OECD PRINCIPLES OF GLP- AKSHAY S.pptx

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1. OECD PRINCIPLES OF GLP HISTORY, CONCEPT AND IMPORTANCE IN DRUG DEVELOPMENT PRESENTED BY AKSHAY S M.PHARM PHARMACOLOGY

2. CONTENTS History behind OECD principles of GLP Basic concept behind the principles Importance of the principles in drug discovery Introduction What is OECD? What are the OECD principles of GLP? Organization and personnel Quality assurance Programs Facilities Apparatus, material and reagent Test system Test and reference items Standard operating procedures Performance of the study Reporting of study results Storage and retention of records and material

3. HISTORY

4. HISTORY Until the mid 1970s reports on studies demonstrating the safety of industrial chemicals, potential drugs and pesticides submitted to the authorities were, on the whole, accepted without question. Scientists were trusted to provide complete, accurate and unbiased data. The case that brought about the change in legislation concerned a large US contract laboratory working for major drug and chemical companies. Prompted by mistakes and inconsistencies in the safety data, a US Government FDA (Food and Drug Administration) expert visited Industrial Bio-Test Laboratories near Chicago where they found serious flaws including: animals kept in unhealthy conditions incomplete safety data false/completely fabricated records The company involved had conducted over 35% of the toxicology tests that supported the registration approvals of many pharmaceuticals, pesticides and food additives which had been granted by the FDA. The safety of all products tested by Industrial Bio-Test Laboratories was questionable because licenses had been granted based on false information. A wider survey by US FDA showed that such problems were not restricted to this one company. Five companies were prosecuted for fraud ; Industrial Bio-Test Laboratories was heavily fined, senior personnel were imprisoned and the company ceased trading

5. HISTORY The investigations of the US Food and Drug Administration (FDA) in laboratories in the USA found a lack of organization and poor management which, it was decided, could only be dealt with by imposing regulations. These regulations were the US GLP regulations. It was soon recognized that there was a need for an international agreement on Good Laboratory Practice , so in 1978 the Organization for Economic Co-operation and Development (OECD) established an expert group on Good Laboratory Practice. The group was led by the USA and included representation from 17 of its member countries , the World Health Organization (WHO), the International Organization for Standardization (ISO) and the European Community Commission. The US FDA GLP regulations were used as the basis for the development of the OECD Principles of GLP . The OECD Principles were published in 1982 as Environmental Monograph 45 'The OECD Principles of Good Laboratory Practice'. These were formally recommended for use in OECD member countries and were widely accepted as the international standard for Good Laboratory Practice. A revised version was published in 1998 taking scientific and technical progress into account. These Principles have been transferred into national law in many countries. For example, member states of the European Union are required by European Directives to include the OECD Principles of Good Laboratory Practice in national law.

6. HISTORY The GLP regulations for non-clinical laboratory studies published by the US-FDA in 1976 ( Baldeshwiler , 2003). The OECD Principles of GLP were first developed by an Expert Group on GLP established in 1978 under the Special Programme on the Control of Chemicals Principles of GLP were adopted by the OECD in 1981 Expert Group was established in 1995 to develop a proposal to revise the Principles of GLP. The Revised OECD Principles of GLP were reviewed in the relevant policy bodies of the Organization and were adopted by Council on 26 November, 1997. Indian GLP Compliance Monitoring Authority  April, 2002.

7. CONCEPT

8. HISTORY While the regulations set out the rules for good practice they also help the researchers to perform their work in compliance with a pre-established plan, and they standardize procedures worldwide . The regulations do not concern the scientific or technical content of the research programs , and they do not aim to evaluate the scientific value of the studies. All GLP texts stress the importance of the following points: 1. Resources : organization, personnel, facilities and equipment. 2. Rules : plans and written procedures. 3. Characterization : test items and test systems. 4. Documentation : raw data, final report and archives. 5. Quality assurance unit

9. IMPORTANCE

10. HISTORY The importance of GLP is to regulate the practices of scientists working on the safety testing of prospective drugs. With the obvious potential impact on consumers and patients recruited for clinical trials, the safety of drugs became a key issue and GLP was seen as a means of ensuring that scientists did not invent or manipulate safety data and a means of ensuring that GLP compliant studies are properly managed and conducted. Hence GLP became the champion of the consumer , the regulatory safeguard , the guarantee that the safety data were being honestly reported to the registration or receiving authorities as the basis of a decision whether or not to allow a new drug onto the market. GLP was imposed on the industry by regulatory authorities, in the same way as good manufacturing practice (GMP) had been before, and good clinical practice (GCP) was to be afterwards.

