Ireland: An Emerald Jewel in Pharma’s Crown
Deirdre Coleman looks at the unique collaboration that exists in Ireland between industry, academia and government bodies and the role this supportive environment plays in building on Ireland's reputation as a global hub for advanced manufacturing and process innovation.
Ireland is the world’s largest net exporter of pharmaceuticals with exports valued at €56 billion, accounting for 50% of Irish exports. The Irish pharmaceutical sector now hosts 14 of the world’s top 15 pharmaceutical companies. A significant amount of Allergan’s global supply of Botox is made in Westport, while Pfizer’s Lipitor, once the world’s top-selling pharmaceutical, anti-cholesterol medicine, is made exclusively in Cork, with historic revenues of over $12 billion. This meteoric rise in pharma investment positions Ireland as one of the top global locations for production, alongside, and in competition with, Singapore, Puerto Rico, and Switzerland.
Moving into activities that generate a higher value and which are less easy to replicate elsewhere will prove critical if Ireland’s pharmaceutical sector is to continue competing successfully with plants overseas, in what is now one of the most globalized industries in the world. Innovation and R&D capability will become the drivers of this continued growth.
Continued Investment
Ireland’s pharmaceutical industry has continued to attract new investment over the last decade, while established companies have continued to re-invest in new capacity. A recent new investment is Regeneron Pharmaceuticals, a company valued at $26bn (€19.7bn) on the NASDAQ, who are earmarked to take over the former 400,000 sq. ft. manufacturing facility of Dell in Limerick. The investment in Limerick (estimated at being in the region of €200 million) will create a second production site for Regeneron after Rensselaer, New York. According to an official statement from Regeneron, the company needs more production capacity to support anticipated commercialization of antibody drug candidates now in late-stage clinical trials and to support clinical requirements for the growing number of early-stage molecules in the Regeneron pipeline.
Examples of recent plant expansions include Eli Lilly who announced plans in 2012 for a €330m investment in its facility in Kinsale, Co Cork which will spearhead the manufacture of next-generation bio-pharmaceutical products and Pfizer, who will invest US$130m in its plants in Ringaskiddy in Cork and Grange Castle in Dublin. Maria Crowe, President of Global Manufacturing Operations for Lilly, who attended the announcement, complimented the Irish government for its long-established pro-business environment and support of the pharmaceutical sector in Ireland through its science and technology policies. “We in Lilly have seen this reflected in our deep and productive relationships with organizations such as the IDA and Irish academic institutions. The output from this commitment to education is also reflected in the excellent candidates who apply to join our company, many of whom have gone on to careers at Lilly operations across the globe”.
Ireland’s Collaborative Research Environment
The collaboration, which includes world leading industry partners such as Pfizer, GSK, Eli Lilly, Merck, Janssen, Roche and Bristol-Myers Squibb is almost unheard of outside of Ireland but focuses on problems of common interest to the industry.
A unique feature of the Irish business environment is the productive collaboration between industry, academia and government agencies. The pharmaceutical industry is forming alliances with these research centers to share costs and avail of the unique skills available in Irish research institutions.
One such research center is the Solid State Pharmaceutical Cluster (SSPC) which was established in 2008 to offer complementary research to industry in areas such as chemical engineering, analytics and pharmaceutics. The SSPC is a unique collaboration between seventeen pharmaceutical companies, eight academic institutions and twelve international academic collaborators. According to Professor Kieran Hodnett, scientific director of the center at University of Limerick, “The collaboration, which includes world leading industry partners such as Pfizer, GSK, Eli Lilly, Merck, Janssen, Roche and Bristol-Myers Squibb is almost unheard of outside of Ireland but focuses on problems of common interest to the industry. The center is the first of its kind in the world. It’s the first time these industries have worked together, nationally and internationally. When corporate headquarters of pharmaceutical companies look at the way we operate in Ireland, they are really impressed. And these are the people who make the decisions where their next investment is going to be”.
The center will carry out research on the key aspects of what it takes to synthesize the pharmaceutically active molecule, to isolate a pure material and to formulate this into a medicine. It is an extension and expansion of an existing multi-partner research collaboration that has a proven track record of successfully bringing together academia and industry to address fundamental challenges in pharmaceutical manufacturing.
