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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) non-clinical safety tests; from physio-chemical properties through acute to chronic toxicity tests.
Contents
- History
- The OECD
- OECD Guidelines for the Testing of Chemicals
- The US FDA
- European Union
- Non OECD member countries
- Klimisch score
- Automated systems
- References
GLP was first introduced in New Zealand and Denmark in 1972, and later in the US in 1978 in response to the Industrial BioTest Labs scandal. It was followed a few years later by the Organization for Economic Co-operation and Development (OECD) Principles of GLP in 1992; the OECD has since helped promulgate GLP to many countries.
GLP applies to non-clinical studies conducted for the assessment of the safety or efficacy of chemicals (including pharmaceuticals) to man, animals and the environment.
GLP, a data quality system, should not be confused with standards for laboratory safety - appropriate gloves, glasses & clothing to handle lab materials safely.
History
GLP was first introduced in New Zealand and Denmark in 1972. GLP was instituted in US following cases of fraud generated by toxicology labs in data submitted to the FDA by pharmaceutical companies. 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.
These issues were made public in the hearings at the US Congress, which led to the FDA’s publication of Proposed Regulations on GLP in 1976, with establishment of the Final Rule in June 1979 (21 CFR 58). The Environmental Protection Agency (EPA) had also encountered similar problems in data submitted to it, and issued its own draft GLP regulations in 1979 and 1980, publishing the Final Rules in two separate parts (40 CFR 160 and 40 CFR 792) in 1983.
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: ENV/MC/CHEM(98)17 part two
GLP is a quality system concerned with the organizational process and conditions under which non-clinical health and environmental safety studies are planned, performed, monitored, recorded, archived and reported.
GLP principles include
- Organization and Personnel
- Management-Responsibilities
- Sponsor-Responsibilities
- Study Director-Responsibilities
- Principal Investigator-Responsibilities
- Study Personnel-Responsibilities
- Quality assurance program
- Quality Assurance Personnel
- Facilities
- Test System Facilities
- Facilities for Test and Reference Items
- Equipment, reagents and Materials
- Test systems
- Physical/Chemical
- Biological
- Test & Reference items
- Standard operating procedures
- Performance of Study
- Study Plan
- Conduct of Study
- Reporting of results
- Archival - 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. They are widely required by agencies doing risk assessments of chemicals.
The US FDA
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.
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.
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).
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.
There are also 'Product Oriented Directives' referring to GLP obligations:
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.
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.
Klimisch score
The Klimisch score system tries to rank the reliability of toxicity studies for use by risk assessors (regulatory agencies). It was published in 1997, by BASF (a chemical company) authors. Studies performed according to GLP are assigned the top rank of 1 (reliable without restriction) and are preferred by agencies. When no GLP study is available for a particular endpoint, a study with a rank of 2 is usually accepted by an agency. Lower ranks typically require a new study to be performed. Klimisch scoring is very widely used in chemical risk assessments. Critics say it is a self-interested bias on objectivity, that a quality system from the regulated party gives their own GLP-complying studies the top rank.
Automated systems
In many instances, the optimal recommended 'no-argument' means of implementing GLP is to develop an automated approach to both Sample Preparation and Sample Measurement. If this can include an overarching 'chain of custody' sample history and data flow, combined with adequate SOP's for calibration & linearization of measuring tools, GLP compliance is virtually assured.
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.