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Dear Sir,
Does the european authority approves the bioequivalence projects with
wider confidence intervals for Cmax 75-133% if yes then on what basis
this wider interval can be choosen.
Regards
Dr. Mary Francis
India
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Dear Mary,
It's true that the european criteria for BE is wider with the range
of 75% - 133% but i don't know the basis for that. I am curious to
see the answer if somebody knows.
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Dr.Mary:
As per EMEA guidelines, the Wider acceptance limits you have mentioned are
for highly variable molecules, I presume that it can be applied where the
intrasubject CV% is more than 30.
There is one more consideration, as the wider range used should be
justified taking into account safety and efficacy considerations of the
drug molecule in question.
Hope this information is what you are looking for.
regards,
bangaru.rk
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[A few replies - db]
From: Dimiter Terziivanov
Subject: PharmPK: Re:EC Bioequivalence
To: David Bourne
MIME-Version: 1.0
Dear Mary,
On 22 July 2002 you wrote:
" Dear Sir,
Does the european authority approves the
bioequivalence projects with wider confidence
intervals for Cmax 75-133% if yes then on what basis
this wider interval can be choosen."
This wider equivalence interval was primarily
suggested by Blume et al. for Cmax in the case of IR
Nifedipine formulations (Blume et al. Pharmaceutische
Zeitung 133:389-393;1988).
This suggestion has been adopted for use in the 9th
draft of the CPMP guidance on BE trials where a BE
limit of 70 to 143% is given for the ratio of Cmax
(CPMP 1991; Steinijans et al. Clin Pharmacokinet.
22:247-253;1992).
I hope this helps.
Dimiter T.
Dimiter Terziivanov, MD,PhD,DSc, Professor
Clinic for Therapeutics and Clinical
Pharmacology, Univ Hosp "St. I.Rilsky",
15 D. Nestorov st, 1431 Sofia, Bulgaria
e-mal: terziiv.aaa.yahoo.com
---
From: BENECH Henri 137577
Date: Tue, 23 Jul 2002 11:27:56 +0200
To: david.aaa.boomer.org
Subject: RE: PharmPK EC Bioequivalence
Dear Francis,
It is also well known that an accurate Cmax is always more difficult to
obtain than an accuracte AUC (because more subjected to the sampling time).
That is why a wider CI for Cmax can be accepted for variable drugs.
Regards
Henri BENECH
Service de Pharmacologie et d'Immunologie
CEA/Saclay 91191 Gif-Sur-Yvette Cedex
---
From: Dimiter Terziivanov
Subject: PharmPK:Re:EC Bioequivalence
To: David Bourne
MIME-Version: 1.0
Dr. Bangaru,
On 22 July 2002 you wrote:
"Dr.Mary:
As per EMEA guidelines, the Wider acceptance limits
you have mentioned are for highly variable molecules,
I presume that it can be applied where the
intrasubject CV% is more than 30. There is one more
consideration, as the wider range used should be
justified taking into account safety and efficacy
considerations of the drug molecule in question.
Hope this information is what you are looking for.
regards,
bangaru.rk"
As far as I know the underlying arguments to
recommending this wider BE range were the particular
features of Cmax as a BA measure rather than the
molecular characteristics of a given drug. The
presumption was the observed larger variations of this
BA measure in comparison with the integrated BA
measure AUC.
Best regards,
Dimiter T.
Dimiter Terziivanov, MD,PhD,DSc, Professor
Clinic for Therapeutics and Clinical
Pharmacology, Univ Hosp "St. I.Rilsky",
15 D. Nestorov st, 1431 Sofia, Bulgaria
e-mal: terziiv.at.yahoo.com
---
From: Dr Fatemeh Akhlaghi
Date: Tue, 23 Jul 2002 11:22:28 -0400
To: david.at.boomer.org
Subject: EC Bioequivalence
Dear All
I have read with interest the discussion on the European standard for
Bioequivalnce testing. Is there any published guidance document on
the Internet? If not where can I contact to obtain a copy of this
document.
Many thanks for your help.
Fatemeh
Fatemeh Akhlaghi, PharmD, PhD
Assistant Professor
Applied Pharmaceutical Sciences
University of Rhode Island
125 Fogarty Hall, 41 Lower College Road
Kingston, RI 02881
USA
Email: fatemeh.-a-.uri.edu
Laboratory Website: http://www.uri.edu/pharmacy/faculty/aps/akhlaghi/index
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The recent CPMP states the following:
"Cmax-ratio
The 90% confidence interval for this measure of relative
bioavailability should lie within an acceptance interval of
0.80-1.25. In specific cases of a narrow therapeutic range the
acceptance interval may need to be tightened.
In certain cases a wider interval may be acceptable. The interval
must be prospectively defined e.g. 0.75-1.33 and justified addressing
in particular any safety or efficacy concerns for patients switched
between formulations."
Laszlo Endrenyi
University of Toronto
PharmPK Discussion List Archive Index page
Copyright 1995-2010 David W. A. Bourne (david@boomer.org)