Future Proofed Pharma

In 1939 [1] the legacy companies of GlaxoSmithKline (GSK) saw potential in Singapore and by 1959 they had set up their first sales office. Three decades later, in the 1970s, one of their sites was built at Quality Road. A further decade later, a second site was established at Jurong and has evolved to be the strategic manufacturing and global supply site for GSK’s New Chemical Entities and critical medicines. This biopharma company’s story of growth is echoed by the many others who came to Singapore for its supportive ecosystem and strategic location. “GSK came here because it sensed Singapore was keen to build up the manufacturing sector of its economy, and most of all, the government leaders had the vision to build a vibrant pharmaceutical industry which would, in time, lead to biotechnology manufacturing,” explains Lim Hock Heng, a Site Director at GSK. Later, the government of newly independent Singapore offered attractive economic incentives “and Singapore presented itself as a good location from which to make and sell antibiotics to big markets in the Middle East countries and Japan,” says Lim.

Singapore now boasts around 30 pharmaceutical manufacturing facilities with the industry employing around 7,000 people. Credit: Reggie Wan/Getty Images

Today the pharmaceutical manufacturing industry is a pillar of Singapore’s economy that currently contributes over three percent to national GDP [2]. “The sector’s manufacturing output today has more than tripled since 2000, producing around S$17 billion worth of products for global markets in 2017 [3],” says Ho Weng Si, Director, Biomedical Sciences, Singapore Economic Development Board. The sector is still expanding. Strong growth has been encouraged by Singapore’s supportive ecosystem of government policies and processes, an excellent track record of quality and regulatory compliance, great connectivity to the region and the rest of the world, and sustained investments in R&D and high quality science infrastructure. “At the turn of the millennium, Singapore envisioned creating a Biopolis in Asia,” said Dr Benjamin Seet, Executive Director of the Biomedical Research Council at ASTAR. “We now have leading research institutions, pull above our weight in science and medicine, and have the first local drugs moving into the clinic.” The island country now boasts around 30 pharmaceutical manufacturing facilities across a wide range of modalities, including active pharmaceutical ingredients (API), biologics, and drug products. The industry employs around 7,000 people. Trends shaping the industry Globally the pharmaceutical manufacturing industry is undergoing radical and rapid challenges, demanding incremental, but also transformational, change. Singapore is already meeting these challenges head-on. For one, there is the need to speed up manufacturing efficiency to reduce the time taken from discovery to when drugs reach the market. Real-time analytical technologies can improve the process and these have been identified as critical by the pharma manufacturing industry, says Professor Lam Kong Peng, Executive Director of ASTAR’s Bioprocessing Technology Institute (BTI). “By leveraging multi-omics platforms that we have invested in over the past few years, BTI can now simultaneously analyze gene, protein, sugar and metabolite profiles in the cell culture that makes the biologic products. This enables a thorough understanding of the biologics manufacturing process to enable efficient development and control of these processes,” says Lam. Precision treatment is also driving change. Improved medical diagnostic tools are allowing personalized strategies that require manufacturing operations to attain high yields, while managing a diverse product mix with low production volumes. “Today’s treatment-centric healthcare model is experiencing notable shifts towards value-based care and precision treatments, alongside a greater focus on prevention and wellness,” explains Weng Si. Manufacturers of personalized drugs must accommodate relatively tiny production runs, highly-specific requirements, and genotype-specific products. These put new pressures on manufacturing by demanding more nimble production