14.

H Out-of-specification results
Here you will find answers to the following
questions:
What is an OOS result?
For which areas do the guidelines apply?
What is the procedure and what must be
taken into consideration?
What demands are to be made on the
documentation?

What is an OOS result?

OOS (out of specification): Result out of
specification
Repetition of the analysis (retesting): Repetition
of the analysis using the same sample or
quantity of samples.
Repetition of sampling (re-sampling): Repetition
of sampling of one batch in accordance with a
predetermined plan; this may deviate from the
original plan.

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Analytical error: Deviation of an analytical result
from the true value due to mistakes made when
carrying out the testing e.g. as a consequence
of technical problems.
Product error: Deviation of an analytical result
from the true value due to insufficient product
quality as a consequence of failure in
manufacturing.
Sample error: Deviation of an analytical result
from the true value due to a failure in sample
preparation, e.g. sampling, sample mix-up,
incorrect labelling, change in quality of samples.
Unknown error: Deviation of an analytical result
from the true value due to an error that cannot
be assigned to the first three categories.

For which areas do the oos apply?

All results that are outside the specifications or

acceptance criteria established by
pharmacopoeias and the manufacturer are dealt
with within the scope of the draft.
This contains analyses for the manufacture of

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active pharmaceutical ingredients (IPC) and
final inspection of active pharmaceutical
ingredients, for excipients, for other components
and for finished products.

Identifying and assessing OOS test results

investigation must be carried out to clarify the

cause of each OOS result
This investigation must be recorded in a report
together with the conclusions made and
measures introduced.
During this process, the validity of the
laboratory results should be checked before
test solutions are discarded.
This means that the same test solution can
be used to check for (apparent) analytical
errors (note: injection errors in the case of a
chromatographic analysis, for example).
The analyst is primarily responsible for
obtaining exact results.
If OOS results are obtained, the supervisor
must be informed.

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B. Responsibility of the supervisor
In the event of OSS results, the supervisor
must proceed with the investigation
objectively, promptly and impartially.
Possible laboratory errors must be clarified
immediately providing that the test solutions
are still available (note: and stable).
The following steps must be assessed:
Discuss the method with the analyst
making sure that everything has been
properly understood and correctly carried
out.
Investigate raw data (chromatogram,
spectra).
System suitability test.
Check standards, solvents, reagents.
Check efficiency of method - also
against validation.
Document everything completely.

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General investigational principles
The investigation should be documented on
a step-by-step basis in the written records
as follows:
Reason for investigation
Summary of critical manufacturing steps
Document check with statement of real
or possible causes
Check for any previous cases of a
similar nature
Corrective action
A. Laboratory phase of an investigation
The following options are available for this
investigation:
Retesting of a partial quantity of the
original sample
The same sample that was originally

taken must be used during retesting (cf.

sampling) and the sample preparation
(initial weighing) is to be repeated.
The analysis is to be carried out by

another analyst.

Testing of a new sample from the batch

(re-sampling)
In exceptional cases, repeat sampling may be
indicated if the first clarifications demonstrate a
large spread of different aliquots. Other test
schedules can also be approved.
Calculation of new data

B. Concluding the investigation

The batch quality is assessed based on the
investigation results and the approval decision is
made.
Interpretation of investigation results
If a cause of the OOS result is found that leads
to the result being declared invalid, it should not
be used for the batch assessment. If the OOS
result demonstrates that the product quality is
impaired (OOS confirmed), the release decision
must take this into account. A confirmed OOS
result must lead to the batch being rejected and
destroyed. An appropriate decision must be

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taken with respect to inconclusive results.
Statistical approaches (outlier tests) are
generally not permissible for chemical analyses.
Reporting
For registration batches, the authorities must be
informed within 3 working days about an OOS
result

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 analyses)
HOW OFTEN will the analysis be
repeated (final criterion to prevent "analysis
into compliance")
A justification for the procedure must be given
and the form must be signed (and therefore
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approved) by the analyst and supervisor prior to
implementation.

Flow diagram

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