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The following message was posted to: PharmPK
Dear friends
For a NCE we developed a bioanalytical method and
validated in human plasma. We need to conduct the
pre-clinical studies in rabbit and rat. By using the
above method we perform the specificity and one
intraday accuracy and precision for rat and rabbit
plasma. We found there is no effect in results with
different species of plasma matrixes.
FDA guidelines suggest the partial validation only
applicable for change in matrix within species (human
plasma to human urine), change in species within
matrix (rat plasma to mouse plasma) and few more.
In our case we use the plasma matrix with different
species (human, rat and rabbit), which is not
mentioned in FDA guidelines. Is our partial validation
data accepted? We perform only the specificity and one
intraday accuracy and precision and we found same
results in all plasma matrixes.
Your comments are more appreciable
Thanks in advance.
G.venkatesh
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Dear Venkatesh,
If I understand correctly, you have gone for one Precision and
Accuracy batch in individual animal matrix. I feel it is not sufficient.
Better you perform cross validation i.e. prepare linearity using
human plasma and QCs (LLOQ QC,LQC,MQC and HQC) in animal matrix. All
QCs should meet their acceptance criteria. This experiment will take
care of your extraction method recovery as well as matrix effect.
Additionally you go for all kind of stability studies like Bench Top,
Long Term, Process and Freeze-Thaw.
Regards,
Jignesh
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The following message was posted to: PharmPK
Dear Dr. Venkatesh:
It is always best to do a full validation in each study species matrix.
Dependent on the functionality of your compound - and its metabolites
(keep
in mind that your method must separate parent from metabolites in each
species matrix) - the various matrices may be quite similar with
respect to
your compound or not.
As with any regulatory submission, the question is not whether you
partial
validation will be accepted, but whether you have done sufficient
science to
prove reasonably that your validation answers the underlying scientific
questions. If you have thorough validation data set for each species
matrix
studied, the probability of acceptance is increased. The more one has to
allude to experiments that were not conducted or data that cannot be
shown,
the higher the risk. Only you and your scientists can make a
determination
of sufficiency to ensure timely and successful review of your
submission.
Hope this helps,
Ian M. Davis, M.S.
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venkatesh: iwould avoid batching anything. Run your 6 accuracy and
precision runs with fresh material9 std and Qc) prepared for each run.
You may also want to run For the sixth run prep a large volume of QCs
sufficient to last through any experimental stabilities, bench top, and
long term, as well as to get through a portion of intended sample
analysis. It is most conservative- minimizes risk, to do this as well
as to use fresh stds and Qc for plate acceptance during validation. If
freeze thaw fails, you are cooked wiht a large batch so it is also
conservative to run freeze thaw with a smaller batch of QCs and before
you commit to preparing a large batch, so FT should be done before the
end of accuracy and precision. Same approach is repeated when you
change species
Ed O'Connor, PhD
Technical Director, Immunoanalytical
Tandem Laboratories
115 Silvia Street
West Trenton, New Jersey
609-228-0243
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The following message was posted to: PharmPK
Dear friends; Hi all
No, you need full validation in the specie you are intended to do
your studies, accepted partial validation if you use the same specie
(Rat ,Human or Rabbit) with different matrix( use urine in sted of
plasma at). Good luck.
Professor Khalil I M Al-Khamis, Ph.D
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Dear Khalil: I am interested in your opinion on the following:
1 In validation do run 6 independent runs that is individually prepared
QC and curves for each plate/run?
For accuracy and precision: Do you use fresh curves and fresh QC fresh
curves and frozen qC
forzen curves and frozen qc?
For sample analysis do you use fresh curvs and frozen QCs
or frozen curves and frozen QC?
Do you agree or disagree with the statement that "since samples are
frozen all validation should be done with frozen materials, and that
since fresh samples will not be seen, fresh curves and QCs are
irrelevant?
Thanks
Ed O'Connor, PhD
Technical Director, Immunoanalytical
Tandem Laboratories
115 Silvia Street
West Trenton, New Jersey
609-228-0243
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Dear Venkatesh,
Though the method validation guidelines says the partial validation
which may restrict to single PA bacth to full validation for change
of matrix between species or change of matrix within species.
In either case it is required to do full validation for change in
matrix, because we are not aware of stability in that particular
matrix, so minimum of 4 PA batches, all stability studies (Excluding
solution) need to be done, along with selectivity & specificity,
Recovery and matrix effect.
Hope this helps you
Rajareddy
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The following message was posted to: PharmPK
Hi,
You only need to do partial validation, such as bench
top stability, three freeze-thaw stability and
autosampler stability as well as long term stability.
Good luck.
Xiaodong
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The following message was posted to: PharmPK
Hi,
In my opinon, according to FDA guidelines, we do not
need to do extraction recovery and matrix effect when
changing species.
Xiaodong
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Think about this for a minute.
Are you going to state that the enzymes and intereferences are the same
species to species?
That is not a valid assumption at all. You should indeed test
recoveries and stabilites in when changing matrices.
Ed O'Connor, PhD
Technical Director, Immunoanalytical
Tandem Laboratories
115 Silvia Street
West Trenton, New Jersey
609-228-0243
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The following message was posted to: PharmPK
Hi,
Enzyme level is differnt form one species to another.
However, it is not necessay to check extraction
recovery and matrix effect since they are all plasma.
For sure we need to check specificity and stability.
Xiaodong
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The following message was posted to: PharmPK
We always re-test the recovery and matrix effect when changing
species and often see differences...................
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Dear Venkatesh,
It is very important no note that the availability of rat/rabbit
matrices and tissues are very scarce therefore 3 Precision &accuracy
curve and no stability evaluation will be required as stabilty is
already proved in human plasma.
Abhijith
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