Annexure – 1

OOS investigation Supplement document for Glassware contamination

OOS/042/15 and OOS/068/15
Page 1 of 5

Objective of the Supplement:

 With reference to OOS no: OOS/042/15 and 00S/068/15, It was noticed that both the
investigation reports conclusion made as glass ware contamination.

Fishbone diagram for root cause identification:

MAN METHOD CONTAMINATION

Pharmacopoeial or inhouse Glassware contamination

method
Laboratory Sample contamination
error /
Analyst Verification System peak/Peak
competent Validated
from injector or OOS in
column unspecified
Impurity
Calibration
Finished product
analytical data Preparation
Repeatability/
RM /Inprocess Calculation part
Reproducibility analytical data

MACHINE MATERIAL MEASUREMENT

 Outcome of both OOS and detailed investigation it is identified the laboratory error that which
the glassware (25/50 ml beaker) used for transfer the final concentration sample solution to
HPLC vial.

 While transferring solution to the HPLC vial using beaker there might be contamination
occurred that is the reason unknown peak eluted in initial analysis of 9020715.This is
concluded in the OOS investigation because during the original solution analysis the final
concentration solution sample transfer to HPLC vial directly the beaker not used.
 Annexure – 1

OOS investigation Supplement document for Glassware contamination

OOS/042/15 and OOS/068/15
Page 2 of 5

 Then the original solution analysis there is unknown peak elute but it is below disregard
limit(0.01%)

 To identify the other root cause if any, following investigation carried out as per fish bone
diagram

 Man/Measurement

1.The person handled the chromatographic system for initial, retest analysis are qualified and
competent to handle HPLC .

2.Discussed the test method with analysis the analysts followed the test procedure there is no
discrepancy observed. Reviewed the raw data there is no calculation error found.

3.Examined the raw data and chromatograms there is no discrepancy found in calculation and
preparation of mobilephase,standard and sample.

4.Reference standard and reagents are used as per test procedure.

5.As a part of OOS investigation different analyst are performed the analysis .
i) initial analysis-Manojkumar
ii)Original solution-Suresh

iii)Retest -Sendhilkumar

6.Sampling:

6.1.1 Sampling of finished product reviewed it is inline with the SOP and moreover original
solution and retesting of original sample complies with the specification hence it is evident that
there is no issue in sample .

 Machine

1.Ensured the HPLC instrument LC-006 which is used for analysis ,the calibration status
shown it is within calibration period .There is discrepancy found in calibration report.

2.The performance of the instrument also good based on the system suitability report it is
verified. Repeatability and reproducibility of the instrument found good.

3.The analytical column (LC-244) which is used for analysis is as per test procedure there is
no discrepancy found moreover baseline and the separation of peak has good.
 Annexure – 1

OOS investigation Supplement document for Glassware contamination

OOS/042/15 and OOS/068/15
Page 3 of 5

 Method

1.The analytical method of related substances used for Phenylephrine HCl is pharmacopoeia
method (EP).

2.The method equivalent study performed in-house related substance method versus is
pharmacopoeia method (EP) before adopt the EP test procedure. Hence there is no issue in
analytical method.(Refer AVR/PHE-02/07).

 Past History

1.While review the past history of similar OOS in Phenylephrine HCl i-e OOS/042/15 has
found with related record.

2.The results are tabulated as below

OOS Original
Initial Retest
Batch.no identified solution/ Status
results/RT results/RT
in RT
0.36% 0.03% Initial results does
9010515 -
RT10.46 RT3.32 not complies
9010515 T-1 - - 0.007%/0.26 complies
9010515 T-2 - - 0.003%/0.26 complies
Unspecified
9010515 T-3 - - 0.005%/0.26 complies
impurity
9010515 T-4 - - 0.007%/10.76 complies
9010515 T-5 - - 0.007%/10.75 complies
9010515 T-6 - - 0.008%/10.76 complies
9010515 T-7 - - 0.008%/0.26 complies

3.Identified error in preliminary OOS investigation the 50 ml beaker has used for transfer the
sample solution in to HPLC vial.After that the original solution testing the sample solution
directly transferred to the vial and the results observed there is no OOS found the calculated
unknown is within limit.

4.Glassware training has given as part of corrective action.

 Annexure – 1

OOS investigation Supplement document for Glassware contamination

OOS/042/15 and OOS/068/15
Page 4 of 5

 Material

1.Rawmaterial,inprocess raw data reviewed there is abnormality found all the obtained results
are well and within specification limit.

2.After review the API OOS investigation the initial results only observed OOS results with
respect to Unspecified impurity .During the original solution, retesting of original sample there
is no OOS found.

3.Hence it is evident that the material does not have any quality issue.

 Contamination

1.Eventhough the rootcause identified as glassware for both OOS investigation the following
hypothetical study also discussed to identify other rootcaue

2.Sytem peak

2.1.0 If it is system peak all the chromatogram it has to be eluted due to mobile phase or
diluent contamination but it not happened in both OOS.

3.The mobile phase has A&B contains Sodium octanesulphonate monohydrate buffer with
different composition with Acetonitrile.Since diluent is little different from mobile phase hence
there is a chance for system peak.

4.If the peak eluted from Injector due to some salt formation or residue in injector (since buffer
used) all original ,retest solution also it has to be eluted but it is not eluted.

4.There is no possible of carryover from injection to injection hence it is ruled out.Column

performance also good there is no extraneous peak observed in the blank except that concern
OOS batch initial analysis(9020715)
 Annexure – 1

OOS investigation Supplement document for Glassware contamination

OOS/042/15 and OOS/068/15
Page 5 of 5

 Corrective action

1.Dedicated glassware's arranged for Chromatographic technique which can be used for the
analysis.

Prepared by : Reviewed by :

Signature : Signature :

Date : Date :