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Dear all,
I'd like to have your opinion on whether a BE study
for two formulations of a compound that is for long
term use should be done after a single dose of each
formulation or at steady state? To me it sounds more
appropriate to do the study after repeated dosing but
I think FDA recommends single dose study.
Any comments?
BP
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Dear Mr.BP,
FDA recommends single dose studies for Immediate release products and
steady state studies are recommended if an Immediate release product is
developed as a modified release product.
With Regards,
V.Radhakrishna
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Dear V.Radhakrishna,
You wrote:
"FDA recommends single dose studies for Immediate
release products and
steady state studies are recommended if an
Immediate release product is
developed as a modified release product."
which is somewhat contrary to what I thought I
understood reading FDA guidelines. Would you be kind
and direct me to the specific guideline that clearly
states a single dose BE study for IR and steady state
study for SR products?
I am grateful for your efforts.
Batul P.
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Probably FDA recommends single dose administration because it is
supposed to be more sensitive to differences in formulation, especially
for Cmax. After multiple-doses the drug reaches steady-state and the
variation in Cmax is minimized.
Paula
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Dear Batul,
There are different regulatory implications of the Bioequivalence
studies required for regulatory submissions of modified release dosage
forms in US and UK generic applications, which are as follows:
US [ref: BA and BE studies for orally administered products, march
2003]: clearly defines that for an ANDA submission steady state studies
are not recommended and we shall require only two studies viz A single
dose, fasting study and a food effect study comparing the highest
strength of the test and the reference listed product.
However, if you look in the European perspective for the modified
release generic applications [ref: CPMP/EWP/280/96, July 1999] they are
as follows:
A] For applications of prolonged release dosage generic applications
one should demonstrate that the performance of the test and reference
formulation is equivalent after single dose and after steady state and
that the effect of food on the in vivo performance is comparable. Hence
summing up we may have to do three studies viz. A single dose- fasting
study comparing the highest strength of test and reference drug; A food
effect study comparing the highest strength of the test and the
reference product and A steady state study on the highest strength.
B] For applications of delayed release generic formulations a fasted
and a fed- study shall suffice.
I hope this is of some help to you.
Regards
Kaushal Prajapati
Torrent pharmaceuticals limited
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Dear Mr.Batul P.
For ANDA submission FDA require both single dose fasting and fed studies
for modified release formulations, but for NDA (IR to Extended release)
FDA
requires single dose fasting, fed and steady state studies.
With Regards,
V.Radhakrishna
Biopharmaceutics
PharmPK Discussion List Archive Index page
Copyright 1995-2010 David W. A. Bourne (david@boomer.org)