options. New technology is also pushing the envelope of both manufacturing activities and business models. “Industry 4.0 and technological advancements like robotics, automation and digitalization are transforming manufacturing activities in the 21st century,” explains Professor Tan Sze Wee, executive director of the Science & Engineering Research Council at ASTAR. This is disrupting traditional business models in manufacturing, as data, machines and systems can now be connected throughout the value chain from production shop-floor to final distribution. “Singapore has the vision to be a leading manufacturing hub, plugged into global centers of excellence to drive the future of manufacturing,” adds Tan. To realize the vision, a swathe of initiatives is paving the way to provide Singapore with the brightest talent, mightiest partnerships, but also the lightest environmental impact. Brightest talent Singapore is future proofing its industry through its emphasis on capacity building of a strong pipeline of talent. The government, together with pharmaceutical companies, has developed new training programs to enable manufacturing-ready talent to meet the growing needs of the local industry. One initiative—the Professional Conversion Programme for the biologics manufacturing industry—has provided training for more than 400 people since 2014. Also, “under this scheme, the Local Biologics Skills Training Programme continues to see strong uptake from industry. Since the programme’s introduction in 2015, more than 170 training places have been filled,” says Weng Si. Other education and training initiatives have been similarly successful. “In the past, attracting bright Singaporeans to research was an uphill battle,” said Saif Khan, Associate Professor in the Department of Chemical and Biomolecular Engineering at NUS. “But now, with industry-academia partnerships taking strong root locally, bright students are increasingly looking to meaningful research pursuits in which they see their efforts potentially making a real impact on people’s lives and the economy,” he said. “Students graduating locally from some of the world’s best institutes of higher learning join the work force each year,” echoes Dr Prasad Kanneganti, Site Director, Pfizer Asia Pacific. “They are driven by a desire to learn new skills and strive for continuous improvement,” Kanneganti says. “Change is very well accepted here by a workforce that is technology savvy.” Supportive IP policies A stable policy environment is also proving business-friendly. Kanneganti describes how IP protection encourages new investments. “IP protection encourages the industry to bring in new manufacturing processes and technologies as well as invest in product and process development,” he says. This is borne out by recent international surveys that give high rank to the local IP regime. Singapore’s IP environment was ranked fourth in the world by the Global Competitiveness Report for 2017-18 [4] and ninth by the 2018 US Chamber International IP Index [5]. Mightiest partnerships The complex and dynamic nature of pharma manufacturing’s future has highlighted the need to strengthen local partnerships in order to pool resources, share risk and increase adoption rates. Singapore is well recognized as a leader here. “The collaboration between public research agencies, major multi-national companies, and a growing crop of local biotechs has created an environment for innovation in this sector to flourish,” says Lam. In particular, common platforms for synergistic partnerships and sharing ideas—often with competitors—to advance technology, otherwise known as “open innovation,” will help companies keep pace with rapidly evolving technology trends. A prime example is the Pharma Innovation Programme Singapore (PIPS) launched in September 2017, which brings together local research organizations such as ASTAR and NUS plus multinational pharmaceutical companies like GSK, Pfizer, and Merck Sharp & Dohme (MSD). PIPS is investing in new manufacturing technologies, with a focus on advanced process control or process analytical technology, bio-catalysis, continuous manufacturing, digitalization & automation, and enhanced pharmaceutical operations.

