1. ECVAM as EU-RL according to 2010/63
Joachim Kreysa
Berlin, 31 January 2011
Last update: 28/12/2018
Author: J.Kreysa

2. ECVAM as Union Reference Laboratory
Art 47: Alternative Approaches; Role of MS & COM
Art 48: The EU – RL
Annex VII: defining the tasks of ECVAM
28/12/2018
ECVAM / J.Kreysa

3. ANNEX VII: ECVAM shall deal with the entire lifecycle of Alternative Methods - from Research to Implementation
Implementation
(Industry, Regulators, CROs)
Research
Regulatory Acceptance
(EU, OECD)
Development
Optimization
incl. independent review
Validation
Last update: 28/12/2018
Author: J.Kreysa

4. ECVAM as Union Reference Laboratory
New elements:
- The EU-RL may collect charges (rules need to be fixed)
- promote 3R also in basic & applied research
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ECVAM / J.Kreysa

5. How will ECVAM meet the requirements of 2010/63? 28/12/2018
ECVAM / J.Kreysa

6. ECVAM: coordinating and promoting the development & use of 3R including in basic & applied research and regulatory testing;
Development:
Identify 3R research needs (DG RTD, other funding bodies)
Participation in RTD projects and in-house projects
Scientific dialog (Workshops, conferences,..)
Produce guidance for test developers and test validators
Use:
Provide a quality control (validation, peer review, confirmation) of alternative methods and their capabilities & limitations
Make info on 3R available (in coop. with MS)
Inform users of test methods (industry) and of test data (regulators)
Training in validated methods
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ECVAM / J.Kreysa

7. Others than ECVAM may carry out validation ECVAM
ECVAM: coordinating the validation of alternative approaches at Union level
Others than ECVAM may carry out validation
ECVAM
Offers Guidance & advice, (guidance docs, helpdesk, VMGs)
Carries out independent peer review of validation studies (ESAC)
Prepares recommendation to policy DGs
clear indication of capabilities & limitations of validated 3R-methods
suggestions on possible regulatory uses
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ECVAM / J.Kreysa

8. ECVAM: exchange of information & running databases & information systems on alternative approaches & their state of development
Conferences & workshops & publications
State of the art reports
Maintain and improve DB-ALM, incl. INVITOX protocols, and ECVAM web-site, interlink with other sites, search guide
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ECVAM / J.Kreysa

9. ECVAM: promoting dialogue between legislators, regulators, and all relevant stakeholders
ESTAF – the ECVAM STAkeholder Forum
is being set up; first meeting in 2011
representation of stakeholders with EU wide reach
relevance of test methods proposed for validation
AD HOC events bringing together
legislators, regulators, industry, biomedical scientists, consumer organisations and animal-welfare groups,
to discuss on the development, validation, regulatory acceptance, international recognition, and application of alternative approaches.
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ECVAM / J.Kreysa

10. Art.47 : Alternative Approaches
Member States shall
identify & nominate laboratories for validation studies
promote 3R approaches and disseminate info thereon
nominate a single point of contact (PARERE, coordinated by ECVAM)
The Commission (policy DGs & ECVAM) shall
set the priorities for validation studies
allocate tasks to the laboratories
take appropriate action for international acceptance of 3R approaches (OECD, ICATM, ICCR)
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ECVAM / J.Kreysa

11. How will ECVAM handle these requirements and link them to its validation process?
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ECVAM / J.Kreysa

12. International coop. Consultation Validation Workflow Output / Docs
ICATM:
establish mutual interest
EU MS / agencies: regulatory relevance
ESTAF: user relevance
1. Test submission handling, scientific/relevance assessment. Decision on entering Validation
Test
Submission (TS)
PARERE | ESTAF Input
ICATM: Propose VMG –
members, send liaison,
comment
Public input on planned
Validation Study (facts,
Data, comments)
2. Validation;
Validation Study Report
Validation Announce-
ment
Validation Study Report (VSR)
3. ESAC peer review of VSR;
ESAC opinion on reliability
and/or scientific validity
ICATM: Propose
Peer Review Group
Members; ESAC observer
ESAC mandate
ESAC Reports & Opinion
ICATM: Comment
on draft ECVAM
recommendations
EU MS / agencies:
ESTAF
4. Draft ECVAM Recommendation 5. ‘Right to be heard’ process
Draft ECVAM Recommendation
Public input (INTERNET)
6. Public Commenting
Public Commenting Report
7. Final ECVAM recommendation incl. ESAC opinion & VSR;
Transfer to policy DGs ; publication
ECVAM Recommendation
28/12/2018
ECVAM / J.Kreysa

