GOOD LABORATORY PRACTICES ?

1. GOOD LABORATORY PRACTICES ?

2. Why we need to follow GLP

3. GLP is quality system concerned with organizational process under which studies /tests are Planned Monitored Recorded Archived Purpose of GLP : Is to promote the development of quality test data and to further improve the protection of human health and environment

4. Present OECD member countries where GLP is compulsory • Austria Italy Spain • Czech Republic Hungary Poland Slovak Republic Norway Turkey • Iceland Switzerland Belgium Denmark Finland France • Germany Greece Ireland • Luxembourg The Netherlands • Portugal Sweden Canada • Mexico United States • Australia Japan • New Zealand South Korea • United Kingdom OECD : Organization for Economic cooperation and development

5. Are we Ready ?

6. Our mind set must be clear and must be ready for challenges

7. GLP a worldwide standardised system GLP GLP GLP

8. OECD PRINCIPLES OF GLP PRACTICE • Test facility Organisation and Personnel • Quality Assurance Programme • Facilities • Apparatus , Material and Reagents • Test and Reference Items • Standard Operating Procedures • Performance of the Study /test • Reporting of the Study results/test results • Storage and Retention of Records and Materials

9. TEST FACILITY ORGANISATION AND PERSONNEL • Ensure that sufficient number of qualified personnel,appropriate facilities, Equipments and Materials are available. • Records of Qualification, Training, Experience and Job description • Valid Standard Operating Procedures are available and accessible to all involved • Maintain all the historical SOP files • Ensure that test and reference items are appropriately characterized • All the raw data generated are fully documented and recorded • All the computer systems are used for testing purpose are validated

10. QUALITY ASSURANCE PROGRAMME • Must have documented Quality assurance programme to conduct the test • Maintain the copies of approved test procedure • Periodic verification of the test procedure • Conduct the inspection to ensure that tests are done as per GLP • Inspect the final report to ensure that methods, procedures and observations are accurately and completely described. • Report all the findings and report.

11. FACILITIES • Test facility should be of suitable size, construction and location to meet the requirements • Design of test facility should provide an adequate degree of separation of the activities to prevent the contamination or mix-up. • Archive facility should provide secure storage of raw data, final report, sample of test item and specimens. • Must have storage room for the equipments • Handling and Disposal of waste procedure • Decontamination and Transportation of waste procedures

12. APPARATUS ,MATERIAL AND REAGENTS • Validated Instruments, Computers that were used to generate , storage and revival of the data. • Apparatus used for testing must be periodically inspected, cleaned, maintained and Calibrated. • Records should be maintained and must be traceable • Chemical, reagents and solutions should be labelled to indicate the identity, Preparation date and expiry date and storage conditions.

13. TEST SYSTEMS • Apparatus / Instruments should be suitably located. • Integrity of the physical/chemical test system should be ensured. • Record of Source, date of arrival and arrival condition of the test system should be maintained.

14. TEST AND REFERENCE ITEMS • Record such as date of receipt, expiry date, quantity received and used must be maintained • Handling ,sampling and storage procedure should be identified in order that the homogeneity and stability are assured. • Storage containers should carry ID information, expiry date , purity, composition,concentration and specific storage conditions. • Test sample of each batch should be retained.

15. STANDARD OPERATING PROCEDURES • Must have written and valid SOP’s for all the laboratory operation and for intended use. • SOP’s should be available for the relevant activity • Deviations from SOP should be documented • SOP’s should be available for , but not limited to following categories. Test and Reference Items – Receipt, identification, labeling, sampling and storage Apparatus - Use, Maintenance, Cleaning, Calibration Computerised system – Validation, Operation, security, change control and back –up

16. REPORTING OF RESULTS • Final report must be prepared for each test/study and must be finally checked and then signed by head of the department. • Report must contain – Title Identification name, Batch number/lot number, reference number Detailed summary test results Statement of Quality

17. STORAGE AND RETENTION OF RECORDS AND MATERAILS • Following should be retained in the archives for the period specified by the appropriate authorities. Only authorised personnel by management will have access to archives. All Raw data Samples of test items ( RM/PM/FP) Report Records of inspection by QA Qualification Records Training Job description of personnel Records and Reports of the maintenance and Calibration equipments Validation documents for computerised systems Historical file of all SOP Environmental monitoring records FINAL DISPOSITION OF ANY ARCHIVES MUST BE DOCUMENTED

