MEETING REPORT:
FIP's
Dissolution Expert Team Goes on the Road with "Dissolution
'99"
The quality of pharmaceuticals in emerging
countries is still of great concern to the FIP and WHO. In the
West and Japan, the methodologies for testing bioavailability
and the role that dissolution plays in this process are well established.
In some cases, appropriate dissolution testing can even result
in waiver of the need to perform bioequivalence studies in man.
In other parts of the world, these concepts are still largely
unexploited.
Under the leadership of Chair Martin
Siewert, the FIP Working Group 4 (Dissolution testing) has initiated
several new and important activities. As well as conducting conferences
on scientific issues concerning dissolution testing of solid oral
dosage forms and special dosage forms1, a workshop program teaching
and demonstrating the latest dissolution techniques in emerging
countries is currently in the pilot phase. As part of this program,
experts from the Working Group are volunteering their time and
effort to set up contacts with scientists and laboratory people
in emerging countries in order to share their experience and expertise
in the field of dissolution as widely as possible. The concept
of the dissolution workshops, which are to be conducted in conjunction
with the World Health Organization, is to combine lectures addressing
both theoretical and practical aspects of dissolution with practical
exercises - a so-called "hands-on" workshop. A trial
run of this "Dissolution Road Tour" was held in Melbourne,
Australia, on July 14th.
Dr. Bill Charman, Professor of Pharmaceutics
at the Victorian College of Pharmacy (Monash University) welcomed
members of the Working Group in his introduction to the"Dissolution
99 - Practical Applications and Regulatory Considerations"
Workshop at the College of Pharmacy on July 14th, 1999. The first
theme to be discussed was the choice of the right dissolution
apparatus. In vivo verification of the in vitro specifications
is the biopharmaceutical part of this choice, while the qualification
of the compendial system to be used is the GMP part of the choice.
Dr. Johannes Kraemer from LQS (Eschborn, Germany) shared his experiences
with the USP's System Suitability Test with the participants.
The FIP Guideline on Dissolution is widely recognized as being
a consensus paper of dissolution experts from academia, regulatory
authorities and industry. This Guideline prefers the use of pharmacopeial
equipment rather than encouraging the use of alternative apparatus
which show no clear advantage over the established equipment.
This is a major step towards international harmonization of dissolution
technologies.
Dr. Jennifer Dressman, Professor
of Pharmaceutical Technology at the University of Frankfurt, presented
results from her research concerning the choice of a suitable
dissolution medium based on classification of the drug according
to the Biopharmaceutics Classification Scheme (BCS). She also
described potential ways of adapting these highly sophisticated
media to the needs of routine quality control laboratories to
provide the best system for discriminating non-bioequivalent batches.
Setting specifications on the basis of in vivo results is already
an FDA requirement, as set forth by Dr. Vinod Shah of the American
Food and Drug Administration in Rockville, Maryland. According
to FDA's recent Guidances for Biowaivers, dissolution testing
of immediate and controlled release oral products in conjunction
with scale-up and post-approval changes plays a key role in regulatory
decision-making. FDA's attempts to accelerate the decision process
are based on scientific research performed by universities in
the USA, Sweden and Germany as well as internal activities. The
implementation of the BCS in the current Guidances is the outcome
of an ongoing worldwide dialogue with scientists from academia
and the industry. Some results have already been implemented by
the Australian Therapeutic Goods Agency (TGA) as reported by Dr.
Anna Rickards, Canberra. She completed the lecture series by explaining
TGA's activities in evaluating dissolution results in the light
of submitted biostudies.
Dr. Chris Porter, also of the Victorian
College of Pharmacy, took on the responsibility for the organization
of the practical demonstrations, which were co-sponsored by Erweka
GmbH, Germany. Mr. Eric Galia (Erweka) installed two of his company's
dissolution systems, complete with on-line spectroscopy for these
demonstrations, while Hoechst Marion Roussel donated the Lasix®
tablets used to illustrate several features of dissolution testing.
One of the demonstrations was to show the influence of buffer
specifications on the dissolution of the active principal, furosemide,
which is a weakly acidic compound. In addition, various aspects
of qualification and calibration of the equipment were addressed.
During the experiments all of the speakers were available in the
laboratory to answer questions concerning the theoretical background
as well as the practical aspects of dissolution testing.
The workshop thus provided a forum for the expanding discussion on the regulatory role of dissolution testing as well as practical knowledge and hands-on experience for the practicing scientist. The more than 60 participants of the workshop agreed that the day at the Victorian College of Pharmacy in Melbourne made them more aware of the increasing necessity to perform dissolution testing with an eye to bioequivalence considerations, and aided them greatly in the selection of appropriate apparatus, methodology and the application of theoretical principles to everyday dissolution testing.
1) "Dissolution Testing of Special
Dosage Forms" Workshop, co-sponsored by the FIP Working Group
on Dissolution Testing and the Royal Pharmaceutical Society's
Pharmaceutical Sciences Group, September 2-3, 1999, London.