..Seidle.et.al,.in.Toxicological.Sciences ..(Full.paper.available.at.http://toxsci .oxfordjournals .org/cgi/content/full/116/2/382)

An.EPAA.workshop.involving.regulators,.academics,.poison.centre.staff.and.industry.representatives.held.in.Brussels.on.16.September.2010.focussed.on.two.areas.stemming.from.the.review ..These.were.assessing.whether.there.are.scientific.drivers.for.acute.toxicity.testing.and.whether.the.available.concordance.data.set.is.adequate.to.support.the.deletion.of.the.requirement.for.dermal.testing.from.relevant.legislation .

Specific. proposals. were. made. for. waivers. that. would. deliver. direct. 3Rs. benefits .. The. outcome. of. the. workshop. will. be.communicated.in.the.workshop.report.which.will.be.made.available.on.the.EPAA.website ..Follow.up.steps.will.include.a.wider.consultation.of.the.key.recommendations.with.regulatory.stakeholders.and.considerations.of.how.the.removal.of.the.dermal.route.as.part.of.default.testing.can.be.implemented .

The workshop concluded that integrated research should be undertaken which would:1 ...Consider.modelling.transport.and.interactions.from.molecular.to.cel-

lular/organelle.levels.(mitochondria.specifically)

2 ...Tightly.integrate.with.in.vitro.stem.cell.experimentation.designed.specifically.to.inform.this.modelling.activity

3 ..Couple.directly.to.systems.modelling.from.cellular.to.organ.level

4 ...Take.account.of.mechanistic.understandings.of.toxic.responses.in.the.liver

5 ...Establish.an.appropriate.infrastructure.for.computation.data.basing.and.sharing .

A.dedicated.team.drawn.from.workshop.members.works.on.the.key.strategic.principles.to.define.a.workable.action.plan .

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wORkshOP ON VACCiNEsThe.EPAA.organised.in.Brussels.a.workshop.on.11-12.January.2010,.together.with.ECVAM,.to.discuss.the.consistency.ap-proach.for.quality.control.of.vaccines ..The.workshop.was.attended.by.about.60.participants.from.industry,.academia.and.regulatory.agencies .

The.consistency.approach.is.based.upon.the.principle.that.the.quality.of.a.vaccine.is.the.consequence.of.the.strict.appli-cation.of.a.quality.system.and.of.a.consistent.production.of.batches ..Through.the.application.of.this.principle,.which.has.been.implemented.for.some.novel.human.vaccines,.agreed.product.characteristics.can.be.tested.in.vitro.during.the.manu-facturing.process.of.a.batch.and.shown.to.be.similar.to.those.of.batches.demonstrated.to.be.safe.and.effective.in.clinical.trials ..The.concept.of.consistency.may.therefore.be.applied.to.conventional.vaccine.production.in.order.to.replace.in.vivo.tests.with.in.vitro.tests.indicative.of.the.quality.of.the.product.whilst.maintaining.the.highest.quality.and.safety.standards .

The. central. recommendation. was. to. include. in. the. European. Pharmacopoeia. monographs. an. explicit. request. from. the.European.Directorate.for. the.Quality.of.Medicines.&.Healthcare.of. the.Council.of.Europe.to.allow.the.application.of. the.consistency.approach ..A.further.result.was.a.plan.for.industry.to.advance.technical.reflection.on.how.this.might.be.applied.to.all.vaccines,.under.the.EPAA.umbrella,.and.with.involvement.of.regulatory.agencies ..The.EPAA.agreed.to.support.the.implementation.of.the.workshop.recommendations.through.a.human.and.a.veterinary.vaccines.platform .

According.to.participants,.the.opportunity.exists.to.introduce.the.approach.into.established.vaccine.production,.with.the.potential.to.replace.in.vivo.tests.with.non-animal.tests.designed.to.demonstrate.batch.quality.and.antigen.quantity ..In.this.way,.the.highest.quality,.safety.and.efficacy.standards.could.be.maintained.while.allowing.for.a.significant.reduction.in.animal.use ..The.report.indicates.how.this.approach.may.be.further.developed.for.application.to.established.human.and.veterinary.vaccines.and.emphasizes.the.continuing.need.for.co-ordination.and.harmonization ..It.also.gives.recommenda-tions.for.work.to.be.undertaken.in.order.to.encourage.acceptance.and.implementation.of.the.consistency.approach .

