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Is it possible to conduct one (common) bioequivalence study for US & EU
regulatory approval purposes. If yes, could you cite
examples/precedents and references
Thanks in advance,
Rajaram Sankaran
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Dear Shankaran,
One can't do like this for producing Generic equivalent products.
The European Reference Product is the one (as per the newlaw effective
May 2005) which is authorised and marketed in any of the EU memeber
state either through centralised procedure or decentralised
procedure.Wherein the refernce product for US generic will be one that
has effective approval for marketting ( under section 505(C)or
505(b)2)in US and you will find that in Orange book with RLD status
"YES".
One can't pick the originator product from US and submit BA/BE refering
to US RLD in Europe even the innovator/distributor is same and under
same brand names they are available in EU and US.
Some times, the two originator products (US & EU) may differ in terms
of composition and release profile.One can use the same exhibit batch
and do the two bioequivalence studies with two Reference product (US &
EU) and submit them to individual authorities.
So far I have come across, only Health Canada has legislative provisons
for allowing this in certain special cases wherein the Product is not
available due to voluntarily withdrawal by originator and one can be
allowed to consider any other countries product as Canadain Reference
Product.
Kind regards,
Pradeep Bhadauria
RANBAXY RESEARCH LABORATORIES.
INDIA.
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Dear Mr. Pradeep,
Your explanation:
"One can't pick the originator product from US and submit BA/BE
refering to US RLD in Europe even the innovator/distributor is same and
under same brand names they are available in EU and US."
I believe that it may be the rule according to the regulatory
requirement. But what can be the logic behind that ?
Dr. Nirav Gandhi
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Dear Dr. Gandhi
you wrote:
>I believe that it may be the rule according to the regulatory
>requirement.
>
True.
>But what can be the logic behind that ?
>
Politics ?
As the group of Prof. Blume of Germany have shown a couple of years ago
for the Innovator of Glibenclamide, formulations marketed in different
European countries *may* not be bioequivalent compared to each other.
Since there is a Level A correlation between dissolution at 15 minutes
and AUC0-3h (if a remember ist correctly), they concluded
*bioinequivalence* based on the in-vivo/in-vitro-correlation.
Nevertheless, it's possible to use the inovator product marketed in
*any* EU-country.
As another example look at Australia's Guidelines: they have adopted the
European BA/BE-guideline in their legislation, with the exception, that
the reference product must be the inovator marketed in Australia.
Regards,
Helmut Schutz
--
Helmut Schutz
BEBAC
Consultancy Services for Bioequivalence and Bioavailability Studies
Neubaugasse 36/11
A-1070 Vienna/Austria
tel/fax +43 1 2311746
http://BEBAC.at http://forum.bebac.at
http://www.goldmark.org/netrants/no-word/attach.html
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Dear Helmat & Nirav,
>From an unbiased regulator's perspective,I have something to add here:
The possible logics behind the rules can be as follows and certainly
have a lot of scientific and legal judgement behind it:
1) Firstly, when one submits a generic application referring to the
innovator product which other than the one approved by the regulatory
agency to whom the generic aaplication is filed for approval ,then on
what basis the agency will approve the generic aaplication as the
innovator product refered in the generic application was never
evaluated by that agency.In order to approve the generic application
the regulatory agency has to refer the originator product' dossier
which is not a legal right in this case of agency as the NDA was
submitted to some other agency. At the end of the day the agency has to
certify that the applicant's generic product is bioequivalent and hence
therapeutic equivalent to the innovator product in reference submitted
under the persuat of law..to whom??..where?? and when??.
2) Secondly, if the two generic applicant file an application for the
same market and one referring to Originator product In US and another
to originator Product in EU in their application and if this rule was
not there in place then it would creat a lot of confusion in the market
place as two generic approved by the agency may not actually be
bioequivalent and therapeutically equivalent to single source
originator product approved by the agency in original. If the SmPC of
the two originator Product available differs significantly then it
imposes serious safety and efficacy issues to those who are switching
over from Branded innovator product to generic product which is then
not similar to the innovator product.For example: Clarithromycin XL
tablets available in EU and US differs significantly in terms of
release profile ( Its quite unlikely that they are bioequivalent) then
what will be the consequences if one reefers EU product in US and visa
versa.
However, all theses rules can be challenged in future to come once you
have innovator Products filed and approved via single CTD ( Common
Technical Document mutually honored by EU,US,Japan etc) sumitted then
it will be less likely that the product in these territory will differ
in SPC significantly.
I hope this makes sense,
Kind Regards,
Pradeep Bhadauria
RANBAXY RESEARCH LABORATORIES
INDIA.
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Dear All,
Long and valid discussions are going on. It is right that we need to do
three or four BE studies for one formulation i.e. for US, EU, Astralia,
Brazil etc. There is one exception which I would like to bring in to
notice of all concerned and that is South Africa. MCC, SA is accepting
the data of BE study carried out with any innovator sample procured
from any part of the world provided the In vitro dissolution data of
Innovator used for BE study, Innovator of South Africa and Test product
should match.
I must say that this is a step forward which only MCC has taken in to
consideration.
Regards
Dr. Milan Satia
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)