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Dear Group:
I have a question on the generic product approval based on passed BE
studies that used EU reference product. Does anyone know are there any
generic products approved by US-FDA based on a bioequivalence clinical
trial that used reference listed product in one of the EU countries
(e.g.: Netherlands, Germany, UK, and France). I understand that for
US-FDA orange book lists a strength as reference listed drug (RLD),
however EU countries each may have their own reference products but
EMEA accepts these products through mutual agreement or something like
that.
I am looking for some kind of lead where FDA accepted a European
(foreign) BE trial that established bioequivalence between test
formulation and EU reference product for marketing the test
formulation in US. In simple words with one EU study can we gain
approval from both EMEA and FDA
Any leads are appreciated.
Prasad
Prasad NV Tata, MS., Ph.D., FCP
Manager-Pharmacokinetics
Mallinckrodt, Inc.
675 McDonnell Blvd.
Saint Louis, MO 63134
e-mail: prasad.tata.-at-.covidien.com
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Hi Prasad,
The only way I've heard a combined study used in more than one
submission is having both the Orange Book reference and the EU
reference in the same trial, in a 3-way crossover. So for instance the
sequences would be Test - Ref1 - Ref2, Ref1 - Ref2 - Test, and Ref2 -
Test - Ref1.
I've never heard of the FDA approving an EU reference, or for that
matter, being anything other than the RLD in the FDA Orange Book.
Hope this helps,
-Dave
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Dear Dr. Dave,
Are you sure that a 3 way BE study using two reference (one from EU,
another from US) and one test product is acceptable to USFDA as well
as EU regulatory agencies (UK, NL etc)?
Is anybody having any experience of submitting this type of BE study?
Please share.
Regards
Anuj Saini
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Dear Mr. Anuj,
You can do a three way study with two different reference formulations
intended for submission to two different regulatory countries. I have
done few such studies and i remember one such study was meant for
canadian and EU submission.
Practically speaking, a three way study with two different reference
drugs is nothing but two different studies with a common test
formulation. It is more cost effective and the major problem will be
the compliance of the subjects, where you cannot afford to lose too
many subjects as drop outs.
Hope this helps you.
Regards
Dr. M. Joseph
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I have not come across any instance where FDA would have ever approved
a BE trial using a EU product in the US. In addition, this trial
cannot be performed in US unless the sponsor gains a Bio-IND approval
to dose an EU product in the states.
If the sponsor wishes to submit the application to the USFDA where the
BE trial utilizes an EU and US approved RLD products then the safest
way would be to write a controlled correspondence or send the study
protocol to the FDA.
Not to forget that there could be a situation where the test product
shows bioequivalence against the US RLD but is not against the EU
RLD. This may complicate the situation but could be salvaged provided
the design and the intent is clearly mentioned in the study protocol
prior to the conduct of the study.
Hope this helps
Manish Issar, Ph.D
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All:
I have never heard of FDA approving a generic product based on a BE
study conducted against the EU reference and would think it highly
unlikely. Likewise I have never heard of the EU approving a generic
study where the Reference product tested was a USA product!
I see no reason why a three wxo type study (Test v US RLD v EU RLD)
would not be acceptable however if the two RLD do not pass against
each other I imagine certainly raise some questions from both sets of
Regulatory agencies.
Just to clarify a previous posting. There is no requirement to file a
BIO-IND in the US to test an EU RLD if the same drug/dosage strength
is approved in the US. For example if you wanted to test Drug X and
there is a 500mg tablet formulation of Drug X approved in both the US
and the EU (or Canada, Brazil etc) they you can conduct a BE study in
the US comparing you test 500mg tablet of Drug X versus the EU 500mg
tablet formulation of Drug X without having to file a BIO-IND.
Best wishes
Chris Hendy PhD
Novum Pharmaceutical Research Services
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The following message was posted to: PharmPK
Simple answer is 'NO'. Basis for ANDA should be from US based product
and should show equivalency between test product and reference drug
product which is marketed and consumed by US patients.
Regards
Chander Kazipeta
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