LABAID PHARMACEUTICALS LIMITED

Plant: 15, Genda, Savar, Dhaka-1340, Bangladesh.

STANDARD OPERATING PROCEDURE

TITLE: PROCEDURE ON DOCUMENT CONTROL DEPARTMENT : Quality Assurance

SOP NO. : SOP/QC/056/02
VERSION NO. : 02
PAGE NO. : Page 1 of 16

ISSUE DATE : 11-January-2016 REVIEW DATE : 11-January-2019

EFFECTIVE DATE : 18-January-2016 SUPERSEDES : SOP/QC/056/01

REVIEW AND APPROVAL

Prepared by: Checked by: Approved by:

[Signature] [Signature] [Signature]

Name : Shiuli Das Name : Md. Saiful Alam Name : Sukhi Karan

Job Title : Sr. Executive, Job Title : Assistant Manager, Job Title : AGM, Quality
Quality Control Quality Control Assurance

Date : Date : Date :

DISTRIBUTION :

1. AGM, Quality Assurance (Original Copy)

2. Quality Control

3. Analytical Laboratory

4. Quality Compliance

DO NOT MAKE A COPY OF THIS SOP. SOPs CAN ONLY BE COPIED BY THE HEAD OF QUALITY
ASSURANCE OR HIS/ HER DESIGNATE.
 LABAID PHARMACEUTICALS LIMITED
Plant: 15, Genda, Savar, Dhaka-1340, Bangladesh.

STANDARD OPERATING PROCEDURE

TITLE: : PROCEDURE ON DOCUMENT CONTROL DEPARTMENT : Quality Assurance

SOP NO. : SOP/QC/056/02
VERSION NO. : 02
PAGE NO. : Page 2 of 16

1. Purpose :
To define a system for the management (i.e. preparation, numbering, review, approval,
implementation, distribution and archive) of Quality Documents.
2. Scope :

This procedure is applied to the quality documents (hereinafter called “documents”),

Holder of Original Document except External document which
consist of reference, national / international standard.

3. Definitions / Abbreviation:

3.1

4. Responsibilities:
The roles and responsibility is as follows:

Roles Responsibility

 Analysis of any product or materials and to notify the OOS results to

Executive, QC
supervisor.

 To ensure the initial investigation of the test parameters and to

Sr. Executive, QC
organize the testing.

 To ensure that this procedure is kept up to date.

 To confirm that the SOP reflects the required working practices.

Manager, Quality Control  To make decision for re-sampling.

 To arrange training on the SOP to all concerned personnel and to

ensure implementation of the SOP after training.

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 LABAID PHARMACEUTICALS LIMITED
Plant: 15, Genda, Savar, Dhaka-1340, Bangladesh.

STANDARD OPERATING PROCEDURE

TITLE: : PROCEDURE ON DOCUMENT CONTROL DEPARTMENT : Quality Assurance

SOP NO. : SOP/QC/056/02
VERSION NO. : 02
PAGE NO. : Page 3 of 16

 Approval of the SOP.

AGM, Quality Assurance  To take the final decision to release the batch.

 To ensure the overall implementation of the SOP.

5. Revision Details:

Sl. Version
Effective date Change History
No. no.

01 01 28-January-2013 New SOP

 Title of SOP has been changed

 Upgraded the contents of “Scope and Procedure”

02 02 18-January-2016
 Inclusion of annexure-II, annexure-III, annexure-IV, annexure-V
and annexure-VI

6. Annexure:

 Annexure-I: Notification of Out of Specification Result

 Annexure-II: Flow Chart for OOS Investigation

 Annexure-III: Out of Specification (OOS) Register

 Annexure-IV: Out of Specification (OOS) Investigation Checklist

 Annexure-V: Out of Specification (OOS) Testing Protocol

 Annexure-VI: Out of Specification (OOS) Investigation Report

7. Procedure:
7.1 The procedure mentioned below shall be followed if a Laboratory result for raw materials sample,
In-process Sample or Finished Product sample fails to meet the Specification.
7.1.1 Analyst shall not destroy the sample preparation / solution and shall retain the prepared solutions,
Standards and Sample solutions until the investigations have been concluded.
7.1.2 Retain all Glassware, Blend & Finished Product Sample.
7.1.3 Check the whole analysis for compliance (Self-check).