Personalized medicine challenges manufacturing with its highly specific requirements and genotype-specific products that demand more nimble production options. Credit: Sigrid Olsson/PhotoAlto/Getty Images

“The PIPS collaboration brings together global thought leaders in advanced manufacturing technology across key players in pharma and leading-edge researchers in Singapore,” explains Maureen O’Shea, an advisor at ASTAR. “A critical success factor for PIPS will be the drive to deploy transformational manufacturing technologies in manufacturing plants in Singapore.” Khan sees benefits from the new ways of thinking that will be catalyzed by this new partnership. PIPS will enable NUS to explore “avant-garde ideas with a larger time horizon for implementation on the manufacturing floor,” he says. “This will ensure a sustainable stream of creative and disruptive ideas for the next generation of pharmaceutical manufacturing processes,” Khan adds. GSK’s Lim agrees: “success in this program will enable Singapore and the participating companies to be a step ahead in applying new technologies needed for new product manufacture.” ASTAR’s Lam confirms that: “this is the kind of innovation in manufacturing processes, developed through public-private partnership (PPP) models, which the industry will need to meet future challenges.” Other innovative partnerships are concerned with developing infrastructure that offers more flexible capacity options. EDB is working with contract manufacturing organizations (CMOs) to expand their capacity for commercial and clinical-scale production, as well as for new modalities such as cell therapy. And there is not just incentives for big pharma to take up residence—smaller companies are supported step by step. New facilities that can be rapidly fitted for single-use technology (SUT) manufacturing platforms can enable quick and easy production set-up within smaller footprints and with lower capital expenditure. An example is the manufacturing cluster at Tuas Biomedical Park. In addition, there is also ready-built facilities at the JTC BioMed Hub @Tuas Biomedical Park, which can be fitted out with existing SUT-manufacturing platforms. Lightest environmental impact The future of pharma manufacturing also needs to consider the sustainability of manufacturing processes. Increasingly, economic competitiveness will be linked with environmental protection. The EDB and GSK have partnered in a Green and Sustainable Manufacturing initiative to improve manufacturing efficiency in pharmaceutical and fine chemical manufacture in Singapore. Providing opportunities across the sector, this collaboration aims to build a capability in Singapore for sustainable pharma manufacturing, which Lim claims will “enable Singapore to become a leader in sustainability research for pharmaceuticals and fine chemicals.” Likewise, many pharmaceutical companies now express a strong commitment to environmental values. In 2012, GSK committed to invest S$60 million to improve antibiotic manufacturing capabilities as part of a S$75 million renewal of their Quality Road site. This, adds Lim, is certainly another act of faith in the future of GSK’s manufacturing capability in Singapore. This investment also involves ‘greening’ production where possible, for example, by applying existing enzymatic technology to replace chemical processes, which would reduce the use of solvents in manufacturing. Pfizer similarly has made several investments over the past 15 years to improve sustainability of manufacturing, including pioneering the application of green chemistry, says Kanneganti. Others in the sector are also considering how existing products can be reworked to improve manufacturing technology that will advance productivity safely, reliably and with less environmental impact. New forefront technologies are already set to plug into the manufacturing pipelines, having been born locally in the labs at NUS. For example, a ‘continuous flow reactor’ system has been developed at NUS by Khan. The system can make potentially hazardous reactions run safely and also allows him to recycle precious metal catalyst required for the reaction. Khan’s technology has been published and patented, and his team is currently working with industry partners to transfer the technology to manufacturing services. Committed to evolve As part of its five-year Research Innovation and Enterprise 2020 plan [6], the Singaporean government has committed S$3.2 billion over 2016-2020 to advanced manufacturing and engineering, of which biologics and pharmaceutical manufacturing is one of eight key industries. The fourth and current phase (2016 - 2020) aims to focus on areas where Singapore has the potential to be internationally competitive, and to align R&D efforts with national healthcare strengths and needs to deliver on health and economic outcomes. Endorsement of Singapore’s approach comes from the 2017 Biopharmaceutical Competitiveness and Investment (BCI) Survey [7] in which Singapore was recognized at the top of the ‘newcomer’ market. Singapore is “introducing measures that capitalize on and bolster existing strengths or latent potential in biopharmaceutical R&D,” says the BCI report. “Though a top performer in all editions of the BCI Survey, in 2017 Singapore’s renewed promotion of collaborative and international models of R&D, enhanced regulatory standards and compliance, and ongoing capacity building are recognized as huge draws for innovators.” The pharmaceutical manufacturing sector in Singapore, having made great strides from the small leap of faith by GSK nearly 80 years ago, is clearly open for business. With the Asian healthcare industry projected by McKinsey and Company to overtake that of the European Union by 2020, Singapore seems to be sitting in the box seat. Certainly, Weng Si is confident that Singapore can accommodate the changes and challenges. “Even as drug discovery and development models continue to evolve, Singapore’s extensive government support and integrated research ecosystem continue to deliver value to pharmaceutical companies,” she says. “Our innovation ecosystem will build on existing strengths to serve the growing healthcare needs and demands of the region, and beyond.” To learn more about pharmaceutical manufacturing in Asia, visit SingaporeBusiness.com. [1] sg.gsk.com/en-sg/behind-the-science/how-we-do-business/partners-in-progress-our-commitment-to-singapore/
[2] Economic Survey of Singapore 2017, Ministry of Trade and Industry [3] Economic Survey of Singapore 2017, Ministry of Trade and Industry [4] http://www3.weforum.org/docs/GCR2017-2018/05FullReport/TheGlobalCompetitivenessReport2017%E2%80%932018.pdf
[5] http://www.theglobalipcenter.com/wp-content/uploads/2018/02/GIPC_IP_Index_2018.pdf
[6] https://www.nrf.gov.sg/rie2020
[7] http://www.pugatch-consilium.com/reports/BCI_2017_Report.pdf

