IMPORTANCE OF QUALITY SYSTEM

1. CONCEPT OF CHANGE CONTROL,
OUT OF SPECIFICATIONS (OOS) AND
OUT OF TRENDS (OOT)
P R E S E N T E R :
MR. AMOGH P. DANDEKAR
FIRST YEAR M.PHARM
DEPT. OF PHARMACEUTICAL QUALITY ASSURANCE
REG.NO: NH0117005
DATE: 14/11/2017
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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)
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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
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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.
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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
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8. CONDITIONS FOR CHANGE CONTROL
 Revalidation
 Requalification
 Increased testing
 Stability analysis
 Document change
 Regulatory action / variation application
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10. OUT OF SPECIFICATIONS
(OOS)
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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.
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12. OOS IS OBSERVED IN ANALYSIS OF:
 Stability study
 Finished product
 In-process
 Raw materials
 Packing materials
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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
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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.
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15. TYPES OF LABORATORY ERRORS
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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
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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.
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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

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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)
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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.
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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 .
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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.
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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
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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
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REFERENCE:

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