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Plant: 15, Genda, Savar, Dhaka-1340, Bangladesh.

STANDARD OPERATING PROCEDURE

TITLE: : PROCEDURE ON DOCUMENT CONTROL DEPARTMENT : Quality Assurance

SOP NO. : SOP/QC/056/02
VERSION NO. : 02
PAGE NO. : Page 4 of 16

7.1.4 Inform immediately to the Supervisor about the OOS result.

7.1.5 Supervisor will discuss with the analyst about the test method and confirm analyst knowledge of
and performance of the correct procedure.
7.1.6 Check if a laboratory error could be the cause of OOS results and inform Manager, QC.
7.1.7 Check and record the present conditions in Notification of out of specification (OOS) result as per
Annexure-I.
7.1.8 Follow the Flow Chart (Annexure-II) for OOS Investigation
7.1.9 The QC Manager should assess the data promptly to ascertain if the results may be attributed to
laboratory error, or whether the results could indicate problems in the manufacturing process.
7.1.10 It is to be clarified together with the QC Manager whether there is an apparent analytical error. A
formal check is to be carried out (Investigation stage 1) using Out of Specification (OOS) Results
Investigation Checklist (Annexure – IV) which shall be issued by QC Manager making entry in the
Out of specification investigation register (Annexure – III) and assigning sequential number as
below:
e.g. OOS-001/16
Where, OOS is the abbreviation of Out of Specification
001 is the sequential number of Out of Specification investigation
/ is separator
16 is last two digits of year 2016
7.1.11 At the first step, the QC Manager along with Analyst shall immediately try to find out any obvious
Error (Example: Calculation error, Power outage, Equipment failure, Testing Error, Incorrect
Instrument Parameters etc.)
7.1.12 If any calculation error is found out, make correction the calculation and release the
material/product; analyst shall be re-trained for the error parts.
7.1.13 If the calculation / documentation are correct, proceed with the investigation of the stepwise
analysis which may include re-examination of the actual solutions, test units, glassware used in
the original measurements and preparations.
7.1.14 The following steps should be taken as part of the investigation:
7.1.14.1 Discuss the test method with the analyst; confirm analyst knowledge of and performance of the
correct procedure.
7.1.14.2 Examine the raw data obtained in the analysis, including chromatograms and spectra, and
identify anomalous or suspect.
7.1.14.3 Confirm the performance of the instruments.
7.1.14.4 Determine that appropriate reference standards, solvents, reagents, and other solutions were

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TITLE: : PROCEDURE ON DOCUMENT CONTROL DEPARTMENT : Quality Assurance

SOP NO. : SOP/QC/056/02
VERSION NO. : 02
PAGE NO. : Page 5 of 16

used and that they meet quality control specifications.

7.1.14.5 Evaluate the performance of the testing method to ensure that it is performing according to the
standard expected based on method validation data.
7.1.14.6 Document and preserve evidence of this investigation.
7.1.14.7 Where a transient equipment malfunction or other problem in the dosage form (e.g. incomplete
extraction) is suspected, re-inject the retained sample preparations to assign a cause for OOS
results.
7.1.14.8 When laboratory error is identified, determine the source of that error (root cause) generating
CAPA as per the SOP for ‘Corrective and Preventive Action’ (SOP/QCOM/015/XX) and take
corrective action to ensure that it does not occur again. Recommend on Out of Specification
(OOS) Results Investigation Checklist (Annexure – IV) for performing a repeat analysis on the
same sample with the same analyst. If the repeat analysis result is passing, void the initial result
and approve the batch based on the re-test result.
7.1.14.9 If no apparent analytical error can be found, i.e. evidence of laboratory error remains unclear,
investigation stage 2 should be conducted to determine what caused the unexpected results,
which may include re-testing and/or re-sampling and further investigation.
7.1.14.10 Before further investigations are carried out during the next step, the subsequent procedure has
to be written down in the testing protocol (Annexure – IV).
7.1.14.11 Tasks in testing protocol:
 “What” is to be done (retesting, re-sampling, etc.)?

 “Who” will be carrying out the investigations (1st analyst, 2nd analyst, etc.)?

 “How” will the investigations be carried out, which equipment, which reagents, additional
analysis of reference samples (state batch and number of analysis)?

 “How often” will the analysis be repeated (final criterion to prevent “analysis” into

“compliance”)?

7.1.14.12 A justification for the procedure must be given by the QC manager prior to implementation of the
testing protocol and the test plan must be approved.
7.1.14.13 The number of retests should be 3 times or more
7.1.14.14 The investigation may involve re-testing a portion of the original sample. The sample used for the
retesting should be taken from the same homogeneous material / product that was originally
collected for the lot/batch, tested and yielded the OOS result. For a liquid, it may be from the
original unit liquid product or composite of the liquid product; for a solid it may be an additional

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Plant: 15, Genda, Savar, Dhaka-1340, Bangladesh.

STANDARD OPERATING PROCEDURE

TITLE: : PROCEDURE ON DOCUMENT CONTROL DEPARTMENT : Quality Assurance

SOP NO. : SOP/QC/056/02
VERSION NO. : 02
PAGE NO. : Page 6 of 16

weighing from the same sample composite that had been prepared by the analyst.
7.1.14.15 Decisions to retest should be based on the objectives of the testing and sound scientific
judgment. Retesting should be performed by an analyst other than the one who performed the
original test.
7.1.14.16 If the result is within specification (passes), the material/product shall be re-analyzed by first
analyst with the same sample and to investigate the first analyst.
7.1.14.17 If investigation of first analyst found satisfactory then release the material/product
7.1.14.18 If the material/product fails by the second analyst also, simultaneously analyze after re-sample
with the previously approved material/product.
7.1.14.19 Re-sampling should involve analyzing a specimen from the collection of a new sample from the
batch. A re-sampling of the batch should be conducted if insufficient quantity of the original
sample remains to perform all further testing or if the investigation shows that the original sample
was not representative of the batch. This would be indicated, for example, by widely varied
results obtained from several aliquots of the original composite (after determining there was no
error in the performance of the analysis). Re-sampling should be performed by the same
qualified, validated methods that were used for the initial sample. However, if the investigation
reveals that the initial sampling method was in error, a new accurate sampling method must be
developed, qualified and documented.
7.1.14.20 If previously approved material/product passes within the specification and material/product
under investigation meets the specification, release the material/product.
7.1.14.21 In case of material if previously approved material passes within the specification and material
under investigation fails to meet the specification, material shall be rejected.
7.1.14.22 In case of product if previously approved product passes within the specification and product
under investigation fails to meet the specification, the laboratory investigation may be extended
to review the quality of the materials (raw & primary packaging) used in manufacturing of the
finished product. If any problem in quality of the materials is identified which may have potential
effect on the OOS scenario, the root cause will be attributed to that problem.
7.1.14.23 The procedure is then to be implemented and the results be evaluated. The results are to be
summarized in Annexure – VI (report level 2).
7.1.14.24 Conclusion must be drawn and it must be stated which individual values will be entered in the
result (on Certificate of Analysis).
7.1.14.25 The error category of the initial OOS result must also be recorded.
7.1.14.26 At measures, a statement must be made explaining how similar OOS results are to be avoided in
future.

