OUT OF SPECIFICATION
SASIDA YOOSOOK
4April 2014
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ISO 17025:2005
4.9 Control of nonconforming testing
and/or calibration work
4.9.1 The laboratory shall have a policy
and procedures that shall be implemented
when any aspect of its testing and/or
calibration work, or the results of this
work, do not conform to its own
procedures or the agreed requirements of
the customer.
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WHO :Good practices for national
Pharmaceutical control
Laboratories
18 Evaluation of test results
18.4 An SOP should be in place for the
conduct of an investigation of an OOS
test result.The SOP should give clear
guidance on the number of retests
allowed (based on sound statistical
principles). All investigations and their
conclusions should be recorded.
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OOS results
all test results that fall outside the
specifications or acceptance criteria
established in drug dossiers, drug master
files (DMFs), official pharmacopoeias, or
by the manufacturer.
(WHO :Good practices for national Pharmaceutical control Laboratories)
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OOS results
all test results that fall outside the
specifications or acceptance criteria
established in drug applications, drug
master files (DMFs), official compendia,
or by the manufacturer.
(US FDA : Guideline for Industry Investigating OOSTesting
Results for Pharmaceutical Production)
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US FDA : Guideline for Industry
Investigating OOS
Testing Results for Pharmaceutical Production
The purpose of the investigation is to
determine the cause of the OOS result.
The source of the OOS result should be
identified either as an aberration of the
measurement process (laboratory error)
or an aberration of the manufacturing
process.
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US FDA : Guideline for Industry Investigating
OOS
Testing Results for Pharmaceutical Production
PHASE I: LABORATORY INVESTIGATION
◦ should include an initial assessment of the
accuracy of the laboratory’s data.
PHASE II: FULL-SCALE OOS INVESTIGATION
◦ consist of a production process review and/or
additional laboratory work
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SOP OOS (no. 2200026 )
Definition
◦ Out of Specification (OOS) means the
test result that falls outside the specifications
or acceptance criteria which has been
specified in the official compendia
monographs or the finished product
specification in registration dossiers.
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SOP OOS (no. 2200026 )
Purpose
◦ This SOP describes the procedure for
investigating out of specification test result.
Application
◦ This procedure is applicable to the test result
that falls outside the specifications or
acceptance criteria
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SOP OOS (no. 2200026 )
Definition
◦ Laboratory error is the cause of OOS
result which may occur from instrument,
reagent, reference standard, environment
condition, test method, analyst and
calculation within laboratory.
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Data record and Used document
Out of Specification Check
List
(WS 2200026/1)
Out of Specification Report
(WS 2200026/2)
List of Out of Specification
(WS 2200026/3)
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PROCEDURE SOP. OOS (no. 2200026 )
1. When the OOS result is found, analyst
should inform laboratory supervisor
immediately.
2. Before start the OOS investigation,
analyst should inform the quality
manager by using the Out of
Specification Report (WS 2200026/2) to
record and number the OOS.
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PROCEDURE SOP. OOS (no. 2200026 )
3. Investigation should be conducted by
the analyst and laboratory supervisor by
using the Out of Specification Check List
(WS 2200026/1).
4. Laboratory supervisor assigns an analyst
to perform the test.
5. Details of the retest procedure should
be written by the analyst or assigned
person and then approved by laboratory
supervisor.
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PROCEDURE SOP. OOS (no. 2200026 )
6. The analyst or assigned person should
perform the test by using the approved
procedure.
7. The analyst or assigned person prepares
the test report for approval by laboratory
supervisor.
8. In case that the cause of OOS could be
identified (If conclusion can be done), the
report should be approved by laboratory
supervisor.
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PROCEDURE SOP.OOS (no. 2200026 )
9. If there is inadequate data to evaluate the
investigating result (suspect result), the
investigation should repeat following the
process 4-8.
10. When the retest has already been
performed and the cause of OOS result
cannot be identified (If conclusion cannot
be done), laboratory supervisor should
inform technical management team.
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PROCEDURE SOP. OOS (no. 2200026 )
11. Technical management team considers
and evaluates the investigating result and
all the data for conclusion and report.
12.When the OOS report is complete, it
should be kept in the sample report and
the copy should be sent to the quality
manager.The OOS will be recorded in
the List of Out of Specification (WS
2200026/3) by the quality manager.
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SOP OOS (no. 2200026 )
DEFINITION
◦ Technical Management Team consists of
director, expert pharmacists, quality
manager and heads of laboratories/centers.
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Retest and reporting procedure
1. When the cause of OOS result can be
identified as a laboratory error.
❑ Retest should be performed on the original
sample by the same analyst.
❑ Reporting procedure: the original test
result will be invalid.The retest result should
be reported.
❑ All of the original data should be retained,
and an explanation should be written.
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Retest and reporting procedure
2. In case of the cause of the OOS result
could not be identified as a laboratory
error:
❑ Retest should be performed by a different
analyst.
❑ The retest should not be done more than 3
times including the test by the first analyst.
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Retest and reporting procedure
❑Reporting procedure can be defined into 2
cases:
❖If the retesting result has confirmed the OOS result,
the original OOS result should be reported. If the
RPD of the mean of the original result and the mean
of the retest result is less than 3%, it can conclude
that the retest result has confirmed the original result.
.The RPD may be justified scientifically.
❖If the OOS result could not be confirmed or the
investigation could not be concluded, the OOS result
should be further considered by the technical
management team.
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