PHARMACEUTICALS & BIOTECHNOLOGY

IN BRIEF

At a time when pharmaceutical and biotechnology businesses around the world are grappling with declining R&D productivity, Singapore’s integrated research ecosystem enables companies to access multidisciplinary capabilities in a single location, which improves R&D decision-making and accelerates drug discovery and development. More than 30 of the world’s leading biomedical sciences companies (including GlaxoSmithKline, Novartis and Takeda) are leveraging Singapore as a key home base to drive innovation, growing the nation’s biopharmaceutical industry by more than 30 per cent in 2011.

The multi-ethnic city-state which is the leading logistics hub globally and has world class intellectual property protection, is now Asia’s fastest-growing bio-cluster, presenting strategic partnership opportunities with research institutes, corporate labs and public hospitals to develop new medicines and future therapies that can be customised for regional and global markets.

OUR EDGE

REGIONAL RESEARCH AND DEVELOPMENT HUB FOR BIOTECHNOLOGY

Focused on developing a vibrant biomedical sciences research ecosystem, Singapore has built up a strong scientific foundation with seven research institutes and five research consortia in key fields that include clinical sciences, genomics, bioengineering, molecular/cell biology, medical biology, bio-imaging and immunology. More than 50 companies are carrying out biomedical sciences R&D that includes drug discovery, translational and clinical research, frequently collaborating with these research institutes.

The city-state has also made significant progress in translational and clinical research. It has built up key infrastructure such as the Investigational Medicine Units dedicated for early-phase trials in public hospitals, as well as the Singapore Clinical Research Institute, which focuses on supporting later-stage trials. These facilities will in turn support the growing community of clinician scientists in Singapore.

New therapies and technologies are constantly made available by clinical research engaged by our hospitals and national speciality centres, in collaboration with some of the world’s top medical institutes, pharmaceutical and medical technology firms. In addition, important leads to new therapies that benefit patients are being discovered through world-class scientific research fostered by the Agency for Science, Technology and Research (A*STAR) and its biomedical research institutes.

In the years ahead, as Singapore builds on its foundation in good science and capabilities in translational and clinical research, the city-state is well positioned to support the industry in its efforts to accelerate the drug discovery process with next-generation technologies, while focusing on key diseases such as cancer, metabolic diseases, neurological diseases, infectious diseases and eye diseases.

WORLD-CLASS CLINICAL EXCELLENCE

Singapore is reputed for its clinical research and clinical trials management activities in Asia. As the secretariat for the APEC Coordinating Centre for Good Clinical Practice (GCP), Singapore plays a strategic role in developing GCP in Asia, steering initiatives such as the training of clinical research personnel and developing a conducive environment for multi-site clinical trials in the region.

These factors have attracted many global pharmaceutical brands to set up their regional clinical trial centres in Singapore. These include Sanofi-Aventis, GlaxoSmithKline, MSD, Novartis, and Sanofi.

Making advancements in cancer research in Singapore is the NUS Cancer Science Institute which develops novel therapy for cancer through clinical trials. The CTRG is a multi-institutional research collaboration of which a few key institutions are the National University Hospital/National University of Singapore, Sydney Cancer Centre/University of Sydney, Johns Hopkins Singapore International Medical Centre, Chinese University of Hong Kong and National Cancer Centre, Singapore.

Several Contract Research Organisations (CROs) have also established operations in Singapore to support the pharmaceutical firms’ growing outsourcing needs. These include global CROs Covance, Quintiles and ICON which manage regional clinical trials from the city-state. These international CROs offer a wide range of services, ranging from Phase I to pharmacovigilance studies. Some are also setting up innovative biomarker discovery and validation services to support their clients.

GOVERNMENT INITIATIVES

A core of clinician scientists has been built up in Singapore through initiatives such as the Singapore Translational Research (STaR) Investigator Award, which is designed to recruit and nurture world-class clinician scientists to undertake translational and clinical research in Singapore, as well as the Clinician Scientist Award (CSA), which provides research funding and salary support to enable medical researchers to devote more time to research.

