Out of specifications (oos)

history of oos,investigation,Phase-I, Phase-II

1. OUT OF SPECIFICATIONS (OOS) Dept. Of Pharmaceutics. Geethanjali College of Pharmacy Cheeryala (V) Keesara (M), Medchal-Malkajgiri Dist. Telangana, INDIA Pin Code-501301. PRESENTED BY ZOHA SULTANA (18Z51R0047) Under the Guidance of Asst. Professor Naga Chandrika M. Pharm Geethanjali College of Pharmacy 1-14 1

2. Handling OOS (Out of Specification) Geethanjali College of Pharmacy 2-14

3. What is Out of Specification (OOS) ? The re sult obtained out of defined test limit is called out of specification. USFDA guideline “Investigating Out of Specification (OOS) Test Results for Pharmaceutical Industry” Published by CDER in Oct 2006. Quality unit should have well define SOP for OOS The scope of SOP should be well defined Geethanjali College of Pharmacy 3-14

4. HISTORY OF OOS GUIDELINE Geethanjali College of Pharmacy 4-14 Event Year USFDA audited Barr Laboratory, identified attempt of “Test until pass” and other abnormality, Resulted in 483 1989/1991/1992 FDA prosecuted Barr Laboratory , Court directed to FDA to draft the OOS guidelines Feb 1993 FDA generated draft OOS guideline Sept 1998 FDA published final OOS guideline Oct 2006

5. Laboratory Investigation Must be Thorough Timely Unbiased Well documented Scientifically sound Oos investigation Geethanjali College of Pharmacy 5-14

6. Laboratory Investigation Check list to identify obvious Laboratory error 1. Analyst qualification and training on intended work 2. Correctness Test specification and Method 3. Instrument calibration or performance 4. Preparation test solutions and dilutions 5. Validity of Reagents and standards 6. Performance of system suitability 7. Correctness of calculation and etc… OOS Investigation –(Phase I) Geethanjali College of Pharmacy 6-14

7. Laboratory Investigation If Analyst Error identified, it should be : => logical and appropriate => not on hypothetical basis Identify appropriate assignable cause for Laboratory error Correct the error, and repeat the analysis to invalidate the OOS. Suggest the Corrective and Preventive actions e.g. training to the Analyst, Requalification of Analyst etc. whatever is scientifically appropriate. OOS Investigation –(Phase I) Geethanjali College of Pharmacy 7-14

8. Extended Investigation If no assignable cause found in Phase I investigation, Phase II investigation should be initiated => Retesting of Material with other analyst (n > 3) => Resampling and testing => Investigation at plant => Further Extend investigation (upon rejection) OOS Investigation –(Phase II) Geethanjali College of Pharmacy 8-14

9. Tool for OOS Investigation & Related Corrective and Preventive action Geethanjali College of Pharmacy 9-14

10. 5M – Tool to Identify the Route cause -Man -Machine -Material -Method -Movement Geethanjali College of Pharmacy 10-14 Identify the Suspect

11. - Target the suspect -Use 5 why technique to reach at root cause -Ask Why, Why, Why, Why and Why five times and try to reach at more probable reason -To check the reason scientifically sound –Process each reason with six sigma technique. -DMAIC Geethanjali College of Pharmacy 11-14 Scan the Suspect

12. Six Sigma Technique (DMAIC) -Define -Measure -Analyze -Improve -Control Geethanjali College of Pharmacy 12-14 Process the Root cause

13. Draw appropriate root cause Root cause should be logical and scientific Collect the historical evidence if any with same process or any other process in the plant Identify the need for extend the investigation to past or future batches… Provide corrective action (corrective action should be reviewed against similar process in the plant for no impact) Conclude the activity in timely manner. Geethanjali College of Pharmacy 13-14 Corrective and Preventive Action

14. DR Ravi Kinhikar https ://www.slideshare.net/DrRaviKinhikar/out-of-specification-oos1 Thank you! Zoha Sultana Geethanjali College of Pharmacy 14-14 Source References and Authors: