GCLP - The Regulatory Revolution

“As Good Clinical Laboratory Practice (GCLP) is based on GCP and Good Laboratory Practice (GLP), a brief history of both is important.
Up and until the early 1970s, many private and public laboratories applied GLP-type principles in one form or another. There were no national/industry regulations.
In 1972, New Zealand formally introduced GLP as a Testing Laboratory Registration Act, covering staff records, procedures, equipment, and facilities. In the same year, Denmark introduced a law to promote GLP.
In August 1976, FDA released a draft GLP document and published GLP regulations in the Federal Register. This resulted from violations noted by the FDA in an investigation of a pharmaceutical company. GLP violations included poor record keeping, data storage, inadequate personnel training, poor test facility management and fraud.
In December 1978, FDA published final GLP regulations and made compliance with them the law in the United States in June 1979. These regulations were collected in Title 21: "Food and Drugs" of the Code of Federal Regulations (CFR) as Part 58: "Good Laboratory Practice for Nonclinical Laboratory Studies. Subsequently, FDA's Office of Regulatory Affairs (ORA) released two Guidance for Industry documents to ensure the proper and consistent interpretation of the directives by industry and by FDA's field investigators. In September 1987, the FDA published its "Final Rule" - Compliance Program Bioresearch Monitoring: Good Laboratory Practices.
The Organization for Economic Co-operation and Development (OECD) Principles of GLP cover organizational process and conditions under which non-clinical health and environmental safety studies are planned, performed, monitored, recorded, archived and reported. A 1989 OECD Council Decision-Recommendation [C(89)87(Final)] established that OECD Member countries, in which testing of chemicals for purposes of assessment related to the protection of human health and the environment being conducted pursuant to the principles of GLP, shall establish procedures for monitoring compliance with GLP based upon facility inspections and study audits. In this regard, the Standards Council of Canada (SCC) established a GLP Compliance Monitoring Authority (GLP MA) recognized by the OECD. It functions in accordance with the OECD document Revised Guides for Compliance Monitoring Procedures for GLP (1995). Data generated in an OECD Member country in accordance with the OECD Principles of GLP is accepted in Member countries for purposes of assessment and other uses relating to protection of human health and the environment; that is, the Mutual Acceptance of Data (MAD).

On the other arm Good Clinical Research Practices developed from past incidents and historical events, the Nazi War Crimes (1939 - 1945) - Led to the Nuremberg Code (1946 &1947). This was the beginning of Human Participant Protections Regulations. After the Nuremberg Code, UN adopted the Universal Declaration of Human Rights of 1948; the Declaration of Helsinki (developed by the World Medical Association (WMA)) – followed in 1964, 5th revision in 2000. In the 6th revision of 2008, it is noted that, in these days of samples often ending up being used for studies far removed from the original reason for collection, the text in paragraph 25 notes that “For medical research using identifiable human material or data, physicians must normally seek consent for the collection, analysis, storage and/or reuse”; the Tuskegee Syphilis Study (1932-1972) – led to the Belmont Report of 1979, and the initial publication of 45 CFR 46 (1974); the 1937 incident when elixir sulphanilamide containing diethylene glycol killed 100 people in 2 months; the drug thalidomide sold from 1957-1961 in about 50 countries under approximately 40 different names, leading to roughly 10,000 children born with severe malformations.

It goes without saying that, while responsibility of GCP rests in the investigator, the laboratory scientist, if different from the investigator, is compelled by GCP to walk the GCLP line. It will not be long before humanity/regulatory authorities hold the laboratory specialist, if different from the investigator, joint and severally liable for GCLP non-compliance and/or misconducts.

Guidelines, codes & regulations have been created in recent decades, and continue to evolve, to guide conduct of research involving human participants.

In an effort to harmonize and gain consensus on international clinical laboratory operations, Good Clinical Laboratory Practice (GCLP) guidelines were originated by a hybrid of GLP and ICH-GCP principles, and were first published and copyrighted by the British Association of Research Quality Assurance (BARQA) (BARQAGCLP).

Subsequently, the Division of AIDS (DAIDS), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health expanded the existing knowledge on GCLP standards by publishing guidelines on GCLP (NIAID-GCLP), with increased implementation guidance based on applicable portions of GLP, Clinical Laboratory Improvement Amendments (CLIA), the College of American Pathologists, and the International Organization for Standardization (ISO 15189).

Both of these GCLP approaches were created to ensure that clinical laboratory results are reliable, repeatable, auditable, and comparable between multiple clinical laboratories. Nevertheless, there are differences in the implementation of GCLP by clinical laboratories causing critical inconsistencies for routine management of operations in support of clinical trials and have caused an urgent need for harmonization of the differences in four central GCLP elements — training, auditing, assay validation, and proficiency testing.

The World Health Organization, on behalf of the Special Programme for Research and Training in Tropical Diseases, published a GCLP guidance which identifies systems required and procedures to be followed within an organization conducting analysis of samples from clinical trials in compliance with the requirements of Good Clinical Practice (GCP).
There is another set of regulations very similar to GLP utilized by clinical laboratories. These are found in 42 CFR Part 493, also known as Clinical Laboratory Improvement Amendments (CLIA) of 1988

Various sponsors have resorted to establishing their own GCLP guidelines.”

From the compilation I made with a passion (not the rigid kind) my take is:

1. There is great need for a GCLP module that regulatory authorities can enforce in clinical trial labs;
2. The GCLP module will replace GLP in clinical trial labs or part thereof;
3. The GCLP module will replace ISO15189 and ISO17025 in clinical trial labs or part thereof;
4. In these requirements, the Laboratory Director/Specialist, if different from the investigator, must be liable for any misconduct related to the lab specimen processing, results reporting, transportation, archiving and retrieval. Where I agree with need to revamp the old aged GCP is where the investigator is always responsible even in areas she/he has no expertise, this must change;
5. GCLP synthesis will involve lab experts, including those who have been implementing GLP, regulatory authorities, etc;
6. Where do we come in – gather this all encompassing GCLP document, identify key participants, lobby, pressure, debate involving these key participants –lab experts, regulatory authorities, industry representatives etc and effect the change we need!!