OECD

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OECD Test Guidelines Adoption Process Patric
Amcoff Test Guidelines Programme Environment,
Health and Safety Division OECD Paris,
France Creating a Humane and Efficient Approach
to Developmental Neurotoxicity Testing-TestSmart
DNT Reston, Virginia, 13-15 March 2006
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Outline of Presentation

• OECD
• The Test Guidelines Programme
• OECD Test Guideline Submission and Adoption
  Process
• Status of draft DNT Test Guideline 426
• Future Improvements of TG 426!

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The Organisation for Economic Co-operation and
Development
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What is the OECD?
A forum in which governments work together to
address the economic, social and environmental
challenges of interdependence and globalisation
A provider of comparative data, analysis and
forecasts to underpin multilateral co-operation
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A tool for governments

• Born after World War II as the Organisation for
  European Economic Co-operation (OEEC) to
  coordinate the Marshall Plan
• Transformed in 1961 into the Organisation for
  Economic Co-operation and Development (OECD) with
  trans-Atlantic and then global reach
• Today the OECD has 30 member countries
• More than 70 developing and transition economies
  are engaged in working relationships with the
  OECD

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A global outreach
OECD Member Countries
Countries/Economies Engaged in Working
Relationships with the OECD
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OECDs mission

• To promote policies designed
• to achieve sustainable economic growth and
  employment and rising standards of living in
  member countries while maintaining financial
  stability, so contributing to the development of
  the world economy
• to assist sound economic expansion in member
  countries and other countries in the process of
  economic development
• to contribute to growth in world trade on a
  multilateral, non-discriminatory basis

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Who drives OECD work?
Council
Oversight and strategic direction
Representatives of member countries and of the
European Commission decisions taken by consensus
Committees
Secretariat
Discussion and implementation
Analysis and proposals
Secretary-General Deputy Secretaries-General Dire
ctorates
Representatives of member countries and
countries with Observer status work with the OECD
Secretariat on specific issues
Annual budget 188 million euros Funded by
member countries
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The OECD Secretariat
Works in two official languages English and
French Staff members are international civil
servants No quota system for national
representation
2300 staff at Paris headquarters
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The Test Guidelines Programme (EHS/ENV)
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The Test Guidelines Programme (TGP)

• Established 1981
• MAIN TASK Develop and revise Test Guidelines for
  the testing of chemicals for human health and the
  environment
• Original publication in 1981 51 TGs
• Today 100 new or updated Guidelines
• At presently 80 projects in the work-plan
• Special activities Endocrine Disrupters Testing
  and Assessment (EDTA VMG mammalian, eco and
  non-animal)

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OECD Council Decision (1981)Mutual Acceptance of
Data (MAD)

• Data generated in the testing of chemicals in an
  OECD Member Country in accordance with OECD Test
  Guidelines and OECD Principles of Good Laboratory
  Practice (GLP) shall be accepted in other Member
  Countries for purposes of assessment and other
  uses relating to the protection of man and the
  environment.
• Avoids duplication of testing by industry
• Avoids non-tariff trade barriers
• Reduces the number of laboratory animals used

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Publication of OECD Test Guidelines

• Test Guidelines are legal instruments in OECD
  Member countries. There are 4 series
• 100 - Physical-Chemical Properties
  (blue)
• 200 - Effects on Biotic Systems
  (green)
• 300 - Degradation and Accumulation (yellow)
• 400 - Health Effects (pink)
• (500 Endocrine Disruption!)
• Guidance Documents - GD (Non-binding)
• Detailed Review Papers DRP (Non-binding)
• Background Review Papers BRD (Non-binding)

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Decision Layers
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THE OECD SUBMISSION AND ADOPTION PROCESS
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Standard Project Submission Form (SPSF)-
Essential criteria

• Defined regulatory need/Data requirement
• Contributes to the International Harmonisation
  of Hazard and Risk Assessment
• Addresses a health or environmental concern
• Considerable support from Member countries
• Lead country or Stakeholder identified

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Standard Project Submission Form (SPSF)-
Desirable criteria

• Test Guideline intended for general/broad use
• Scientifically valid, reliable and relevant
• Addresses endpoints not yet covered
• Existing national/regional protocols as a basis
• Animal welfare concerns are addressed
• Contributes to saving resources
• For Guidance Documents
• essential or helpful
• linked to (a) specific TGs or for general
  guidance

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Common Stumbling-blocks in the Development Process

• Material supporting the performance/validity of
  the test is not attached or of poor quality
• Statistical evaluations, scientific references,
  validation reports, peer review reports, etc.
• Validation criteria outlined in OECD GD No.34 ? ?
• A poorly written draft Test Guideline
• A poorly defined/or changed regulatory purpose of
  the TG
• Low level of commitment by the lead country
• Need for Expert Consultation or DRP

