1. Good Laboratory Practice - general information Pirkko Puranen Senior Inspector, Ph.D. Inspectorate

2. Lääkealan turvallisuus- ja kehittämiskeskus Non-clinical health and environmental safety studies Experimental studies are needed to support registration and marketing authorisation applications of chemicals and medicines Study data is used in assessing safety of chemicals and medicines to human health and enviroment Data is usually provided by the applicant The laboratory may be part of the applicant company or an external contract laboratory 28.6.2013Pirkko Puranen TAIEX 1

3. Lääkealan turvallisuus- ja kehittämiskeskus Reliability of data based on non-clinical health and environmental safety studies? How the registration authority can know, if data generated in a safety study is reliable? How the applicant can prove the reliability of data to the registration authority How the reliability of data can be shown in the international framework, when authority, applicant and testing laboratory may be located in different countries? 28.6.2013Pirkko Puranen TAIEX 1

4. Lääkealan turvallisuus- ja kehittämiskeskus Commonly agreed minimum criteria how to generate the data (Common test quidelines) Technical requirements (equipment, chemicals, calibrations, test animals…) Adequate laboratory (prevention of mix-ups and cross contaminations…) Skills and qualifications of laboratory personnel Documentation (traceability, transparency, reliable archiving after the study…) Management (overall responsibility) Overall responsibility of a study (study director) Proper planning, performing and reporting of the study Clear responsibilities of personnel involved Independent quality assurance to inspect and verify that the criteria are fulfilled 28.6.2013Pirkko Puranen TAIEX 1

5. Lääkealan turvallisuus- ja kehittämiskeskus Good Laboratory Practice = GLP Defined in OECD (Organisation for Economic Co-operation and Development) Series on Principles of Good Laboratory Practice (GLP) and Compliance Monitoring 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. GLP covers pharmaceutical products, pesticides, cosmetics, veterinary drugs, food additives, feed additives and industrial chemicals 28.6.2013Pirkko Puranen TAIEX 1

6. Lääkealan turvallisuus- ja kehittämiskeskus OECD Series on Principles of Good Laboratory Practice (GLP) and Compliance Monitoring OECD Principles of GLP - No 1: OECD Principles of Good Laboratory Practice GLP consensus documents - No 4: Quality Assurance and GLP - No 5: Compliance of Laboratory Suppliers with GLP Principles - No 6: The Application of the GLP Principles to Field Studies - No 7: The Application of the GLP Principles to Short Term Studies - No 8: The Role and Responsibilities of the Study Director in GLP Studies - No10: The Application of the Principles of GLP to Computerised Systems - No 13: The Application of the OECD Principles to the Organisation and Management of Multi-Site Studies 28.6.2013Pirkko Puranen TAIEX 1

7. Lääkealan turvallisuus- ja kehittämiskeskus Guidance Documents for Compliance Monitoring Authorities - No 2: Revised Guides for Compliance Monitoring Procedures for Good Laboratory Practice - No 3: Revised Guidance for the Conduct of Laboratory Inspections and Study Audit - No 9: Guidance for the Preparation of GLP Inspection Reports 28.6.2013Pirkko Puranen TAIEX 1 OECD Series on Principles of Good Laboratory Practice (GLP) and Compliance Monitoring

8. Lääkealan turvallisuus- ja kehittämiskeskus OECD Series on Principles of Good Laboratory Practice (GLP) and Compliance Monitoring Guidance Documents for Compliance Monitoring Authorities Advisory Documents of Working Group on GLP - No 11: The Role and Responsibility of the Sponsor in the Application of the Principles of GLP - No 12: Requesting and Carrying Out Inspections and Study Audits in Another Country - No 14: The Application of the Principles of GLP to in vitro Studies - No 15: Establisment and Control of Archives that Operate in Compliance with the Principles of GLP Position Papers - The Use of Laboratory Accreditation with reference to GLP Compliance Monitoring - ”Outsourcing” of Inspection Functions by GLP Compliance Monitoring Authorities 28.6.2013Pirkko Puranen TAIEX 1

