GLP in the European UnionEcolabel detergents, GLP and accreditation

Maik Schmahl Brussels, 25/03/2010Chemicals Unit

Outline

• What is GLP? How has it developed?

• The role of the Member States, the European Commission and the OECDCommission and the OECD

• Cooperation with European Agencies and regulatory authorities

• GLP and accreditation: differences and similarities

Good Laboratory Practice -Definition:

• Quality system concerned with the organisational process and the conditions under which non -clinical conditions under which non -clinical health and environmental safety studies are planned, performed, monitored, recorded, archived and reported.

GLP – Objectives:

• Promote the quality and validity of datagenerated in the testing of chemicals

• Protect human health and the environment• Protect human health and the environment

• Facilitate data recognition

� Avoidance of duplicative testing� Animal welfare� Time and resource efficiency � Avoidance of non-tariff barriers to trade

GLP – the history

• 1975 FDA inspections were made at a contract research laboratory (Industrial Biotest Corporation), 20.000 studies for hundreds of drugs and pesticides

• Experiments were poorly conceived, carelessly • Experiments were poorly conceived, carelessly executed or inaccurately analyzed or reported

• Data fraud :� Reporting of observations for animals previously designated

as dead or euthanized� Pathology summary altered to present more favorable

findings

• Original records were unavailable for review

GLP – the history

• Incomplete or absent drug administration records

• Questionable experience of personnel involved in the studiesinvolved in the studies

• Original records neither signed or dated• Management did not assure critical

review of data or proper supervision of personnel

GLP - History:• 1976 : GLP regulation of FDA on non-clinical labora tory studies• 1978 : OECD establishes expert group • 1981 : OECD Council Decision on Mutual Acceptance of Data (MAD):

GLP-Principles contained in Annex II• 1983 : Recommendation concerning compliance monitoring• 1987/88 : EU adopts GLP Directives• 1989 : OECD Council Decision-Recommendation on Compliance

• Guides for Compliance Monitoring Procedures for GLP• Guidance for the Conduct of Laboratory Inspections and Study Audits

• 1995 : REVISED GUIDANCE FOR GLP MONITORING AUTHORITIESFOR COMPLIANCE MONITORING PROCEDURES FOR GOOD LABORATORYPRACTICE (GUIDES) + New expert group on GLP - Principles

• 1997 : Adoption of Revised GLP- Principles• 1999 : Amendment of EU GLP Directives following OEC D• 2004: Codification of GLP Directives

GLP in the EC - Legal Framework• Directive 2004/10/EC

• on the harmonisation of laws, regulations and administrative provisions relating to the application of the principles of GLP

• Directive 2004/9/EC• on the inspection and verification of GLP

= Codified versions of Directive 87/18 EEC and Directive 88/320/EEC + amendments.

GLP in the EC - Legal Framework• Internal Market

For Chemicals:REGULATION (EC) No 1272/2008 OF THE EUROPEANPARLIAMENT AND OF THE COUNCIL on classification,labelling and packaging of substances and mixtures(replacing Directive 67/548/EEC (classification, packaging andlabelling and packaging of substances and mixtures(replacing Directive 67/548/EEC (classification, packaging andlabelling of chemical substances) and Directive 88/379/EEC (forpreparations, as replaced by Dir. 1999/45/EC))

� REGULATION (EC) No 1907/2006 OF THEEUROPEAN PARLIAMENT AND OF THE COUNCIL of 18December 2006 concerning the Registration, Evaluation,Authorisation and Restriction of Chemicals (REACH)

GLP in the EC - Legal Framework

• Internal MarketDirectives for special chemicals:

• Medicinal Products (Directive 2001/83/EC amended by 2003/63/EC)

• Veterinary Medicinal Products (Directive 2001/82/EC )• Veterinary Medicinal Products (Directive 2001/82/EC )

• Plant Protection Products (91/414/EEC)

• Biocides (98/8/EC)

• Feed Additives (Regulation 429/2008: detailed rules for 1831/2003)

• Food Additives (89/397/EEC – GLP required in guidance)

• Cosmetics (76/768/EEC, 93/35/EEC as amended)

GLP: Role of the Member StatesArticle 3.1 of Directive 2004/10/EC:

Member States shall adopt the measures necessary for verification of compliance with the principles of good laboratory practice. These measures shall include, practice. These measures shall include, in particular, inspections and study checks in accordance with the recommendations of the OECD in this area.

