Good laboratory practice


In the experimental research arena, good laboratory practice or GLP is a quality system of management controls for research laboratories and organizations to ensure the uniformity, consistency, reliability, reproducibility, quality, and integrity of products in development for human or animal health through non-clinical safety tests; from physio-chemical properties through acute to chronic toxicity tests.
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 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 products in development for man, animals and the environment. GLP, a data and operational quality system, is not the same as standards for laboratory safety - appropriate gloves, glasses and clothing to handle lab materials safely. The principles of GLP aim to ensure and promote safety, consistency, high quality, and reliability of chemicals in the process of non-clinical and laboratory testing. GLP is not limited to chemicals and also applies to medical devices, food additives, food packaging, colour additives, animal food additives, other non-pharmaceutical products or ingredients, biological products, and electronic products.

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 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. The Environmental Protection Agency 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 in 1983.

The OECD

Following Decision C,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/CHEM17 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
  1. Organization and Personnel
  2. * Management-Responsibilities
  3. * Sponsor-Responsibilities
  4. * Study Director-Responsibilities
  5. * Principal Investigator-Responsibilities
  6. * Study Personnel-Responsibilities
  7. Quality assurance program
  8. * Quality Assurance Personnel
  9. Facilities
  10. * Test System Facilities
  11. * Facilities for Test and Reference Items
  12. Equipment, reagents and materials
  13. Test systems
  14. * Physical/Chemical
  15. * Biological
  16. Test and reference items
  17. Standard operating procedures
  18. Performance of study
  19. * Study Plan
  20. * Conduct of Study
  21. Reporting of results
  22. 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 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.
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. It was published in 1997, by BASF authors. Studies performed according to GLP are assigned the top rank of 1 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.