Good lab practices (GLP)
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The document discusses Good Laboratory Practices (GLP). It provides definitions and history of GLP. GLP refers to a quality management system for laboratories conducting non-clinical safety studies. It aims to ensure reliability and integrity of test data. Key aspects of GLP include organization, SOPs, facilities, equipment, test systems, study planning and reporting, archiving. Non-compliance can result in disqualification and rejection of study data by regulatory agencies.
![HISTORY
• In 1981 an organization named OECD (Organization for
Economic Co-operation and Development) produced GLP
principles that are international standard.
• OECD has since helped promulgate GLP to many countries.
• Following Decision C(97),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/CHEM(98)17 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.[5]](https://image.slidesharecdn.com/goodlabpracticesglp-181210114607/85/Good-lab-practices-GLP-5-320.jpg)
Good lab practices (GLP)
- 1. Good Laboratory Practices (GLP) Dr Ravi Kant Agrawal, MVSc, PhD Senior Scientist (Veterinary Microbiology) Food Microbiology Laboratory Division of Livestock Products Technology ICAR-Indian Veterinary Research Institute Izatnagar 243122 (UP) India
- 2. GLP: GOOD LABORATORY PRACTICE • The phrase Good Laboratory Practice or GLP specifically refers to a quality system of management controls for research laboratories and organizations to ensure the uniformity, consistency, reliability, reproducibility, quality, and integrity of chemical (including pharmaceuticals) non-clinical safety tests; from physio- chemical properties through acute to chronic toxicity tests. • Medicines and Healthcare products Regulatory Agency- UK which defines GLP as: “Good Laboratory Practice (GLP) embodies a set of principles that provides a framework within which laboratory studies are planned, performed, monitored, recorded, reported and archived”. • GOOD LABORATORY PRACTICE applies to non-clinical studies conducted for the assessment of the safety or efficacy of chemicals (including pharmaceuticals). • GLP, a data quality system, should not be confused with standards for laboratory safety – appropriate gloves, glasses & clothing to handle lab materials safely.
- 3. GLP • An internationally recognized definition of GLP: “Good Laboratory Practice (GLP) embodies a set of principles that provides a framework within which laboratory studies are planned, performed, monitored, recorded, reported and archived”. These studies are undertaken to generate data by which the hazards and risks to users, consumers and third parties, including the environment, can be assessed for pharmaceuticals (only preclinical studies), agrochemicals, cosmetics, food additives, feed additives and contaminants, novel foods, biocides, detergents etc. GLP helps assure regulatory authorities that the data submitted are a true reflection of the results obtained during the study and can therefore be relied upon when making risk/safety assessments. GLP is an FDA regulation.
- 4. HISTORY • The term GLP was first used in New Zealand in 1972. • 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. • GLP is a formal regulation that was created by the US FDA (United states food and drug administration) in 1978. • GLP was instituted in US following cases of fraud generated by toxicology labs in data submitted to the FDA by pharmaceutical companies. As a result of these findings, FDA promulgated the Good Laboratory Practice (GLP) Regulations, 21 CFR part 58, on December 22, 1978 (43 FR 59986). The regulations became effective June 1979. • Assure the quality and integrity of safety Nonclinical laboratory studies • Although GLP originated in the United States, it had a world wide impact. • Non-US companies that wanted to do business with the United states or register their pharmacies in the United States had to comply with the United States GLP regulations. • They eventually started making GLP regulations in their home countries. • CFR: Code of Federal regulations
- 5. HISTORY • In 1981 an organization named OECD (Organization for Economic Co-operation and Development) produced GLP principles that are international standard. • OECD has since helped promulgate GLP to many countries. • Following Decision C(97),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/CHEM(98)17 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.[5]
- 6. WHY WAS GLP CREATED? • In the early 70’s FDA became aware of cases of poor laboratory practice all over the United States. • FDA decided to do an in-depth investigation on 40 toxicology labs. • They discovered a lot fraudulent activities and a lot of poor lab practices. • Examples of some of these poor lab practices found were 1. Equipment not been calibrated to standard form, therefore giving wrong measurements. 2. Incorrect/inaccurate accounts of the actual lab study. 3. Inadequate test systems.
- 7. FAMOUS EXAMPLE • One of the labs that went under such an investigation made headline news. • The name of the Lab was Industrial Bio Test. This was a big lab that ran tests for big companies such as Procter and Gamble. • It was discovered that mice that they had used to test cosmetics such as lotion and deodorants had developed cancer and died. • Industrial Bio Test lab threw the dead mice and covered results deeming the products good for human consumption. • Those involved in production, distribution and sales for the lab eventually served jail time.
