Biopharmaceutics drug classification and international drug regulation

187 Pages·2000·2.28 MB·English

Symposia series
Biopharmaceutics
drug classification
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drug regulation
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Symposia series
Biopharmaceutics
drug classification
and
international
drug regulation
Seminars and Open Forums
Tokyo, Japan • July 15, 1997
Geneva, Switzerland • May 14, 1996
Princeton, NJ USA • May 17, 1995
Including
the Panel Discussions
Contents
Introduction
by Gordon Amidon, University of Michigan (U.S.A.) and Roland Daumesnil, Capsugel 5
Dr. Akira Kusai, Ph.D.
Tokyo Japan, July 15, 1997 7 Sankyo Company (Japan)
The Present Status of Formulation
Design of Oral Dosage Forms
Chair:
in the Japanese Industry
71
Prof. Mitsuru Hashida, Ph.D.
Kyoto University, (Japan)
Prof. Gordon L. Amidon, Ph.D.
Panel Discussion
University of Michigan (U.S.A.)
Prof. Yuichi Sugiyama, Ph.D.
Opening Remarks 9 University of Tokyo (Japan)
Mr. Norio Ohnishi
Lectures Fujisawa Pharmaceutical Company (Japan)
Prof. Jun Watanabe, Ph.D.
Prof. Gordon L. Amidon, Ph.D.
Nagoya City University (Japan)
University of Michigan (U.S.A.) 85
Rationale of a Biopharmaceutics
Classification System (BCS) for New
Drug Regulation. Update July 1997
11
Dr. Larry Lesko, Ph.D.
FDA (U.S.A.)
The Biopharmaceutics Classification
System: a Policy-Implementation
Approach. Update July 1997
29
Prof. Jennifer Dressman, Ph.D.
Goethe University, Frankfurt (Germany)
Physiological Aspects
of the Design of Dissolution Tests
45
Prof. Shinji Yamashita, Ph.D.
Setsunan University (Japan)
Rationale Approach to Predict Human
Drug Absorption from in vitro Study
59
2
Prof. Jean-Marc Aiache, Ph.D.
Geneva Switzerland, May 14 1996 103 Faculty of Pharmacy, Clermont-Ferrand
(France)
Drug Formulations: their Impact upon
Chair: Prof. Michael Newton, Ph.D. Drug Classification and in vitro/in vivo
The School of Pharmacy, Correlations
145
University of London (UK)
Opening Remarks 105 Panel Discussion 157
Lectures
Prof. Gordon L. Amidon, Ph.D.
University of Michigan (U.S.A.) Princeton NJ USA,May 17 1995 173
A Biopharmaceutic Classification
System. Update May 1996
107
Chair: Prof. George Digenis, Ph.D.
University of Kentucky, Lexington (U.S.A.)
Prof. Hans Lennernäs, Ph.D.
University of Uppsala (Sweden) Opening Remarks 175
Human Permeability Determinations
and in vitro and Animal Correlations Lectures
113
Prof. Gordon L. Amidon, Ph.D.
Prof. Geoffrey Tucker, Ph.D. University of Michigan (U.S.A.)
The Royal Hallamshire Hospital, The Rationale for a Biopharmaceutics
Scheffield (UK) Drug Classification
177
In vivo Bioequivalence Assessments
127
Dr. Larry Lesko, Ph.D.
Dr. Larry Lesko, Ph.D. FDA (U.S.A.)
FDA (U.S.A.) Biopharmaceutics Drug Classification
Biopharmaceutic Classification System and International Drug Regulation:
(BCS): a Policy Implementation A Policy Implementation Approach
195
Approach. Update May 1996
139
Panel Discussion 203
3
Venues
Seminars and Open Forums
SPONSORED BY CAPSUGEL, DIVISION OF WARNER-LAMBERT
Geneva
Princeton
Princeton NJ USA • May 17, 1995
Geneva Switzerland • May 14, 1996
Tokyo Japan • July 15, 1997
4
Introduction
D
uring our visit to Japan in November 1994 we discussed the theoretical principles
of the Biopharmaceutics Drug Classification (BCS). We both came to the
conclusion that creating the opportunity to discuss publicly with the scientific
community through open discussion and presentation can significantly impact the
future applications of the BCS. A significant step in the process towards international
harmonization. Creating a platform for the exchange of scientic ideas is an established
Capsugel commitment. Building upon worldwide interest, Capsugel was pleased to
organize this series of symposia for the pharmaceutical scientific community.
Product quality and performance is an important concern of regulatory authorities
because over the lifetime of a product there are often many changes in formulation,
equipment, manufacturing process or site of manufacture. Furthermore, after patent
Tokyo
expiration there may be multiple manufacturers of a given product which are approved
for marketing on the basis of in vitrodissolution or bioequivalence tests without further
demonstration of safety and efficiency. The BCS has been developed — with the
support of the FDA — to facilitate rational and scientifically sound regulations in the
assessment of product quality and performance. Until the issuance of SUPAC-IR,
which includes an early form of the BCS, the regulatory approach was based on the
concept of in vivo bioequivalence based on C-max and AUC rather than the mech-
anistic approach.
Our effort in creating these open forums was very well received. Comments from the
participants and speakers have been very supportive and these scientific discussions
outside of the regulatory arena raised many questions about the limitations and
possible applications of the BCS. The classification system focuses mainly on
bioequivalence, but can we integrate the first-pass hepatic metabolism in the BCS?