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OECD Validation Criteria

• Available in
• GUIDANCE DOCUMENT NO. 34 ON THE VALIDATION AND
  INTERNATIONAL ACCEPTANCE OF NEW OR UPDATED TEST
  METHODS FOR HAZARD ASSESSMENT (2005)
• Applicable to all sorts of tests
• Solna principles from WSs in 1996 and 2002 based
  on criteria from ICCVAM and ECVAM
• Criteria for principles of validation
• Criteria for principles of regulatory acceptance
• Updated Test Guidelines need to meet the same
  requirements as new TGs
• Patented tests (e.g., Corrositex)

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Common Stumbling-blocks in the Development Process

• Material supporting the performance/validity of
  the test is not attached or of poor quality
• Statistical evaluations, scientific references,
  validation reports, peer review reports, etc.
• Validation criteria outlined in GD No.34 ?
• A poorly written draft Test Guideline
• A poorly defined/or changed regulatory purpose of
  the TG
• Low level of commitment by the lead country
• Need for Expert Consultation or DRP

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(No Transcript)
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Example of regulatory acceptability at OECD level
for a test method developed in the EU

• RD 3-10 years !?
• Pre-validation 2 years
• Validation 3 years
• Peer review 2 years
• EU regulatory acceptance 2 years
• OECD regulatory acceptance 2 years

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Refocusing of the Test Guidelines Programme

• Main aim To more efficiently develop new or
  revised validated Test Guidelines that meet the
  regulatory need of Member countries
• Better control of new proposals
• Lead countries need to clearly state their degree
  of commitment
• timelines for deliveries
• number of researchers involved
• estimated costs, etc.
• Revision of the SPSF and Guidance Document No.1
  on Test Guidelines Development underway

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Status and Background of Draft Test Guideline 426
(DNT)
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Status of draft Test Guideline 426 (DNT)

• Meetings in Ottawa (March-95) and Copenhagen
  (June-95) initiated the development of
• Test Guideline 426 for Developmental
  Neurotoxicity
• Guidance Document No.20 for Neurotoxicity Testing
  (adopted 2004)
• Guidance Document No. 43 for Mammalian
  Reproductive Testing and Assessment (2006-2nd
  draft)

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Development of TG 426

• Consultation Meeting of Experts in Copenhagen,
  June 1996
• Drafting of Guideline proposal lead by USA and
  Denmark
• Submission of 1st draft to the OECD Secretariat
  in February 1998
• 1st Circulation to the WNT in December 1998

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Development of TG 426

• Revision of the draft TG 426 based on comments
  received
• Revised 2nd Draft TG circulated to WNT in
  October 1999
• Comments received from 11 Member Countries and
  BIAC
• Ad hoc Expert Group established
• Lead by the Secretariat

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Development of TG 426

• The preferred approach by the 12th WNT (2000)
  was
• Joint Meeting of ILSI and OECD on Developmental
  Neurotoxicity Testing, October, 2000
• Technical agreement on preferred approach at the
  meeting
• Revision of the Draft Test Guideline Proposal
• Circulation of a 3rd revised version to the WNT
  in December 2000

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Development of TG 426

• A revised 4th version of TG426 was circulated to
  the WNT in September 2003
• 8 Member countries, EC, BIAC and ICAPO commented
• Due to the severity of comments the Secretariat
  consulted with Dr. Crofton of US EPA
• Expert Consultation Meeting was held in May 2005
  at MHLW in Tokyo to resolve the last blocking
  issues

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Development of TG 426

• A 5th version will be circulated to the WNT for
  comments in March/April 2006 together with a
  supportive retrospective performance assessment
  document
• The nature and severity of comments will
  determine how to move ahead
• Need for Lead Country!

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Future Improvements of TG 426
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Future Improvements of TG 426

• Dialogue needed between researchers and
  regulators
• Need for new technologies (omics) as prescreens
  
• Paradigm shift in regulatory toxicology REACH
  as a driving force!
• Need for diversified testing and development of
  testing strategies for specific DNT endpoints
• Implications for MAD!
• TGs 404/405 Appendices Tiered Testing
• EDTA Conceptual Framework as an example!?

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The OECD Conceptual Framework for Testing and
Assessment of Endocrine Disrupters as agreed by
the EDTA6 (2002)
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Synopsis

• OECD Test Guidelines are legally binding
  instruments in OECD member countries (MAD)
• The Test Guideline submission and adoption
  process is time consuming, however, when
  consensus is reached the regulatory
  implementation is usually rapid
• The most common factors that delay Test Guideline
  development is lacking information on the
  performance and validation status of the test
  method
• The draft TG 426 will be circulated to the WNT
  in spring 2006 and hopefully adopted during 2006
• Severity of comments will determine the future of
  TG426!
• New strategies for (DNT) testing should be
  discussed at the WNT and JM

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Contact details

• www.oecd.org
• Patric.Amcoff_at_oecd.org