OOS INVESTIGATION FOR ESOMEPRAZOLE Mg USP

AR No.: RM/180069)
VASUDHA PHARMA CHEM LIMITED OOS No.: OOS/18/004
UNIT-IV Phase-I

1. Summary of issue:
In RS by HPLC tests for Esomeprazole mg USP sample AR No. RM/180069 as per in house specification
is found out of specification result and the details of OOS are as follows,

Table-I

Date of Result
RS by HPLC Specification
analysis
Prep-1 Prep-2 Avg
Omeprazole N-Oxide ND ND ND NMT 0.1%
Omeprazole sulfone
0.025 0.02 0.02 NMT 0.2%
(Related compound A)
03/03/2018
Any other individual
0.073 0.18 --- NMT 0.1%
impurity
Total impurities 0.095 0.21 --- NMT 0.5%

2. Investigation:
2.1 Investigation has been initiated to find out the root cause for the failure of RS by HPLC Results for
Esomeprazole mg USP sample AR No.: RM/180069 batch No. CES-B/1802013. The cross functional
team consisting of Quality Control personnel.

2.2 Preliminary investigation by Analyst / Immediate supervisor:

Residual solvents test for Esomeprazole mg USP performed by GC, analyst Mr.MMVSV Prasad on
03/03/2018, by using instruments HPLC ID No. LC-03 as per current approved procedure SP & TP No.:
QCD/SP&TP/RMA0012, version No.00.
2.3 Instruments calibration Verification:
Verified the calibration details of the instrument which are used for the analysis and the details are
tabulated below:

Table-II
Instrument ID: Calibrated on Calibration Due
LC-03 03/10/2017 02/03/2018

Verified the calibration status of Balance ID No: AB-02 and details are tabulated below:
Table-III
Balance ID No. Calibrated on Calibration Due
AB-03 03/02/2018 03/03/2018
Inference: The instruments used for analysis are within the calibration acceptance period.

Page 1 of 4
 OOS INVESTIGATION FOR ESOMEPRAZOLE Mg USP
AR No.: RM/180069)
VASUDHA PHARMA CHEM LIMITED OOS No.: OOS/18/004
UNIT-IV Phase-I

2.4 Analyst Qualification & training details:

The analyst involved in the analysis is qualified and details are tabulated below.

Table-IV
Name of the Analyst Date of Qualification Qualification due date
Mr.MMVSV Prasad 05/04/2017 04/04/2019

The analyst trained on STP.

2.5 Method Verification:
Analyst followed the current approved test procedure of SP & TP No.: QCD/SP&TP/RMA0012, Version
No.:00.
2.6 Sample Verification:
The following observations were made upon sample verification by the team.
Sampling done by Mr. S. Surya Narayana patrudu as per sampling plan. He is trained on Raw material
sampling SOP (QCD/SOP/003/01) and he sampled on several products.
 Sample received on 01/03/2018.
 Analysis started on 01/03/2018.
2.7 Review of Raw data:
Review the raw data and weight prints and found that weights of the sample taken for the analysis are in
line with the SP & TP.
 Verified the sample weight in rawdata and found no abnormality.
 Verified Calculations and found ok.
2.8 Verification of glass ware:
 Verified the glass ware used for the analysis (i.e. class-A), it’s cleaned & physically verified by the
analyst before analysis.
2.9 Verification of Reagents and working standards:
Verified the reagents which are used for the test are within the validity period. The details are given
below:

Table-V
S.No Name of the reagent Make Batch No Valid up to
Mono basic sodium
1 Rankem J077B16 26/12/2018
phosphate
2 Dibasic sodium phosphate Rankem J037A16 07/12/2019
3 Phosphoric acid Rankem R145E17 07/09/2018
4 Acetonitrile Fischer scientific 234546417 02/03/2019
Omeprazole working
5 ---- OME/WS-01/17 28/06/2018
standard
Page 2 of 4
Omeprazole related
6 ----- OME-004/56/01 10/02/2019
compound A
 OOS INVESTIGATION FOR ESOMEPRAZOLE Mg USP
AR No.: RM/180069)
VASUDHA PHARMA CHEM LIMITED OOS No.: OOS/18/004
UNIT-IV Phase-I

 Based on the above data found that validity period of reagents within the validity period.
2.10 Environment conditions:
Verified the temperature records of dissolution Room in QC, found all readings were within the
acceptance criteria. Details are given below.
Hygrometer ID: QCD/DTH04
Table-VI
Temperature(°C) Humidity
Date
Min Max Min Max
03/03/2018 23.1 24.6 55 60

Acceptance criteria: Temperature 25 ± 2° C.

There was no abnormality observed regarding atmospheric conditions during the analysis.
2.11 Verification of Column:
 Analyst used the column ID: LC/OP/AS&DI &RS/001/17 for the testing of Residual solvents by GC
with HSS for Esomeprazole mg USP sample AR No.: RM/180069
 Verified the column log book and found that 372 injections are made by using this column and found
column is in good condition.
2.12 Previous History:
 There is NO similar History

2.13 Root cause identification check points:

S.No. Possible chances Justification Remarks

NO error found in
01. Verified the weight slips of samples through raw
Sample weighing weighing.
data and log book.
NO Error is found in
Sample, standard As discussed with analyst, he transferred
02. preparation and s sample and standard
weighed quantity as per STP
dilutions preparation and dilutions.

Verified the column injections and found 372

03. Column performance NO error found.
runs.

Page 3 of 4
 OOS INVESTIGATION FOR ESOMEPRAZOLE Mg USP
AR No.: RM/180069)
VASUDHA PHARMA CHEM LIMITED OOS No.: OOS/18/004
UNIT-IV Phase-I

2.14 Conclusion:
 Informed to vendor on above failure, they suggested to perform the mobile phase preparation,
sample and standard preparation in amber colour vails.
 Based on the above investigation check list with supporting data and vendor suggestion Re-perform
the analysis with same sample.
Signatures of Investigation team:

Name Designation Department Signature & Date

N. Venkatswara rao Sr. Executive Quality Control

Y.S.S RAM KUMAR Asst. manager Quality Control

A.L.V Prasad Manager Quality Assurance

Page 4 of 4