Good Laboratory Practice (GLP)

GLP: Good Laboratory Practice

• GLP is an FDA regulation that embodies principles providing a framework for laboratory studies.
• This framework ensures studies are planned, performed, monitored, reported, and archived correctly.
• GLP is often mistaken for general laboratory safety standards like wearing safety goggles.

History of GLP

• The FDA created GLP as a formal regulation in 1978.
• GLP originated in the US but had a global impact.
• Non-US companies wanting to do business or register pharmacies in the US had to comply with US GLP regulations.
• These companies then started creating GLP regulations in their own countries.
• In 1981, The Organisation for Economic Co-operation and Development (OECD) produced GLP principles that have become international standard.

Reasons for GLP creation

• In the early 1970s, the FDA became aware of many cases of poor laboratory practices across the US.
• The FDA decided to investigate 40 toxicology labs in depth.
• These investigations uncovered fraudulent activities and poor laboratory practices.
• Poor practices included:
  • Equipment not calibrated to standard measures, giving incorrect data.
  • Incorrect or inaccurate study accounts.
  • Inadequate test systems.

Famous Example of lack of GLP

• Industrial Bio Test, a major lab conducting tests for large companies like Procter and Gamble, was subject to an investigation.
• This investigation made headline news
• Mice used to test cosmetics developed cancer and died.
• The lab threw out the dead mice and covered up the data, falsely deeming the products safe for human use.
• Those involved in production, distribution, and sales for the lab eventually faced jail time.

Objectives of GLP

• Ensure the data submitted accurately reflects the results obtained during the study.
• Ensure data is traceable.
• Promote international acceptance of tests.

Mission of GLP

• Properly perform tests.
• Archive records and materials.
• Maintain apparatus, material, and reagent facilities.
• Have quality assurance programs.
• Outline performance for the study.
• Report study results.
• Have standard operating procedures (SOP).
• Ensure personnel and test facility organization.

Standard Operating Procedures (SOP)

• SOPs are written procedures for a laboratory program.
• They define how to conduct protocol-specified activities.
• SOPs are often written as a chronological list of steps.
• SOPs explain how procedures should work.

SOP Information

• Routine inspection, cleaning, maintenance, testing, and calibration should be defined.
• Required actions to respond to equipment failure should be defined.
• Analytical methods should be defined.
• Raw data must be defined.
• Procedures for keeping records, reporting, storage, mixing, and retrieval of data should be kept.

Statistical Procedures for Data Evaluation

• Statistical procedures should not be chosen from a textbook alone.
• Practitioners in a specific field may adopt standards deemed acceptable in that field.
• Regulatory agencies often describe acceptable statistical procedures.

Instrumentation Validation

• This process is necessary for all analytical laboratories.
• Data from faulty instruments can appear valid.
• Calibration and re-validation frequency depends on the instrument and its use in the lab.
• Reports must be discontinued whenever an instrument's performance exceeds control limits.

Instrument Validation Records

Equipment records should contain:

• Name of the equipment.
• Manufacturer.
• Model/type for identification.
• Serial number.
• Date received.
• A copy of operating instructions.

Reagent/Materials Certification

• Policies should ensure reagents are specified in the standard operating procedure.
• Purchasing and testing should be quality assured.

Reagents and Solutions Requirements

• Reagents and solutions must be labeled.
• Deteriorated or outdated reagents and solutions should not be used.
• The date opened must be included.
• Storage should be under ambient temperature.
• The expiration date must be included.

Analyst Certification

• Acceptable proof of satisfactory training or competence in specific laboratory procedures must be established for each analyst.
• Qualification can come from education, experience, or additional training but should be documented.
• There should be sufficient people
• Certification requirements vary.

Laboratory Certification

• Laboratory certification is normally done by an external agency.
• Evaluation focuses on:
  • Adequate space.
  • Ventilation.
  • Storage.
  • Hygiene.

Specimen/Sample Tracking

• Tracking varies among laboratories.
• You must maintain the irrefutable connection between analytical data and the specimen or samples obtained.
• The original sample source must be recorded and unmistakably linked to the analytical data.

Documentation and Maintenance of Records

• Record maintenance provides documentation for potential legal challenges due to decisions based on analytical results.
• A general guideline for regulated laboratories involves maintaining records for at least five years.
• The required duration for record maintenance varies by situation.

Important Questions for Analytical Instrument Use

• Intended Use: What is the equipment being used for?
• Specification: Is the instrument within specification, and is there documentation to prove it?
• Deviation: If outside specifications, how much does it deviate?
• Correction: If outside specifications, what was done to correct the defect?
• Traceability: Can instrument testing and calibration standards be traced back to national standards?

Disqualification of a Facility

• Disqualification is needed before a workplace experiences noncompliance consequences.
• The FDA defines disqualification as a testing facility's exclusion from completing or starting laboratory studies due to not following Good Laboratory Practice manual compliance standards.

Possible Violations of Compliance

• Falsifying information to get registration permits, and other required records.
• Falsifying information related to testing protocols, ingredients, observations, and data.
• Failure to prepare, retain, or submit written records demanded by law.

Grounds for Disqualification:

• The testing facility did not comply with regulations implemented by the GLP manual.
• Non-compliance led to adverse data outcomes, affecting study validity.
• Previous warnings or rejected tests have not adequately improved facility compliance.

Consequences of Noncompliance

• The FDA will notify the test facility of its consequences of non-compliance.
• The commissioner will send the facility a written disqualification proposal.
• A regulatory disqualification hearing will be scheduled.
• If the commissioner finds the facility is compliant after the hearing, a written statement terminating disqualification will be sent to the facility.
• The study may be reinstated if disqualifications did not affect its integrity and outcome.

Upon Disqualification

• If the commissioner finds the facility noncompliant after the hearing, a final noncompliance order will be sent.
• Studies done before or after the disqualification need to be determined as acceptable.
• If the study is determined unacceptable, then the facility must prove that the study was not affected by the noncompliance that led to disqualification.
• The facility may not receive or be considered for research or marketing permits, and the study is rejected once finally disqualified.

More details about Disqualification

• The commissioner may notify the public/interested parties and federal agencies the facility contacted.
• The FDA may ask other agencies whether to support the facility under the disqualification.
• Civil or criminal proceedings may occur at the commissioner's discretion.
  • There are fines of up to $50,000 and/or 1 year imprisonment for knowingly committing crime.
  • Fines of up to $5,000 for all others after failing to improve after being issued a minor violation.
  • Heavier penalties for those involved in distribution or sales.
• The FDA may turn it over to federal, state, or local law enforcement.
• The facility's sponsor may terminate/suspend the facility from conducting non-clinical studies for permit.
• Sponsors must notify the FDA in writing within 15 working days that the facility is suspended or terminated, and explain why.

Reinstatement of a Disqualified Facility

• The testing facility may be reinstated as an acceptable non-clinical study to be given to the FDA, if commissioner is certain that the study meets Good Laboratory Practice standards.
• The facility must write to the commissioner explaining why it should be reinstated and what actions it will take/has taken to prevent future disqualification problems.
• The commissioner will inspect the facility and determine if it shall be reinstated.
• The commissioner required to notify all persons that were notified of the disqualification, including the facility itself, if the facility is reinstated.