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I would like get opinion on the following "Food effect" issue from who
had
experience with OGD at FDA.
The reference product label clearly states "when the drug product
administered with food the bioavailability of the drug product
increases".
Therefore we are planning to conduct ONLY non-fasting 2-way crossover
BE
study to establish bioequivalence between test and reference products.
My
question is the one has to conduct fasting BE study also to establish
bioequivalence prior to filing ANDA to FDA.
I am aware of the Food effect Guidance, which clearly states when it
is NOT
necessary to conduct the food effect study. However I have not seen a
clear
statement about not conducting fasting study if there is a food effect
in
any of the current guidances (e.g., Food effect Guidance or
Bioavailability and Bioequivalence -General considerations Guidance.
I would greatly appreciate your input on the matter
Kindly
Sibel D. Ucpinar, Ph.D.
In Vitro Drug Metabolism and Pharmacokinetic
CEDRA Corporation
E-Mail: sucpinar.at.cedracorp.com
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You have to conduct both Fasted and Fed BE study and to establish BE
between the products, you need to fulfill the 80-125% requirement for
both studies, i.e. fasted ref vs. fasted test AND fed ref vs. fed test.
hope this helps.
Partha Roy, Ph.D.
Forest Research Institute
Forest laboratories Inc.
Jersey City, NJ 07311
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It is my understanding from talking to the OGD of the FDA that the
default
study is a fasting design - which must always be done. This might be
mentioned in the FDA guidance for the statistical analysis of
bioequivalence studies.
Then, as you imply, a fed study is necessary if the label makes a claim
about the effect of food (one way or another). There are however,
exceptions to this rule - which can only safely resolved by contacting
the
FDA in such a way as to not annoy them with an obvious question.
In other words, there may be a way to avoid a fed study, but a fasting
study should always be done - UNLESS there is a safety issue by taking
the
drug in the fasting state. Again, my suggestion in this remote case,
would
be to contact the FDA - with an interesting question.
Good Luck,
Edmond Edwards, Ph.D.
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The following message was posted to: PharmPK
Taskin,
If you plan to label your drug as only to be given with a high fat meal,
then I might expect the FDA to grant you a food study only approval,
but I
doubt it. If the drug can be given to patients in the fasted state, you
must study it fasted. A label "take with food" will not make it happen.
Remember, just because you can match the fed state, that is not
assurance
you can match the fasted state.
Art Straughn, Pharm.D.
Professor and Director
Drug Research Laboratory
University of Tennessee
874 Union Ave
Suite 5P
Memphis, TN 38163
E-mail: ASTRAUGHN.aaa.UTMEM.EDU
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The following message was posted to: PharmPK
It was not mentioned whether the test formulation was a generic dosage
form
intended to be fully interchangeable with the innovative product. If
this is
the case then the test formulation should be bioequivalent under fed and
fasted states since in real life patients would be taking the drug
either on
an empty stomach or with meals.
If the bioavailability of the drug increases when taken with food then
it
would be prudent to take the drug formulation with food. Increased
bioavailability normally results in less variability providing more
consistent blood concentrations. In such a case bioequivalency under fed
state becomes even more important.
Aziz Karim
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The following message was posted to: PharmPK
The type of studies to be conducted all depends upon the formulation,
whether it is a conventional or controlled release dosage form.
It is necessary to conduct a BE study under fasting condition
irrespective
of the formulation and the food effects.
There are instances where bioequivalence cannot be conducted under
fasting
condition because of adverse events.Then in that case fed condition is
preferred over fasting because of safety aspects.
Each study have to be reviewed on case by case basis.
Dr. Mary Francis
Pliva d.d- India
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The following message was posted to: PharmPK
Dear Dr. Sibel,
The two generic equivalent may differ in terms of lebeling
requirement also in some cases ,this mandates you to conduct both
the food effect and fasting state studies to determine precisely
the formulation variables ( Fasting state) and biological factors
( fed state).
Fed state studies does not necessarily determine the variability
as other studies like multiple dose may better address the issue
of high variability.
Moreover , in some cases it is because of the formulation nature
like Gastro-retentive delivery systems, you need to justify the
label for which you have to have both studies to document the
bioequivalence. However, it is advisable to take up this issue to
division of bioequivalence for the protocol approval.
Hope this serves the purpose.
Kind regards,
Pradeep S. Bhadauria
Ranbaxy Research Laboratories.
INDIA.
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)