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Australasian Biotechnology (backfiles)
AusBiotech
ISSN: 1036-7128
Vol. 6, Num. 5, 1996
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Australasian Biotechnology,
Volume 6 Number 5, September/October 1996, pp.272-
276
A Master's Program in Biopharmaceutical Science
by I.R. Neering*, S.M. Mahler+ and M.W. Fryer*
* School of Physiology and Pharmacology, University of NSW,
Sydney 2053
+ Department of Biotechnology, University of NSW, Sydney
2053
Code Number: AU96010
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Introduction
The quality of Australia's tertiary education system, like
that of its medical research, is widely recognised. However,
the majority of the science courses available are generic,
giving students a broad basic education rather than a
career-oriented training. As career options become more
specialised the need to build on that fundamental background
has become evident, and in response to this need the CRC for
Biopharmaceutical Research has developed a Masters program in
Biopharmaceutical Science directly aimed at the focussed
training of staff for the biopharmaceutical industry.
The Cooperative Research Centre for Biopharmaceutical Research
is uniquely equipped to develop such a course. It is a joint
venture of the Garvan Institute of Medical Research, the
University of NSW (Department of Biotechnology and the School of
Physiology and Pharmacology), the Biomolecular Research Institute
(BRI), St Vincent's Hospital, CSL Ltd. and Peptide Technology
Limited. Thus it combines academic expertise in molecular and
cell biology, production and scale-up, and physiology and
pharmacology - all areas crucial to the identification, design
and development of biopharmaceuticals - with the commercial
approach of two companies with a biopharmaceutical focus. Whilst
the primary aim of the Centre is to provide a coordinated
research base for the development of an Australian
biopharmaceutical industry, it also has an educational commitment
aimed at reinforcing Australia's ability to play an active role
in the international marketplace for these products. If
Australia is to realise its potential as a significant producer
of biotechnology-sourced pharmaceuticals into the next
millennium, it needs to develop the scientific infrastructure in
terms of human resources to underpin the research, development
and marketing of these products.
Background
Traditionally most of the development of pharmaceuticals used in
Australia is carried out overseas, with the presence of the large
pharmaceutical companies being limited to their marketing and
regulatory arms. Increasingly, however, new potentially valuable
therapeutic compounds are now being developed and manufactured
within Australia by Australian companies. The major companies
involved in the Australian biopharmaceutical industry include
CSL, Fauldings, Biotechnology Australia, AMRAD, Peptide
Technology Ltd., Biota Holdings and Cortecs International. At the
same time the industry is becoming increasingly internationalised
with some of the large multinational organisations becoming major
share holders in companies which originated in Australia. Coupled
with this, the forming of strategic alliances through joint
ventures and technology licensing agreements is evidence that the
Australian biotechnology industry is adopting a more
international business focus, identifying and exploring niche
areas in a competitive world market. The ability to form such
strategic alliances means that by subcontracting out aspects of
product development, quite small groups of individuals can
exploit a potentially new and innovative therapeutic compound
through the creation of virtual drug development corporations
(Lightfoot, 1996).
Traditionally, the pharmaceutical companies have recruited staff
with either a pharmacy degree or a basic science degree with
physiology, pharmacology, microbiology or biochemistry major. The
larger biopharmaceutical companies such as those mentioned above
also employ graduates with degrees in biotechnology, biochemistry
or bio-process engineering. Staff with this kind of background
are then trained by their organisation to perform regulatory
affairs, product specification and development of formulations
involving conventional pharmaceuticals.
As the potential of biotechnologically engineered pharmaceuticals
becomes more fully realised the need for graduates with knowledge
encompassing both conventional pharmacology and biotechnology as
well as regulatory affairs and business issues will become
paramount. No single program offered instruction in all of these
disciplines.
With this in mind, in 1994 the CRC for Biopharmaceutical
Research, in conjunction with the University of NSW, established
an on-campus Master of Applied Science Degree in
Biopharmaceuticals in response to the perceived current and
future need for specialist instruction in biopharmaceutical
development in Australia. The course is offered by the Faculty
of Applied Science and administered through the Department of
Biotechnology, and the School of Physiology and Pharmacology at
UNSW. The MAppSc (Biopharmaceuticals) incorporates course work
at the University and a supervised research project relevant to
the pharmaceutical/biopharmaceutical industry, undertaken by
students under the auspices of the partners of the Centre. The
course covers a broad spectrum of disciplines, including
biochemistry, biotechnology, physiology and pharmacology, and
ranges from principles to advanced studies in each discipline.
Our first group of graduates from the program have all found
employment within the pharmaceutical industry.