Other initiatives to grow this base of clinician scientists include:

- The Translational & Clinical Research (TCR) Flagship Programme which presents a platform for researchers and clinician scientists to collaborate in solving scientific problems and translate their research into quality healthcare solutions for patients (bench-to-bed solutions). Each awarded TCR flagship programme comes with a five-year budget of up to S$25 million.
- The Competitive Research Programme (CRP) is a funding scheme that supports a broad base of research ideas, through a competitive bottom-up approach. The scheme supports R&D programmes that help to identify new potential strategic research areas in which Singapore can invest to develop core capabilities for new industries of the future, including those in the biomedical sciences translational and clinical research areas. Each award is for a maximum of S$10 million per programme, over three to five years.
- The Health Services Research Competitive Research Grants (HSR-CRGs) is a Ministry Of Health (MOH) research grant established in 2009 to promote the conduct of HSR and enable the translation of HSR findings into policy and practice. Principal Investigators (PIs) from local public healthcare or academic institutions are eligible for this grant which provides a maximum of S$1 million over a two-year period.

In addition, the Biopharmaceutical Manufacturers’ Advisory Council (BMAC), an industry-government group comprising of local pharmaceutical plant site directors and government agencies, underscores Singapore’s commitment to lead the manufacturing curve with a highly-skilled manufacturing workforce, a track record of quality and process development capabilities by upgrading employees’ skills, training new workers and promoting best practices.

REGULATORY FRAMEWORK

Singapore seeks to provide a pro-innovation environment that facilitates the development of innovative therapies, while ensuring global standards of safety, quality and efficacy. This is bolstered by the active involvement of the Singapore Health Sciences Authority (HSA) in defining new regulatory frameworks and pursuing new areas of research in regulatory sciences over the years. In 2009, the HSA Academy was set up to foster greater synergies across the agency’s unique conglomeration of diverse scientific and biomedical capabilities. More importantly, it would also serve as an enabler for growing thought leadership in Singapore. In addition to organising scientific meetings and symposia, the academy also seeks to facilitate discussions on cutting edge issues in the forensic and analytical sciences, regulatory science and transfusion medicine.

In 2011, HSA joined hands with the Massachusetts Institute of Technology (MIT’s) Center for Biomedical Innovation and five other companies – Bristol-Myers Squibb, Johnson & Johnson, Life Technologies, Pfizer and Quintiles ¬– in its NEWDiGs (New Drug Development ParadIGmS) programme for demonstration projects in regulatory science and oncology innovation. NEWDiGs will also evaluate components of more flexible and adaptive regulatory models with an initial focus on Progressive Authorisation.

HSA has also forged MOUs with leading regulatory agencies around the world including the U.S. Food and Drug Administration, China’s State Food and Drug Administration and UK’s Medicines and Healthcare Products Regulatory Agency.

In 2009, Singapore was also accepted into OECD’s Mutual Acceptance of Data framework that enables data from GLP-compliant preclinical trials conducted in Singapore to be accepted by 30 OECD and non-OECD members including the US, EU and Japan.

BIOMEDICAL RESEARCH INSTITUTES

Over the past 20 years, Singapore has steadily built a strong foundation of basic and clinical research through its biomedical research institutes under A*STAR which have gained the regard of the global scientific community.

Bioinformatics Institute

The Bioinformatics Institute (BII) was established as the computational biology research and postgraduate training institute as well as a national resource centre in bioinformatics. The BII focuses on theoretical approaches aimed at understanding biomolecular mechanisms that underlie biological phenomena, the development of computational methods to support this discovery process, and experimental verification of predicted molecular and cellular functions of genes and proteins with biochemical methods.

Bioprocessing Technology Institute

The Bioprocessing Technology Institute’s (BTI) mission is to develop manpower capabilities and establish cutting-edge technologies relevant to the bioprocess community. Spearheading bioprocess R&D, the BTI has core expertise in expression engineering, animal cell technology, stem cells, microbial fermentation, product characterisation, downstream processing, purification and stability, with supporting proteomics and microarray platform technologies. BTI, with its R&D and its GMP manufacturing capabilities, bridges the gaps between discovery, process development and commercialisation.

