1. 1 Brazilian Health Surveillance Agency and Ministry of Agriculture WORKSHOP ON LABORATORY QUALITY SYSTEMS São Paulo, 22-24 September 2003 Good Laboratory Practice OECD System for Mutual Acceptance of Data in the Assessment of Chemicals Dian.Turnheim@oecd.org

2. 2 OECD Principles of GLP Quality System Good Laboratory Practice (GLP) is a quality system concerned with the organisational process and the conditions under which non-clinical health and environmental safety studies are planned, performed, monitored, recorded, archived and reported.

3. 3 OECD Principles of GLP Management Tool  Address the responsibility of and requirements for a test facility’s organisation and personnel, quality assurance programme, physical plant, apparatus, materials and reagents.  Principles governing the following are provided: conditions for establishing and maintaining test systems; receipt, handling, sampling, characterisation and storage of test and reference substances; standard operating procedures; performance of the study; reporting of results; storage, retention and retrieval of records and materials

4. 4 OECD Principles of GLP Legal Requirement The application of GLP is a legal requirement in OECD countries for the conduct of safety studies for regulatory purposes.

5. 5 OECD Principles of GLP Regulatory Tool Unless specifically exempted by national legislation, “apply to all non-clinical health and environmental safety studies required by regulations for the purpose of registering or licensing pharmaceuticals, pesticides, food and feed additives, cosmetic products, veterinary drug products and similar products, and for the registration of industrial chemicals.”

6. 6 OECD Principles of GLP enable correct evaluation of safety test data enable mutual acceptance of data enable the avoidance of duplicative testing enable the avoidance of technical trade barriers improve the protection of human health and the environment serve as a quality system

7. 7 OECD Principles of GLP “principles” or “basic assumptions” or “starting points” not: “detailed regulations” or a “cookbook”

8. 8 OECD Principles of GLP GLP is not concerned with scientific design, but is concerned with scientific integrity So, GLP will never prescribe a methodology, but will see if a certain method is applied correctly Methods are described in e.g. the OECD Guidelines, textbooks etc.

9. 9 HARMONISATION IN THE AREA OF GLP OECD Principles of GLP: a single standard for test facilities throughout OECD and for all chemical substances GLP Compliance Monitoring: mutually acceptable procedures Interpretation of GLP Principles: Consensus Documents International liaison: network of national Monitoring Authorities (Working Group on GLP) [Regulatory requirements: scope of application of GLP] Harmonisation for Mutual Acceptance of Data

10. 10 Harmonisation for Mutual Acceptance of Data OECD COUNCIL ACTS ON GOOD LABORATORY PRACTICE 1981 Council Decision on Mutual Acceptance of Data in the Assessment of Chemicals [C(81)30/Final] 1989 Council Decision/Recommendation on Compliance with Principles of Good Laboratory Practice [C(89)87/Final] 1997 Council Decision on Adherence of Non-Member Countries to the Council Acts related to the Mutual Acceptance of Data [C(97)114/Final]

11. 11 OECD Council Acts related to GLP - 1981 OECD PRINCIPLES OF GOOD LABORATORY PRACTICE Integral part of 1981 Council Decision on Mutual Acceptance of Data in the Assessment of Chemicals [C(81)30/Final, Annex II) “Decides that 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 shall be accepted in other Member countries for purposes of assessment and other uses relating to the protection of man and the environment.”

12. 12 OECD Council Acts related to GLP - 1981 ANNEXED TO 1981 MAD DECISION continuing work in the Environment, Health and Safety Programme OECD Guidelines for the Testing of Chemicals OECD Principles of Good Laboratory Practice Updating Programme Work to facilitate harmonised approaches to GLP compliance and interpretation of GLP Principles

13. 13 OECD Council Acts related to GLP - 1981 HARMONISATION FOR MUTUAL ACCEPTANCE OF DATA THEORY Policy: 1981 Council Decision Tools: Test Guidelines/GLP Principles PRACTICE Use of Test Guidelines: straightforward Compliance with GLP: statement by laboratory POTENTIAL PROBLEMS Verification of compliance Recognition of national compliance monitoring procedures Disharmonised national tools

14. 14 OECD Council Acts related to GLP - 1989 1989 COUNCIL DECISION - RECOMMENDATION ON COMPLIANCE WITH PRINCIPLES OF GOOD LABORATORY PRACTICE C(89)87(Final) I.Compliance Monitoring: Decides that national Compliance Monitoring Procedures be implemented (1983 Recommendation) based on laboratory inspections and study audits national compliance monitoring authority certification of GLP compliance by test facility Recommends application of guidance in Annexes

15. 15 OECD Council Acts related to GLP - 1989 1989 COUNCIL DECISION - RECOMMENDATION ON COMPLIANCE WITH PRINCIPLES OF GOOD LABORATORY PRACTICE C(89)87(Final) II.International Aspects: Decides that countries recognise assurance by another country that data have been generated under GLP, if there is: 1) authority(ies) for international liaison 2) exchange of relevant information 3) information on GLP compliance of a specific laboratory