11. These Principles of Good Laboratory Practice should be applied to the non-clinical safety testing of test items contained in pharmaceutical products, pesticide products cosmetic products, veterinary drugs food additives, feed additives industrial chemicals . Test items are frequently synthetic chemicals, but may be of natural or biological origin. Unless specifically exempted by national legislation, these Principles of Good Laboratory Practice apply to all non-clinical health and environmental safety studies for the purpose of registering or licensing pharmaceuticals, pesticides, food and feed additives, cosmetic products, veterinary drug products and similar products, and for the regulation of industrial chemicals.

12. INTRODUCTION

13. HISTORY Organization for Economic Co-operation and Development (OECD) is an intergovernmental organization (OECD Secretariat, located in Paris, France ) Representatives of 29 industrialized countries in North. America, Europe and the Pacific, as well as the European Commission, meet to co-ordinate and harmonize policies, discuss issues of mutual concern, and work together to respond to international problems The Principles of Good Laboratory Practice (GLP) have been developed to promote the quality and validity of test data. used for determining the safety of chemicals and chemicals products. WHAT IS OECD?

14. HISTORY In 1979 and 1980 , an international group of experts. established under the Special Programme on the Control of Chemicals developed the "OECD Principles of Good Laboratory Practice“ Good Laboratory Practice (GLP) is a quality system concerned with the organizational process and the conditions under which non-clinical health and environmental safety studies are planned, performed, monitored, recorded, archived and reported. Principles involves: WHAT IS OECD PRINCIPLES OF GLP?

15. ORGANIZATION AND PERSONNEL

16. HISTORY THE KEY PERSONNEL IN GLP

17. QUALITY ASSURANCE PROGRAMS

18. HISTORY An internal control system designed to ascertain that the study is in “compliance" with the Principles of GLP. The test facility should have a documented QAP. The Quality Assurance Programme should be carried out by an individual or by individuals designated by and directly responsible to management and who are familiar with the test procedures .

19. FACILITIES

20. HISTORY GENERAL The test facility should be of suitable size, construction and location to meet the requirements of the study and to minimize disturbance that would interfere with the validity of the study. TEST SYSTEM FACILITIES There should be storage rooms or areas as needed for supplies and equipment . Storage rooms or areas should be separated from rooms or areas housing the test systems and should provide adequate protection against infestation, contamination, and/or deterioration . The test facility should have a sufficient number of rooms or areas to assure the isolation of test systems and the isolation of individual projects, involving substances or organisms known to be or suspected of being biohazardous.

21. HISTORY FACILITIES FOR HANDLING TEST AND REFERENCE ITEMS To prevent contamination or mix-ups, there should be separate rooms or areas for receipt and storage of the test and reference items , and mixing of the test items with a vehicle 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 un-timely deterioration . WASTE DISPOSAL Handling and disposal of wastes should be carried out in such a way as not to jeopardize the integrity of studies. This includes provision for appropriate collection, storage and disposal facilities , and decontamination and transportation procedures.

22. TEST SYSTEMS

23. HISTORY PHYSICAL/CHEMICAL Apparatus used for the generation of physical/chemical data should be suitably located and of appropriate design and adequate capacity. BIOLOGICAL Proper conditions should be established and maintained for the storage, housing, handling and care of biological test systems, in order to ensure the quality of the data. Newly received animal and plant test systems should be isolated until their health status has been evaluated. All information needed to properly identify the test systems should appear on their housing or containers. Individual test systems that are to be removed from their housing or containers during the conduct of the study should bear appropriate identification, wherever possible.

