Annexure – I

OOS investigation

Product Name : Pseudoephedrine Base

Batch Number : 804515

OOS Number : OOS/075/15

Test Parameter : Related substance by HPLC

Description of the OOS:

 During the related substance analysis of pseudoephedrine base the un-identified impurity found
0.15 % (Retention time 5.19min) against the limit NMT 0.1% for the batch number 804515.
Detailed Investigation:

 The analysis was performed in HPLC ID. NO-LC003 ,Verified it's calibration status found
satisfactory.
 Interacted with the analyst about his knowledge in instrument and test method found
satisfactory.
 Reviewed the raw data (Preparation of sample standard) and system suitability chromatogram
there is no discrepancy observed.
 In the same sequence three batches has been analyzed i-e 804315 ,804415 and 804515 .In that
804515 batch only the unidentified impurity found 0.15%.The results were tabulated below
Batch no Unidentified Unidentified impurity Spec limit
impurity @RT in results in %
minutes
804315 3.67 0.005 NMT 0.1%
804415 5.246 0.04 NMT 0.1%
804515 5.193 0.15 NMT 0.1%

 Hence the initial OOS laboratory investigation started with retesting of original solution for the
batch number 804515,the results were tabulated below
Batch no Unidentified Unidentified impurity Spec limit
Original solution impurity @RT in results in %
minutes
804515 5.188 0.15 NMT 0.1%

 During the OOS initial investigation it is carried out as per attached check list there is no
 obvious laboratory found .Hence it is decided to start the full scale investigation to find out the
root cause of this failure after getting QA comments.

 To confirm the OOS ,it is decided to analysis one passed batch along with OOS batch. The
obtained results were tabulated below

Batch no Unidentified Unidentified Unidentified Spec limit

Reanalysis with impurity @RT in impurity impurity results in %
passed batch minutes results in % (previous result)
804415 3.76 0.002 0.04 NMT 0.1%
804515 3.761 0.003 0.15 NMT 0.1%

 In the initial analysis the unidentified impurity observed at the retention time of about 5
minutes for the batch numbers 804415 and 804515 ,the obtained results were 0.04% ,0.15%
respectively.

 At the same time in the reanalysis of these above mentioned two batches at the retention of
about 5 minutes there is no peak observed. The unidentified peak observed at the retention time
of 3.7 minutes only .In that same retention time initial analysis also unidentified impurity
found about 3.7 minutes.

Comparison table of initial analysis and retest-1 at the RT about 3.7

minutes(Unidentified impurity)

Batch no Unidentified impurity Unidentified Unidentified impurity Spec limit

@RT in minutes impurity results in results in %
% Retest-1 results with RT
Initial analysis
804415 3.67 0.004 3.76RT 0.002 NMT 0.1%
804515 3.67 0.004 3.76RT 0.003 NMT 0.1%

 Hence the unidentified impurity found at 5 minutes might have been the contaminant peak. It
might have contaminated in during the sample preparation of glassware's such as volumetric
flask,pipets .

 To reconfirm the result it is decided to test the oos batch and 804315 batch with another
chemist. The obtained results were tabulated below,
Retest-2
Batch no Unidentified impurity Unidentified impurity results in % Spec limit
@RT in minutes Retest-2
804315 - ND NMT 0.1%
804515 - ND NMT 0.1%

 After completion of Retest 2 it is clearly identified that the initial analysis the unidentified
peak observed about 5 minutes due to contamination of solution or glassware's.

 Hence it decide to invalidate the chromatograms of initial analysis and the results taken from
retest analysis for release the batch.
Root cause

 Based on the above detailed investigation the root cause of the OOS it may be due to
Contamination of glassware's or solution during the preparation.

Corrective action

 The Re-testing - 1 has been performed with another chemist with one passed batch
Bach No.:804415, both batch result complies as per specification.

 The Re-test -1result complies as per specification hence the Re-test -2 performed with other
batches analyzed in the same sequence and Re-test-2 results complies as per specification.

 The Re-test -1 and Re-test -2 both analysis there is no impurity detected at the retention time
5.19 min and result .

 The initial analysis result invalidated.

Preventive action

 The training has to be given as per glassware cleaning standard operation procedure for all
analyst and casual labors who are all involving cleaning of glasswares.

Prepared by Reviewed by

Date : Date :