“GSK came here because it sensed Singapore was keen to build up the manufacturing sector of its economy, and most of all, the government leaders had the vision to build a vibrant pharmaceutical industry which would, in time, lead to biotechnology manufacturing,” explains Lim Hock Heng, a Site Director at GSK. Later, the government of newly independent Singapore offered attractive economic incentives “and Singapore presented itself as a good location from which to make and sell antibiotics to big markets in the Middle East countries and Japan,” says Lim.

Singapore now boasts around 30 pharmaceutical manufacturing facilities with the industry employing around 7,000 people. Credit: Reggie Wan/Getty Images

The island country now boasts around 30 pharmaceutical manufacturing facilities across a wide range of modalities, including active pharmaceutical ingredients (API), biologics, and drug products. The industry employs around 7,000 people.

Trends shaping the industry

Globally the pharmaceutical manufacturing industry is undergoing radical and rapid challenges, demanding incremental, but also transformational, change. Singapore is already meeting these challenges head-on.

For one, there is the need to speed up manufacturing efficiency to reduce the time taken from discovery to when drugs reach the market. Real-time analytical technologies can improve the process and these have been identified as critical by the pharma manufacturing industry, says Professor Lam Kong Peng, Executive Director of A*STAR’s Bioprocessing Technology Institute (BTI). “By leveraging multi-omics platforms that we have invested in over the past few years, BTI can now simultaneously analyze gene, protein, sugar and metabolite profiles in the cell culture that makes the biologic products. This enables a thorough understanding of the biologics manufacturing process to enable efficient development and control of these processes,” says Lam.

Precision treatment is also driving change. Improved medical diagnostic tools are allowing personalized strategies that require manufacturing operations to attain high yields, while managing a diverse product mix with low production volumes. “Today’s treatment-centric healthcare model is experiencing notable shifts towards value-based care and precision treatments, alongside a greater focus on prevention and wellness,” explains Weng Si. Manufacturers of personalized drugs must accommodate relatively tiny production runs, highly-specific requirements, and genotype-specific products. These put new pressures on manufacturing by demanding more nimble production options.

New technology is also pushing the envelope of both manufacturing activities and business models. “Industry 4.0 and technological advancements like robotics, automation and digitalization are transforming manufacturing activities in the 21st century,” explains Professor Tan Sze Wee, executive director of the Science & Engineering Research Council at A*STAR. This is disrupting traditional business models in manufacturing, as data, machines and systems can now be connected throughout the value chain from production shop-floor to final distribution. “Singapore has the vision to be a leading manufacturing hub, plugged into global centers of excellence to drive the future of manufacturing,” adds Tan.

To realize the vision, a swathe of initiatives is paving the way to provide Singapore with the brightest talent, mightiest partnerships, but also the lightest environmental impact.

Brightest talent

Singapore is future proofing its industry through its emphasis on capacity building of a strong pipeline of talent. The government, together with pharmaceutical companies, has developed new training programs to enable manufacturing-ready talent to meet the growing needs of the local industry. One initiative—the Professional Conversion Programme for the biologics manufacturing industry—has provided training for more than 400 people since 2014. Also, “under this scheme, the Local Biologics Skills Training Programme continues to see strong uptake from industry. Since the programme’s introduction in 2015, more than 170 training places have been filled,” says Weng Si.

