Good Laboratory Practice

In the experimental (non-clinical) research arena, the phrase good laboratory practice or GLP specifically refers to a quality system of management controls for research laboratories and organizations to try to ensure the uniformity, consistency, reliability, reproducibility, quality, and integrity of chemical (including pharmaceuticals) pre-clinical safety tests.

GLP was instituted following cases of animal test fraud by pharmaceutical and industrial chemical (mainly pesticide) manufacturers. Industrial BioTest Labs (IBT) was the most notable case, where thousands of safety tests for chemical manufacturers were falsely claimed to have been performed or were so poor that police investigators could not piece together what work had been done...even though IBT superficially delivered the test results their contracts with the manufacturers specified.

The original GLP regulatory mandate was promulgated in 1978 by US-FDA (though they may have got it from the New Zealand medicines agency) and published in the Federal Register 43 FR 59985-60020. It was followed a few years later by US-EPA, and (as outlined in the Organisation for Economic Co-operation and Development (OECD) Principles of GLP in 1992) the OECD has since help promulgate it to many countries, helping them place it into their national regulations.

GLP applies to nonclinical studies conducted for the assessment of the safety or efficacy of chemicals (including pharmaceuticals) to man, animals and the environment. An internationally recognized definition of GLP can be found on the website for the Medicines and Healthcare products Regulatory Agency-UK which defines GLP as:

Good Laboratory Practice (GLP) embodies a set of principles that provides a framework within which laboratory studies are planned, performed, monitored, recorded, reported and archived. These studies are undertaken to generate data by which the hazards and risks to users, consumers and third parties, including the environment, can be assessed for pharmaceuticals (only preclinical studies), agrochemicals, cosmetics, food additives, feed additives and contaminants, novel foods, biocides, detergents etc.... GLP helps assure regulatory authorities that the data submitted are a true reflection of the results obtained during the study and can therefore be relied upon when making risk/safety assessments.

GLP, a data quality system, should not be confused with standards for laboratory safety - appropriate gloves, glasses & clothing to handle lab materials safely.

GLP and the OECD

Following Decision C(97),186/Final of the OECD Council, data generated in the testing of chemicals in one OECD Member Country, in accordance with OECD Test Guidelines and the Principles of GLP are accepted in all other OECD Member Countries. OECD: EMV/MC/CHEM(98)17 part two

GLP is a quality system concerned with the organisational processing process and conditions under which non-clinical health and environmental safety studies are planned, performed, monitored, recorded, archived and reported.

GLP principles include

1. Organization and Personnel
   • Management-Responsibilities
   • Sponsor-Responsibilities
   • Study Director-Responsibilities
   • Principal Investigator-Responsibilities
   • Study Personnel-Responsibilities
2. Quality assurance program
   • Quality Assurance Personnel
3. Facilities
   • Test System Facilities
   • Facilities for Test and Reference Items
4. Equipments, reagents and Materials
5. Test systems
   • Physical/Chemical
   • Biological
6. Test & Reference items
7. Standard operating procedures
8. Performance of Study
   • Study Plan
   • Conduct of Study
9. Reporting of results
10. Storage of Records and Reports

OECD Guidelines for the Testing of Chemicals

OECD publishes OECD Guidelines for the Testing of Chemicals, which are guidelines that usually have to be followed for GLP compliance.

GLP and the USFDA

The United States FDA has rules for GLP in 21CFR58. Preclinical trials on animals in the United States of America use these rules prior to clinical research in humans.

Research in the US not conducted under these restrictions or research done outside US not conducted according to the OECD Guidelines (or FDA rules) might be inadmissible in support of a New Drug Application in the US.

GLP and the European Union

Since 1987 the European Council had adopted two basic Directives and a Decision relating to the application of the GLP principles. Directive 2004/10/EC has replaced Directive 87/017/EEC as of 11 March 2004; Directive 2004/9/EC has replaced Directive 88/320/EEC as of 11 March 2004.

• " Directive 2004/10/EC of the European Parliament and of the Council of 11 February 2004 on the harmonisation of laws, regulations and administrative provisions relating to the application of the principles of good laboratory practice and the verification of their applications for tests on chemical substances."

This directive lays down the obligation of the Member States to designate the authorities responsible for GLP inspections in their territory. It also comprises requirements for reporting and for the internal market (i.e., mutual acceptance of data).

• " Directive 2004/9/EC of the European Parliament and of the Council of 11 February 2004 on the inspection and verification of good laboratory practice (GLP)".

