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Dear all
I have a question in the Bioequivalence studies. During recovery
evaluation in the method validation the recovery section is evaluated
by comparing the peak areas of the extracted QC samples with the areas
of the equivalent pure standard solution samples, however from
regulatory point of view is the QC amount result considerable; is it
acceptable to use the areas of failed amount QCs to evaluate recovery?.
Thanks in advance
Isra
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The following message was posted to: PharmPK
Dear Isra,
As you said a failed QC is the one FAILED. so you should not go for
reporting such a value to the regulatory if your batch is failed. when
you fullfull the pass criteria for a precision and accuracy batch then
you may have to consider taking the value else omit the value.
In case batch passes with few QCs as failed, then also you may
consider them because recovery is a treated as a global parameter and
is consistant irrespective of the concentration within the range of
the curve. In such a case the global standard deviation of recovery
for all the samples put together will be most often within the limit.
Hope this helps.
Santosh Tata
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The following message was posted to: PharmPK
If they failed they failed.
You could also prepare standards in matrix vs initial mobile phase and
compare recoveries over the range.
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Dear Isra,
For extraction recovery experiment it would be more appropriate to
compare the peak areas of the extracted QC samples with the areas of
the samples generated by extracting plasma blanks and spiked with
equivalent neat standards (as 100 %). Here, you are simulating same
matrix components in both set of samples, and evaluating the amount of
the extraction.
Performing the extraction recovery experiment need not to be under a
calibration curve, Then the question doesn't arise like failed or
passed. Do the experiment with 6 replicates at each concentration
level (at 3 QC levels).
Hope I answerd ur question
Best regards
Raja Reddy
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Dear Isra,
Recovery experiment in method validation can be done in two ways. 1)
Aqueous: In this method extracted area is compared with that of
aqueous area of same concentration. 2) Post Extraction recovery: In
this method plasm blanks are processed as per method and during
reconstitution( If it is LLE method) or Elution( if SPE method)
Working Quality control and Internal standard are spiked. In recovery
experiment sample identification is kept as unknown instead of QC.
Outlier can be applied to area which is abnormal and then calculate
the recovery.
thanks,
with regards,
Rashmi Shiju
Dhirubhai Ambani Life Sciences,R-282,T.T.C. Inustrial area,Opp. Rabale
stationnavimumbai-400701
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Dear Isra,
yes we can calculate recovery on the basis of using QC level sample ,
what we are doing is , taking mean of area of all batch QCs
(extracted) and comparing area with that of unextracted.
i think we can should avoid taking failed QC as Failure might be due
to any reason like processing error or spiking error or etc. in such
case due to including 1 or 2 QC s in total mean it might spoil the
case !
so its advisable to take passing QC s only
--
dear rashmi,
i think recovery is critical area and ti apply outlier in recovery is
questionable so if we have run of P&A showing all passed QC then its
better to go for that
regarding Post extraction recovery , Does FDA accept it ? as what i
feel is that neat recovery which you mentioned in case one is more
advisable as it does show actual recovery of drug from matrix of
plasma as in post extraction recovery we have already removed the
substance which might interfere in drug attachment so it will give you
high recovery which would not be indeed!
please share your view
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Dear Isra
You are not determining accuracy of recovery QC against calibration
standards, so where's the question of fail or pass? The areas for both
extracted QC and unextracted QC should be consistent. Generally the
samples are extracted at LQC, MQC, HQC level and post extracted
aqueous similar concentration samples are prepared and injected. Their
absolute areas are compared and mean global recovery calculated.
Regulatory point of view is that recovery should be consistent,
precise and reproducible. Therefore if any of the sample is having an
area inconsistent with rest of the areas please investigate and repeat
the exercise.
Regards
Bharat Sawnani
Group Leader
Wockhardt
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