The on campus course proved so successful that requests for
enrolment for the 1996 academic year exceeded the number of DEET
funded places available. Clearly, there was a demand for this
type of program. Accordingly, In 1996 the Centre established an
open learning program in biopharmaceuticals for external students
based on the internal MAppSc (Biopharmaceuticals). This is now
being offered within Australia, and the CRC is working towards
its use for distance education overseas. There have been strong
expressions of interest from the UK, Malaysia, Hong Kong, which
are the initial target countries for marketing the course.
The Course
Admission to the program
The course is open to graduates with a four year degree in
biotechnology, pharmacology or a related discipline. Biochemistry
is a prerequisite for entry. For those with only a three year
degree, usually a BSc, applications are considered from those who
have acquired equivalent qualifications or industry experience.
Experience to date with our on-campus students has indicated that
more students have a background in molecular biology or
microbiology than in pharmacology. A high proportion of students
have little background in any of these areas though quite a
number of on-campus students and all of our distance students
already work in the pharmaceutical industry.
Course work
With the financial assistance of a grant from the New South Wales
Government eight learning modules have been developed, based on
the same material taught in our on-campus Master s program. Each
module consists of subject text, printed readings (reprints of
relevant original articles) and self test questions and may also
contain audiovisual material in the form of audio and video
tapes. The eight unit learning resource modules are constituted
as follows:
Basic principles of drug action
This module covers general principles of pharmacodynamics and
pharmacokinetics. Pharmacodynamics considers drug-receptor
interactions, the basis of dose response curves, reversible and
irreversible antagonists, partial agonists and related topics.
Events following the drug receptor interaction which include
stimulation of second messenger systems and the pharmacology of
ion channels are described. The principles governing
pharmacokinetics and their clinical importance are discussed in
some detail.
Selected topics in pharmacology
For this module the topics were chosen to enable students to gain
knowledge of the diversity of receptors in the human body with
which drugs commonly interact to produce their main clinical
effects or their side effects/toxicological actions. The module
begins with an introduction to the autonomic nervous system then
works through autonomic receptors, receptors for histamine and
serotonin, then to the newer areas of peptide receptors and
cytokines, the latter areas being those for which drugs are now
being developed. With this background plus some reading material
on drugs affecting the central nervous system, it is felt that
students will be able to read and understand the pharmacology of
most drugs in clinical use.
Techniques for drug development
This module extends the concepts introduced in the basic
pharmacokinetics section. More advanced pharmacokinetic problems,
such as compartmentation, kinetics of effects and problem solving
are included. A detailed section deals with receptor binding and
includes a video which describes the practical and theoretical
aspects of this technique. The determination of molecular
structure and quantitation of drugs in the body are vital aspects
of drug development. Accordingly, included in this module, is a
section on techniques used in the assay of pharmaceutical
compounds. This section deals with some of the latest assay
techniques including MALDI mass spectrometry.
Discovery and development of new medicines
This module gives an overview of most aspects of the development
of new drugs. Examples of drugs derived from both natural
products (plants) as well as those developed using synthetic
programs are discussed. Screening of compounds for activity and
the issues of toxicological testing are also examined. All phases
of clinical trials are dealt with and the viewpoints of both
pharmaceutical company and clinical investigator put forward.
Regulatory issues and ethical problems are also considered.
Production of recombinant products
In this module, some basic recombinant DNA techniques and
heterologous protein expression are examined in prokaryotes and
eukaryotes. For prokaryotes, Escherichia coli is the model
species chosen and for eukaryotes, the yeast and mammalian cell
systems are described. The advantages and disadvantages of the
various expression cell systems are outlined. The vectors used
for cloning of the protein genes are also described and
illustrated. Cloning of genes into the vectors, production and
subsequent characterisation of the recombinant protein are also
described. The examples are actual biopharmaceutical products
currently produced by the biotechnology industry and students are
referred to published journal papers throughout the modules.
Principles of fermentation and downstream processing
The units in this module were chosen to give students a good
understanding of the fundamental principles associated with
biopharmaceutical manufacture and put regulatory principles into
the context of biopharmaceutical manufacture. Basic fermentation
principles for the large scale culture of bacterial and mammalian
cells to produce recombinant protein biopharmaceuticals are
discussed. This is followed by a thorough study of the main unit
operations associated with product recovery, commonly referred
to as downstream processes. The principles of Good Manufacturing
Practice, relevant to all aspects of drug manufacture including
fermentation and product recovery operations are discussed. Also
discussed are modern methods of product characterisation which
form a critical component of the regulatory procedure.
