Change control oos oot

IMPORTANCE OF QUALITY SYSTEM

1. CONCEPT OF CHANGE CONTROL, OUT OF SPECIFICATIONS (OOS) AND OUT OF TRENDS (OOT) PRESENTER: MR. AMOGH P. DANDEKAR FIRST YEAR M.PHARM DEPT. OF PHARMACEUTICAL QUALITY ASSURANCE REG.NO: NH0117005 DATE: 14/11/2017 1

2. content Concept of Change control Procedure of change control Management of change control Conditions of change control Out of specifications(OOS) Out of trends(OOT) 2

3. CONCEPT OF CHANGE CONTROL Change : any modification to product, document, process, equipment, instrument, system, facility etc . Change control : procedure reviews, verifies, regulates, manages, approves and controls changes made to the existing operating system or facility or process or procedure or document or product of any combination 3

4. CONCEPT OF CHANGE CONTROL The key principles of change control are : What was done, why, when, where, by whom, how Results, including the impact of changes to other processes. 4

5. MANAGEMENT OF CHANGE CONTROL Written procedures should be established and maintained to control changes for: Processes, Facilities, Utilities Methods , Validation, Computer systems Training and training materials Regulatory filings and Quality systems Changes should be justified and documented. All changes that have the potential to impact the quality, safety and efficacy should be evaluated, reviewed and approved 5

6. 6 CHANGE CONTROL CYCLE

7. PROCEDURE OF CHANGE CONTROL 7

8. CONDITIONS FOR CHANGE CONTROL Revalidation Requalification Increased testing Stability analysis Document change Regulatory action / variation application 8

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10. OUT OF SPECIFICATIONS (OOS) 10

11. OUT OF SPECIFICATIONS (OOS) Out of Specification (OOS) means the test result that falls outside the specifications or acceptance criteria which has been specified in the official compendia monographs or the finished product specification in registration dossiers. 11

12. oos is observed in analysis of: Stability study Finished product In-process Raw materials Packing materials 12

13. US FDA : Guideline for Industry Investigating OOS Testing Results for Pharmaceutical Production PHASE I: LABORATORY INVESTIGATION should include an initial assessment of the accuracy of the laboratory's data. PHASE II: FULL-SCALE OOS INVESTIGATION consist of a production process review and/or additional laboratory work 13

14. LABORATORY ERROR Laboratory error is the cause of OOS result which may occur from instrument, reagent, reference standard, environment condition, test method, analyst and calculation within laboratory. 14

15. Types of laboratory errors 15

16. PROCEDURE OF OOS REPORTING TO LABORATORY SUPERVISOR RECORDING AND NUMBERING OF OOS INVESTIGATION BY ANALYST LABORATORY TESTING APPROVAL BY LAB. SUPERVISOR TESTING BY ANALYST 16

17. PROCEDURE OF OOS PREPARATION OF TEST REPORT EVALUATION OF SUSPECT RESULTS. INVESTIGATION BY TECHNICAL MANAGEMENT TEAM. CONCLUSION AND REPORT OF DATA. EVALUATION BY QUALITY MANAGER. 17

18. OOS INVESTIGATIONS Re-testing: The analysis of original sample at the time of phase- I laboratory investigation . Re-sampling: The original batch is sampled by QA second time after QA head authorization for re-analysis . Re-analysis: The analysis of re-sampled material for the verification of results, if manufacturing investigation does not have root cause. 18

19. 19 Regulatory impact on oos Stability study required OOS should be reported to RA OOS batch should not be sold to Regulatory market OOS batch can not be blend with fresh approved batch OOS batch can not be directly sell to the market

20. OUT OF TRENDS (OOT) 20

21. WHAT IS OUT OF TREND (OOT) ? A result that does not follow the expected trend, either in comparison with other stability batches or with respect to previous results collected during a stability study . More complicated than a comparison to specification limits. 21

22. CRITERIA TO CONSIDER A RESULT AS OOT ! For ASSAY: 5% Change in initial value of assay. For IMPURITIES: Between 0.1 to 0.2 % increase or decrease as per initial reports . 22

23. Oot can be due to:- ASSIGNABLE CAUSE : Laboratory errors NON- ASSIGNABLE CAUSE: Non-laboratory errors. 23

24. Method for identifying oot For the purpose of this study, data from ongoing stability studies of a final drug product with a shelf life of 36 months is used. The ongoing studies were conducted on 10 batches of Product X. (solid dosage form) The ongoing studies were conducted for 36 months in stability chambers at a constant temperature of 25 °C ± 2 °C and relative humidity of 60% ± 5% in accordance with the ICH guideline Q1A. Analyst should carry out a assay at a time point of 0,3,6,9,12,18,24 and 36 months for all batches. 24

25. Types of oot determination: Regression-control-chart-method . The regression-control-chart method is used to compare the results within the batch and detect present OOT results. For the purpose of this method, the tenth batch is examined . By-time-point method. The by-time-point method is used to determine whether a result is within expectations on the basis of experiences from other batches measured at the same stability time point. 25

26. Oot cycle 26

27. WHO, Quality Assurance of Pharmaceuticals, Vol 2, Second Edition http ://www.who.int/medicines/areas/quality safety/ quality_assurance /production/en / Choudhary A. What is Change Control ? . Pharmaguideline.com. 2017 . Available from: http:// www.pharmaguideline.com/2010/11/what-is-change-control.html Fda.gov . 2017 . Available from: https:// www.fda.gov/downloads/drugs/guidances/ucm070287 OOS , OOT, OOC, and OOSC Pharmtech.com. 2017 Available from: http:// www.pharmtech.com/oos-oot-ooc-and-oosc 27 REFERENCE:

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