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STANDARD OPERATING PROCEDURE

TITLE: : PROCEDURE ON DOCUMENT CONTROL DEPARTMENT : Quality Assurance

SOP NO. : SOP/QC/056/02
VERSION NO. : 02
PAGE NO. : Page 7 of 16

7.1.14.27 During investigation of an OOS result, review the previous investigation reports to determine
whether a similar occurrence has taken place.
7.1.14.28 When the laboratory investigation does not determine that laboratory error caused the OOS
result and testing result appears to be accurate, the laboratory investigation/report to be handed
over to QA manager for a full-scale failure investigation as per the SOP for ‘Deviation Procedure’
(SOP/QCOM/003/XX).
7.1.14.29 In case the process error is identified during failure investigation, suitable corrective action shall
be taken. Sample shall then be analyzed as per routine procedure and accordingly release, if the
results are okay.
7.1.14.30 Quality Assurance Manager will initiate the CAPA based on root cause found in the failure
investigation. CAPA must be implemented within agreed time lime. All CAPAs must be
implemented based on criticality.

Annexure-I
Notification of Out of Specification (OOS) result

LABAID PHARMACEUTICALS LIMITED

Plant: 15, Genda, Savar, Dhaka-1340, Bangladesh.

Notification of Out of Specification (OOS) result

1. Name of product :
2. Batch No. :
3. Date of Manufacture :
4. Date & Time of Analysis :
5. Name of Analyst :
6. Type(s) of OOS :
7. Analytical Specification No. :
8. Method Ref. No. :
9. Equipment used (details)
a) Name :

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Plant: 15, Genda, Savar, Dhaka-1340, Bangladesh.

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TITLE: : PROCEDURE ON DOCUMENT CONTROL DEPARTMENT : Quality Assurance

SOP NO. : SOP/QC/056/02
VERSION NO. : 02
PAGE NO. : Page 8 of 16

b) Calibration date and time :

c) Others :
10. Reference standard details :
11. Reagents used :

12. Environmental condition :

Remarks

Analyzed By: Checked By:

Name : Name :
Designation: Designation:
Date : Date :

ANNEXURE – II
OUT OF SPECIFICATION (OOS) FLOW CHART

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SOP NO. : SOP/QC/056/02
VERSION NO. : 02
PAGE NO. : Page 9 of 16

Analysis
Result

Release NO OOS Result?

YES Inform QC
Supervisor/Manager
Document Calculation Preliminary
and Correct Error Investigation
Invalid
Result
Obvious
Error Investigation Stage 1
Obvious analytical error
Repeat (Check list)
Analysis No Error
(n=1) Laboratory Found
Error

Laboratory
Investigation

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TITLE: : PROCEDURE ON DOCUMENT CONTROL DEPARTMENT : Quality Assurance

SOP NO. : SOP/QC/056/02
VERSION NO. : 02
PAGE NO. : Page 10 of 16

Testing Protocol Investigation Stage 2

Unobvious analytical or other
error (Testing protocol)

NO Re-testing (n≥3) Re-sampling Further investigation

Investigation
concluded?

YES

Analytical error Sample error Product failure Unknown error

Investigation Report
Investigation
CAPA
report
Review

ANNEXURE – III

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SOP NO. : SOP/QC/056/02
VERSION NO. : 02
PAGE NO. : Page 11 of 16

OUT OF SPECIFICATION (OOS) REGISTER

Date OOS No. Product / Batch Stage Test Description of Sign & Remarks
Material No. / Lot OOS date
Name No.

Annexure-IV
OUT OF SPECIFICATION (OOS) INVESTIGATION CHECKLIST

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SOP NO. : SOP/QC/056/02
VERSION NO. : 02
PAGE NO. : Page 12 of 16

LABAID PHARMACEUTICALS LIMITED

Plant: 15, Genda, Savar, Dhaka-1340, Bangladesh.

OUT OF SPECIFICATION (OOS) INVESTIGATION CHECKLIST

Specification Reference No. : Valid from :
Analytical Method Reference No.: Valid from :
Out of Specification Reference No.: Out of Specification Date:
Enclosure:
Investigation of OOS Results (Report Level 1):
Sample identification
Product / Material Name :
Product / Material Code :
Batch No. /Lot No. : Mfg. Date: Exp. Date:

OOS Result
Stage :

Test : Results : Limit :

Analyzed By : Date :

Checklist
Possible cause YES NO Not Applicable
Documentation
i) Calculation error
ii) ………………..
iii) ………………..
Procedure
i) Incorrect procedure
ii) Deviation from procedure
Working Standard
i) Correct standard
ii) Expiration date OK
iii) Storage OK
iv) Initial weight OK
v) Dilution OK
vi) ………………..

