Unraveling the Mystery of Ireland's Pharm-Attractions

PTE: Can you give us an overview of the pharmaceutical industry in Ireland? Heavey: Ireland has been a location of choice for the manufacturing of blockbuster drugs such as Lipitor, Zyprexa, Singulair and Risperdal. Major drugmakers including Pfizer, Novartis, Roche, Merck, Johnson & Johnson, Eli Lilly, Bristol-Myers Squibb and Servier have been manufacturing in Ireland for several decades. These established pharmaceutical companies have been joined by a new wave of biotech firms such as Amgen, Genzyme, Biomarin, Alkermes and Jazz Pharmaceuticals during the past few years.

The industry has significantly diversified in recent years with 10 new facilities dedicated to the manufacturing of therapeutic proteins or vaccines and employment in this subsector rising from 500 in 2003 (when Schering-Plough was the only company with a biologic production facility) to more than 5000 employed in biopharmaceutical manufacturing in 2013. A well-known example is the Pfizer Grange Castle facility, where more than $2 billion was invested to create a fully integrated biopharmaceutical facility with capabilities in manufacturing therapeutic protein drug substances and drug products, including prefilled syringes and sterile fill-finish of conjugated vaccines. Other examples include the Janssen Biologics manufacturing facility in Cork for perfusion and fed-batch production of therapeutic proteins, and Eli Lilly’s recent $300-million expansion of the monoclonal-antibody production facility in Cork. Genzyme established a sterile fill-finish facility in Waterford more than 10 years ago. The facility was rewarded for its excellent regulatory track record by an additional investment and mandate to manufacture the insulin product Lantus following Sanofi’s acquisition of Genzyme. Other recent investments in sterile fill-finish have come from Merck and Amgen.

PTE: What makes Ireland attractive to pharmaceutical companies? Heavey: While many commentators focus on Ireland’s 12.5% corporation tax rate, Ireland’s strong reputation in regulatory compliance is key in attracting and maintaining pharmaceutical investment. The Irish Medicines Board, an agency of the government’s Department of Health, has a good reputation as a regulator in monitoring pharmaceutical manufacturing facilities. Irish facilities are able to maintain a high regulatory compliance track record because they can draw on an educated and flexible workforce with dedicated training and retraining programs to develop the specific skills required in the pharmaceutical industry.

PTE: What role does the government play in ensuring that Ireland remains competitive and sustainable for the pharmaceutical industry?

Heavey:

IDA Ireland, an agency of the Department of Jobs Enterprise and Innovation, has been the Irish government’s agency focused on attracting foreign direct investment for more than 40 years. IDA has a dedicated team working to attract new and repeat investment from the life-science industry (i.e., pharmaceuticals, medical devices, food and healthcare services). The agency provides companies with advice and support in finding property solutions and in dealing with areas such as local planning or permitting, visas or work permits for key staff and utility supply. IDA’s life science team has a strong network of key opinion leaders in the pharmaceutical manufacturing industry. The teams in Ireland and overseas regularly liaise with industry leaders to get a sense of emerging needs and how Ireland can address those needs. For example, in the past decade, when a number of new blockbuster therapeutic proteins were emerging, IDA kept up to date on the rising industry needs in terms of global capacity constraints, global skills shortages, the need for titre improvements, increasing requirements for process and product characterisation and new manufacturing technologies such as single-use systems.

IDA has provided grant support to companies willing to invest in process R&D in their Irish manufacturing facilities. For example, in 2005, IDA’s sister agency, Science Foundation Ireland (SFI), provided €4 million in R&D grant support for a collaboration between Wyeth and Professor Martin Clynes from the National Institute for Cellular Biotechnology (NICB) to better understand the biological basis for productivity in biopharmaceutical manufacturing (2). As a result, many companies have established dedicated in-house R&D teams to increase yields, better understand processes through advanced process analytical technology and ensure consistency of product through optimisation of detailed analytical methodologies. The government, through IDA, also invested €60 million in the establishment of the National Institute for Bioprocess Research and Training (NIBRT), which is a dedicated facility to support the growing biopharmaceutical sector in Ireland.

PTE: Given the financial crisis in Europe, what steps is the government taking to boost R&D productivity in Ireland?
Heavey: While Ireland’s third level educational system has long had a strong reputation for output of well-educated graduates, the primary focus up until 2000 had been on education rather than research. From 2000 to 2008, government spending on R&D, primarily through universities, rose significantly to a peak of approximately €900 million, putting Ireland on par with the average in developed nations based on OECD figures.

Since the financial crisis, successive governments have decided to maintain this level of investment in R&D, while implementing significant cuts in other areas of public expenditure. The government has recently implemented a process of research prioritisation, where key figures from the industry provided input on areas where the government should direct a greater proportion of its R&D budget to ensure maximal economic impact.

In the pharmaceutical space, the decision was made to place increased focus on investment in science and engineering around process development and optimisation for current therapeutic platforms such as small-molecule and therapeutic-protein drug substance and drug product. Investment in research in these areas will also ensure that Ireland is well positioned for the emergence of new therapeutic platforms such as next generation vaccines, antibody-drug conjugates, drug-device combinations, nucleic acid-based products, biomaterials and cell therapy.

