Good laboratory practice guidelines. GLP IN INDIA.

�SCOPE� �GOOD LABORATORY PRACTICE PRINCIPLES� GLP IN INDIA. Content of the Final Report � Conduct of the Study STANDARD OPERATING PROCEDURES

1. PRESENTED BY SELVARAJ.P PH.D SCHOLAR OCT-2019 BATCH GUIDE DR.SASI.VAITHILINGAN PROFESSOR CUM VICE-PRINCIPAL VMCON PONDICHERRY. SEMINAR ON GOOD LABORATORY PRACTICE GUIDELINES

2. INTRODUCTION Good Laboratory Practice (GLP) deals with the organization, process and conditions under which laboratory studies are planned, performed , monitored, recorded and reported. GLP data are intended to promote the quality and validity of test data 4/16/2020 VMRF(DU) NSG19OCT07

3. Con’t “If experimental work is conducted in compliance with GLP, with or without the aid of computer, it should be possible for an inspector, maybe four or five years hence, to look at the records of the work and determine easily why, how and by whom the work was done, who was in control, what equipment was used, the results obtained, any problems that were encountered and how they were overcome”.( Weller) 4/16/2020 VMRF(DU) NSG19OCT07

4. HISTORY The term GLP was first used in New Zealand in 1972. GLP was instituted in US following cases of fraud generated by toxicology labs 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. 4/16/2020 VMRF(DU) NSG19OCT07

5. Con’t Assure the quality and integrity of safety Nonclinical laboratory studies  In 1981 an organization named OECD (organization for economic co-operation and development ) produced GLP principles that are international standard.  4/16/2020 VMRF(DU) NSG19OCT07

6. GLP DEFINITION Good Laboratory Practice(GLP) is a quality system concerned with the organisational process and the conditions under which non-clinical health and environmental safety studies are planned , performed, monitored, recorded, archived and reported. 4/16/2020 VMRF(DU) NSG19OCT07

7. GLP Clinical lab- Human blood test Non clinical lab- Just research, not related to human patients GLP refers to a quality system of management controls for laboratories where research is taking place, the labs are not treating humans. 4/16/2020 VMRF(DU) NSG19OCT07

8. PURPOSE OF GLP 1. To promote the development of quality test data 2. Obtain reliable and reproducible data 3. Obtain comparable data between countries 4. Achieve international confidence in study data 5. Avoid repetition of studies 6. Enable reconstruction of studies 4/16/2020 VMRF(DU) NSG19OCT07

9. Con’t 7. Optimise animal conditions 8. Shorten the registration time of the drug 9. To decrease the occurrence of mistake 10. Limit waste resources 11. Ensure high quality of result 12. Ensure comparability of results 13. Promote mutual recognition of results. 4/16/2020 VMRF(DU) NSG19OCT07

10. SCOPE GLP is a requirement in regulatory non-clinical safety testing of the following test items :- 1.Pharmaceutical products- 2. Pesticide products- 3. Cosmetic products- 4. Veterinary products- 5. Food additives- 4/16/2020 VMRF(DU) NSG19OCT07

11. Con’t 6. Feed additives 7. Industrial chemicals 8. Repeated dose toxicity (sub-acute and chronic) 9. Reproductive toxicity 10. Mutagenic potential Carcinogenic potential 11. Local tolerance studies 4/16/2020 VMRF(DU) NSG19OCT07

12. BASICS FUNDAMENTAL POINTS Resources Characterisation Rules Results Quality Assurance 4/16/2020 VMRF(DU) NSG19OCT07

13. GOOD LABORATORY PRACTICE PRINCIPLES Test Facility Organisation and Personnel Quality Assurance Programme Facilities Apparatus, Material, and Reagents Test Systems Test and Reference Items Standard Operating Procedures Performance of the Study Reporting of Study Results Storage and Retention of Records and Materials 4/16/2020 VMRF(DU) NSG19OCT07

14. 1.Test Facility Organisation and Personnel 1.1 Test Facility Management’s Responsibilities 1.2 Study Director’s Responsibilities 1.3. Principal Investigator’s Responsibilities 1.4 Study Personnel’s Responsibilities 4/16/2020 VMRF(DU) NSG19OCT07

15. 1.1.Test Facility Management’s Responsibilities Responsibilities of management Sufficient number of qualified personnel, Ensure the maintenance of a record Job description for each professional and technical individual. Documented approval of the study plan by the Study Director. 4/16/2020 VMRF(DU) NSG19OCT07

