Good Laboratory Practices Mubashir Maqbool
- 1. GOOD LABORATORY PRACTICE (GLP) PRESENTED TO : DR. RANDHIR SINGH PROF. MMCP, MMDU MULLANA AMBALA PRESENTED BY : MUBASHIR MAQBOOL M.PHARMACY (PHARMACOLOGY)
- 2. GOOD LABORATORY PRACTICE In the experimental (non-clinical) research arena, Good laboratory practice or GLP is a quality system of management controls for research laboratories and organizations to ensure the uniformity, consistency, reliability, reproducibility, quality, and integrity of products in development for human or animal health (including pharmaceuticals) through non-clinical safety tests, from physio-chemical properties through acute to chronic toxicity tests.
- 3. HISTORY In response to malpractice in research and development activities by pharmaceutical companies and contract facilities used by them. The malpractice included cases of fraud, lack of proper management and organization of studies performed to generate data for regulatory dossiers. GLP first came in to enforce in USA due to some fraud data generated by toxicology lab to FDA. Industrial Bio Test Labs (IBT) was the most notable cases, where thousands of safety test for chemical manufactures were falsely claimed to have been performed or were so poor. (Test carried for lotion and deodorant – cancer)
- 4. 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
- 5. 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. To ensure and promote safety, consistency, high quality, and reliability of chemicals in the process of non-clinical and laboratory testing.
- 6. MISSION OF GLP Archiving of records and materials. Apparatus, material and reagent facilities. Quality assurance programs. Performance of the study. Reporting of study results. Standard operating procedures (SOP) Personnel and test facility organization
- 7. GLP MAINLY GIVES STRESS ON FIVE POINTS: Resources: organization, personnel, facilities & equipment. Characterization: Test items and test system. Rules: Study plans(or protocol) and written procedure. Results: Raw data, final report and archives. Quality Assurance.
- 8. PRINCIPLE OF GLP Test Facility Organization and Personnel Quality Assurance of Programme Facilities Apparatus, Material, and Reagents Test Systems Test and Reference Items Performance of the study results Reporting of Study results Storage and Retention of Records and Materials
- 9. TEST FACILITY ORGANIZATION AND PERSONNEL Test Management’s Responsibilities Study Director’s Responsibilities Study Principal Investigator’s Responsibilities Study Personnel’s Responsibilities
- 10. A. TEST MANAGEMENT’S RESPONSIBILITIES Sufficient number of qualified personnel, appropriate facilities, equipment, and materials are available for the timely and proper conduct of the study. Ensure the maintenance of a record of the qualifications, training, experience. Job description for each professional and technical individual. Documented approval of the study plan by the study director.
- 11. B. STUDY DIRECTOR’S RESPONSIBILITIES Approve the study plan. Any amendments to the study plan by dated signature. Availability of SOPS to the personnel. Raw data generated are fully documented and recorded.
- 12. C. PRINCIPAL INVESTIGATOR’S RESPONSIBILITIES The Principal Investigator will ensure that the delegated phases of the study are conducted in accordance with the applicable principles of Good Laboratory Practice. Execute the plan of work as per GLP. Management of Research: Integrity Design Conducting Reporting
- 13. D. STUDY PERSONNEL'S RESPONSIBILITIES Responsibility Knowledge Goal Setting No excuses Self Control Health Precautions
- 14. 2. QUALITY ASSURANCE PROGRAM The purpose of quality assurance program is to assure that all laboratory testing is performed according to the principles of current GLP. This is carried out by the quality assurance department which has authority to authorize all the quality related documentation. The quality assurance department is staffed by individuals who are knowledgeable of, and familiar with the laboratory testing.
- 15. RESPONSIBILITIES OF QUALITY ASSURANCE PERSONNEL Maintain all approved study plan & SOPs have access to up-date copy of Master Schedule. Verify the study plan contains the information require for compliance with principle of GLP(Verification should be documented.) QA personnel must be independent from scientists involved in the operational aspects of the study being performed.
- 16. 3. FACILITIES A. TEST SYSTEM FACILITY: Sufficient number of rooms or areas assure the isolation of test system & the isolation of individual projects involving substance or organisms known to be or suspected of being bio-hazardous. There should be storage rooms or areas as needed for supplies & equipment. Area should be available for the diagnosis, treatment & control of disease, in order to ensure that there is no unacceptable degree of deterioration of test system.
- 17. B. ARCHIVE FACILITY: Archive facilities should be provided for the secure storage & retrieval of study plans raw data, final report, samples of the test items and specimens. Archive design & archive conditions should be protect contents from untimely deterioration. C. WASTE DISPOSAL Handling disposal of wastes should be carried out in such a way as not to the integrity of studies. This includes provision for appropriate collection, storage & disposal facilities & decontamination & transportation procedures.