The.full.report.should.be.submitted.for.publication.in.a.peer.reviewed.journal.by.the.end.of.2010 .

in the meantime, the EPAA steering Committee agreed on follow-up actions:1 ...Organise.a.workshop.to.secure.the.agreement.of.the.appropriate.members.including.regulatory.authorities,.for.identifying.current.

alternative.initiatives.amongst.stakeholders,.for.prioritising.the.tests.to.be.replaced.according.to.specific.criteria,.and.for.recommend-ing.minimum.validity.criteria.for.acceptance.of.alternatives.to.in.vivo.testing.methods .

2 ...Facilitate. the. exchange. of. technical. information. on.test.methods.and,.if.relevant,.reagents.and.materials .

3 ...Create.working.groups.focussing.on.specific.meth-ods. with. the. support. of. experts. from. Academia,.EDQM,.OMCLs,.ECVAM,.EVM.and.IFAH,.regulatory.au-thorities.and.experts.from.FDA.and.WHO…

4 ...Establish. proof. of. concept. for. specific. tests. identi-fied.through.workshops.before.validating.the.meth-od.and.before.proposing.the.alternative.method(s).to. standardisation. bodies. such. as. EDQM. with. the.support.of.stakeholders .

5 ...Support. dissemination. through. publications. in. sci-entific.journals

OVERViEw OF EPAA ACTiViTiEs iN 2010

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ThEmATiC REViEw ON REPROdUCTiVE TOxiCiTy sUPPORTEd By ThE EPAATo.implement.one.of.the.three.main.objectives.agreed.on.during.2009,.the.EPAA.decided.in.2010.to.promote.a.mechanism.by.which.regulators,.industry.and.other.parties.are.provided.with.concise,.comprehensive.and.peer-reviewed.information.regarding.existing.Replacement,.Reduction.or.Refinement.methods.(3Rs).for.regulatory.safety.testing .

The.first.in.this.series.is.the.provision.of.an.up-to-date.picture.of.alternative.methods,.from.development.to.regulatory.ac-ceptance,.in.use.for.reproductive.toxicity.testing.of.chemicals.and/or.formulations ..(This.review.does.not.cover.methods.to.detect.developmental.neurotoxicity.and.endocrine.disruptors,.which.could.be.part.of.a.separate.review) .

The.review.is.carried.out.by.a.scientific.consultant.under.the.overall.coordination.of.ECVAM.and.it.is.financially.supported.by.the.EPAA.industry.partners ..Companies.were.invited.to.provide.input.on.the.in.vitro.methods.used.by.industry.by.com-pleting.a.questionnaire.that.was.made.available.on.the.EPAA.website ..Another.questionnaire.addressing.in.vivo.Reduc-tion.and.refinement.methods.or.Integrated.Testing.Strategies.(ITS).is.under.preparation.and.shall.complement.this.first.project .

The.outcome.of.the.review.will.be.disseminated.via.the.ECVAM.DataBase.service.on.ALternative.Methods.to.animal.experi-mentation.(DB-ALM).http://ecvam-dbalm .jrc .ec .europa .eu .

DB-ALM.ensures.a.wide.and.targeted.distribution.of.the.results.reached.having.the.DB-ALM.over.2000.subscribed.users.from.75.countries.covering.all.relevant.user.profiles.in.the.topic.area.of.animal.alternatives .

ThE ExTENdEd ONE-gENERATiON sTUdyThis.was.an.EPAA.initiative,.which.has.been.worked.on.for.a.long.time,.and.has.been.reported.on.in.previous.years ..EPAA.industry.partners.have.made.available.data.and.prepared.a.protocol.to.promote.an.extended.one-generation.study.origi-nally.developed.for.plant-protection.products,.for.wider.use.in.the.chemical.sector ..Final.acceptance,.however,.is.the.com-petence.of.the.OECD .

