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TAIEX Workshop 52344 - on Implementation of REACH and CLP Regulations Problems of mutual acceptance of test data produced in non-MAD country test facilities Guido Jacobs_Belgian-GLP Monitorate Moscow, 28 June 2013 Rue Juliette Wytsmanstraat 14 | 1050 Brussels | Belgie T +32 2 642 5230| email: [email protected] fgov. be | site web: www. glp. be; https: //intranet. iph. fgov. be/
Outline • Mutual Acceptance of Data • European Community_ECHA • Experiences with inspections abroad
What is the OECD Mutual Acceptance of Data (MAD) system? The OECD is a forum for discussion where governments express their points of view, share their experiences and search for common ground. If Member countries consider it appropriate, an accord can be embodied in a formal OECD Council Act, which is agreed at the highest level of OECD, the Council. In the area of chemicals, for example, there is a Council Act relating to the Mutual Acceptance of Data (MAD).
Why a Mutual Acceptance of Data (MAD) system? • The testing of chemicals is labour-intensive and expensive. Often the same chemical is being tested and assessed in several countries. • Because of the need to relieve some of this burden, the OECD Council adopted a Decision in 1981 stating that data generated in a Member country in accordance with OECD Test Guidelines and Principles of Good Laboratory Practice (GLP) shall be accepted in other Member countries for assessment purposes and other uses relating to the protection of human health and the environment.
• European Community • Austria, Belgium, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Luxembourg, The Netherlands, Poland, Slovak Republic, Slovenia, Portugal, Spain, Sweden, United Kingdom • Iceland, Norway, Switzerland, Turkey, Israel Canada, Mexico, United States, Chile Australia, Japan, New Zealand, South Korea • •
Non-OECD countries and MAD • This system also covers non-OECD countries which have requested adherence to the OECD GLP and to join the MAD system. • These non-OECD countries can be divided in two groups: 1) Countries which are full adherents to the OECD MAD system. 2) Countries which are provisional adherents to the OECD MAD system.
Full adherent economies (“associates”) Countries which are full adherents to the OECD MAD system will accept data from OECD member countries and other adhering countries generated under MAD conditions. In addition non-clinical safety data developed in these countries must be accepted by OECD and adhering countries. Full Adherents: • South Africa, Singapore, Malaysia, India Brazil*, Argentina* (*For industrial chemicals, pesticides and biocides only) •
Provisional adherent economies (“participants”) Countries which are provisional adherents to the OECD MAD system need to accept data from OECD member countries and other adhering countries generated under MAD conditions. However, during the period of provisional adherence, GLP monitoring activities conducted by the GLP MA located in the country of the provisional adherence do not have to be accepted by the full members of the OECD MAD Decision. Provisional Adherents: Thailand
Observers/Invitees (not MAD, non OECD) • • • China, Taiwan, Russia • On-going review of Russia as an OECD Accession country • Scope is end of 2015 • But first an “on site evaluation” of russian organisation and training by OECD team is needed (has taken 7 years for India!)
MUTUAL ACCEPTANCE OF DATA IN THE ASSESSMENT OF CHEMICALS: http: //www. oecd. org/env/ehs/mutualacceptanceofdatamad. htm • • avoids duplication of studies saves resources reduces animal testing eliminates non-tariff trade barriers creates a level playing-field reduces time-to-market € 150, 000 in annual savings that accrue to governments and industry from working together, through OECD (*) * Cutting Costs in Chemicals Management - How OECD Helps Governments and Industry, Paris 2010
Implicated authorities • Monitoring authorities • • At the moment about 54 Receiving authorities >100 • For Europe : ECHA, EMA, EFSA
COUNTRY B, C, D, . . COUNTRY A 3 REGULATORY AUTHORITY Submits TEST FACILITY, TEST SITES file 7 Information 4 Requests Information on GLP Compliance Status of the Laboratory or Study Audit 1 OECD Database of GLP compliant Test Facilities 5 Inspection and/or Study Audit 2 Overview Information GLP MONITORING AUTHORITY 6 Requests Information GLP MONITORING AUTHORITIES involved 12
Duty to inform each other • All monitoring authorities in the MAD must send in the beginning of each year a consolidated overview of test facilities inspected to the OECD (and to the European Commission). • The overview contains the whole history of each test facility ever inspected; « period of compliance » , « period of pending » , « in and out of programme » , « different addresses » .
OECD Secretary • The consolidated overviews are stored on a password protected part of the OECD server, where monitoring authorities can consult the information. • Important is that Study director should use the same name and address in their test report as on their certificate. Otherwise the monitoring authority will not find back the test facility. • If a TFM wants to be sure that a test site is GLP certified he should contact the monitoring authority of his country.
What studies does ECHA accept as GLP studies? • In general, ECHA accepts data as GLP data where this data comes • (i) from countries which are OECD member states or full adherents to the OECD Mutual Acceptance of Data (MAD) system • (ii) from countries which are provisional adherents to the OECD MAD system and in which laboratories have been inspected jointly by the GLP Monitoring Authority concerned and by an OECD GLP Monitoring Authority.
