GLP in the European Union
Maik Schmahl
Chemicals Unit
Zagreb, 17/12/2010
Outline
• What is GLP? How has it developed?
• GLP and accreditation: differences and
similarities
• The role of the Member States, the European
Commission and the OECD
• Cooperation with European Agencies and
regulatory authorities
Good Laboratory Practice Definition:
• 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 – Objectives:
• Promote the quality and validity of data
generated in the testing of chemicals
• Protect human health and the environment
• Facilitate data recognition
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Avoidance of duplicative testing
Animal welfare
Time and resource efficiency
Avoidance of non-tariff barriers to trade
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.
• 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.
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
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 – FDA Survey
• Incomplete or absent drug
administration records
• Questionable experience of personnel
involved in the studies
• Original records neither signed or dated
• Management did not assure critical
review of data or proper supervision of
personnel
GLP - History:
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1976 : GLP regulation of FDA on non-clinical laboratory 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 AUTHORITIES
FOR COMPLIANCE MONITORING PROCEDURES FOR GOOD LABORATORY
PRACTICE (GUIDES) + New expert group on GLP - Principles
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1997 : Adoption of Revised GLP- Principles
1999 : Amendment of EU GLP Directives following OECD
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 EUROPEAN
PARLIAMENT AND OF THE COUNCIL on classification,
labelling and packaging of substances and mixtures
(replacing Directive 67/548/EEC (classification, packaging and
labelling of chemical substances) and Directive 88/379/EEC (for
preparations, as replaced by Dir. 1999/45/EC))
 REGULATION
(EC)
No
1907/2006
OF THE
EUROPEAN PARLIAMENT AND OF THE COUNCIL of 18
December 2006 concerning the Registration, Evaluation,
Authorisation and Restriction of Chemicals (REACH)
GLP in the EC - Legal Framework
• Internal Market
Directives for special chemicals:
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Medicinal Products (Directive 2001/83/EC amended by 2003/63/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 States
Article 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,
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
Belgium
Czech Rep.
Denmark
Finland
France
Germany
Greece
Hungary
Ireland
Italy
Netherlands
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
16
16
15
27
13
118
163
6
39
5
97
29
6
7
6
25
2
57
14
130
791
(including 42 efficacy-residue study sites)
(no MJV yet !)
GLP in the EU - Practicalities
Role of the Commission inside the EU:
 ensure uniform application of the GLP
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
Practice
• 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 site
http://ec.europa.eu/enterprise/sectors/chemicals/documents/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
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
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
Acts on Mutual Acceptance of Data.
 Non-clinical safety data must be accepted
by OECD and adhering countries
OECD
More 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 OECD
member countries and other adhering economies
while they establish GLP compliance monitoring
programme
• Brasil and India will join MAD in 2011
• Next: China?
Relevant agencies
• European Medicines Agency (EMA)
http://www.ema.europa.eu
• ECHA (European Chemicals Agency)
http://echa.europa.eu/
• EFSA (European Food Safety Authority)
http://www.efsa.europa.eu/
Example: EMA GLP Inspections
• 1995 - 2003 : only 2 GLP Inspection Requests by
CPMP
• 2004 - 2007: 6 GLP Inspection Requests by CHMP –
study audits
• 2008 – 4 GLP Inspection Requests by CHMP – study
audits
• 9 Marketing Authorisation Applications for medicines
for human use
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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)
Co-operation with receiving authorities
• 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.
GLP – Costs and benefits
• True: GLP is more demanding and costly
than ISO 17025
• Has to be seen as part of OECD mutual
aceptance of data system
• OECD estimate: Environment, Health and
Safety Programme safes € 153 mn p.a.
• Source:
Cutting Costs in Chemicals Management - How OECD Helps
Governments and Industry, Paris 2010
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:
Good co-operation with receiving authorities
necessary for the effective and correct
implementation of GLP
Unnecessary to require laboratories already
working under GLP to get ISO 17025
accreditation
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.