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To the group:
Regarding the Bioanalytical Validation of the Quantification Method
in a Bioequivalence study of a product which is a fixed-dose
combination product (Levodopa/Carbidopa or Benserazide or Zidovudine/
Lamivudine or any other):
* Are you obliged to perform each part of the validation process:
Accuracy, Precision, Recovery, Stability of each drug always in the
presence of the other?
* Would it be enough if you demonstrate Selectivity and perform
the Calibration/Standard curve of each drug (extracting from plasma)
both in the presence and in the absence of the other showing no
interaction/interference at all?
* Could you advice me about any international guideline which
addresses particularly this matter?
Thanking in advance, Silvia
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The following message was posted to: PharmPK
Dear Silvia
I feel there is no exact guidelines on this issue. This issue may come
up in upcoming Crystal City meeting on Bioanalytical issues.
I think there won't be any concerns, If you have a single validated
method to determine all analytes.
But if you have separate method I feel atleat you should perform one
experiment like precision & accuracy spiking all analytes. Some of them
they do OTC interference test, similarly you can do for other analytes
which are required to be quantitated.
I appreciate if some one comment on my suggestions.
Thanks in advance.
Nagesh
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Dear Silvia,
The ideal would be to have a validated method that simultaneously
quantifies both drugs. However, FDA guidance does not require this,
and if it is not practical, then validating each method separately
should be adequate.
If you demonstrate lack of interference of each drug on the other,
then it should not be necessary to have both drugs in all standards,
controls, etc., for the validation. However, doing so may reduce the
number of samples you need to prepare and may shorten HPLC run times.
For each analyte, I also recommend testing for interference of any
important metabolites from both administered drugs that might be
present in plasma.
Tom
Thomas Tarnowski, Ph.D.
ttarnowski1.at.aol.com
650 692-9296
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Dear Silvia,
I'm in agreement with the previous answers.
In the event that two separate assays are used, we prepare QC samples
which will mimic the clinical samples (i.e. QC samples with the
presence of both drugs).
Eventhough both methods were shown to be specific, you have no idea
what will happen during the sample storage at -20 or -80oC when both
of them are present.
Therefore, when the long term stability assessment will be done, you
will now if the presence of each compound has an impact on the other.
Regards,
Sylvain Mandeville, Ph.D.
LAB Research Inc.
www.labinc.hu
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)