Monoclonal Antibody Technology
The first unit of this module serves as an introduction to
immunology, emphasising the areas of immunology relevant to
antibody production. In addition, the structure of antibody
molecules is studied in detail. The second unit discusses the
processes in the production of hybridomas, the specialised cells
which produce monoclonal antibodies. This unit includes
information on immunisation protocols, methods of cell fusion and
selection and the production of human monoclonal antibodies by
EBV-transformed B cells. Unit 3 is associated with the more
recent developments in antibody engineering techniques. The phage
display system and genetic manipulations for the production of
humanised antibodies and antibody fragments are described in
detail. Unit 4 covers the applications of monoclonal antibodies
both for in vivo diagnostics and for therapy. Also, some
of the more recent innovations such as the production of
recombinant immunotoxins are described.
Regulatory considerations, patent issues and licensing
The Code of Good Manufacturing Practice as it applies to the
production of recombinant biopharmaceuticals and the
establishment of Standard Operating procedures (SOPs) for a
production process are examined in this module. There is also an
overview of the current state of evolution of the biotechnology
industry. The concept of licensing as a viable approach to
biopharmaceutical development is discussed as are details of the
licensing process itself. The module also introduces the student
to the concept of intellectual property as it relates to
biopharmaceuticals and provides some guidelines on its
management. The creation and protection of intellectual property
is the basis on which the development and commercialisation of
biopharmaceuticals is built and as such is of vital concern to
the industry. The module also provides a detailed consideration
of patents and trade secrets as well as touching on trade mark
registrations, industrial design registrations and copyright.
During the academic session, distance students participate in a
number of tutorials conducted as a teleconference with the
author(s) of their printed lecture notes. The tutorials are
structured and questions for discussion are distributed to
students well in advance of the tutorial session. In addition
students have access via the telephone, e-mail or fax to the
lecturers. Students are also required to submit written
assignments based on the lecture material or on additional
reading that has been requested. The assignments and performance
at tutorials constitute a form of continuous assessment and are
worth 50% of the overall grade for each of the eight modules.
Project
As mentioned above for the on campus program, completion of a
supervised project is also a requirement for the distance
program. This departs from the present trend in Master's programs
which, increasingly, are by course work only. While the
administrative load and time demands on academic staff associated
with research projects are greater than in simple course-work
programs, it was felt that training in independent research
methodology is vital if individuals are to pursue effective
careers in industry.
Project topics can be drawn from any relevant area: regulatory
affairs, licensing and patenting or a laboratory bench project
involving any of the core scientific subjects studied in the
program. The aim here is not only to complete an independent
piece of work but to train students in library research, data
presentation and all of the associated skills of industry related
research activities.
Projects are sourced from industry, the CRC and from the
University of NSW. For those projects carried out in an industry
setting, an adviser from the relevant industry is appointed. An
academic supervisor from the CRC or University is also appointed.
The student thus has two individuals who can provide support and
advice during the course of the project and who can offer
different perspectives on the work being undertaken. These two
individuals also serve as examiners on completion of the project.
Occasionally, security issues may arise, as for example when one
of our students was involved in a project examining patenting
issues on a viral protein. In this case, the academic supervisor
was required to sign a non-disclosure agreement.
It may not always be possible for students to do an industry or
laboratory based project because of limited access to these
facilities perhaps as a result of the remote location of the
student. Under this circumstance a literature based project with
a University or CRC based supervisor would satisfy the research
requirement. As our distance program develops, we are
establishing links with other CRCs and with appropriate
departments in other universities both in Australia and overseas.
These universities will act as nodes for course delivery and
provide the infrastructure, both academic and laboratory based,
to effectively expand our geographical range of project
supervision.
The Future
As the course develops we are looking to improve the
dissemination of our material. An increasing use of the Internet
is characterising our distance program especially through the use
of e-mail for student notification, assignment submission and
off-line tutorials. In the future we expect to set up a usenet
group for conferencing and are looking into the effectiveness of
putting the course material itself onto the Internet. We have a
home page which details information for those interested in the
course, at the address:
http://pathology.med.unsw.edu.:80/Physiology/teaching/external
/biopharm/.
As we establish links with other universities and CRCs we expect,
by drawing upon their expertise, to increase the breadth of our
course by the addition of further modules; vaccine development,
growth factors, gene therapy and formulation have already been
identified as potential additional modules and their development
with experts in the relevant fields is now in progress. This is
essential for an area which is changing and developing as rapidly
as the biopharmaceutical industry.
References
Lightfoot, G. Drug discovery and VDDCs. Drug Discovery Today,
1: 255-260, 1996.
Copyright 1996 Australian Biotechnology Association Ltd.
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