Development and Validation of Alternative Methods to Animal Tests

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Development and Validation of Alternative
Methods to Animal Tests Intelligent Testing
Strategies Thomas Hartung Roland Schenkel DG
Joint Research Centre
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JRCs Mission
to provide customer-driven scientific and
technical support for the conception,
development, implementation and monitoring of EU
policies the JRC functions as a reference
centre of science and technology for the EU,
independent of private and national interests...
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JRCs role for animal welfare legislation
for Directive 86/609/EEC the JRChas
established ECVAM 1991 as a reference centre for
the develop-ment and validation of
alternativetesting methods to replace, reduce
or refine the use of laboratory animals.
ECVAM promotes the availabilityand assesses the
suitability of alternative methods independent
of private and national interests...
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The field of alternative approaches in 2005
Legislation
RD FP6 7
International harmonisation
Validationaccelerated
Industry Contri- bution
Intelligent Test Strate-gies
Database
Evidence-based toxicology
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Status of alternative methods for cosmetics
published
Taskforce chaired by DG ENTR and ECVAM 5 DG of
Commission 5 Trade associations 3 Animal welfare
NGOs OECD 75 experts produced 280 page
report Nucleus of the Partnership
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Meeting the timelines of the 7th amendment REACH
2a ( 3a)
3 2a
gt 3a
Resulting last possible entry into
validation 2009 deadline 2002 2013 deadline
2006
Consequences Focus on validation not new
developments Speed up the process
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Speeding up the validation process

• Modular approach (2004)- retrospective
  validation- separation of reproducibility and
  predictive capacity testing
• Reference Laboratory
• Accelerated peer-review
• Collaboration with regulators

Resulting last possible entry into
validation 2009 deadline 2005 2013 deadline
2009
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The new dimension of development of alternative
methods
DG JRC ECVAM
Policy-DGs ECB (DG JRC)
DG RTD
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JRC ECVAM Validated Alternatives
Making cosmetics and chemicals legislation
feasible
Achievements Goals

• validation accelerated
• database of methods
• harmonisation with US OECD
• network of 400 experts
• teaming up with stakeholders
• over 40 tests under validation

• REACH
• Intelligent Testing Strategies

• Cosmetics 7th amendment
• Phase out animal experiments in 10 years

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The gift from validation to life
sciences Validation of alternative tests is one
of the rare examples of quality assurance in
biomedical research (relevance, not only
reproducibility) Evidence-based medicine goes
in vitro! Evidence-based Toxicology know how
good the test is, which you apply Tools -
Validation studies - Quality assurance (GLP,
GCCP) - Systematic review Meta-analysis
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Towards an Evidence-based Toxicology
Expert-based vs. evidence-based toxicology
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Can the same tests be applied for new and
existing substances?

• New substances
• No knowledge about toxicity
• Low established commercial value
• Problem of false-negatives

• Existing substances
• Experience from use
• High commercial value
• Problem of false-positives

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Limitations of current animal tests

• Example Reproductive toxicity
• 85 of animal use in REACH (17 million) for 5.500
  substances
• 1 real positive substances, 71 correct
  prediction between species (Bailey 2005)
• Result 55 real-positives and 1500
  false-positives

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Why Testing Strategies instead of tests?

• Single tests can be optimised only to reduce
  either false-positive (economical
  problem)orfalse-negative (safety
  problem)results
• Optimise work, costs, animal numbers and safety

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ITS purpose finding the right balance
Safety
CostsAnimals
Test Strategy
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Components of Intelligent Testing Strategies

• Use of existing data
• In-vitro tests
• Optimised in-vivo tests
• Thresholds of toxicological concern
• SARs / QSARs and modelling
• Read-across and chemical categories
• Exposure assessment/exposure-based waiving

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An Intelligent Testing Ecotoxicology
Today Concentration killing 50 of algae, water
flee and fish is determined (48 to 60 fish)
lowest value
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JRC report on ITS

• Report published on occasion of the 7th November
  conference
• Analysis of ITS needs and opportunities for REACH

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Facilitate validation
What we do not know
ClassicalValidation
What we would like to know
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The way forward

• Map research and strategies
• Bundle stakeholder activities
• Develop an action program with concrete
  commitments
• Organisational support to the Partnership
• Monitoring of Implementation