Other education and training initiatives have been similarly successful. “In the past, attracting bright Singaporeans to research was an uphill battle,” said Saif Khan, Associate Professor in the Department of Chemical and Biomolecular Engineering at NUS. “But now, with industry-academia partnerships taking strong root locally, bright students are increasingly looking to meaningful research pursuits in which they see their efforts potentially making a real impact on people’s lives and the economy,” he said.

“Students graduating locally from some of the world’s best institutes of higher learning join the work force each year,” echoes Dr Prasad Kanneganti, Site Director, Pfizer Asia Pacific. “They are driven by a desire to learn new skills and strive for continuous improvement,” Kanneganti says. “Change is very well accepted here by a workforce that is technology savvy.”

Supportive IP policies

A stable policy environment is also proving business-friendly. Kanneganti describes how IP protection encourages new investments. “IP protection encourages the industry to bring in new manufacturing processes and technologies as well as invest in product and process development,” he says. This is borne out by recent international surveys that give high rank to the local IP regime. Singapore’s IP environment was ranked fourth in the world by the Global Competitiveness Report for 2017-18 [4] and ninth by the 2018 US Chamber International IP Index [5].

Mightiest partnerships

The complex and dynamic nature of pharma manufacturing’s future has highlighted the need to strengthen local partnerships in order to pool resources, share risk and increase adoption rates. Singapore is well recognized as a leader here. “The collaboration between public research agencies, major multi-national companies, and a growing crop of local biotechs has created an environment for innovation in this sector to flourish,” says Lam.

In particular, common platforms for synergistic partnerships and sharing ideas—often with competitors—to advance technology, otherwise known as “open innovation,” will help companies keep pace with rapidly evolving technology trends. A prime example is the Pharma Innovation Programme Singapore (PIPS) launched in September 2017, which brings together local research organizations such as A*STAR and NUS plus multinational pharmaceutical companies like GSK, Pfizer, and Merck Sharp & Dohme (MSD). PIPS is investing in new manufacturing technologies, with a focus on advanced process control or process analytical technology, bio-catalysis, continuous manufacturing, digitalization & automation, and enhanced pharmaceutical operations.

Khan sees benefits from the new ways of thinking that will be catalyzed by this new partnership. PIPS will enable NUS to explore “avant-garde ideas with a larger time horizon for implementation on the manufacturing floor,” he says. “This will ensure a sustainable stream of creative and disruptive ideas for the next generation of pharmaceutical manufacturing processes,” Khan adds. GSK’s Lim agrees: “success in this program will enable Singapore and the participating companies to be a step ahead in applying new technologies needed for new product manufacture.” A*STAR’s Lam confirms that: “this is the kind of innovation in manufacturing processes, developed through public-private partnership (PPP) models, which the industry will need to meet future challenges.”

Other innovative partnerships are concerned with developing infrastructure that offers more flexible capacity options. EDB is working with contract manufacturing organizations (CMOs) to expand their capacity for commercial and clinical-scale production, as well as for new modalities such as cell therapy. And there is not just incentives for big pharma to take up residence—smaller companies are supported step by step. New facilities that can be rapidly fitted for single-use technology (SUT) manufacturing platforms can enable quick and easy production set-up within smaller footprints and with lower capital expenditure. An example is the manufacturing cluster at Tuas Biomedical Park. In addition, there is also ready-built facilities at the JTC BioMed Hub @Tuas Biomedical Park, which can be fitted out with existing SUT-manufacturing platforms.

Lightest environmental impact

The future of pharma manufacturing also needs to consider the sustainability of manufacturing processes. Increasingly, economic competitiveness will be linked with environmental protection. The EDB and GSK have partnered in a Green and Sustainable Manufacturing initiative to improve manufacturing efficiency in pharmaceutical and fine chemical manufacture in Singapore. Providing opportunities across the sector, this collaboration aims to build a capability in Singapore for sustainable pharma manufacturing, which Lim claims will “enable Singapore to become a leader in sustainability research for pharmaceuticals and fine chemicals.”

Likewise, many pharmaceutical companies now express a strong commitment to environmental values. In 2012, GSK committed to invest S$60 million to improve antibiotic manufacturing capabilities as part of a S$75 million renewal of their Quality Road site. This, adds Lim, is certainly another act of faith in the future of GSK’s manufacturing capability in Singapore. This investment also involves ‘greening’ production where possible, for example, by applying existing enzymatic technology to replace chemical processes, which would reduce the use of solvents in manufacturing. Pfizer similarly has made several investments over the past 15 years to improve sustainability of manufacturing, including pioneering the application of green chemistry, says Kanneganti.

Others in the sector are also considering how existing products can be reworked to improve manufacturing technology that will advance productivity safely, reliably and with less environmental impact. New forefront technologies are already set to plug into the manufacturing pipelines, having been born locally in the labs at NUS. For example, a ‘continuous flow reactor’ system has been developed at NUS by Khan. The system can make potentially hazardous reactions run safely and also allows him to recycle precious metal catalyst required for the reaction. Khan’s technology has been published and patented, and his team is currently working with industry partners to transfer the technology to manufacturing services.

Committed to evolve

As part of its five-year Research Innovation and Enterprise 2020 plan [6], the Singaporean government has committed S$3.2 billion over 2016-2020 to advanced manufacturing and engineering, of which biologics and pharmaceutical manufacturing is one of eight key industries. The fourth and current phase (2016 - 2020) aims to focus on areas where Singapore has the potential to be internationally competitive, and to align R&D efforts with national healthcare strengths and needs to deliver on health and economic outcomes.

Endorsement of Singapore’s approach comes from the 2017 Biopharmaceutical Competitiveness and Investment (BCI) Survey [7] in which Singapore was recognized at the top of the ‘newcomer’ market. Singapore is “introducing measures that capitalize on and bolster existing strengths or latent potential in biopharmaceutical R&D,” says the BCI report. “Though a top performer in all editions of the BCI Survey, in 2017 Singapore’s renewed promotion of collaborative and international models of R&D, enhanced regulatory standards and compliance, and ongoing capacity building are recognized as huge draws for innovators.”

The pharmaceutical manufacturing sector in Singapore, having made great strides from the small leap of faith by GSK nearly 80 years ago, is clearly open for business. With the Asian healthcare industry projected by McKinsey and Company to overtake that of the European Union by 2020, Singapore seems to be sitting in the box seat. Certainly, Weng Si is confident that Singapore can accommodate the changes and challenges. “Even as drug discovery and development models continue to evolve, Singapore’s extensive government support and integrated research ecosystem continue to deliver value to pharmaceutical companies,” she says. “Our innovation ecosystem will build on existing strengths to serve the growing healthcare needs and demands of the region, and beyond.”

To learn more about pharmaceutical manufacturing in Asia, visit SingaporeBusiness.com.

[1] sg.gsk.com/en-sg/behind-the-science/how-we-do-business/partners-in-progress-our-commitment-to-singapore/

[2] Economic Survey of Singapore 2017, Ministry of Trade and Industry

[3] Economic Survey of Singapore 2017, Ministry of Trade and Industry

[4] http://www3.weforum.org/docs/GCR2017-2018/05FullReport/TheGlobalCompetitivenessReport2017%E2%80%932018.pdf

[5] http://www.theglobalipcenter.com/wp-content/uploads/2018/02/GIPC_IP_Index_2018.pdf

[6] https://www.nrf.gov.sg/rie2020

[7] http://www.pugatch-consilium.com/reports/BCI_2017_Report.pdf

Trends shaping the industry#

Brightest talent#

Supportive IP policies#

Mightiest partnerships#

Lightest environmental impact#

Committed to evolve#