Annexure – I

OOS investigation

Product Name : Pseudoephedrine HCl

Batch Number : 514115-514315

OOS Number : OOS/083/15

Test Parameter : Related substance by HPLC(BP/EP)

Description of the OOS:

 During the related substance analysis of pseudoephedrine HCl the un-identified impurity
found 0.67 % (Retention time 6.327 min) against the limit NMT 0.1% for the test -2
preparation of batch number 514115 .
Detailed Investigation:

 The analysis was performed in HPLC ID. NO-LC002 ,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 other two batches has been analyzed i-e 514215 and 514315 .In that
514115 batch only the unidentified impurity found 0.67%.The results were tabulated below

Batch no Unidentified Unidentified impurity Spec limit

impurity @RT in results in %
minutes
514115 6.327 0.67 NMT 0.1%
514215 BDL BDL NMT 0.1%
514315 3.993 0.06 NMT 0.1%

 To find out the root cause for this issue Acetone was spiked in the sample 0.1 %.The peak was
found at retention time about 4.69 minutes and the same time there is no unknown peak found
in 6.327 minutes.
 Batch no Unidentified Unidentified impurity Spec limit
Original sample impurity @RT in results in %
minutes
514115 ND ND NMT 0.1%
514115 4.69(Acetone) spiked --

 After completion of the test the retesting of original sample with Acetone spiking, it is clearly
identified there is no unknown peak observed refer chromatogram data file:LCD2151319.

 To confirm this results reanalysis of same sample (514115-514315) with new sequence started

 After completion of analysis the chromatogram and raw data was verified there is no unknown
peak observed in all samples. Results were tabulated below

Reanalysis of same sample:

Batch no Unidentified impurity Unidentified Unidentified impurity Spec limit

@RT in minutes impurity results in results in %
% Reanalysis results with RT
Initial analysis
514115 6.327 0.67 BDL(ND) NMT 0.1%
514215 BDL(ND) BDL(ND) BDL(ND) NMT 0.1%
514315 3.993 0.06 BDL(ND) NMT 0.1%

 Hence the unidentified impurity found at 6.327 minutes might have been the contaminant peak.

 Based on interaction with analyst, it was understood that

1.New vials used for analysis which indicates there is no possibility of vial contamination.

2.Dedicated glassware’s used for analysis which indicates there is no possibility of

glassware contamination.

3.Analyst who used for this analysis is well familiar in this product which indicates
confident about the analyst.

4. There is no extra peaks in blank, standard injections which indicates there is no

contaminant during the analysis.

5.System washed/ flushed every analysis before start the analysis and after that mobile
phase purging/rinsing/stabilization given, hence if any impurity not eluted in the column it
must be eluted at least after two or three injections which indicates there is no issue in
system or carry over due to column

Based on the investigation , there is no proper root cause was identified. Hypothetically that
unknown peak may be due to un retained peak from column or injector or glassware.
 During investigation it was noticed that same sample performed in USP and found there is no
any unknown peaks found particular sample which indicates there is no issue in the product.

Root cause

 Based on the above detailed investigation the root cause of the OOS it may be conclude that
unknown laboratory error such as un retained peak from column or injector or glassware

Corrective action

 The initial analysis result invalidated.

 Reanalysis of original sample results were taken for release the batch

Preventive action

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

 Adequate system washing to be given for system and column with appropriate solvent to avoid
any storage of chemical residue in injector.

Prepared by Reviewed by

Date : Date :