The document provides guidelines for handling out of specification test results as outlined by the USFDA. It defines an out of specification result as one that falls outside the defined test limits. It discusses the USFDA's OOS guidelines published in 2006 and notes that quality units should have a defined SOP for addressing OOS results. The SOP scope should be well defined and investigations into OOS results should be thorough, timely, unbiased, well documented, and scientifically sound. Laboratory investigations should check for errors and, if none are found, a phase II investigation including retesting and investigation at the plant may be initiated. Tools like 5M, 5 whys, DMAIC and root cause analysis should be used to identify

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
1

2. Handling OOS
(Out of Specification)

3. The result 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

4. 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

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…

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.

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)

10. 5M – Tool to Identify the Route cause
-Man
-Machine
-Material
-Method
-Movement

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

12. Six Sigma Technique (DMAIC)
-Define
-Measure
-Analyze
-Improve
-Control

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.

14. DR Ravi Kinhikar
https://www.slideshare.net/DrRaviKinhikar/out-of-specification-
oos1
Thank you!
Zoha Sultana