13. International coop.
Consultation
Validation Workflow
Output / Docs
ICATM:
establish mutual interest
EU MS / agencies: regulatory relevance
ESTAF: user relevance
1. Test submission handling, scientific/relevance assessment. Decision on entering Validation
Test
Submission (TS)
PARERE | ESTAF Input
Pre-Submission arrives at ECVAM
Start Validation?
Who (f (resources,
capacities))?
Promising?
Priority ?
Invite full submission
Consult PARERE, ESTAF, ICATM
Organise & carry out Validation in line with modular approach in order to generate a complete dossier for peer review
Ready for which
stage of Validation?
yes
Back to developer
28/12/2018
ECVAM / J.Kreysa

14. International coop. Consultation Validation Workflow Output / Docs
ICATM:
establish mutual interest
EU MS / agencies: regulatory relevance
ESTAF: user relevance
1. Test submission handling, scientific/relevance assessment. Decision on entering Validation
Test
Submission (TS)
PARERE | ESTAF Input
ICATM: Propose VMG –
members, send liaison,
comment
Public input on planned
Validation Study (facts,
Data, comments)
2. Validation;
Validation Study Report
Validation Announce-
ment
Validation Study Report (VSR)
3. ESAC peer review of VSR;
ESAC opinion on reliability
and/or scientific validity
ICATM: Propose
Peer Review Group
Members; ESAC observer
ESAC mandate
ESAC Reports & Opinion
ICATM: Comment
on draft ECVAM
recommendations
EU MS / agencies:
ESTAF
4. Draft ECVAM Recommendation 5. ‘Right to be heard’ process
Draft ECVAM Recommendation
Public input (INTERNET)
6. Public Commenting
Public Commenting Report
7. Final ECVAM recommendation incl. ESAC opinion & VSR;
Transfer to policy DGs ; publication
ECVAM Recommendation
28/12/2018
ECVAM / J.Kreysa

15. Output: Validation Report, ready for independent peer review by ESAC.
International coop.
Consultation
Validation Workflow
Output / Docs
ICATM: Propose VMG –
members, send liaison,
comment
Public input on planned
Validation Study (facts,
Data, comments)
2. Validation;
Validation Study Report
Validation Announce-
ment
Validation Study Report (VSR)
Define Validation Study
VMG
Validation study,
generating lacking
info.
Public consultation,
Consult ICATM
Ready for which
stage of Validation?
Output: Validation Report,
ready for independent peer review by ESAC.
Stop
28/12/2018
ECVAM / J.Kreysa

16. International coop. Consultation Validation Workflow Output / Docs
ICATM:
establish mutual interest
EU MS / agencies: regulatory relevance
ESTAF: user relevance
1. Test submission handling, scientific/relevance assessment. Decision on entering Validation
Test
Submission (TS)
PARERE | ESTAF Input
ICATM: Propose VMG –
members, send liaison,
comment
Public input on planned
Validation Study (facts,
Data, comments)
2. Validation;
Validation Study Report
Validation Announce-
ment
Validation Study Report (VSR)
3. ESAC peer review of VSR;
ESAC opinion on reliability
and/or scientific validity
ICATM: Propose
Peer Review Group
Members; ESAC observer
ESAC mandate
ESAC Reports & Opinion
ICATM: Comment
on draft ECVAM
recommendations
EU MS / agencies:
ESTAF
4. Draft ECVAM Recommendation 5. ‘Right to be heard’ process
Draft ECVAM Recommendation
Public input (INTERNET)
6. Public Commenting
Public Commenting Report
7. Final ECVAM recommendation incl. ESAC opinion & VSR;
Transfer to policy DGs ; publication
ECVAM Recommendation
28/12/2018
ECVAM / J.Kreysa

17. ECVAM as EU-RL thrives with its networks
PARERE – Preliminary Regulatory Relevance Assessment, single points of contact, MS competent authorities
COM services and EU agencies
ESTAF – ECVAM STAkeholder Forum (Ind, NGOs, Academia)
ECVAM network of Validation Laboratories
not yet set up, waiting for MS nominations
will include all MS-nominated labs with clear capacity profile
allows identifying best suitable lab for validation studies
Ad hoc networks of expertise, work shops, conferences, ESAC-WGs, manned from ECVAM Expert Panel (EEP)
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ECVAM / J.Kreysa

18. Thank you for your attention !
EUROPEAN CENTRE FOR THE
VALIDATION OF ALTERNATIVE METHODS
28/12/2018
ECVAM / J.Kreysa