19. Typical Laboratories incidents

20. Handling of OOS, OOT ,CAPA, Deviations and incidences Must have all the required SOP’s Must have Proper training for investigation Scientific Justification Root cause analysis to avoid reoccurrence

21. Root Cause Analysis RCA is a problem solving method • Aimed at identifying the root cause of problems , instead of addressing obvious symptoms • Adequate measures at root cause, minimize the problem occurrence • Tool for continuous improvement • Initially, it is a reactive method of problem detection and solving • Now, it is a pro-active method - need to forecast the possibility of event even before it could occur

22. General Principles of RCA • Aiming performance improvement measures at root causes is more effective than merely treating the symptoms of a problem. • To be effective, RCA must be performed systematically, with conclusions and causes backed up by documented evidence. • There is usually more than one potential root cause for any given problem. • To be effective the analysis must establish all known causal relationships between the root cause(s) and the defined problem. • Root cause analysis transforms an old culture that reacts to problems to a new culture that solves problems before they escalate

23. Examples: Cause and Effect Effect : Assay results below specification and resulted in OOS a > b > c > d > e (Low assay problem) Assume each of these factors is as described below: • e: HPLC /GC not calibrated / out of calibration • d: Analyst training record /specific training • c: Method is not specific or validated • b: Chemicals used for testing are not pure • a: weighing of sample /Balance calibration Cause: HPLC out of calibration, RSD of Standards was out side the acceptable limits.

24. Basic elements of root cause • Materials • Defective raw material • Wrong type for job • Lack of raw material • Machine / Equipment • Incorrect tool selection • Poor maintenance or design • Poor equipment or tool placement • Defective equipment or tool • Mother nature / Environment • Orderly workplace • Job design or layout of work • Surfaces poorly maintained • Physical demands of the task • Forces of nature • Management • No or poor management involvement • Inattention to task • Task hazards not guarded properly • Other (horseplay, inattention....) • Stress demands • Lack of Process • Methods • No or poor procedures • Practices are not the same as written procedures • Poor communication • Management system • Training or education lacking • Poor employee involvement • Poor recognition of hazard • Previously identified hazards were not eliminated • 4ME (Man, Machine, Materials, Method and Environment).

25. Cause Effect Cause and Effect analysis Method Machine Man Problem Secondary cause Primary cause Mother Nature Materials Management

26. EXPECTATIONS OF ANALYSTS • Should have GLP knowledge • Appropriate technical and scientific training • Compliance with study plans, methods and SOPs • Responsible for recording raw data promptly and accurately • Responsible for the quality of their data

27. FINDINGS – ANALYST • Potential problems or deficiencies relating to the analyst: • -Traceability • - Equipment • - Solution, reagents and standard prep. • - Analyst – who/were they trained? • - Date - when? • - Study/ Test - what number?

28. EXPECTATIONS – LABORATORIES • Condition • Housekeeping • Separation of activities • Availability of SOPs

29. FINDINGS – LABORATORIES • Poor housekeeping -> cross contamination • Weighing of samples and reference item • Non availability of SOPs, methods, • Sample receipt procedures

30. EXPECTATIONS – COMPUTERISED SYSTEMS • Does the instrument capture, store and manipulate data? If the answer is yes: • Has the system been validated? • Is the system fit for purpose? • Serviced and maintained, calibrated. • Are staff appropriately trained? • Are relevant SOPs available? • Is the system captured in the QA Programme?

31. EXPECTATIONS – COMPUTERISED SYSTEMS • Is the system fit for purpose? • Is a service contract in place? • Is there a record of maintenance? • Are individual components identified? When is re-validation required? • Is there evidence of regular calibration? • Are system suitability tests performed? • Is trending done?

32. FINDINGS – INSTRUMENTATION • Inadequate validation or calibration • Raw data not defined • Staff not appropriately trained or training not documented • Errors or missing information in the data

33. SUMMARY AND WHAT INSPECTOR EXPECTS • A good quality system consisting of: • - the right people in the right jobs • - a good programme of training • - robust polices and procedures • - controlled and consistent ways of working • - effective QA • People who undertake key study roles to be fully conversant with the Principles of GLP and their legal responsibilities • Understand and appreciate how these responsibilities should be applied in practice and the implications if they are not

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