What can be the agreed surrogates for human permeability? What about the
hydrodynamics in the in vitro dissolution system? Can we develop the BCS so that in
future it provides specific guidance on how to predict the bioavailability? Can we use
the BCS to predict food-induced changes? It is significant that during this series of
seminars the BCS served as a basis to focus the attention of the scientific community
on these key issues.
Our ultimate goal in organizing and publishing these symposia was to provide timely
industry output at the evolutionary stage of the FDA proposal. The lectures given in
the three regions are combined into the proceedings. Your feedback will tell us if we
achieved our objectives.
We are looking forward to hearing from you.
Gordon L. Amidon, Ph.D. Roland Daumesnil
Professor of Pharmacy, Director Global Business Development-
The University of Michigan (U.S.A.) Pharmaceutical, Capsugel
5
Tokyo
Japan
July 15, 1997
7
Tokyo, Japan, July 15 1997
Opening Remarks
T
he title of this symposium is Biopharmaceutics Drug Classification and International
Drug Regulation: seminar and open forum.
The theme is the development of oral drug formulations, especially from the regulatory
perspective. To be more specific, it will deal with the evaluation and prediction of
absorption, as well as with the associated drug development regulations and the
challenges and issues involved, particularly from the perspective of the FDA. The
symposium will especially focus on the basics: the theories and the mechanical
perspectives.
The same symposium on the same theme has already taken place in two other parts
of the world, the USA and Europe. In 1995, a symposium was held in Princeton and
last year there was another in Switzerland, where Professor Newton of London
University took the chair. Today’s meeting completes the series by being held in Japan,
the third major geographical zone relevant to the worldwide pharmaceutical industry.
Till now, each zone has had its own regulations and guidelines but this is changing,
and today offers you access to the latest information on the regulations.
Our programme includes speakers from abroad, as well as five Japanese contributors.
Each of the speakers will first make their presentation, and this will then be followed by
a panel discussion.
The panel discussion will start with short presentations by our distinguished Japanese
contributors, who represent industry and academia, and then it will be opened up to
general discussion on the international drug regulations and the classification of drugs.
We do have a simultaneous interpretation service today, although since all the
international conferences which take place in Japan are held in English, you perhaps
do not need one. However, since we will be dealing with regulations, it will be
important to retain details in one’s head, and this is why we decided to supply the
service.
The first speaker is the co-chairman, Professor Gordon L. Amidon from the University
of Michigan, who of course needs no introduction. He is an authority both on
gastrointestinal (GI) absorption and on the in vivo/in vitrocorrelation. The title of his talk
is the Rationale for a Biopharmaceutical Drug Classification System, which covers the
whole area of today’s symposium topics.
I would like to give the floor to Professor Amidon.
Professor Mitsuru Hashida, Chairman
9
Rationale
of a Biopharmaceutics
Classification System (BCS)
for New Drug Regulation
Update July 1997
Professor Gordon L. AMIDON, Ph.D.
11
Rationale and Implementation
of a Biopharmaceutics Classification
System (BCS) for New Drug Regulation
Professor Gordon L. Amidon, Ph.D.
Charles R. Walgreen, Jr.Prof. of Pharmacy
The University of Michigan
College of Pharmacy
Ann Arbor, MI 48109-1065
Professor Gordon L. Amidon: Thank you Pro- dards for bioequivalence. The situation now is that
fessor Hashida and I want to thank you personally we are working on an FDA guidance on classifying
for your effort in assisting in arranging this workshop drugs and we will present to you today its current
and discussion. I also want to thank Dr. Lesko for status. We hope that you will comment on this ap-
his willingness to participate. proach to regulating drugs because I think it is es-
sential and critical to have a good scientific basis for
The workshop in the form sponsored by Capsu-
drug regulatory standards.
gel was initiated at my request in the interest of ha-
ving a scientific development-type of audience to I myself am not a development scientist. I am an
listen, critique and provide input into what I think of academic and so I do not have a full appreciation of
as new biopharmaceutic and bioequivalent stan- many issues involved in the development, scale-up
dards for drug development and drug regulation. and clinical testing of oral drug delivery systems. So
I welcome your comments and input because we
I believe that we are entering a new era in oral
want the regulatory standards to be mechanisti-
drug delivery sytems in drug delivery systems gene-
cally-based and useful in improving the quality and
rally, of course, but particularly in oral drug delivery
systems, where optimisation of oral delivery is going performance of drug products.
to be an increasingly important development effort. My original title was: Rationale for a Biopharma-
But optimisation is very difficult with current regula-
ceutic Drug Classification System, which I have now
tory guidelines because of the complexity of asso-
changed to: Rationale and Implementation of a Bio-
ciating the bioavailability and the clinical efficacy
pharmaceutics Classification System (BCS) for New
claims.
Drug Regulation.
So, in order to improve drug delivery and drug
The two slight modifications in this title are im-
regulation, we need scientifically-based, mechanisti-
portant. The first is intended to show that it is a
cally-based, regulatory standards. But our current
biopharmaceutic classification system we are tal-
standard in the United States is just empirical, ba-
king about: there is no drug. The reason being that
sed on bioequivalent plasma levels.
we want to regulate drug products, not just a drug
The discussion and work with the FDA that but drug products. We are a drug product based-
I have been doing over the past six or seven years industry. The second modification is intended to
first began through a one-year sabbatical that show that our focus is on new drug development:
I spent at the FDA, which led on to establishing a how to facilitate and accelerate the Phase I, II, III or
strong collaboration with Dr. Lesko and other scien- IV development of good formulations for human
tists at the FDA, to develop new regulatory stan- pharmaceuticals.
13