16. 16 OECD Council Acts related to GLP - 1989 ANNEXES: GUIDANCE FOR COMPLIANCE MONITORING Annex I:Revised Guides for Compliance Monitoring Procedures (1995) Annex II:Revised Guidance for the Conduct of Laboratory Inspections and Study Audits (1995) Annex III:Revised Guidance for the Exchange of Information Concerning National Programmes for Monitoring Compliance with Principles of GLP (1995) (includes guidance for the preparation of annual overview of facilities inspected)

17. 17 COUNTRY ACOUNTRY B REGULATORY AUTHORITY TEST FACILITY GLP MONITORING AUTHORITY Information Requests Information GLP MONITORING AUTHORITY Information Report Inspection and/or Study Audit Requests Information on GLP Compliance Status of the Laboratory or Study Audit Submits Data OECD Council Acts related to GLP - 1989

18. 18 Harmonisation of Compliance Monitoring Procedures INFORMATION EXCHANGE GOAL:Recognition (by Country A) of Country B’s assurance that specific data have been generated under GLP MEANS: Country A’s confidence in Country B’s procedures for Monitoring Compliance with GLP BASED IN: Knowledge and understanding of Country B’s procedures OECD’S ROLE: Working Group on GLP Promote the flow of information Establish harmonised procedures On-site evaluation

19. 19 Harmonisation for Mutual Acceptance of Data 1981 MAD Decision (with GLP Principles) + 1989 Decision - Recommendation on Compliance with GLP (with guidance for compliance for monitoring) = THEORETICAL Basis for Ensuring Confidence In practice:  OECD assists Member countries to implement these Council Acts 1990: OECD Working Group on GLP 1998: Evaluation of Compliance Monitoring Programmes through Mutual Joint Visits (on-site evaluation)  OECD assists non-member countries to implement GLP and Compliance Monitoring 1997: Council Decision on Adherence of non-member countries

20. 20 Harmonisation of Compliance Monitoring Procedures OECD WORKING GROUP ON GLP Comprises representatives of national Monitoring Authorities (~ 40) Meets at least once a year (reports to the Joint Meeting) Discusses administrative and policy issues related to harmonisation of compliance monitoring and international liaison Exchange of information Harmonisation of inspection procedures Oversight of OECD activities on GLP -- Training Courses -- Consensus Workshops -- Non-Member Countries Review of implementation of Council Acts by Member and non-member countries -- On site evaluation visits

21. 21 OECD Council Acts related to GLP - 1997 NON-OECD COUNTRIES AND MUTUAL ACCEPTANCE OF DATA Council Decision on Adherence of Non-Member Countries to Council Acts Related to MAD: C(97)114/Final Harmonisation of Standards Possibility of Adhering to OECD Council Acts: C(81)30(Final): implementation of GLP and Test Guidelines in test facilities -- participate in Test Guidelines Programme C(89)87(Final): establishment of national compliance monitoring authority -- participate in GLP Working Group

22. 22 OECD Council Acts related to GLP - 1997 Procedure for Adherence of Non-Member Countries to Council Acts Related to MAD Annex to [C(97)114]/Final i)Information from Secretariat ii)Council invites non-member country to confirm acceptance of data developed under MAD iii)Technical support to non-member country iv)Participation in Test Guidelines and GLP activities (on site evaluations) v)After full implementation, full membership (MAD)

23. 23 MAD and Non-Member Countries Rights of, and Obligations of Non-Member Countries adhering to the OECD Council Acts related to the Mutual Acceptance of Data Data developed in test facilities in non-member countries in accordance with C(81)30 (Final), OECD Guidelines for Testing of Chemicals, and OECD Principles of GLP, will be accepted by OECD countries and non-member countries adhering to MAD system for the purpose of assessment of chemicals, pesticides, pharmaceuticals, etc. IF……………

24. 24 MAD and Non-Member Countries …………..IF National GLP Compliance Monitoring Procedures in the non-member country have been shown to be in accordance with those in OECD Countries [C(89)87/Final], i.e.: are based on laboratory inspections and study audits are overseen by a national GLP compliance monitoring authority designated by government require declarations of compliance by laboratory management apply OECD guidance in Annexes to C(89)87/Final successful on-site evaluation visit

25. 25 MAD and Non-Member Countries In the same spirit: Data developed in OECD countries (and non-member countries adhering to MAD) under the same conditions will be accepted by the non-member country in question. MUTUAL ACCEPTANCE OF DATA IN THE ASSESSMENT OF CHEMICALS: avoids duplication saves resources reduces animal testing eliminates non-tariff trade barriers creates a level playing-field reduces time-to-market

