OOS Investigation case study-7 (Assay)
OOS observed in Assay test.
(Single preparation test and duplicate injections from same vial) During investigation when
you found any root cause in Preliminary or hypothesis testing, before planning
of re-analysis, Use any of Investigation tools (5 Why, 6 M etc to rule all
other probabilities)Review it thoroughly and plan the negative experiment if
required to make the investigation more adequate.
During investigation when you found any
root cause in Preliminary or hypothesis testing, before planning of
re-analysis, Use any of Investigation tools (5 Why, 6 M etc to rule all other
probabilities)Review it thoroughly and plan the negative experiment if required
to make the investigation more adequate.
Description of Event:
OOS result observed in Assay test.
Result: 97.4% (From same vial Injection-1: 99.8%,
Injection-2:94.9%)
-Limit: 95.0 - 105.0%.
Mean result is within specification limit,
but one injection result from same vial is 94.9% which is not complying to the
specification limit, hence OOS initiated.
Preliminary investigation:
During preliminary investigation checked all possibilities
for lower Assay results like Instrument error (No pressure fluctuation , no air
bubble in mobile phase/Rinse line ) Calculation error (wrong weight, wrong
potency etc.), Standard preparation error (recovery factor of standard and
control standard is 99.8%) and all other possible causes for lower result, but
no error is identified in preliminary investigation.
During review of pressure graph it was
notice that though there is no pressure fluctuation, but at zero time (during
injection) subject injection pressure is lower than other all injections
pressure (Blank, Standard, control standard and injection-1 of sample (99.8%
result).
Zoom pressure graph: (In normal
scale graph this pressure difference may not be visible).
Based on above observation there might
be possibility that during second injection due lower pressure complete planned
volume (20µl) is not drawn by injector.
So to rule the instrument error hypothesis
testing should be planned as still we are not sure that which result is true
i.e. 99.8% or 94.9% .
Re-measurement:
Hypothesis testing is performed to rule out instrument error,
vial filling error, dilution error etc. Hypothesis is planned on different HPLC
system and all other things are remain same.
Same vial result is found within specification limit (Mean
99.6%, Injection-1: 99.7%, Injection-2: 99.5%)
Refilled (100.1%) and re-dilution (99.8%) results are found
well with in specification limit.
Based
on outcome of hypothesis , repeat testing/re-analysis can be planned from same aliquot/sample
and invalidate the initial OOS result.
Now the question is
,
Why one injection result is lower?, Is this due to low pressure
at zero time, If yes, then why lower pressure at zero time in one injection? Is
this momentary instrument malfunction? Or any other reason. We have to hand over
instrument to service engineer to identify the root cause for low pressure.
Based on service engineer
report ,scientific rational and justification we can conclude the OOS with
proper CAPA.
Impact
Assessment:
As an Impact assessment we have to evaluate at least
last 05 analysis on same instrument and after rectification of error at least
03 analysis.
During investigation when you found any
root cause in Preliminary or hypothesis testing, before planning of
re-analysis, Use any of Investigation tools (5 Why, 6 M etc to rule all other
probabilities)Review it thoroughly and plan the negative experiment if required
to make the investigation more adequate.
Description of Event:
OOS result observed in Assay test.
Result: 97.4% (From same vial Injection-1: 99.8%,
Injection-2:94.9%)
-Limit: 95.0 - 105.0%.
Mean result is within specification limit, but one injection result from same vial is 94.9% which is not complying to the specification limit, hence OOS initiated.
Preliminary investigation:
During preliminary investigation checked all possibilities
for lower Assay results like Instrument error (No pressure fluctuation , no air
bubble in mobile phase/Rinse line ) Calculation error (wrong weight, wrong
potency etc.), Standard preparation error (recovery factor of standard and
control standard is 99.8%) and all other possible causes for lower result, but
no error is identified in preliminary investigation.
During review of pressure graph it was
notice that though there is no pressure fluctuation, but at zero time (during
injection) subject injection pressure is lower than other all injections
pressure (Blank, Standard, control standard and injection-1 of sample (99.8%
result).
Zoom pressure graph: (In normal
scale graph this pressure difference may not be visible).
Based on above observation there might
be possibility that during second injection due lower pressure complete planned
volume (20µl) is not drawn by injector.
So to rule the instrument error hypothesis
testing should be planned as still we are not sure that which result is true
i.e. 99.8% or 94.9% .
Re-measurement:
Hypothesis testing is performed to rule out instrument error,
vial filling error, dilution error etc. Hypothesis is planned on different HPLC
system and all other things are remain same.
Same vial result is found within specification limit (Mean
99.6%, Injection-1: 99.7%, Injection-2: 99.5%)
Refilled (100.1%) and re-dilution (99.8%) results are found
well with in specification limit.
Based
on outcome of hypothesis , repeat testing/re-analysis can be planned from same aliquot/sample
and invalidate the initial OOS result.
Now the question is
,
Why one injection result is lower?, Is this due to low pressure
at zero time, If yes, then why lower pressure at zero time in one injection? Is
this momentary instrument malfunction? Or any other reason. We have to hand over
instrument to service engineer to identify the root cause for low pressure.
Based on service engineer
report ,scientific rational and justification we can conclude the OOS with
proper CAPA.
Impact
Assessment:
As an Impact assessment we have to evaluate at least
last 05 analysis on same instrument and after rectification of error at least
03 analysis.
Excellent, helpful tpoic
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