16. 1.2 Study Director’s Responsibilities Approve the study plan. Amendments to the study plan Availability of SOPS to the personnel. Raw data generated are fully Computerised systems used Final report Ensure that after completion (including termination) 4/16/2020 VMRF(DU) NSG19OCT07

17. 1.3 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. 4/16/2020 VMRF(DU) NSG19OCT07

18. 1.4 Study Personnel’s Responsibilities Knowledgeable Instructions Recording Responsibilities Health precaution Access to the study plan and appropriate Standard Operating Procedures Recording raw data Health precautions 4/16/2020 VMRF(DU) NSG19OCT07

19. 2. QUALITY ASSURANCE PROGRAMME 1.Quality assurance personnel 2.Study plan contains the information-verification 3.Conduct inspections Study-based inspections Facility-based inspections Process-based inspections. 4.Records of such inspections should be retained 5. Prepare and sign a statement, 4/16/2020 VMRF(DU) NSG19OCT07

20. 3. FACILITIES 3.1 General 3.2 Test System Facilities 3.3 Facilities for Handling Test and Reference Items 3.4 Archive Facilities 3.5 Waste Disposal 4/16/2020 VMRF(DU) NSG19OCT07

21. 3.1 General The test facility should be of suitable size, construction and location The design of the test facility should provide an adequate degree of separation of the different activities to assure the proper conduct of each study 4/16/2020 VMRF(DU) NSG19OCT07

22. 3.2 Test System Facilities  Sufficient number of rooms or areas assure the isolation of test systems and the isolation of individual There should be storage rooms or areas as needed. Areas should be available for the diagnosis, treatment and control of diseases 4/16/2020 VMRF(DU) NSG19OCT07

23. 3.3 Facilities for Handling Test and Reference Items To prevent contamination or mix-ups, there should be separate rooms Storage rooms or areas for the test items should be separate from rooms or areas containing the test systems. They should be adequate to preserve identity, concentration, purity, and stability, and ensure safe storage for hazardous substances. 4/16/2020 VMRF(DU) NSG19OCT07

24. 3.4 Archive Facilities Archive facilities should be provided for the secure storage and retrieval of study plans, raw data, final reports, samples of test items and specimens. Archive design and archive conditions should protect contents from untimely deterioration. 4/16/2020 VMRF(DU) NSG19OCT07

25. 3.5 waste disposal Handling and disposal of wastes should be carried out in such a way as not to jeopardise the integrity of studies. This includes provision for appropriate collection, storage and disposal facilities, and decontamination and transportation procedures 4/16/2020 VMRF(DU) NSG19OCT07

26. 4. APPARATUS, MATERIAL, AND REAGENTS Apparatus, including validated computerised systems, Apparatus used in a study should be periodically inspected, Chemicals, reagents, and solutions should be labelled to indicate identity Date and stability should be available. The expiry date may be extended on the basis of documented evaluation or analysis. 4/16/2020 VMRF(DU) NSG19OCT07

27. 5. TEST SYSTEMS 5.1 Physical/Chemical Physical/chemical data should be suitably located The integrity of the physical/chemical test systems should be ensured. 4/16/2020 VMRF(DU) NSG19OCT07

28. 5.2 Biological Proper conditions should be established and maintained for the storage Newly received animal and plant test systems should be isolated Records of source date of arrival Biological test systems should be acclimatised to the test environment Test systems used in field studies should be located so as to avoid interference 4/16/2020 VMRF(DU) NSG19OCT07

29. 6. TEST AND REFERENCE ITEMS 6.1 Receipt, Handling, Sampling and Storage 1. Records including test item and reference item 2. Handling, sampling, and storage procedures should be identified 3.Storage container(s) should carry identification information, expiry date, and specific storage instructions 4/16/2020 VMRF(DU) NSG19OCT07

30. 6.2 Characterisation Each test and reference item should be appropriately identified Co-operation between the sponsor and the test facility Test item is administered in a vehicle, stability of the test item in that vehicle should be determined. A sample for analytical purposes from each batch of test item should be retained for all studies except short-term studies 4/16/2020 VMRF(DU) NSG19OCT07

31. 7. STANDARD OPERATING PROCEDURES 1. Test and Reference Items 2. Apparatus, Materials and Reagents 3. Record Keeping, Reporting, Storage, and Retrieval 4. Test System (where appropriate) 5. Quality Assurance Procedures 4/16/2020 VMRF(DU) NSG19OCT07