In.accordance.with.principles.of.consistency.as.set.out.at.the.2009.the.EPAA.Conference,.it.makes.sense.that.where.the.EPAA.starts.an.action.that.proves.to.have.value.and.potential,.the.European.Commission.and/or.industry.pursue.that.ac-tion.in.their.particular.fields.of.activity.and.competence . .

In.2010,.a.number.of.expert.discussions.were.held.by.the.OECD.to.advance.the.project ..It.is.expected.that.the.Extended.One-Generation.study.test.guideline.will.be.put.forward.for.a.formal.adoption.at.OECD.and.then.at.the.Council.level.in.spring.2011 ..The.exact.use.of.the.guideline.within.the.different.EU.regulatory.frameworks.will.still.need.to.be.determined .

The objectives of the Reproductive Toxicity review are to provide: an up-to-date overall picture of the state-of-the-art of alternative methods in use for assessing (aspects of ) reproductive toxicity at any stage of development: from development, through (formal) validation, to regulatory acceptance. Ready-to-use information will be presented for each method with their potential and limitations as peer-reviewed data sheets with predetermined criteria for data content as developed by ECVAm, that ensures the data quality. The review will be made available within dB-ALm benefitting from its data retrieval facilities and the large scientific and regulatory community who subscribed to this service ensuring a wide and targeted distribution of the project outcome. The project started in may 2010 and is expected to deliver a good overview before the end of the year.

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ThE EPAA AwARdsTo.increase.awareness.of.alternatives.and.promote.them.to.young.scientists,.the.EPAA.launched.two.awards.in.2010.-.one.dedicated.to.scientists,.and.one.to.communication .

With.the.science.award,.the.EPAA.is.offering.support.of.up.to.€100,000.for.the.development.and.regulatory.acceptance.of.3Rs.alternative.methods ..The.focus.is.on.practical.steps.to.improve.the.acceptance.and.implementation.of.the.3Rs.in.the.regulatory.context ..Finance.will.be.provided.to.the.institution.of.the.successful.candidate.to.allow.a.one-year.extension.of.an.existing.postdoctoral.contract,.to.promote.the.transition.from.innovative.and.experimental.alternative.approaches.to-wards.industrial.application.and.regulatory.acceptance ..The.call.was.launched.in.June.2010,.and.received.13.submissions

With.its.communication.prize,.the.EPAA.is.offering.€3,000.for.an.essay.or.article.that.broadens.awareness.of.the.role.of.safety.assessment.and.regulatory.compliance.in.product.development.and.that.promotes.replacement,.reduction.and.re-finement.(3Rs) ..The.key.criterion.for.the.winning.essay.is.that.it.will.help.inform.the.wider.policy.community.and.decision-makers.about.the.opportunities.and.challenges,.including.limitations,.offered.by.scientific.and.technological.progress ..The.call.was.launched.in.June.2010.and.7.entries.were.received .

As.part.of.its.policy.to.widen.understanding.and.acceptance.of.the.3Rs.approach,.the.EPAA.also.provides.support.for.other.organizations’.events ..The.EPAA.website.carries.details.of.criteria.for.applications.for.sponsorship,.the.selection.process,.and.the.conditions.for.validating.sponsorship .

The.EPAA.continued.to.implement.an.active.communication.policy.especially.through.its.website,.newsletters.and.contri-butions.in.several.3Rs-related.scientific.conferences .

ThE NExT EPAA ACTiON PROgRAmmEReaching.the.end.of.the.original.first.programme,.the.EPAA.needed.a.new.plan,.to.develop.actions.reflecting.its.partners’.continued.commitment.to.3Rs .

The.new.Action.Programme,.for.2011-2015,.is.based.on.a.critical.assessment.of.the.first.programme,.in.2006-2010,.and.on.likely.upcoming.scientific,.policy.and.legislative.challenges ..It.also.reflects.structural.changes.the.EPAA.implemented.in.2009.to.increase.its.efficiency.and.make.the.best.use.of.resources .

It.is.more.selective.than.its.precursor,.with.activities.prioritised.on.the.basis.of.their.relevance.to.EU.sectoral.legislation,.animal.welfare.legislation.and.policies,.to.unmet.scientific.challenges,.to.tangible.impact.on.numbers.and.welfare.of.labo-ratory.animals,.and.to.the.EPAA.partners’.competence.and.resources ..It.also.provides.for.flexibility.in.planning.activities.and.for.regular.review.to.adapt.them.to.circumstances .