- 8. OBJECTIVES OF GLP • GLP makes sure that the data submitted are a true reflection of the results that are obtained during the study. • GLP also makes sure that data is traceable. • Promotes international acceptance of tests.
- 9. GLP Principles 1. Organization and Personnel Management-Responsibilities Sponsor-Responsibilities Study Director-Responsibilities Principal Investigator-Responsibilities Study Personnel-Responsibilities 2. Quality assurance program Quality Assurance Personnel 3. Facilities Test System Facilities Facilities for Test and Reference Items 4. Equipment, reagents and Materials 5. Test systems Physical/Chemical Biological 6. Test & Reference items 7. Standard operating procedures 8. Performance of Study Study Plan Conduct of Study 9. Reporting of results 10. Archival - Storage of Records and Reports
- 10. Basic elements in GLP • Personnel Sponsor Management Study director Quality Assurance • Facility Laboratory Operation Animal care Equipment Reagents Storage 10 • Documents Standard Operating Protocols Reports Archiving • Test and Control Articles Characterization Handling Storage
- 11. Personnel • Qualification of personnel: The assumptions is that in order to conduct GLP studies with right quality a couple of things are important; 1)There should be sufficient number. 2)The personnel should be qualified. • Sponsor: Sponsor: person who initiates and supports non-clinical laboratory study, a person who submits non-clinical study to FDA or testing facility that initiates and conducts the study. • Facility management: Responsibilities of facility management is well defined. They designate a study director, as well as assure quality assurance unit is available, test and control articles are characterized. 12/10/18 11
- 12. • Study director: He has overall responsibilities for technical conduct safety studies, as well as interpretation, analysis, documentation and reporting of results. • Quality Assurance unit: The quality assurance unit (QAU) serves an internal control function. It is responsible for monitoring each study to assure management that facilities, equipment, personnel, methods, practices, records, controls, SOPs, final reports (for data integrity), and archives are in conformance with the GLP/GALP 12/10/18 12
- 13. Instrumentation Validation • This is a process necessary for any analytical laboratory. • Data produced by “faulty” instruments may give the appearance of valid data. • Equipment shall be adequately inspected, cleaned & maintained • Equipment used for assessment of data shall be tested, calibrated and/or standardized • Scales & balances should be calibrated at regular intervals (usually ranging from 1-12 months) • The frequency for calibration, re-validation and testing depends on the instrument and extent of its use in the laboratory. • Whenever an instrument’s performance is outside the “control limits” reports must be discontinued. • Equipment records should include: Name of the equipment and manufacturer Model or type for identification Serial number Date equipment was received in the laboratory Copy of manufacturers operating instruction (s)
- 14. Important questions to be answered for any analytical instrument • What is the equipment being used for? • Is the instrument within specification and is the documentation to prove this available? • If the instrument is not within specifications, how much does it deviate by? • If the instrument is not within specifications what action has been taken to overcome the defect? • Can the standards used to test and calibrate the instrument be traced back to national standards?
- 15. Reagent/ Materials Certification This policy is to assure that reagents used are specified in the standard operating procedure. Purchasing and testing should be handled by a quality assurance program. Requirements: Reagents and solutions shall be labeled Deteriorated or outdated reagents and solutions shall not be used Include Date opened Stored under ambient temperature Expiration date 12/10/18 15
- 16. Documents: Standard Operating Procedures (SOP) Written procedures for a laboratories program. They define how to carry out protocol-specified activities. Most often written in a chronological listing of action steps. They are written to explain how the procedures are suppose to work Routine inspection, cleaning, maintenance, testing and calibration. Actions to be taken in response to equipment failure. Analytical methods Definition of raw data Keeping records, reporting, storage, mixing, and retrieval of data 12/10/18 16
- 17. Statistical Procedures for Data Evaluation Statistical procedures are not simply chosen from a text book Practitioners in a particular field may adopt certain standards which are deemed acceptable within that field. Regulatory agencies often describe acceptable statistical procedures. 12/10/18 17
- 18. Test and control articles • Control articles or reference substances as they re- called in the OECD principles are of utmost importance as they are commonly used to calibrate the instrument. • Main requirements for control articles are: the identity, strength, purity, composition and other characteristics should be determined for each batch and documented. • The stability of each test and articles should also be determined. • Certified reference standards can be purchased from appropriate suppliers. If standards are not available , the recommendation is to take a lot of your own material and analyze, certify and use it as the standard. 12/10/18 18
- 19. Analyst Certification Some acceptable proof of satisfactory training and/or competence with specific laboratory procedures must be established for each analyst. Qualification can come from education, experience or additional trainings, but it should be documented Sufficient people Requirements of certification vary 12/10/18 19
- 20. Laboratory Certification Normally done by an external agency Evaluation is concerned with issues such as Adequate space Ventilation Storage Hygiene 12/10/18 20
- 21. Documentation and Maintenance of Records Maintenance of all records provide documentation which may be required in the event of legal challenges due to repercussions of decisions based on the original analytical results. General guidelines followed in regulated laboratories is to maintain records for at least five years Length of time over which laboratory records should be maintained will vary with the situation 12/10/18 21
- 22. Specimen/Sample Tracking • Vary among laboratories • Must maintain the un-mistakable connection between a set of analytical data and the specimen and/or samples from which they were obtained. • Original source of specimen/sample(s) must be recorded and unmistakably connected with the set of analytical data.