The Directive requires that the OECD Revised Guides for Compliance Monitoring Procedures for GLP and the OECD Guidance for the Conduct of Test Facility Inspections and Study Audits must be followed during laboratory inspections and study audits.

• 89/569/EEC Council Decision of 28 July 1989 on the acceptance by the European Economic Community of an OECD decision / recommendation on compliance with principles of good laboratory practice.

There are also 'Product Oriented Directives' referring to GLP obligations:

• REACH Regulation) of 18 December 2006 and Directive 2006/121/EC of 18 December 2006
• Medicinal products; Directive 2001/83/EC on the Community code relating to medicinal products for human use of 6 November 2001 as amended by Commission Directive 2003/63/EC
• Veterinary Medicinal Products; Directive 2001/82/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to veterinary medicinal products
• Cosmetics; Council Directive 93/35/EEC amending for the 6th time directive 76/768/EEC
• Feedingstuffs; Regulation (EC) No 1831/2003 of the European Parliament and of the Council of 22 September 2003 on additives for use in animal nutrition
• Foodstuffs; Directive 89/107/EEC
• Novel Foods and novel food ingredients; Regulation (EC) No 258/97 of the European Parliament and of the Council of 27 January 1997 concerning novel foods and novel food ingredients
• Pesticides; Council Directive 91/414/EEC of 15 July 1991 concerning the placing of plant protection products on the market
• Biocides; Directive 98/8/EC of the European Parliament and of the Council of 16 February 1998 concerning the placing of biocidal products on the market
• Detergents; Directive 98/8/EC Regulation (EC) No 648/2004 of the European Parliament and of the Council of 31 March 2004 on detergents
• EC Ecolabel; Commission Decision 2005/344/EC of 23 March 2005; establishing ecological criteria for the award of the Community eco-label to all-purpose cleaners and cleaners for sanitary facilities

In the meantime the EU has concluded Mutual Acceptance Agreements in the area of GLP with Israel, Japan and Switzerland. By means of the Treaty of the European Economic Area of 13 September 1993, the European Regulations and Directives also apply to Iceland, Liechtenstein and Norway.

GLP and non-OECD member-countries

An inspection in non-member economies by OECD inspectors will not guarantee that data generated in compliance with GLP will be accepted in other member countries than the one to which they are submitting data and which has thus sent inspectors to verify the accuracy of their compliance statement.

Criticism of GLP

GLP studies require adequate and permanent documentation of everything involved in an experimental test: staff qualifications, valid study design, standard operating procedures (SOPs), training, performance, formulation and statistical analyses, and the retention of summary/individual data; so that there can be confidence in the study's design, performance and its results, and anyone (as public agencies have access to the GLP records) can subsequently fully reconstruct the study.

In the contrary academic scientists also perform basic/exploratory experimental research to: identify unknown potential hazards of chemicals, elucidate the mode/mechanism of action for known toxicants, and explore novel toxic endpoints. Accordingly, their experimental methods vary in the delivery route of the test chemical, the number of test animals and the range of doses. Overall, their methods are far more varied than the GLP test protocol is; and (at least before peer review) academics do not like to share their results or methods with other laboratories competing for grant money. These factors make it very hard for regulatory agencies to use the results of academic researchers in chemical risk assessment.

Klimisch score

In the Klimisch score system, studies generally performed to GLP are assigned a score of 1 (reliable without restriction).

GLP and automated systems

Implementing GLP on an automated system, as an intellectual and labour-intensive task, requires a GxP company to make a great amount of effort. To ease the burden of this management, Webster et al. have provided a tutorial for users to quickly embark on and do the job properly.

See also

• GxP
• Good Automated Manufacturing Practice
• Joint Committee for Traceability in Laboratory Medicine
• International Laboratory Accreditation Cooperation
• International Federation of Clinical Chemistry and Laboratory Medicine (IFCC)
• Drug development
• ISO 15189
• Verification and Validation

External links

• Comparison of difference versions of GLP (Comparison OECD, FDA and EPA GLP)
• Medicines and Healthcare products Regulatory Agency-UK (MHRA-UK definition of GLP)
• current Good Analytical Laboratory Practice [cGALP]
• Good Laboratory Practice (Organisation for Economic Co-operation and Development)
• OECD Series on Principles of Good Laboratory Practice and Compliance Monitoring
• Belgian Monitoring Authorithy for GLP