Genome Institute of Singapore

Established in June 2000, the Genome Institute of Singapore (GIS) is a national flagship initiative with a global vision that seeks to use genomic sciences to improve public health and prosperity. As a centre for genomic discovery, GIS pursues the integration of technology, genetics, and biology towards the goal of individualised medicine. Its scientific focus is to investigate post-sequence genomics; to understand the genetic architecture of pan-Asian populations with emphasis on cancer biology, pharmacogenomics, stem cell biology and infectious diseases.

Institute of Bioengineering & Nanotechnology

The Institute of Bioengineering and Nanotechnology (IBN) spearheads the advancement of biomedical sciences in Singapore. Positioned at the interface of two frontiers of engineering, IBN is focused on creating knowledge and cultivating talent to develop technology platforms that will spur the growth of new industries.

Since 2003, the Institute of Bioengineering and Nanotechnology (IBN) has carved out a unique niche at the interface of bioengineering and nanotechnology with its impactful research. IBN is helmed by Executive Director, Professor Jackie Ying, who was a Professor of Chemical Engineering at the Massachusetts Institute of Technology (1992 - 2005). Under her direction, IBN conducts research at the cutting-edge of bioengineering and nanotechnology. Its programs are geared towards linking multiple disciplines across engineering, science and medicine to produce research breakthroughs that will improve healthcare and our quality of life.

Research Capabilities

- Drug and Gene Delivery
- Cell and Tissue Engineering
- Biosensors and Biodevices
- Pharmaceuticals Synthesis and Nanobiotechnologies

Institute of Medical Biology

The Institute of Medical Biology (IMB) has a strategic, programme-directed portfolio of research focused on issues at the critical interface between basic science and medicine. It aims to facilitate the development of translational research by building bridges between clinical and basic science.

IMB currently hosts research programmes concerned with different aspects of human diseases. Programmes include the Singapore Onco-Genome project, Regenerative Medicine, Papillomavirology, Epithelial Biology and the Lab of Stem Cell Biology from the Singapore Stem Cell Consortium (SSCC). IMB helps scientists and clinicians work closely together to support, inform and refine each other’s strengths and specialisations to increase the efficiency of the translation process, and ultimately contribute towards a better quality of life.

Institute of Molecular and Cell Biology

The Institute of Molecular and Cell Biology (IMCB) was established to help develop and support biomedical R&D capabilities in Singapore. Today, IMCB has established itself as a world-class research institute in biomedical sciences with research activities focusing on six major fields: Cell Biology, Developmental Biology, Structural Biology, Infectious Diseases, Cancer Biology and Translational Research with core strengths in cell cycling, cell signalling, cell death, cell motility and protein trafficking.

IMCB’s recent achievements include being part of an international consortium that successfully sequenced the entire pufferfish (Fugu) genome—a world’s first. IMCB was also awarded the Nikkei Prize 2000 for Technological Innovation, in recognition of its growth into a leading international research centre and its collaboration with industry and research institutes world-wide.

Singapore Institute for Clinical Sciences

The Singapore Institute for Clinical Sciences (SICS) mission is the development of disease-oriented clinical and translational research programs in focused disease areas. SICS is distinguished by its focus on clinical sciences and the use of innovative approaches and technologies that enable the efficient and effective study of human health and diseases. The institute aims to attract, train and nurture clinician-scientists and serve as a critical bridge linking basic research undertaken by A*STAR Research Institutes and clinical research programmes in Singapore’s public hospitals, disease centres and universities.

PUBLIC-PRIVATE PARTNERSHIPS

Presenting a stellar bio-cluster in Asia, Singapore has established a strong track record and foundation in biomedical sciences manufacturing and R&D activities. In addition, Singapore provides diverse partnership opportunities with its public-sector research institutes, base of leading pharmaceutical and biotechnology companies, clinical-research units in hospitals and international research organisations.

For example, Roche established its Singapore Hub for Translational Medicine (CHF 100 million) with 30 scientists on board to partner with Singapore’s scientific and medical institutions. The multi-disciplinary team aims to generate insights into disease biology to accelerate drug discovery and development.

Bayer Healthcare invested an additional S$14.5 million in five projects with local academic institutions to advance R&D to improve early diagnosis and treatment of cancer. Additionally, GlaxoSmithKline (GSK) established its first Academic Centre of Excellence in Singapore and its first four projects focusing on early-stage research in ophthalmology, regenerative medicine and neuro-degeneration to elucidate new mechanisms of action for innovative medicines.

Today, Singapore has established world-class scientific and clinical excellence that enables pre-clinical development in mouse models and early-phase clinical testing of novel drug candidates to be carried out in one location. In 2011, Maccine inked a collaboration with A*STAR’s Singapore Bioimaging Consortium to form a comprehensive Translational Imaging Industrial Lab (TIIL) to push the boundaries in state-of-the-art preclinical imaging to enhance the drug development process.

Meanwhile, Siena Biotech is partnering A*STAR’s Experimental Therapeutics Centre to develop molecular inhibitors of a major signalling pathway in oncology to target difficult-to-treat forms of cancer such as gastric cancer, leukaemia and brain tumours. Humalys SAS and Cytos Biotechnology are working with the Singapore Immunology Network to develop antibody-based therapies for infectious diseases that are prevalent in Asia.

Also partnering with A*STAR, research institutes and hospitals, Novartis (which houses more than 100 researchers from 18 nationalities at the Novartis Institute for Tropical Diseases) teamed up with the Swiss Tropical and Public Health Institute, and The Scripps Research Institute. Together, they have discovered a new drug against malaria called spiroindolone NITD609. This breakthrough comes at a time when drug-resistant strains are becoming an increasing threat in the region due to irrational drug use and poor-quality or counterfeit medicine.

Singapore’s strong and growing process R&D capabilities are also helping companies based here to break new ground in both small-molecule and biologics production. A major collaboration between a Singapore public institute and a leading pharmaceutical company is the S$2 million public-private partnership between GSK Biologicals and A*STAR’s Bioprocessing Technology Institute to collaborate on vaccine and adjuvant system-related research projects. In 2009, Singapore’s Institute of Chemical and Engineering Services (ICES) opened a pilot-scale laboratory facility that will enable greater collaborations with pharmaceutical companies in process development.

MANUFACTURING BASE

Attracted by the excellent physical and regulatory infrastructure, global connectivity and skilled manpower available in Singapore, many leading biopharmaceutical companies (including Abbott, GlaxoSmithKline, Lonza, MSD, Novartis, Pfizer and Sanofi-Aventis) have chosen to make Singapore their global manufacturing base. These companies operate multi-purpose plants with the capability to manufacture a wide range of active pharmaceutical ingredients (APIs), biologics and nutritionals. The country has also made significant inroads in biologics manufacturing, with Baxter, Lonza, GlaxoSmithKline and Roche announcing their investments to set up major biologics facilities that amount to US$2 billion in capital expenditure. To date, all pharmaceutical manufacturing facilities that have commenced commercial operations have received validation from international regulators such as the US Food and Drug Administration (FDA) and the European Medicines Agency (EMEA).

Convinced of Singapore’s competitive advantages, many pharmaceutical and biotechnology companies have diversified their operations over the years to include other manufacturing activities besides APIs. Key examples include:

- GlaxoSmithKline (GSK) presented close to S$8 million in research funding to 14 principal investigators under the GSK-Singapore Partnership for Green and Sustainable Manufacturing (GSM) in 2011. This was the second round of projects to be awarded research funding under the S$33 million GSK-Singapore Partnership for Green & Sustainable Manufacturing and the principal investigators will be conducting research in the areas of chemical-, physical- and bio-transformations, facilities and supply chain, equipment and technical operations, life cycle assessment, and solvent selection and optimisation. The GSK-Singapore Partnership for Green & Sustainable Manufacturing seeks to develop innovative solutions as the global pharmaceutical industry grapple with the need to enhance sustainability and optimise their global operations.
- Lonza invested CHF 10 million to expand its biopharmaceutical development services platform in Singapore in 2011. Lonza’s Development Services business, the front-end of the biological mammalian custom manufacturing process, offers customised and innovative services used in the development of robust biomanufacturing processes. The expansion in Singapore will consist of the addition of 1858 m² of state-of-the-art laboratory space and associated equipment, and will support cell line construction, upstream and downstream process development, and a broad range of analytical services. The facility will integrate seamlessly with Lonza’s biological manufacturing facility in Singapore, creating a full-service biopharmaceutical development and manufacturing site that offers customers a complete range of services from development through pre-clinical and small-scale manufacturing, all the way through to large-scale commercial supply.
- Abbott’s S$450 million nutritional powder manufacturing plant in Singapore, its first major capital investment in Asia and its largest nutritional investment to date. This S$450 million state-of-the-art facility was completed in April 2008 to meet the increased demand for Abbott Nutritional Products in the region. The Singapore facility will produce over 45 million kgs of powder nutritional products a year, including hallmark Abbott brands including Similac Advance® infant formula, Gain® growing-up milk for older babies and toddlers, Pediasure® and Grow®.

Singapore remains committed to developing a manpower base that is ready for manufacturing requirements of the future. The pharmaceutical and biotechnology manufacturing sector in Singapore is currently supported by a growing base of more than 4,800 skilled engineers and technicians. Companies can also access a workforce of more than 300,000 skilled employees in related sectors (e.g. chemicals, electronics, engineering).

Representing a thriving sector of Singapore’s economic growth, the biopharmaceutical sector contributed about S$22.8 billion in output and over 6,000 jobs in 2011. Compared to 2010, the biopharmaceutical sector expanded by more than 30% in 2011. According to Datamonitor, Singapore was the third fastest growing nation globally in the export of pharmaceutical goods from 2000 to 2010.

GLOBAL TALENT POOL

Singapore is now home to more than 6,000 researchers from across the globe. On top of home-grown talent such as Soo Khee Chee (Founding Director, National Cancer Centre), Wong Tien Yin (Director, Singapore Eye Research Institute) and Goh Boon Cher (Head and Senior Consultant, Department of Haematology-Oncology, National University Cancer Institute), many world-renowned scientific talent have moved to Singapore to head the city-state’s research institutes, consortia and laboratories.

These luminaries include Edward Holmes (former Vice Chancellor, University of California, US), Judith Swain (former Dean for Translational Medicine, University of California, US), Sir George Radda (former Chief Executive, Medical Research Council, UK), Sir David Lane (former Chief Scientist, Cancer Research UK), Axel Ullrich (former Managing Director, Max Planck Institute for Biochemistry, Germany), Philippe Kourilsky (former Professor and Chair of Molecular Immunology, College de France, France) and Yoshiaki Ito (former Director of Institute for Virus Research, Kyoto University, Japan).

In addition, top clinical research talent such as Ranga Krishnan (Dean, Duke-NUS Graduate Medical School), Michael Hayden (Founder of the Centre for Molecular Medicine and Therapeutics, University of British Columbia, Canada) and Nicholas Paton (Senior Clinical Scientist, UK Medical Research Council’s Clinical Trials Unit) are based in Singapore and contribute to the thriving research environment here.

EDUCATION & TRAINING

Singapore recognises the need for training in complex manufacturing processes to facilitate technology transfer as well as the importance of nurturing the next generation of scientists.

Since launching a national scholarship programme in 2001, A*STAR has nurtured over 1,000 local PhD graduates in the world’s top universities. Its A*STAR Investigatorship (A*I) award aims to attract bright young researchers to carry out independent research in Singapore’s public-sector research institutes.

At the institutional level, the National University of Singapore (NUS) has partnered Duke University to establish the Duke-NUS Graduate Medical School, Singapore’s first graduate medical school. In 2010, Harvard’s Beth Israel Deaconess Medical Center announced its collaboration with NUHS where both parties will exchange scientific, academic and technical information, identify opportunities for cooperation, exchanges and joint research in common interest areas, and jointly organise academic and scientific seminars and conference. In addition, Singapore is investing in integrated facilities that will house research, education and training in one location. They include the Centre for Translational Medicine at NUHS and the new Khoo Teck Puat Building at the SGH Campus, where Duke-NUS Graduate Medical School Singapore is co-located with the Singapore General Hospital.