9. Lääkealan turvallisuus- ja kehittämiskeskus History of GLP 1975 USA FDA found fraud data in safety studies 1976 : USA FDA established GLP regulation on non-clinical laboratory studies 1978 : OECD established expert group 1981 : OECD Council Decision on Mutual Acceptance of Data (MAD): GLP-Principles in Annex II 1987/88 : EU adopted GLP Directives 1997 : Revised OECD GLP- Principles 1999 : Amendment of EU GLP Directives following OECD 2004: Codification of GLP Directives 28.6.2013Pirkko Puranen TAIEX 1

10. Lääkealan turvallisuus- ja kehittämiskeskus OECD Mutual Acceptance of Data (MAD) A GLP study is accepted in another member country To avoid repeating safety studies already performed in another member country To save resources Animal welfare point of view if animal testing Each member country is responsible of their own GLP programme and inspections in their own country 28.6.2013Pirkko Puranen TAIEX 1

11. Lääkealan turvallisuus- ja kehittämiskeskus GLP inspections by national authorities GLP test facilities and sites are regularly inspected by national GLP authorities Each GLP facility is inspected before entering the national GLP programme During routine inspections the laboratories, storages and archives are visited, personnel training and qualification data, SOPs, QA system and master schedule of studies as well as some selected studies are reviewed At the final meeting of the inspection the possible findings are reported to the test facility representatives A written inspection report is prepared Test facility has to correct possible deviations Receiving authority may ask a study audit of some specific GLP study Other OECD GLP WG member countries are informed about non- compliances in GLP studies 28.6.2013Pirkko Puranen TAIEX 1

12. Lääkealan turvallisuus- ja kehittämiskeskus OECD GLP Working group Annual meeting once in a year Harmonisation of intepretations of GLP Principles Training courses for inspectors Public information provided on a web page and meetings with industry On-site-visit programme: - GLP programme from each member country is evaluated about every 10 th year by two other member countries - GLP programme of a new member country is evaluated before joining Informal cowork between member countries, mutually agreed joint inspections 28.6.2013Pirkko Puranen TAIEX 1

13. Lääkealan turvallisuus- ja kehittämiskeskus Terminology of a GLP organisation and test facility Test facility Test site Multi-site study Sponsor Study director (SD) Principal investigator (PI) Quality assurance (QA) Standard operating procedures (SOPs) Master schedule of studies 28.6.2013Pirkko Puranen TAIEX 1

14. Lääkealan turvallisuus- ja kehittämiskeskus Test facility and organisation Test facility management - responsibility of the overall test facility and resource management Study director - overall responsibility of a individual study Principal investigator - responsibility of delegated study phase Other study personnel - responsibility of their duties All personnel involved in the studys should have adequate training and qualifications 28.6.2013Pirkko Puranen TAIEX 1

15. Lääkealan turvallisuus- ja kehittämiskeskus Quality assurance programme Designated QA personnel QA-inspections: study-based (critical phases), facility-based and process-based Inspection of the final reports QA maintains copies of all approved study plans and SOPs QA verifies the study plans 28.6.2013Pirkko Puranen TAIEX 1

16. Lääkealan turvallisuus- ja kehittämiskeskus GLP study Study plan - signed by SD - study plan amendments - study plan deviations Conduct of the study - according to the plan - SOPs followed - raw data: all original records and documentation, immediately recorded Study report - signed and dated by SD, extent of GLP indicated - QA statement and list of inspections - results Archiving - final report, raw data, study plan and test and reference items and specimens have to be archived 28.6.2013Pirkko Puranen TAIEX 1

17. Lääkealan turvallisuus- ja kehittämiskeskus How to recognise a GLP study Structure of the report, statements of SD and QA Copy of a GLP certificate (not granted by all countries) In problem cases national authorities will provide help (access to OECD database, data request to other OECD GLP WG member country) 28.6.2013Pirkko Puranen TAIEX 1

18. Lääkealan turvallisuus- ja kehittämiskeskus Thank you! Questions, discussion, comments? 28.6.2013Pirkko Puranen TAIEX 1