32. 8. PERFORMANCE OF THE STUDY 8.1 Study Plan A written plan should exist prior to the initiation of the study. IT should also be approved by management and the sponsor Any amendments to the study plan should be justified and approved. Deviations from the study plan should be described, explained, acknowledged For short-term studies a general study plan accompanied by a study specific supplement may be used. 4/16/2020 VMRF(DU) NSG19OCT07

33. 8.2 Content Identification of the Study, the Test Item and Reference Item a). A descriptive title b). A statement which reveals the nature and purpose of the study c) .Identification of the test item by code or named) the reference item to be used 4/16/2020 VMRF(DU) NSG19OCT07

34. 2. Information Concerning the Sponsor and the Test Facility a) Name and address of the sponsor b) Name and address of the test facilities and test sites involved c) Name and address of the study director d) Name and address of the principal investigator and the phase delegated by the study director and under the responsibility of the principal investigator 4/16/2020 VMRF(DU) NSG19OCT07

35. 3. Dates The date of approval of the study director and by the management and sponsor and if required by national regulation /legislation in the country where the study is being performed. The proposed experimental starting and completion dates. 4/16/2020 VMRF(DU) NSG19OCT07

36. 4. Test Methods Reference to the OECD Test Guideline or other test guideline or method to be used. 5. Issues a) The justification for selection of the test system; b) Characterisation of the test system c) The method of administration and the reason for its choice e) Detailed information on the experimental design, 4/16/2020 VMRF(DU) NSG19OCT07

37. 8.3 Conduct of the Study A unique identification should be given to each study The study should be conducted in accordance with the study plan All data generated during the conduct of the study should be recorded directly computerised system design should provide for the retention of full audit trials to show the changes in the data without obscuring the original data 4/16/2020 VMRF(DU) NSG19OCT07

38. 9. REPORTING OF STUDY RESULTS 9.1 General 1. A final report should be prepared for each study 2. Reports of Principal Investigators 3.The final report should be signed and dated by the Study Director 4. Corrections and additions to a final report should be in the form of amendments 5.Reformatting of the final report to comply with the submission requirements 4/16/2020 VMRF(DU) NSG19OCT07

39. 9.2 Content of the Final Report 1 . Identification of the Study, the Test Item and Reference Item 2. Information Concerning the Sponsor and the Test Facility 3. Dates 4. Statement 5. Description of Materials and Test Methods 6. Results 7. Storage 4/16/2020 VMRF(DU) NSG19OCT07

40. 10. STORAGE AND RETENTION OF RECORDS AND MATERIALS The study plan, raw data, samples of test and reference items, specimens and the final report of each study. Records of all inspections performed by the Quality Assurance Programme, as well as master schedules. Records of qualifications, training, experience and job descriptions of personnel. Records and reports of the maintenance and calibration of apparatus. Validation documentation for computerised systems. 4/16/2020 VMRF(DU) NSG19OCT07

41. GLP IN INDIA National GLP-compliance Monitoring Authority was established by the Department of Science & Technology Approval of the Union Cabinet on April 24, 2002 A provisional member of the OECD for GLP. India is an Observer to the OECD’s Working Group on GLP The Authority has trained 33 experts in the country as GLP inspectors. 4/16/2020 VMRF(DU) NSG19OCT07

42. CONCLUSION GLP is an FDA regulation which is accepted and approved as international standards by OECD to avoid the fraud activities of the testing laboratories Every one makes mistake that's why GLP needed 4/16/2020 VMRF(DU) NSG19OCT07

43. 9. REFERENCE 1. OECD Principles of Good Laboratory Practice (as revised in 1997), ENV/MC/CHEM(98)17, OECD, Paris, 1998. (No.1 in OECD Series on Good Laboratory Practice and Compliance Monitoring) 2. https://www.who.int/tdr/publications/documents/glp-handbook.pdf 3. OECD PRINCIPLES AND GUIDANCE FOR MONITORING – ISBN 92-64-01282-6 – © OECD 2005. Good Laboratory Practice Regulations Fourth Edition edited by Sandy Weinberg. Handbook: good laboratory practice (GLP): quality practices for regulated non-clinical research and development - 2nd edition. P.P. Sharma “how to practice GLP” vandana publication. 42 4. https://en.wikipedia.org/wiki/Good_laboratory_practice 4/16/2020 VMRF(DU) NSG19OCT07