PTE: The benefits of collaboration between the pharmaceutical industry and academia are widely recognised. What is the government doing to encourage and promote more of such partnerships?

Heavey: The research prioritisation exercise is an example of a government initiative specifically aimed at increasing industry-academic collaboration. In Ireland, we do have some ground to make up in terms of industry-academic linkages in the life-science area. While the industry is predominantly focused on process development and manufacturing, Irish universities have had a significant focus on basic biomedical research that has more relevance to drug discovery units back at pharmaceutical headquarters. While basic biomedical research is worth supporting, there will be increased focus on investment in process R&D by the government to support greater linkages with industry.

The investment in NIBRT predated the research prioritisation exercise and is already an excellent example of a dedicated research center completely focused on process development and product characterisation in the therapeutic protein space. Demonstration of the relevance of NIBRT to industry needs come from the fact that in the past three years, almost 50% of the operating expenses of NIBRT have come from industry revenue. Another recent investment by the government’s research-funding agency, SFI, was in a research center to support the small-molecule manufacturing sector. The Synthesis and Solid State Pharmaceutics Cluster had an extremely successful pilot phase between 2008 and 2012 where it attracted a large set of collaborations with industry and has recently received an additional investment of more than €30 million from SFI and €10 million from industry.

PTE: What would you say is the future outlook of the pharmaceutical industry in Ireland over the next five years?

Heavey: Ireland has, like many other locations, been hit by some rationalisation by the pharmaceutical industry as it dealt with mergers and acquisitions, patent expirations and increasing pressure on reimbursement. However, employment in the sector is now at the same level as it was before the financial crisis in 2008 due to the 30% year-on-year growth in employment in the biopharmaceutical subsector. I would expect to see significant growth into the future, especially in the area of biopharmaceutical manufacturing and sterile fill-finish.

IDA is particularly focused on attracting some of the ‘mid-cap’ and emerging biotech companies that are establishing themselves with new technology platforms such as antibody-drug conjugates or with products that are getting rapid approval because of their compelling efficacy in targeted patient subpopulations. Many of the older small-molecule drug-substance manufacturing facilities have seen recent reinvestment in capital equipment and R&D projects to significantly increase productivity and flexibility. These facilities are now well positioned to support the manufacturing of a diverse range of highly potent compounds.

This is an extremely important development with the inexorable trend towards the model of the niche-buster drug, where low-volume production involving complex chemistry and high containment will become increasingly common. Ireland’s success in adopting biopharma, with an excellent regulatory track record and output of skilled employees, would suggest that there is significant opportunity for further growth in this subsector.

Other areas of particular opportunity that will be drivers of growth in Ireland lie in convergence between the key manufacturing sectors in Ireland. I see four obvious areas where Ireland can offer a unique value proposition in convergence:

• Within the pharmaceutical space, Ireland’s capability in the manufacturing of highly potent small molecules and in the production of biopharmaceuticals would suggest that Ireland is well positioned to become a location of choice for manufacture of conjugated products, such as increasingly complex conjugated vaccines and antibody-drug conjugates.

• Ireland has a thriving medical device sector, with more than 25,000 people employed, and exports that rival those of Germany. Significant opportunities exist in leveraging this device capability in the development and manufacturing of drug-device combinations, such as inhalers and auto-injectors. Such devices will likely become increasingly important in differentiating innovator products versus generics and biosimilars.

• Ireland’s food industry is extremely strong with Ireland being one of the largest exporters of dairy products globally. Significant opportunities exist in overlap between the food and pharmaceutical industry in areas such as medicinal food and so-called nutraceuticals, where Ireland’s reputation for innovation, productivity and quality will be key.

• Finally, Ireland has a strong microelectronics manufacturing sector with companies such as Intel and Analog Devices investing heavily in R&D and high-tech manufacturing. A recent development has seen a number of multinational and indigenous companies from various sectors come together to form the Irish Centre for Manufacturing Research. This initiative, hosted by Intel, is focused on applying research on manufacturing productivity and process analysis across multiple sectors. Growth of this initiative could help to establish Ireland as a key location globally for “smart manufacturing” in pharmaceuticals, where increased use of advanced PAT systems, sensor networks and advanced analytics will support industry in creasing productivity while simultaneously maintaining the highest regulatory standards.
  

The tight geographic clustering of companies undertaking advanced manufacturing and the strong culture of communications, open-mindedness and flexibility in the Irish workforce are attributes that uniquely position Ireland as a base to exploit these opportunities.

References

1. IDA Ireland, www.idaireland.com/business-in-ireland/life-sciences-pharmaceuti/, accessed 30 Aug. 2013.
2. In-Pharma, “Wyeth taps Irish expertise for biopharma R&D,” www.in-pharmatechnologist.com/Processing/Wyeth-taps-Irish-expertise-for-biopharma-R-D, accessed 6 Aug. 2013.