- 23. What happens if a workplace does not comply with federal/National Good Laboratory Practice standards? National Accreditation Board for Testing and Calibration Laboratories (NABL)
- 24. Disqualification of a Facility • Before a workplace can experience the consequences of non-compliance, an explanation of disqualification is needed • The FDA states the purpose of disqualification as the exclusion of a testing facility from completing laboratory studies or starting any new studies due to not following the standards of compliance set by the Good Laboratory Practice manual.
- 25. Possible Violations • Falsifying information for permit, registration or any required records. • Falsifying information related to testing ~ protocols, ingredients, observations, data equipment etc. • Failure to prepare, retain, or submit written records required by law.
- 26. Grounds for Disqualification • The testing facility failed to comply with one or more regulations implemented by the GLP manual. • The failure to comply led to adverse outcomes in the data; in other words, it affected the validity of the study. • Warnings or rejection of previous studies have not been adequate to improve the facility’s compliance.
- 27. Consequences of Noncompliance • The FDA states the following consequences of noncompliance: – The commissioner will send a written proposal of disqualification to the testing facility – A regulatory hearing on the disqualification will be scheduled – If the commissioner finds that after the hearing, the facility has complied, then a written statement with an explanation of termination of disqualification will be sent to the facility – Thus, if it can be shown that such disqualifications did not affect the integrity and outcome of the study itself, or did not occur at all, then the study may be reinstated at the will of the commissioner
- 28. Upon Disqualification… • If the commissioner finds that the facility was non- compliant on any of the grounds after the hearing, then a final order of non-compliance will be sent to the facility with explanations • If a testing facility has been disqualified, any studies done before of after the disqualification will need to be determined as essential to a decision (acceptable or not) • If the study is determined unacceptable, then the facility itself may need to show that the study was not affected by the non-compliance that led to the disqualification • Once finally disqualified, the facility may not receive or be considered for a research or marketing permit and the study is rejected.
- 29. Upon Disqualification… • The commissioner may notify the public and all interested persons, including other federal agencies the facility may have contacted • The FDA may ask the other agencies to consider whether to support the facility or not under the disqualification • Civil or criminal proceedings may occur at the discretion of the commissioner – Fines of up to $50,000 if one knowingly commits crime and/or 1 year imprisonment~ for registration applicants and producers – Fines up to $5,000 all others~ civil penalty after failing to improve after a minor violation warning was issued~ only those involved in testing will be given civil penalties – Those involved in the distribution or sales will be assessed more heavy penalties, such as criminal penalties • The FDA may turn it over to the federal, state or local law enforcement • The facility’s sponsor may terminate or suspend the facility from doing any non- clinical study for a permit • The sponsor is required to notify the FDA in writing within 15 working days that the facility is to be suspended or terminated and why
- 30. Reinstatement of a Disqualified Facility • The testing facility may be reinstated as acceptable non-clinical study to be turned into the FDA if the commissioner can be certain that future studies will be conducted in compliance with the Good Laboratory Practice standards and that any current studies integrity have not been severely harmed by the disqualification • The disqualified facility will be required to put in writing to the commissioner reasons why it should be reinstated and any actions the facility will take or have taken to assure any disqualification problems will not happen again. • The commissioner will inspect the facility and determine if it shall be reinstated • If it is reinstated, the commissioner is required to notify all persons that were notified of the disqualification including the facility itself
- 31. References http://www.sjsu.edu/faculty/chem55/55glpout.htm http://www.labcompliance.com/tutorial/glp/default.aspx? sm=d_a UGA Office of the Vice President for Research Wikipedia
- 32. Thanks Acknowledgement: All the material/presentations available online on the subject are duly acknowledged. Disclaimer: The author bear no responsibility with regard to the source and authenticity of the content. Questions???