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Dear members,
I would like to know whether change in the strain of a species need
to generate partial validation data. For example we have generated
full valiodation for one of our NCE in Sprague Dawley rat plasma and
now we are about to perform a GLP study in Long Evans rats and the
matrix remails same i.e., plasma. In this case do we need to generate
partial validation in Long Evans rat plasma?
As far as my knowledge goes USFDA does not mention anything in this
regard. Does anybody come across this kind of situation and if
anybody hold any references or guidance or citations regarding the
same, please do reply back.
Thanks,
Shivva Vittal
DMPK LAB,
Dr.Reddy's Laboratories,
HYD-INDIA
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The following message was posted to: PharmPK
Dear Mr Shiva,
This issue was discussed in 3rd AAPS/FDA bioanalytical workshop but no
decisive argument came forward in this matter. The general trend of
the debate was that validation experiments to address such differences
should not be considered the norm and should be performed when there
are method-related concerns that can be attributed to a specific
strain or sex-related difference.
So go ahead an identify you own requirements and give some suggestions
to FDA to make a new rule to be followed!
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Dear Vittal,
Though change in strain with same matrix type may not be mentioned in
FDA guidance for a partial validation. As per my logic goes, we
should do partial validation with 2 PA batches, recovery and matrix
effect. As we know that strain variation may have different matrix
components which may interfere in the sample analysis.
Hope this may help you
We welcome expert comments on rhis
Thank you
Raja Reddy
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Dear Shivva Vittal,
Regarding need or desirability for validation of different animal
strains, the FDA guidelines do not require it, but there are
certainly cases where it would be a good idea. We had cases in the
past where the pharmacokinetic properties of a new drug were
substantially different for different rat strains or different mouse
strains. At least partial validation to show that there was no
analytical difference in the method for plasma from the two strains
provided compelling evidence that it was a PK difference and not a
bioanalytical method difference.
-Tom
Thomas L. Tarnowski, Ph.D.
Bioanalytical Development
Elan Pharmaceuticals, Inc.
800 Gateway Boulevard
South San Francisco, CA 94080
thomas.tarnowski.aaa.elan.com
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Dear Shivva
It would be better to go for one precision and accuracy batch, where
plot linearity using Sprague Dawley rat plasma and 3 replicates at
each QC level using Long Evans rats plasma. This would rule out
matrix effect and recovery issues by changing strain.
Regards,
Jignesh S. Kotecha
Scientist 1(Discovery Bioanalytical)
Torrent Research Centre,
P.O. BHAT
DIST. GANDHINAGAR
INDIA 382428
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The following message was posted to: PharmPK
What is the nature of the Strain? All strains can not considered
equal, you
certainly would not necessarily want to use Brattleboro rats to evaluate
vasopressin antagonists. OR substitute WKY for Fischer.
Ed O'Connor, Ph.D.
Laboratory Director
Matrix BioAnalytical Laboratories
25 Science Park at Yale
New Haven, CT 06511
Web: www.matrixbioanalytical.com
Email: eoconnor.aaa.matrixbioanalytical.com
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I thing you need to do partial validation mainly study the matrix
effect, recovery and selectivity.
I hope this will help you . All the best.
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