It.has.three.main.objectives:.increase.international.coordination.on.scientific.and.regulatory.matters;.improve.the.quality.of.the.links.with.national.regulators.in.the.EU;.and.profile.more.the.EPAA.when.it.is.about.the.merits.of.all.3Rs.methods

The. Platform. on. Science. will. aim. to. identify. knowledge/scientific. gaps. in. the. fields. of. computational. chemistry. and.systems.biology.and.will.recommend.areas.for.further.research.in.these.fields:.(i).identify.and.address.research.needs.for.developing.or.optimising.alternative.methods.through.relevant.programmes.and.calls.for.proposals.of.the.European.Commission. and. other. research. funding. institutions;. (ii). seek. involvement. of. young. scientists. and. scientists. from.areas.not.directly.related.to.biosciences.to. increase.knowledge.and. leverage.understanding.of.3Rs.within.scientific.community;.and.(iii).assess.the.feasibility.of.technology.transfer.across.sectors.(e .g ..optimization.of.study.design.in.toxicological.testing) .

The.Platform.on.3Rs.in.Regulation.aims.at.(i).identifying.areas.where.implementation.of.regulatory.requirements.could.be.optimized/rationalized.in.line.with.the.3Rs.principles;.(ii).fostering.regulatory.acceptance.of.rationalised.acute.toxicology.testing.methodologies.(including.waiver.of.one.of.the.administration.routes);.(iii).supporting.further.development.of.the.scientific.data.to.promote.the.vaccines.consistency.approach;.(iv).promoting.acceptance.of.the.extended.one-generation.study. by. regulatory. authorities;. and. (v). understanding. regulators’. requirements. for. levels. of. confidence. in. integrated.testing.strategies .

The.Platform.on.Dissemination.&.Communication.aims.at.(i).reviewing.key.3Rs.topics,.so.as.to.present.the.options.avail-able.today.to.regulators.and.users.in.a.form.of.thematic.reviews;.(ii).developing.communication.tools.that.improve.un-derstanding.of.the.results.3Rs.approaches.can.deliver.in.different.sectors;.(iii).defining.mechanisms.to.provide.greater.access.to.information.and.opportunities.to.connect.those.who.have.and.those.who.need.information;.and.(iv).promoting.the.potential.of.alternative.approaches.with.young.scientists .

A.mid-term.revision.of.the.programme.is.foreseen.in.2013 .

OVERViEw OF EPAA ACTiViTiEs iN 2010

Annual Report 2010

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“I hope and expect that we will witness much activity in the area of 3R development during the coming years. Promotion of alternatives is an ongoing task of highest importance. Each time we propose new legislation, or revise existing legislation that involves the use of animals, the EU legislator will assess how on the basis of experience acquired, we can improve the promotion of the 3Rs. Against this background, work on the 3Rs, that is not only Replacement but equally Reduction and Refinement, and the work pursued by the EPAA remain key in the Commission’s strategy on alternative approaches.”.Gustaaf.Borchardt,.Director.for.Water,.Chemicals.and.Biotechnology.in.the.European.Commission’s.DG.Environment

A LOOk BACk OVER ThE FiRsT FiVE yEARs (2006-2010)With.the.platform.on.science,.the.EPAA.started.in.2006.to.evaluate.opportunities.for.wider.application.of.testing.strategies.being.developed.as.the.Agricultural.Chemical.Safety.Assessment.(ACSA).approach.for.reproductive.toxicity,.e .g .,.for.regula-tory.testing.under.REACH ..This.led.to.the.establishment.of.an.OECD.task.force.in.2007,.and.feasibility.studies.conducted.by.four.EPAA.member.companies.that.are.close.to.completion.at.the.end.of.2010 ..The.approach.promises.to.deliver.real.animal.welfare.benefits:.refinement,.and.a.reduction.in.the.number.of.animals.used.(more.than.40%.compared.to.the.two-generation.study) ..It.is.now.up.to.OECD.to.make.a.final.decision.on.whether.and.how.to.implement.this.important.reduction.approach .