Some statistics (2006)Laboratories in EU Member State programmes

Austria 16Belgium 16Czech Rep. 15Denmark 27Finland 13France 118Germany 163Greece 6Hungary 39Ireland 5Ireland 5Italy 97 (including 42 efficacy-residue study sites)Netherlands 29Poland 6Portugal 7Romania 6 (no MJV yet !)Slovakia 25Slovenia 2Spain 57Sweden 14United Kingdom 130

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GLP in the EU - Practicalities

Role of the Commission inside the EU:

� ensure uniform application of the GLP principles and compliance monitoring in all principles and compliance monitoring in all Member States

� facilitate acceptance of data among MS

GLP - Role of the Commission inside the EU

What we do to achieve this:

• Regular meetings of Member State experts in the Working Group on Good Laboratory PracticePractice

• Management of lists of inspected laboratories (CIRCA website)

• Build up contacts between receiving authorities and monitoring authorities (e.g. EMEA, ECHA)

• Specific exercises for confidence building: evaluation visits

The GLP web sitehttp://ec.europa.eu/enterprise/sectors/chemicals/do cuments/classification/laboratory-practice/

The password-protected CIRCA web site

GLP in the EU - Foreign Relations

Role of the Commission outside the EU:� supplement and co-ordinate views of MS in

international fora (OECD) � correct application of MAD Decision � correct application of MAD Decision

between EU and other OECD countries� acceptance of data through formal

agreements on Mutual Recognition (MRA)(Japan, Switzerland, Israel)

GLP in the EU - Foreign Relations

OECD:

� The OECD Principles of GLP are an integral part of the 1981 Council Decision on the part of the 1981 Council Decision on the Mutual Acceptance of Data in the Assessment of Chemicals (revised 1997)

� Countries can have confidence in the quality and rigour of safety tests

OECD

• Non member-countries:� South Africa, Slovenia, Israel and

Singapore are full adherents to Council Singapore are full adherents to Council Acts on Mutual Acceptance of Data.

� Non-clinical safety data must be accepted by OECD and adhering countries

OECDMore non-member economies to join :• Period of provisional adherence began in

2007 (India, Argentina and Brazil ) and 2008 (Malaysia )

• Provisional adherents will accept data from • Provisional adherents will accept data from OECD member countries and other adhering economies while they establish GLP compliance monitoring programme

• Next: China?

Relevant agencies

• European Medicines Agency (EMA)http://www.ema.europa.eu

• ECHA (European Chemicals Agency)• ECHA (European Chemicals Agency)http://echa.europa.eu/

• EFSA (European Food Safety Authority) http://www.efsa.europa.eu/

Example: EMEA GLP Inspections for CPMP (Centralised Procedure)

• 1995 - 2003 : 2 GLP Inspection Requests by CPMP • 2004 - 2007: 6 GLP Inspection Requests by CHMP –

study audits• 2008 – 4 GLP Inspection Requests by CHMP – study

auditsaudits• 9 Marketing Authorisation Applications for medicines

for human use� 9 Test facilities, 2 in EU, 4 in Canada, 3 in Non-OECD� 41 studies audited Inspection duration of 3 – 6 days� 29 studies so far found to be GLP compliant� 12 studies found to be not compliant with GLP (in full or

partially)

GLP and the eco-label for detergents

• For example: Commission Decision 2003/31/EC establishing revised ecological criteria for the award of the Community eco-label to detergents for dishwashers

• Annex, Chapter on Assessment and verification • Annex, Chapter on Assessment and verification requirements:

Where possible, the testing should be performed by laboratories that meet the general requirements of EN ISO 17025 or equivalent

GLP vs ISO 17025• Laboratory accreditation addresses and

underwrites the technical competence of a laboratory to carry out specified determinations on a continuing basis to defined standards. defined standards.

• A laboratory accredited according to ISO 17025 can be considered to have satisfied many of the GLP requirements.

• However, certain fundamental requirements of the GLP Principles are not covered by or are less stringent in laboratory accreditation

GLP vs ISO 17025• Not covered:

� use of study plans � Study Director as a concept

• More stringent requirements under GLP:� recording and reporting of data� management of data retained in archives to allow

complete reconstruction of a study� programme of independent quality assurance

including internal audits of every study.

Conclusions• EC has strong interest in effective and correct

implementation of GLP in the Member States and in the world:� Necessity for Internal Market� High level of protection of Health and Environment

• GLP is there for you:• GLP is there for you:Good co-operation with receiving authorities necessary for the effective and correct implementation of GLPUnnecessary to require laboratories already working under GLP to get ISO 17025 accreditation

Any questions ?Any questions ?Disclaimer :This presentation does not constitute any formal commitment on behalf of the European Commission and represents the views and opinions of its author only.