Professor Gavin Walker, Bernal Chair of Pharmaceutical Powder Engineering, University of Limerick and his research team are working to build Ireland's reputation for research excellence in the pharmaceutical sector. “The overarching goal of the SSPC is to better understand mechanisms, control processes and predict outcomes for the efficient and sustainable production of safe medicines. This will be achieved by utilizing a molecule-to-medicine approach that encompasses chemical synthesis, crystal engineering, and drug production and manufacture. Through novel structures like the SFI (Science Foundation Ireland) funded SSPC center, the PMTC (Pharmaceutical Manufacturing Technology Centre) and NIBRT (National Institute for Bioprocessing Research & Training), industry can now access additional expertise and facilities they need to help identify innovative solutions to common process manufacturing problems. Working in partnership with the industry, we are supporting a transformation in Ireland from being a center of excellence in pharmaceutical manufacturing to being a global hub for advanced manufacturing and process innovation”.
Projects of Common Industry Interest
The SPCC works mainly on longer term projects to further the understanding, the prediction and control of the fundamental science and engineering involved in advanced pharmaceutical manufacturing.
Projects undertaken by the SSPC include research centering on the solid state area where the drug is taken from being a molecule and turned into a powder form. Sample projects include the following:
- Best Practice in Crystallization website (BPX), the world’s first pharmaceutical best-practice portal for compound crystallization which will operate out of the University of Limerick and is designed for use by the pharmaceutical industry and academic institutions. The aim of a web portal of this kind is to provide R&D support for the pharmaceutical industry and academic research by developing strategic partnerships and sharing best-practice techniques.
- Identification of currently unknown critical attributes in APIs and excipients that lead to failures during formulation
- Understanding the mechanisms that control product crystal properties such as crystal structure, purity, shape and size
According to Dr. Mary Shire, Vice President of Research, University of Limerick, “The level of industry academic engagement has been exceptional and is seen as a model internationally of how to get industry and academia to work in real partnership. The result of the success of the model has earned SSPC global brand recognition both in academia and industry. This is evidenced by the fact that the new center has extended its membership to include 8 additional companies and 12 international academic institutions from North America, Europe and Asia. The new center has an expanded scope which now covers the full range of the process from the synthesis of the molecule to the crystallization (isolation) of the material and formulation of this active material into the medicines we all take. The scale of the center has also increased to over three fold its original size and this brings it to the level of comparable centers of excellence internationally”.
Cost Savings through Manufacturing Innovation
Despite a new environment marked by tighter regulation and stiffer pricing constraints, the pharma sector can restore lost value by focusing intently on manufacturing innovation. The winners under these more difficult conditions will be companies that recast their approach to operations and learn from proven innovators in other sectors. It is estimated that the top 30 pharmaceutical companies in the world could save $10 billion by taking just 16% off their cost of goods. These savings will be found in the manufacturing functions through ongoing innovation.
In an increasingly competitive marketplace, pharmaceutical companies are looking at innovative ways to increase the agility and efficiency of their manufacturing. Initiatives such as process analytical technology (PaT), quality by design (Qbd) and lean manufacturing can reduce lead time, increase process robustness and improve manufacturing flexibility.
By applying intelligence to process data and introducing science into the analysis of process information, pharmaceutical companies can inject more competitive advantage into their manufacturing processes.
Moving Up the Value Chain
For Ireland’s pharmaceutical sector, the competitive challenges from overseas have meant evolving from bulk manufacturing of active agents to adding complementary activities, finishing completed products and researching and developing new products and production methods. IDA Ireland’s strategy focus has been to encourage companies to start earlier and finish later by adding activities from the pre-clinical stages to the launch. The emphasis is on introducing Irish-generated research as early as possible in the development cycle. Such value adding activities have only been possible through the expanding skill set of Irish workers and closer tie-ins with academia.
The future of the industry lies in embracing the concepts of manufacturing and supply-chain excellence, as well as those of on-site innovation, such as process and product development. Ultimately, if Irish sites achieve this goal and the country can become a global center of excellence for development and manufacturing, they will be well positioned to participate meaningfully in discovery-related activities. Also, opportunities for indigenous companies in areas such as high-end synthesis, biotechnology, contract research, specialist centers and contract manufacturing will inevitably emerge. Hence, a much more embedded, integrated and sustainable sector will develop, proving a win-win for all stakeholders involved.