With.the.help.of.scientists.from.various.fields,.including.outside.the.life.sciences.field,.the.EPAA.explored.“New.perspectives.on.safety.testing” ..This.reflection.addressed.forward-looking.issues,.including.future.hazard.iden-tification.with.regards.to.chronic.repeat.dose.systemic.toxicity.without.the.use.of.animal.test-ing,.and.novel.approaches.for.the.characterization.of.the.potential.hazards.of.chemicals.and.drugs ..The.EPAA.explored.which.areas.of.science.and.technology.could.create.new.approaches.to.safety.assessment ..As.a.follow.up,.scientific.workshops.were.organised.to.discuss.the.po-tential.of.computational.chemistry.and.systems.biology.,stem.cells.in.future.safety.testing.and.in.vitro.ADME.(Physiologically-based.pharmacokinetic/toxicokinetic.(PBP/TK).models.are.ide-ally.suited.for.the.integration.of.data.produced.from.in.vitro.testing.systems/in.silico.models.into.a.biologically.meaningful.framework,.and.for.the.extrapolation.to.in.vivo.condition ..An.EPAA-workshop. on. this. topic. is. planned. for. autumn. 2011) .. Conclusions. from. these. discussions.were.considered.in.the.forward.research.agenda.(such.as.the.call.for.proposals.and.projects.selected.in.the.joint.EC-COLIPA.research.programme.on.systemic.toxicity.under.FP7) ..Addition-ally,.the.EPAA.succeeded.in.engaging.the.wider.scientific.community,.thereby.providing.greater.legitimacy.to.investment.in.research.into.alternatives .

Where.barriers.to.validation.were.detected,.the.EPAA.partners.have.jointly.developed.pro-cedures.that.should.help.submission.and.evaluation.of.applications.by.ECVAM.or.request./provision.of.information.by.companies,.in.particular.through.calls.at.an.early.stage.before.the.finalisation.of.protocols.for.validation.studies .

An.important.objective.of.the.EPAA.is.to.improve.the.implementation.of.3Rs.in.European.regulatory.testing.and.decision.making ..It.therefore.aims.to.identify.optimised.approach-es.on.testing.and.risk.assessment.strategies.in.existing.and.upcoming.legislation.and.their.implementation ..In.this.re-spect,.the.EPAA.strives.to.share.experience.and.evaluate.consistency.across.sectors,.to.analyse.hot.spots,.and.to.identify.policy.drivers.for.testing ..Currently,.the.EPAA.is.following.up.on.suggestions.from.earlier.debates.and.workshops.relating.to.the.involvement.of.regulators.at.an.early.stage.of.method.validation;.better.dissemination.of.information.about.avail-able.alternatives;.and.the.inclusion.of.3Rs.on.the.agendas.of.all.relevant.international.regulatory.meetings ..Cooperation.between.industry.and.regulators.on.the.basis.of.scientifically.solid.case.studies.is.becoming.stronger.and.more.tangible ..Examples.include.implementation.of.the.consistency.approach.in.vaccines.testing.or.reduction.strategies.in.acute.toxicity.testing .

In.terms.of.communication,.the.creation.of.a.joint.understanding.between.industry.and.Commission.partners.of.the.life.cy-cle.of.product.research.and.development,.and.of.the.value.and.limitation.of.alternative.approaches.in.this.context,.makes.it. possible. today. to. have. open. discussion. about. the. challenges. and. how. to. address. them .. Maintaining. understanding.among.all.the.EPAA.partners.is.a.continuous.process,.particularly.in.view.of.its.widening.audience ..Disseminating.informa-tion.to.wider.audience,.including.policy.makers,.is.one.of.the.challenges.for.the.future ..The.EPAA.website.and.newsletter.are.a.good.start ..The.communication.award.was.initiated.by.the.EPAA.to.promote.the.communication.of.complex.scientific.matters.in.lay.language.and.in.a.way.that.can.inform.decision.making.and.policy.debates .