26. 26 MAD and Non-Member Countries OECD Countries and non-member countries require the same standards for non-clinical health and environmental safety studies to be used for regulatory purposes to register, license or notify chemicals and chemical products: The OECD Principles of GLP and require compliance monitoring to be done according to the same procedures (verified through OECD Working Group on GLP): OECD Guides for Compliance Monitoring Procedures for GLP and OECD Guidance for the Conduct of Laboratory Inspections and Study Audits

27. 27 MAD and Non-Member Countries OECD Working Group on GLP Ensures harmonisation of GLP compliance monitoring among countries establishes agreed procedures examination of compliance monitoring programmes through on-site evaluation visits Non-Member countries adhering to MAD system use agreed procedures take part in development of further guidance are subject to on-site evaluation visits

28. 28 MAD and Non-Member Countries Procedure for Adherence to MAD Council Acts SOUTH AFRICA: - Full Member since 2003  SLOVENIA: - Provisional Adherence since 1999 - MJV in 2003  ISRAEL: - Provisional Adherence in 2003  INDIA: - Secretariat missions, 1998, 2000, 2003 - Invitation to Working Group in Sept 2002 - Participation in OECD Training Courses for GLP Inspectors, 1999, 2002 - Provisional Adherence in 2003  BRAZIL: - Secretariat missions, 1998, 2001, 2002, 2003 - Invitation to Working Group in January 1998 - Participation in OECD Training Courses for GLP Inspectors, 1999, 2002 (Step 1)  RUSSIA: - OECD Workshop on MAD, 1997 - Secretariat consultation, 2003 (Step 1)  CHINA: - Secretariat consultation, 2002, 2003 (Step 1)

29. 29 OECD and Brazil Procedure for Adherence to OECD Council Acts Related to MAD Step 1: Information from Secretariat 1998- First contact between OECD Secretariat and Brazilian authorities - Brazil invited to present its GLP compliance monitoring programme to OECD Working Group on GLP (ad hoc invitation from Council) 1998 - 2000- Implementation of specific Brazilian requirements for verification of GLP compliance -- raises problems for laboratories in OECD countries

30. 30 OECD and Brazil Procedure for Adherence to OECD Council Acts Related to MAD Step 1: Information from Secretariat (continued) 2001:Brasilia Meeting with IBAMA and INMETRO – agreement on acceptance of data developed by OECD countries under MAD 2002:Rio de Janeiro – informal consultation with IBAMA, AVISA, Ministry of Agriculture, Ministry of Foreign Affairs, INMETRO 2003:São Paulo, AVISA/Ministry of Agriculture Workshop - Letter from Brazilian government to OECD requesting that the process for provisional adherence to the OECD Council Acts related to MAD begin - Consideration by OECD Council

31. 31 OECD and Brazil Procedure for Adherence to OECD Council Acts Related to MAD Step 2: Council invites Brazil to provisionally adhere to MAD Council Acts, initially for three years Brazil must confirm in writing at this time that it will accept safety data generated under MAD in OECD countries (and adhering non-member countries) Brazil can take part in all OECD work related to Test Guidelines and GLP 2/5

32. 32 OECD and Brazil Procedure for Adherence to OECD Council Acts Related to MAD Step 3: Provision of technical support to Brazil to implement a GLP compliance monitoring programme which is harmonised with those in OECD: through Working Group on GLP bilateral co-operation in OECD as appropriate 3/5

33. 33 OECD and Brazil Procedure for Adherence to OECD Council Acts Related to MAD Step 4: Brazil names an Observer to the Working Group on GLP: Takes part in all activities: Meetings of Working Group Consensus Workshops Steering Groups On site evaluation teams Training Courses, etc. Brazil names an Observer to the Test Guidelines National Co-ordinators Meetings: Takes part in all activities: Meetings of TG Co-ordinators Expert Groups, etc. On site evaluation in Brazil 4/5

34. 34 OECD and Brazil Procedure for Adherence to OECD Council Acts Related to MAD Step 5: Full Membership in Council Acts related to MAD C(81)30 (Final) C(89)87/Final Invitation by Council -- same rights and obligations of OECD countries: Annual contribution to OECD budget for MAD programme based on Brazilian GDP 5/5

35. 35 Mutual Acceptance of Data 3 Council Decisions accepted by: 1981 MAD 1989 Compliance 1997 Non-Members Mutual Recognition 30 Member countries AUS, AU, BE, CAN, CZ, DK, FIN, FR, GER, GR, HU, ICL, IRE, IT, JP, KO, LU, MEX, NL, NO, NZ, PO, PT, SK, SP, SWE, SWI, TU, UK, USA Non-Member countries South Africa 2003 Slovenia Israel India (provisional) Brazil China Russia etc.

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37. 37 OECD GLP WEBSITE: HTTP://WWW.OECD.ORG/ENV/GLP