The word biopharmaceuticals was initially used to describe therapeutic proteins produced using recombinant DNA techniques. More recently, the term has been expanded to include a wider range of products, such as oligonucleotide and antisense technology, and now covers pharmaceuticals, which are inherently biological in nature due to the use of biotechnology in their method of manufacture.
The success of biopharmaceuticals in addressing previously intractable diseases and in providing bio-rational therapies has led to them becoming an important and rapidly growing segment of the pharmaceutical industry. Global sales of biopharmaceuticals now represents more than US$60 billion a year, accounting for approximately 10 per cent of the pharmaceutical market, with a growth rate of more than 20 per cent a year. Importantly, biopharmaceuticals account for more than 20 per cent of new therapeutics approved by regulatory authorities such as the US Food and Drug Administration (FDA), and more than 40 per cent of new products currently under development.
Particularly exciting has been the rapid growth in the application of monoclonal antibodies, products whose early promise as ‘magic bullets’ – capable of specifically targeting tumour cells – was never realised because of immunogenicity problems associated with proteins of murine origin.
However the development of chimeric (mouse/human), humanised and, now, fully human antibodies able to be made at large scale by recombinant mammalian cells, has opened up many applications for this exciting class of biopharmaceuticals. Clearly the production of such large complex molecules is becoming a fact of life for an industry that grew up on small molecules.
How then is Australia positioned in this rapidly expanding field?
Australia’s high-quality bioscience research has resulted in several contributions to global biopharmaceuticals. The world’s first cancer vaccine, Gardasil® (the vaccine for human papilloma virus developed by Professor Ian Frazer FAA FTSE and the late Dr Jian Zhou of the University of Queensland) and the discovery of the colony stimulating factors by Professor Don Metcalf and colleagues at the Walter and Eliza Hall Institute in Melbourne, are the two products which rapidly spring to mind as success stories, each having been used to successfully treat millions of patients.
However, on the whole Australia does not perform as well as it should in the commercialisation of its high quality bioscience research. Although we rank well for our population on the number of publications and citations, we are well down on patents filed and commercial returns from the research.
While Australia’s lack of a large indigenous, research-active pharmaceutical industry has probably been an historic reason for limited commercialisation of our bioscience research output, there are now a growing number of small and medium enterprises (SME) actively commercialising new biopharmaceutical products.
One of the key drivers behind the establishment of the Federal Government’s Pharmaceuticals Industry Action Agenda (PIAA) was “The realisation by both industry and Government that Australia could gain a larger share of the industry’s global activity by better commercialising Australian innovation and focusing on those parts of the value chain in which we have a competitive advantage.”
The PIAA determined that the limited number of biopharmaceutical manufacturing facilities and capability in the country was an impediment to the local biopharmaceutical industry fulfilling its potential, and that there was a need for a small scale mammalian cell biopharmaceutical production facility to provide local access to drug developers requiring small amounts of complex biological material for pre-clinical work and for human clinical trials. Such a facility would bridge the infrastructure gap in the national biotechnology manufacturing value chain and allow Australian industry to capture more of the value from global drug development.
The Queensland Government has addressed this deficiency by forming Biopharmaceuticals Australia (BPA), a national scale-up manufacturing facility that will produce new biopharmaceuticals to international GMP (Good Manufacturing Practice) standards required for testing in pre-clinical and clinical trials.
In a related development, the recent National Collaborative Research Infrastructure Strategy (NCRIS) provided funds from Federal and state sources to a number of groups in Australia for them to provide biopharmaceutical development capability for Australian researchers.
The Australian Institute of Bioengineering and Nanotechnology (AIBN) at the University of Queensland was successful in becoming a major node in the NRCIS Biotechnology Products Capability, and has assembled an excellent team of people with global experience in the development of biopharmaceutical production processes to the high purities required for a human therapeutic.
The facility is housed in custom-designed clean rooms and laboratories in the new $73 million AIBN building and builds on the research expertise in the institute in the field of mammalian cell expression, purification and characterisation of complex biopharmaceuticals and antibodies. Facilities include:
Together with the other partners in the NCRIS capability (Monash University, the University of NSW, CSIRO, and Hospira and Radpharm from the private sector) this investment in infrastructure, when coupled with the BPA initiative, will help fill the gap for Australian researchers as they move their products from the laboratory to the all-important human clinical trials.
The development cascade for a new biopharmaceutical from discovery research through to human clinical trials and ultimate regulatory approval is a long and complex process.
In addition to the developments described above in the areas of bioprocess development including pre-clinical manufacture and scale-up, formulation stability and quality studies, and ultimately GMP manufacture, there have also been national developments in other key areas for the development chain such as pre-clinical and toxicology testing, and in the design and running of clinical trials.
Taken together, this suite of capabilities has effectively filled the main gaps that existed in Australia in the development chain for a new biopharmaceutical, so that it will now be possible for local groups to take their new products from a research discovery through to human clinical trials, a key milestone in capturing the maximum commercial value for the product.
By Peter Gray
Source: ScienceAlert Australia & New Zealand http://www.sciencealert.com.au/opinions/20080608-17754.html
First published in Australian Academy of Technological Sciences and Engineering's Focus Magazine, number 150, 'Biomedical Technology'