The.EPAA’s.approach.to.dissemination.of.information.on.the.3Rs.has.been.refined.by.the.“market.place”.concept.it.created,.to.bring.information.to.those.who.need.it.through.workshops,.direct.presentations.to.regulatory.bodies,.and.thematic.re-views ..The.lead.theme.of.2010.-.2Rs.-.is.an.example.where.sharing.good.practice.holds.out.the.prospect.of.quicker.results.than.trying.to.change.the.regulatory.set.up .

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European Commission.DG.Enterprise.and.Industry.DG.Research.DG.Environment.DG.Joint.Research.Centre.DG.Health.and.Consumer.Protection

With. a. view. to. increasing. efficiency,. EPAA.maximises. coordination. on. the. cross-cut-ting. themes. that. are. central. to. extending.the. use. of. 3Rs .. It. operates. through. three.platforms. -. one. focused. on. scientific. is-sues,.one.on.legislation.and.acceptance.of.alternative. methods,. and. one. on. dissemi-nation.and.communication .

ThE EPAA PARTNERs

Federations..Soaps.and.detergents.(AISE).Chemicals.(CEFIC).Cosmetics.(COLIPA).Crop.Protection.(ECPA).Pharmaceuticals.(EFPIA).Bio-Industries.(EuropaBio)..Animal.Health.Europe.(IFAH-Europe)

Companies.Abbott.Astra.Zeneca.Avon.BASF.Bayer.Beiersdorf.Boehringer.Ingelheim.Chanel.Colgate-Palmolive.Dow.DSM.Elizabeth.Arden.Estée.Lauder.Evonik/Degussa.Glaxo.SmithKline

.Henkel

..Intervet.-.Schering.Plough.Animal.Health.Johnson.&.Johnson.Kanebo.Kimberly-Clark.L’Oréal.LVMH.Merck..Merck.Sharp.and.Dohme.Novartis.Novo.Nordisk.Novozymes.Pfizer.Procter.&.Gamble.Reckitt.Benckiser

..Roche.(F ..Hoffmann-La.Roche)

.Sanofi-Aventis

.Serono

.Shiseido

.Solvay.Chemicals

.Syngenta

.Unilever

Small.&.Medium.size.Enterprises.(SMEs).Euroderm.StratiCELL

ThE EPAA PROjECTs UNdERwAy•.New.perspectives.on.safety.-.follow-up:.Computational.chemistry.and.systems.biology•.New.perspectives.on.safety.-.follow-up:.Stem.cells•.Acute.toxicity.testing•.Consistency.of.production.approach.in.biologicals/vaccines.(veterinary.and.human)•.Address.barriers.to.validation.&.Support.of.ongoing.validation.studies•.Address.barriers.to.regulatory.acceptance•.Validation.and.regulatory.acceptance.of.ITS•.Technology.transfer:.extended.one-generation.study.for.reprotox•.Enhance.dissemination.of.3Rs.information.to.target.audiences•.EPAA.awards•.External.communication•.Internal.communication

gOVERNANCEIn.2010,.the.EPAA.Steering.Committee.met.on.2.February,.28.April,.17.June.and.21.Septem-ber ..A.fourth.meeting.is.scheduled.for.Decem-ber.2010 .

The. Mirror. Group. met. on. 3February. and. 22.September,. expressing. support. for. ongoing.and. envisaged. EPAA. work,. providing. valuable.suggestions. and. advice .. Members. of. the. Mir-ror. Group. were. increasingly. involved. in. EPAA.projects,.as.were.representatives.of.the.organ-isations.personalities.of.which.are.member.of.the.Mirror.Group .

Minutes.are.made.available.on.the.EPAA.web-site .

Since. the. end. of. 2009,. three. platforms. -. Sci-ence,.3Rs.in.Regulation.and.Communication.&.Dissemination.-.organise.the.work.on.different.projects.and.ensure.their.consistency:

Science:.new.perspectives.on.safety

3Rs. in.Regulation:.acute.tox,.consistency.ap-proach. in. vaccines. testing,. post-validation.review

Communication.&.Dissemination:.3Rs’.market.place,.thematic.reviews

Further.info.is.available.at www.epaa.eu.com

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Secretariat.45.Avenue.d’Auderghem1040.Brussels.Tel:.+32.2.295.66.00e-mail:.entr-epaa@ec .europa .eu

www.epaa.eu.com

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