In addition, NUSAGE promotes Good Practices in Manufacturing (GMP), clinical research (GCP) and health product safety or vigilance (GVP). Collaborating with key industry leaders and leading government agencies, NUSAGE is one of the first industry-wide training initiatives in the region and complements company specific training centres in Singapore, as well as basic training for those interested to join the industry. Post-graduate programmes offered by NUSAGE include training in pharmaceutical manufacturing and clinical research.

EDB has also partnered with GSK in 2010 to draw up a 10-year strategic roadmap which includes a joint endowment fund to support graduates in public health policy research along with plans to build up capabilities in sustainable manufacturing.

DEDICATED INFRASTRUCTURE

Singapore’s medical advancements have been propelled by the Government’s strong commitment to basic and clinical R&D.

Biopolis

The establishment of the Biopolis (at one-north), a state-of-the-art infrastructure for the life sciences, has enabled Singapore to develop swiftly into a global biomedical sciences hub advancing human healthcare. Biopolis co-locates public sector research institutes with corporate labs and is designed to foster a collaborative culture among the institutions and organisations under its roof.

Tuas Biomedical Park

Tuas Biomedical Park (TBP) is a 360-hectare stretch of ready-prepared and specifically-zoned land set aside by the government for pharmaceutical and biologics manufacturing.

MOVING AHEAD

Against the backdrop of housing over half of the world’s population, a 2010 report published by market research firm RNCOS E-Services estimated Asia’s drug industry to be worth US$168 billion and growing at a rate of over 12 per cent per annum. As Asian countries develop economically, their healthcare expenditure is also increasing exponentially. The region’s growing middle class and ageing population have increased the market demand for non-essential and therapeutic treatments.

The incidence of lifestyle-related illnesses has increased with higher standards of living and longer lifespans—for example, the increasing number of Asians with heart disease, which is linked to overconsumption of fatty foods, and lung cancer due to smoking, has created an increasingly important market for the drug industry. Both public and private sector organisations are introducing health insurance schemes, which have also increased the demand for drugs and medication.

However, although R&D expenditure has grown astronomically over the years, the amount of new medicines produced has not increased significantly along with it. Multinational drug makers have to alter their strategies as their research efforts are failing to engender new drugs to replenish the patented products pipeline. Pharmaceutical companies will have to work more closely with governments, regulators and the healthcare community to make the medicine patients really need, test them as quickly and effectively as possible, and provide a more holistic healthcare service.

As global drug companies move to capture the expertise in external partners to strengthen their pipeline of new drugs, Singapore’s high-quality basic and clinical research makes it a leading partner in Asia for R&D collaborations. Between 2000 and 2010, Singapore’s biomedical manufacturing output had quadrupled from S$6 billion to S$23.3 billion and the industry has grown to account for about 5 per cent of the national GDP.

More than S$1.49 billion is spent on biomedical R&D annually. After a decade of its foray into the biomedical sciences sector, employment in biomedical R&D has more than doubled from 2,200 to over 5,000 between year 2000 and 2010. Likewise, employment in biomedical manufacturing output went from 6,000 to 14,000 over the same period. With more than 50 biomedical sciences companies and 30 research institutes, Singapore manufactured over S$27 billion worth of medicines and medical devices for global markets in 2011.

Looking ahead, Singapore has committed S$16.1 billion in continued support of research, innovation and enterprise activities between 2011 and 2015. Out of the S$16.1 billion, S$3.7 billion is dedicated to enhancing existing biomedical R&D infrastructure, integrating multi-disciplinary research and translating basic science into tangible outcomes.

KEY FACTS

1. Asia presents fast emerging as a global powerhouse for biomedical science industry

2. Trusted base to attract the region's market, global talent, and intellectual property

3. Strong scientific foundation with seven research institutes and five research consortia in key fields for accelerating drug discovery.

4. The 2.4 million sqft of Biopolis is the collaboration of R&D success between public sector research institutes with corporate labs under

one roof.

5. Manufacturing new medicines

6. Forging strategic partnerships

OPPORTUNITIES