ECHA Conditions to accept GLP studies conducted in non MAD countries? Studies that are conducted in a laboratory situated in a country which has not joined the OECD MAD system can be accepted by ECHA as GLP compliant studies under the following conditions: 1) Prior to the performance of the study the GLP compliance of the laboratory has been inspected by: • • an EU GLP Monitoring authority (including Norway through EEA agreement) (or GLP Monitoring Authorities with whom the EU holds Mutual Recognition Agreements or other GLP Monitoring Authorities of OECD member states or full adherents to the OECD Mutual Acceptance of Data (MAD) system on a case-by-case basis) 2) And the laboratory has been found to be operating in compliance with GLP principles.
Statement of GLP compliancy: It is not acceptable that a study director (SD) claims GLP compliancy for a study when his test facility and/or one of his study test sites, is not reported in the OECD database. All “non GLP conform test facilities” (e. g. certificate of compliance) involved should be taken up in the Study Directors’ GLP Compliance statement by making reference to the certificate of a GLP MA or eventually other International accepted as equal Quality Systems followed. Ps. REACH website has not foreseen yet to report this
Foreign facilities on the Belgian programme • Nutrichem (Beijing_P. R. China) - February 2006, May 2008, June 2010 • FMC (Shanghai_P. R. China) - November 2006, November 2008, October 2011, March 2012, May 2013 • Wuxi App Tec (Shanghai_P. R. China) - May 2011 • Laprode (Hanghzou_P. R. China) - October 2011 • Covance (Shanghai_P. R. China) • July 2011 and May 2013 IIT (Pune_India) - June 2009, now in Indian program • CRL (Shanghai_P. R. China) - January 2010 • Wuxi App Tec (Suzhou_P. R. China) - June 2010 - CDSER_SIMM (Shanghai_P. R. China) - March 2012, now in Swedish program - CRL (Canada) - Augustus 2006, April 2009, now in Canadian program - Demeter_Huikwang (Tainan_Taiwan) - May 2013 Pilarquim (Shanghai_P. R. China) • May 2011 and March 2013 • •
Process of an inspection in a Non-MAD country • Request for to be taken up on a GLP programme http: //www. glp. be/documents/Belgian. GLPManual_ed 3(revised 2009 b). pdf • • • At least one sponsor has intention to register for REACH in europe. All SOPs translated in English Per study director involved, one OECD “GLP” study finished Study plan, study report and raw data available in english Costs for inspections paid by test facility
Process of an inspection in a Non-MAD country • Inspection in situ. (2 -5 days); eventually joint inspection with regional authority • 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. • At the final meeting of the inspection the possible findings are reported to the test facility representatives
Process of an inspection in a Non-MAD country • • • A written inspection report is prepared Test facility has to correct possible deviation when test facility is found GLP compliant a “Certificate conform to Directive 2004/9/EC” will be given for a defined period of 18 till 36 months. Certificate can be used for registering at ECHA database. (see: Frequently Asked Questions about REACH, June 2011, Version 4, Published on 23 June 2011) • 21
Process of an inspection in a Non-MAD country • Results are yearly reported to OECD and EC database • Facility is reported on the website www. glp. be • Test facility will be taken-up in a GLP programme • Regular (every 18 -36 months) GLP re-inspections to verify consistency/amelioration
Study audits in non-MAD countries • Each European Monitoring can send auditors for a dedicated study of concern at the request of: • • The European Regulatory Authorities (ECHA, EMA, EFSA) or other receiving Authorities • to verify the accuracy of a compliance statement of a test facility in a non-member country. • (Is already done for requests of EMA and EFSA)
• 24, 675 chemical registration dossiers on 30 November 2010 (first deadline under the REACH regulation). • Automated completeness check for these dossiers • Compliance check will be performed for at least 5% of the submitted dossiers for each tonnage band. • For studies claimed to be done according to GLP, a GLP claim verification procedure has been developed. • Procedure includes checking status of the laboratory, requesting full study report and requesting, if deemed necessary, a study audit from a GLP monitoring authority. However, ECHA does not anticipate a need to initiate study audits frequently.
Possible triggers for audits in the non MAD country No statement signed by the study director that the study was conducted according to the GLP principles against a prior approved study plan or the statementions that part of the study was not done under GLP-circumstances Study director or some subcontracted laboratories involved in the study are located in a non-EU country that is not covered by the OECD Mutual Acceptance of Data Decision
The study report does not include a description, or the description is inadequate, of the methods and materials used, the test system used, the dosage information, transformation, calculations or operations performed on the data/ Characterisation Info about test and reference substances is missing or not correct identified, No reference to stability studies, no info about stability in preparations with specific solvent. Stability and temperature conditions not followed during transport from sponsor to test facility or in test facility
Thanks for your attention, Remarks or questions can be sent to: Guido. [email protected] be Skype: wiv-isp. gjacobs