24. TEST AND REFERENCE ITEMS

25. HISTORY RECEIPT, HANDLING, SAMPLING AND STORAGE Records including test item and reference item characterization, date of receipt, expiry date, quantities received and used in studies should be maintained. Handling, sampling, and storage procedures should be identified in order that the homogeneity and stability are assured to the degree possible and contamination or mix-up are precluded. Storage container(s) should carry identification information, expiry date, and specific storage instruction CHARACTERIZATION Each test and reference item should be appropriately identified (e.g., code, name, biological parameters). The stability of test and reference items under storage and test conditions should be known for all studies. In cases where the test item is supplied by the sponsor, there should be a mechanism, developed in co-operation between the sponsor and the test facility , to verify the identity of the test item subject to the study. If the test item is administered or applied in a vehicle, the homogeneity , concentration and stability of the test item in that vehicle should be determined.

26. STANDARD OPERATING PROCEDURES

27. A test facility should have written Standard Operating Procedures approved by test facility management that are intended to ensure the quality and integrity of the data generated by that test facility. Documented procedures which describe how to perform tests or activities normally not specified in detail in study plans or test guidelines. Deviations from Standard Operating Procedures related to the study should be documented and should be acknowledged by the Study Director and the Principal Investigator(s), as applicable. A test facility should have written SOPs approved by management in language interpretable to those who are going to use them (Frederick, 2006) SOPS should be available for the following categories of activities:

28. APPARATUS, MATERIALS AND REAGENTS

29. HISTORY Apparatus , including validated computerized systems , used for the generation, storage and retrieval of data , and for controlling environmental factors relevant to the study should be suitably located and of appropriate design and adequate capacity. Apparatus and materials used in a study should not interfere adversely with the test systems. Chemicals, reagents, and solutions should be labelled to indicate identity (with concentration if appropriate), expiry date and specific storage instructions. Information concerning source, preparation date and stability should be available. The expiry date may be extended on the basis of documented evaluation or analysis. Provision for appropriate collection, storage and disposal facilities, and decontamination and transportation procedures.

30. PERFORMANCE OF THE STUDY

31. HISTORY Study Plan: For each study, a written plan should exist prior to the initiation of the study. The study plan should be approved by dated signature of the Study Director and verified for GLP compliance by Quality Assurance personnel . For short-term studies, a general study plan accompanied by a study specific supplement may be used. Amendments to the study plan should be justified and approved by dated signature of the Study Director and maintained with the study plan. Deviations from the study plan should be described, explained, and dated in a timely fashion by the Study Director and/or Principal Investigator(s) and maintained with the study raw data

32. Content of the Study Plan: Conduct of study: A unique identification should be given to each study. All data generated during the conduct of the study should be recorded directly, promptly, accurately, and legibly by the individual entering the data. Data generated as a direct computer input should be identified at the time of data input by the individual(s) responsible for direct data entries.

33. REPORTING OF THE STUDY RESULTS

34. HISTORY A final report should be prepared for each study. Reports of Principal Investigators or scientists involved in the study should be signed and dated by them. Corrections and additions to a final report should be in the form of amendments. 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 :Experimental starting and completion dates 4. Statement A Quality Assurance Programme statement listing the types of inspections made and their dates, including the phase(s) inspected, and the dates any inspection results were reported to management and to the Study Director and Principal Investigator(s), if applicable. Confirm that the final report reflects the raw data.

35. 5. Description of Materials and Test Methods Description of methods and materials used; Reference to OECD Test Guideline or other test guideline or method 6. Results a) A summary of results; b) All information and data required by the study plan; c) A presentation of the results, including calculations and determinations of statistical significance; d) An evaluation and discussion of the results and, where appropriate e)Conclusions 7. Storage The location(s) where the study plan, samples of test and reference items, specimens, raw data and the final report are to be stored.

36. STORAGE AND RETENTION OF RECORDS AND MATERIALS

37. REFERENCES

38. https://www.oecd.org/chemicalsafety/testing/overview-of-good-laboratory-practice.htm Introduction to OECD principles of GLP, https://glp.abdn.ac.uk/ https://ntp.niehs.nih.gov/iccvam/suppdocs/feddocs/oecd/oecd_glpcm.pdf , OECD Principles on Good Laboratory Practices http://www.oecd.org/ehs/