Background of GLP

In 1969, the Office of New Drugs and the Office of Marketed Drugs developed a plan to inspect laboratories that conducted animal research. The program was expanded, with the help of the Office of Compliance, to include directed inspections of facilities whose submitted studies had raised questions regarding their validity, or in cases where a tip regarding scientific misconduct had been received. The result of these initial investigations was the discovery of quality control problems, the lack of industry standards in animal toxicological testing, and the related recording and reporting of data. It was also noted that important findings were not reported promptly and, in some cases, even withheld from the FDA.Two companies were investigated under what is now known as the Kennedy Commission. For the purpose of this training, we'll refer to them as Company A and Company B:

Company B

Company A

Origins of GLP

Issues identified during FDA investigation

Animal Housing

Training

Item on Test

Control

Mice in rat cages

Drowning Deaths

Badly trained staff

Poor Practices

Inadequately formulated

Stability Info not known

No point of control

No plan for testing

Origins of GLP

Origins of GLP

The data was so bad that it was difficult to determine whether it was:

Fraud

Incompetence

Missing records

Data

Reports

Following these study issues, the reports that were issued were incomplete, so they didn't contain the full circumstances of the study – they were misleading. However, the information was protected and presented in a way that would put the product in the best possible light.

For example, they stated there were no tumours discovered in the animals by the end of the study but they didn't mention this was because they had removed them before the end of the study.

1979

1981

Now

FDA GLP regulations

OECD GLP Principles(revised 1989/1997)

OECD Consensus and advisory documents

Questions were asked as to whether the practices seen at Company A and Company B were isolated cases that existed only at the laboratories inspected, or if they were systemic problems that existed nationwide. It was decided that proof of an industry-wide trend was not necessary, rather a corrective program of inspection of laboratories and manufacturers, the promulgation of standards for good laboratory practices and a system for quality assurance would be developed without delay.

Origins of GLP

Europe followed the OECD GLP principles, which have been revised several times.

Currently, the OECD has issued some more recent documents, so the most recent one that was issued was Document 24.

Origins of GLP: Question One

Origins of GLP: Question Two

Definition and scope of GLP

GLP triangle

Origins of GLP

Key historical investigations

Global adoption and evolution

Comparison to ISO and other standards

Origins of GLP: Summary

Global adoption and evolution

The US government finalised GLP regulations in 1979 (21 CFR Part 58), and Europe followed with the OECD GLP principles, continually updated to reflect current standards.

Company B producing several major pharmaceutical and food products. Suspicions about data came in 1972 while studies were being performed to gain approval for long-term use of a aspartame.

Company B

A researcher not affiliated with the company submitted an article to the Journal of the National Cancer Institute (NCI), which showed that the above drug caused cancer in his animal study. The submission of long-term toxicology studies on Flagyl was then scrutinised, and it was found that there were discrepancies between individual and summary data.

We'll delve into this futher on the next slide.

Definition and Scope of GLP

Good Laboratory Practice (GLP) is a quality system and management structure ensuring the integrity and quality of non-clinical health and environmental safety studies.

Comparison with ISO and other standards

GLP focuses on non-clinical laboratory practices enforced by government agencies, while ISO covers a broader range of voluntary international standards across various industries. Lowercase "glp" refers to general good practices without formal accreditation or monitoring.

20XX

1979

From this, the proposed GLP regulations based on the Company B document were written and published in the Federal Register on 19 November 1976. These regulations provided a uniformly applicable, process-oriented approach to ensure the quality and integrity of nonclinical laboratory studies. The regulations also established the requirement for a quality assurance unit in testing facilities, which would be responsible for assessing the facility’s compliance with the regulations, SOPs, and assuring that studies were conducted according to the protocol written for each study. The final GLP regulations were published on 22 December 1978 and became law on 20 June 1979.This is 21 CFR Part 58, a part of the Code of Federal Regulations that prescribes good laboratory practices for conducting non-clinical laboratory studies.

Key historical investigations

Investigations at two laboratories revealed significant scientific misconduct, prompting the establishment of GLP regulations to ensure data integrity and quality.

Origins of GLP

GLP regulations were developed in response to scientific misconduct and quality control issues discovered in toxicology studies in the 1970s, leading to federal regulations to standardise non-clinical laboratory practices.

GLP Triangle

GLP studies are conducted to support new product licenses and must meet regulatory authority requirements for compliance.

Data

In the above image, there are some abbreviations of TBD and TDA... these are not the abbreviations you'd think they were.

• TBD is too badly decomposed
• TDA is technician destroyed animal

Company conducting research for the US government, for chemical and pharmaceutical companies, both foreign and domestic.

Company A

Products supported by research included drugs, insecticides, herbicides, food additives, pesticides, cosmetics, and cleaning products.

Based on the deficiencies found in data submitted to the FDA submission, the FDA was prompted to inspect the facility, which lasted from April 1976 until July of that same year.

We'll delve into this further on the next slide.