Possible cause YES NO Not Applicable

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SOP NO. : SOP/QC/056/02
VERSION NO. : 02
PAGE NO. : Page 13 of 16

Condition of sample
i) Correct sample
ii) Storage OK
iii) Initial weight OK
iv) Dilution OK
v) ………………
vi) ………………
Balance ( Balance ID : )
i) Calibration OK
Instrument ( Instrument ID : )
i) Calibration OK
ii) Parameter set Correctly
iii) Injector Correct
iv) Detector correct
v) …………………..
vi) ………………….
System Suitability Test (SST)
i) System suitability test carried out
ii) SST OK
iii) ……………….
iv) ……………….
Reagent
i) Physical appearance OK
ii) Validity OK
Volumetric standard solution.
i) Physical appearance OK
ii) Validity OK

Diagnosis YES NO Not Applicable

Apparent evaluation fault
OOS Testing level 2

Measures:

Designation Signature Date

Analyst
Supervisor/ Manager, QC
AGM, QA

Annexure-V

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VERSION NO. : 02
PAGE NO. : Page 14 of 16

OUT OF SPECIFICATION (OOS) INVESTIGATION PROTOCOL

LABAID PHARMACEUTICALS LIMITED

Plant: 15, Genda, Savar, Dhaka-1340, Bangladesh.

OUT OF SPECIFICATION (OOS) INVESTIGATION PROTOCOL

Specification Reference No. : Valid from :
Analytical Method Reference No.: Valid from :
Out of Specification Reference No.: Out of Specification Date:
Enclosure:

Sample identification
Product / Material Name :
Product / Material Code :
Batch No. /Lot No. : Mfg. Date: Exp. Date:

Repetition of Analysis (retesting)

Analyst Number of determinations
i) Analyst 1
ii) Analyst 2
iii) …………….
Instrument Comments
i) Instrument (ID: )
ii) Instrument (ID: )
)Reagent
i) Same reagents
ii) Other reagents
Others
i) Analysis of reference sample
ii) ……………..
Repetition of sampling (re- sampling)
i) Sampling plan
Additional investigations

Reasoning:
………………………………………………………………………………………………………………….

Name Designation Signature Date

Analyst
Supervisor/ Manager, QC
AGM, QA

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VERSION NO. : 02
PAGE NO. : Page 15 of 16

Annexure-VI
OUT OF SPECIFICATION (OOS) INVESTIGATION REPORT

LABAID PHARMACEUTICALS LIMITED

Plant: 15, Genda, Savar, Dhaka-1340, Bangladesh.

OUT OF SPECIFICATION (OOS) INVESTIGATION REPORT

Valid from :
Analytical Method Reference No.: Valid from :
Out of Specification Reference No.: Out of Specification Date:
Enclosure:
Investigation of OOS Results (Report Level 2):
Sample identification
Product / Material Name :
Product / Material Code :
Batch No. /Lot No. : Mfg. Date: Exp. Date:

Repetition of Analysis (retesting) by Analyst-2

Assigned By/ Date: Assigned To/ Date:

Results Limit Remarks

Test-1
Test-2
Test-3
Test-4
Test-5
Average
Analyzed By : Date :

Repetition of Analysis (retesting) by Analyst-1 in case of sample comply with Analyst –2

Assigned By/ Date: Assigned To/ Date:

Results Limit Remarks

Test-1
Test-2
Test-3
Test-4
Test-5
Average
Analyzed By : Date :
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Plant: 15, Genda, Savar, Dhaka-1340, Bangladesh.

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Repetition of Sampling & Analysis

Assigned By/ Date: Assigned To/ Date:
Results Limit Remarks
Test-1
Test-2
Test-3
Test-4
Test-5
Average
Analyzed By : Date :

Measures:

Designation Signature Date

Name
Analyst
Supervisor/ Manager, QC
AGM, QA

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