- 18. 4. APPARATUS, MATERIAL, REAGENTS A. APPARATUS: Apparatus, including validated computerized system, used for the generation, storage & retrieval of data, & for controlling environmental factors relevant to the study. Apparatus used in a study should be periodically inspected, cleaned, maintained, & calibrated acc. to SOP. Equipment record should be maintained:- Name, Mode, Serial no., Date of received & Manufacturing Operating Instructions.
- 19. APPARATUS, MATERIAL, REAGENTS CON... B. MATERIAL & REAGENT: Chemicals, reagents & solutions should be labelled to indicate Identity (with conc. if appropriate) Expiry date & specific storage instructions. Information concerning source, preparation date & stability shoud be available. The expiry date may be extended on the basis of documented evaluation or analysis. Date ofopening should be mentioned. Purchase & testing should be handled by an QA personnel.
- 20. 5. TEST SYSTEM
- 21. 6. TEST SYSTEM & REFERENCE ITEMS The test system could be animal, aplant, a baterium, an isolated organ, a field or other ecosystem or even analytical equipments, etc. Physical & Chemical Test Sytems: Appropriate design and adequate capacity of apparatus used for the generation of data. Integrity of physical/chemical test system. Biological Test System: Proper conditions for storage, housing, handling, & care. Isolation of newly received animal & plant test system until health status is evaluated. Humanely destruction of inappropriate test system.
- 22. 7. PERFORMANCE OF THE STUDY Study Plan Content of the Study Plan Dates Test Methods Issues (where applicable) Records A lis of records to be retained. Conduct of the study
- 23. RULES Rules for organizing & conducting GLP studies must be defined in documents approved by management. Rules defining who does what, how, when, and where, are called prescriptive document. 2 Main Types of Prescriptive Documents: 1. The Protocol(or study plan): The protocol is a high level document which defines the study design. 2. Standard Operating Procedures (SOP): SOPs are instructions on hw to perform the routine procedures that make up a good part of th study.
- 24. STANDARD OPERATION PROCEDURE (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
- 25. 8. REPORTING OF STUDY RESULTS Name and address of test facility. Date of start and finish of the study. Name of the study Director. Objectives of the study. Details of the test system. Prescription of the test system. Details of dosing, route, & duration. Summary of findings. Discussion. Conclusion. References.
- 26. Final report should be signed by study Director. Once its been signed, it cannot be changed. The amendment must indicate what is being changed or added to the report & why the modification is being made. The amendment must be signed by the study director and must be audited by the QAU (Quality Assurance Unit).
- 27. 9. STORAGE & RETENTION OF RECORDS & MATERIAL The study plan, raw data, samples of test & reference items, specimens and final report of each study. Records of all inspections prformed by the QA program, as well a master schedule. Records of qualifications, training, experience and job descriptions of personel. Records & reports of the maintenance & calibration of apparatus Validation documentation for computerized systems.
- 28. ARCHIVES Archives is not a simple place for storage of old materials. Safe depository of invaluable information. What is left at the end of the study is usd to demonstrate the validity & traceability of the scientific results. FUNCTION: Long term, secure storage & fast retrieval of data Contains all original scientific data, master documents reports, endpoint of regulated work. SECURITY: Only authorized entry permited- as per SOP. Protection agaist fire, flood and vandalism if possible.
- 29. DISQUALIFICATION OF A FACILITY Before a workplace can experience the consequences of noncompliance, an explanation of dis qualification is needed. The FDA states the purpose of disqualification as the exclusion of a testing facility from completing laboratory studies or atarting any new studies due to not following the standards of compiance set by the GLP manual. POSSIBLE VIOLATIONS: Falsifying information for permit, registration, or any required records. Falsifying information related to testing protocols, ingredients, observations, data equipments etc. Failure to prepare, retain, or submit written records reuired by law.
- 30. CONSEQUENCES OF NONCOMPLIANCE The FDA states the following consequences of noncompliance: The commissioner will send a proposal of disqualification written to the testing facility. A regulatory hearing on the disqualification will be scheduled. If the commisioner finds that after hearing. the facility has complied, then a written statement with an explation of termination of disqualification will be sent to the facility. Oncefinally disqualified, the facility may not recieve or be considered for a research or marketing permit and the study is rejected. The commissioner may notify the public and all intrested person, including other fedearl agencies the facility may have contacted.
- 31. LABORATORY CERTIFICATION Normally done by an external agency Evaluation is concerned with issues such as Adequate space Ventilation Storage Hygiene