GLP

What is GLP?

GLP stands for Good Laboratory Practice, a quality system guideline covering the organizational process and conditions under which non-clinical laboratory studies are planned, performed, monitored, recorded, reported, and archived. GLP ensures the quality and integrity of safety test data submitted to the government for the issuance of research permits.

Do You Need to Comply with GLP?

Below is a table based on FDA guidance to help research laboratories determine if a specific study or activity must comply with Good Laboratory Practice:

GLP Compliance Required GLP Compliance Not Required

  • studies on animal health products: overdosage studies in the target species, animal safety studies in the target species, tissue residue accumulation and depletion studies, and udder irritation studies
  • when safety studies done to determine the potential drug-abuse characteristics of a test article are required to be submitted to the FDA as part of an application for a research or marketing permit
  • chemical procedures used to characterize the test article, to determine the stability of the test article and its mixtures, and to determine the homogeneity and concentration of test article mixtures
  • validation trials conducted to confirm the analytical methods used to determine the concentration of test article in animal tissues and drug dosage forms
  • safety studies on cosmetic products
  • organoleptic evaluation of processed foods
  • work done to develop chemical methods of analysis or to establish the specifications of a test article
  • chemical procedures used to analyze specimens (e.g. clinical chemistry, urinalysis)


GLP is also not required during early development stages such as discovery, screening, basic research, and concept assessment. According to the World Health Organization, GLP compliance is typically limited to Stage 2 of the drug development process.

Image source: WHO TDR GLP

Definition of GLP Terms

Testing facility or test facility – the research laboratory conducting the non-clinical study
Test article or test item – the product being studied or tested; the subject of the study
Test system – these are:

  • any animal, plant, microorganism to which either the test or control article is applied
  • any biological, chemical, or physical system used in the study

Control article or reference item – a product that is:

  • not the test article, feed, or water
  • applied to the test system
  • used to provide a basis for comparison with the test article

Good Laboratory Practice Guidelines

Below are Good Laboratory Practice guidelines for the different elements of a study:

Personnel

Before the study begins, the testing facility manager must appoint a study director who will be responsible for the overall conduct of the study and its GLP compliance. The testing facility must also have a Quality Assurance Unit (QAU) which is separate from or independent of the testing facility organization or management.

Facility & Equipment

The testing facility should provide separation of activities to prevent interference and other disturbances which may compromise the study. There must be separate areas for:

  • the receipt and storage of the test and control articles
  • the mixing of the test and control articles with a carrier
  • the storage of the test and control article mixtures
  • the housing of the test systems

All equipment used in the study should be periodically calibrated and maintained. Records of calibration and maintenance should be kept and made available to operators of equipment

Characterization

Personnel performing the study should know the following about each test and control article:

  • identity, purity, composition, and stability
  • date of receipt, expiry date, and storage instructions
  • quantity received and quantity used

Study Plan or Protocol

The study plan or protocol is the master guidance document for the conduct of the study. It outlines how the study should be performed and contains the general time schedule for the study and its various stages. It also includes the method and materials used in the study.

The protocol must go through approval, review, and discussion before the study begins. This process starts with the study director preparing the protocol and discussing its contents with personnel and other study staff. After discussion, the study director must then approve the protocol by affixing their dated signature.

Once the protocol has been approved by the study director, it must be reviewed by the QAU, who will assess its compliance with Good Laboratory Practice. At this point in the process, personnel should be instructed on the duties assigned to them in the protocol as well as receive their own copies of the protocol.

Standard Operating Procedures

Each of the separate areas in the testing facility should have Standard Operating Procedures (SOPs), especially for routine procedures. SOPs must be approved by the testing facility manager and any deviations from SOPs need to be authorized by the study director.

Final Report

The final report is ultimately the responsibility of the study director, who prepares and approves the report. Key features of the final report are:

  • a complete and accurate account of the conduct of the study
  • any deviation from an intended course of action (such as SOP or protocol)
  • scientific interpretation of results and critical discussion
  • GLP Compliance Statement by the study director

Storage of Records

Throughout the course of the study, the study director will be responsible for ensuring that all data pertaining to the study is captured and included in records that are safely stored. These records and documents such as the protocol, the final report, and standard operating procedures will then be archived at the end of the study.

Only personnel authorized by the testing facility manager can access archived records. Additionally, every instance of records being accessed, removed from, or returned to the archives must be logged. It is also recommended that records in the archives be indexed for organized retrieval.

Retention of Records

The required retention period for archived records varies depending on national GLP regulations. For research laboratories in the US, use the following guide questions based on Subpart J of 21 CFR Part 58 ("Good Laboratory Practice for Nonclinical Laboratory Studies"):

  • Were the results of the study submitted to the FDA?
    • If YES: Is the study supporting an Investigational New Drug (IND) application or an application for Investigational Device Exemption (IDE)?
      • If Yes: Archived records must be retained at least 5 years after the date on which the results of the study were submitted to the FDA.
      • If No: Archived records must be retained at least 2 years after the date on which the application for a research or marketing permit was approved by the FDA.
    • If NO: Archived records must be retained at least 2 years after the date on which the study was completed, terminated, or discontinued.