ver the last two decades, there has been an increasing number of biopharmaceuticals entering clinical trials. Many of these drugs are a new class of therapeutic proteins produced by living cells through microbial fermentation or mammalian cell culture. Such drugs, termed "bio-pharmaceuticals," are in contrast to the many traditional small-molecule drugs (pharmaceuticals) manufactured by synthetic chemical processes.

The large-scale production of therapeutic proteins is referred to as biologics manufacturing. The term "biologics" is used to classify an agent derived from living sources - such as therapeutic serums, antitoxins, vaccines, and biological therapeutics - that induces immunity in infectious diseases.

Living cells can be genetically engineered through recombinant DNA technology to produce important therapeutic proteins (recombinant proteins). Some well-known examples of recombinant protein drugs with high worldwide sales figures are insulin for diabetes, interferon beta-1a for multiple sclerosis, and human factor IX for the treatment of haemophilia.

Another type of therapeutic proteins is monoclonal antibodies (antibodies that are produced by a single clone of cells). Due to the high specificity of such antibodies for its target, they are used today in drugs such as Rituxan^® to target malignant tumour cells in cancer therapy.

Worldwide, there are more than 500 biologic products in various stages of clinical trials. The Freedonia Group estimates that the demand for biologics in the US will advance almost 12% annually, to over US$56 billion in 2006. The successes of recent therapeutic proteins and the fact that manufacturing facilities require long lead times in design, construction and validation, have also prompted analysts to estimate a global shortage of biologics manufacturing capacity. While the biologics manufacturing industry is no longer in its infancy, it looks set to grow further as advances in biologics research bring on new product innovations.

Since 1990, Singapore has been building up its capabilities in biologics manufacturing. Today, the Bioprocessing Technology Institute (BTI) and A-Bio Pharma Pte Ltd (A-Bio) are the country's key anchors of scientific expertise and commercial production for biologics. BTI is funded by the Agency for Science, Technology and Research (A*STAR) through its Biomedical Research Council, while A-Bio is 100% owned by Bio*One Capital, a subsidiary of Singapore-based EDB Investments Pte Ltd.

BTI focuses on bioprocess science and engineering research. Bioprocessing covers the two phases of growth of living cells, followed by recovery and purification of the final protein product. The institute's area of interest is to understand how to enhance the productivity and quality of recombinant proteins and monoclonal antibodies from living cells. To date, the institute's research achievements have included a protein-free, chemically-defined media for growing cells that comply with regulatory guidelines (due to the lack of animal-derived components in the media) and a chemical cocktail that prolong cell viability.

A-Bio, on the other hand, aims to be a leading biologics contract manufacturer of therapeutic proteins for major pharmaceutical and biotechnology companies. Currently, A-Bio's good manufacturing practice (GMP) 200-litre (L) facility houses several process development laboratories, a 200L GMP production train, quality control laboratories, and offices.

In anticipation of increased demand for clinical trial materials (from potential customers), detailed design to expand A-Bio capacity up to 2 x 500L is expected to start before the end of this year. Future plan is to build a large-scale facility at Tuas Biomedical Park with a reputable partner. This large-scale facility will provide a full range of manufacturing solutions to cover process development, optimisation, manufacturing scale-up, GMP production, quality control, and regulatory compliance.

Daniel Wang, Institute Professor at the Department of Chemical Engineering, Massachusetts Institute of Technology, and Chairman of BTI's scientific advisory board, takes stock of the island republic's efforts in biologics: "Singapore is unique - it looks to the future and invests in people and infrastructure. The numerous research and training collaborations available are useful in helping BTI (and the country) become first class in terms of the science and talent. In infrastructure, the research institutes of A*STAR, such as the BioInformatics Institute and the Genome Institute of Singapore, are available to collaborate with BTI in its research efforts."

For more information contact Bioprocessing Technology Institute at admin@bti.a-star.edu.sg and A-Bio Pharma Pte Ltd at info@a-bio.com

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