On the side of a highway just over 3 kilometers from the center of Ireland's capital, University College Dublin is a concrete monument to post-1960s architecture, and no great beauty. At first glance, there is little to suggest what might have persuaded Pauline Rudd and her well-regarded research team to set up home there, leaving behind Oxford University's dreamy spires and world-leading academic prestige.
"It was my third job offer from Dublin," says Rudd. "I turned down the first two, because I didn't want to leave my group. It was all or none of us." Offer number three, which came from Ireland's National Institute for Bioprocessing Research and Training (NIBRT), was for the full package.
|
|
Dublin rooftops
|
Rudd's warmth and enthusiasm seem a world away from the sharp-suited world of the pharmaceutical business. What finally persuaded her to move was the chance to play a part in seeing their years of research transferred into industry. "This would have been very difficult at Oxford," she says.
NIBRT, established in 2006, underlines Ireland's determination to hang on to the pharmaceutical manufacturing industry it has developed in recent decades. Currently, Ireland's pharmaceutical exports are worth €27.7 billion ($43 billion US) annually, representing a whopping 40% of the country's total manufacturing exports, and the sector is Ireland's largest payer of corporation tax.
As the industry shifts its emphasis from chemistry-based small molecules to more complex, biologically derived entities, industry players want to ensure they get a slice of this new high-value biologics action, as companies consider offshoring more established processes to lower-cost locations in Asia.
"The vision was that this industry needed something different," says Eamonn Sheehy of Ireland IDA, the government agency responsible for attracting overseas investment into the country. "The companies [multinationals already established in Ireland] came to us and said: 'You have got to help.'"
IDA's response was to create a new institute, funded at €71.9 million ($110 million US) over seven years, to tackle what it sees as the two biggest problems facing biologics manufacturers. The first was training, and the new center will eventually produce 600 students per year, right up to PhD level, with the required skill set to run complex biologics processes. The other challenge was to recruit principal research investigators who were experts in the different parts of the process, from developing a therapeutic protein to manufacturing it.
NIBRT was formed through the collaboration of four Irish colleges: University College Dublin (UCD), Trinity College Dublin, Dublin City University, and the Institute of Technology in Sligo. In April 2008, Maurice Treacy, previously the director of life sciences with Science Foundation Ireland, was appointed CEO.
Virtual Institute, Real Clients
So far, NIBRT operates as a 'virtual' organization, using the resources of the four colleges. This includes an upstream bioprocessing laboratory at University College Dublin, which companies can use for training purposes to replicate their own manufacturing processing on a pilot scale. Permission for planning has just been secured for a dedicated 6,000-m2 facility on the UCD campus, due to become operational by early 2010.
"You could look at us as a facilitator," says Killian O'Driscoll, NIBRT's director of projects. He points to a tailored training program developed for Pfizer as a good example of what the institute does. The program combined training models from two universities, with some developed in-house in collaboration with outside suppliers. "So instead of Pfizer having to go to all these people, we packaged together six training modules, got them accredited by University College Dublin, and they are delivered in-house to Pfizer staff on a Saturday morning."
Other training clients include Centocor, Eli Lilly, and Wyeth, which have codeveloped a joint masters program in engineering and science with NIBRT.
The research side of the operation is also gaining traction, and NIBRT's scientists are currently working on contract projects for Merck Serono, Dyadic, Shire, and AstraZeneca. The institute has also entered into two long-term research projects with Organon and Eli Lilly, both in the area of glycobiology.
In this respect, getting Rudd on board was a smart move. "Almost 80% of the biopharmaceuticals on the market at the moment, both for treatment and diagnosis, are antibodies," she says. The drug industry has yet to grasp exactly what is happening in the glycosylation processes it uses to create these antibodies, she says.
One barrier to better understanding the process has been a lack of cheap, user-friendly techniques for analyzing sugar structures on proteins. A high-throughput HPLC-based method Rudd and her colleagues have developed may fill that gap. The technique, the fruit of five years of work, mainly at Oxford, allows analysis of up to 96 samples per week on a single HPLC instrument. This is ten times faster than conventional technologies.
"The analysis draws industry in," says O'Driscoll. "Once they see that, they get interested in the science behind glycosylation and in creating longer-term collaborations."
Optimizing the Process
On the other side of Dublin from Rudd and her colleagues, another initiative aimed at helping industry understand complex bioprocesses is underway. The Center for Bioanalytical Research (CBAS), based at Dublin City University, combines know-how from different academic centers for the benefit of industry partner Bristol-Myers Squibb (BMS).
The project brings together expertise in glycosylation pathways from the National University of Ireland and Galway's National Center for Biomedical Engineering with leading-edge biosensor technology developed at Dublin City University's National Center for Sensor Research.
Currently midway through a six-year contract, more than 30 academic researchers and nine people from BMS work at the center, developing biomolecular, imaging, and sensor technologies for online and wireless analysis of biologics.
"We are developing new diagnostics to optimize the bioprocess, stopping it at the right point, and defining in full detail the raw materials that are going into the media," explains Harry Holthofer, the head of the new center. Holthofer, a slim, sprightly Finn and self-confessed caffeine junkie, was previously director of Technomedicum at the University of Helsinki.
"What we are analyzing are really complex mixtures, and our area of expertise is picking the needles from the haystack," says Holthofer. "Usually it takes eight to 10 hours to analyze results, but we have been able to shorten that to, in some cases, four minutes, characterizing the bioprocess at all steps."
BMS is not the only business in the industry facing challenges in process analysis. Consequently, CBAS negotiated a deal whereby the university partners will own all intellectual property generated from the project, allowing them to license it across the sector. "We provide a very cost-effective solution," Holthofer says, claiming that with CBAS' expertise, the industry could improve its process efficiency by as much as 40%. "You are talking about savings of tens of millions of dollars," he adds.
The Right Recipe
This April, the two new Dublin centers, NIBRT and CBAS, came together with other Irish researchers in the field to form a networking group called GlycoScience Ireland. Rudd is enthusiastic about where this will take the institutes. "We have all the ingredients," she says. "I am certain that Ireland will become the key center in Europe for glycosylation."
Some industry observers fret that these initiatives may be too little, too late. Matt Moran, director of the industry lobby group, PharmaChemical Ireland, says NIBRT was slow to get going. "Our view is that they didn't really engage industry enough at the outset."
Another industry observer who thinks things have happened a bit slowly is Seamus Kelly, director and head of biopharma with the PM Group, an Irish-headquartered project-management and engineering consultancy. "The right noises are now being made," Kelly says, "but these things should have been put in place 10 years ago. NIBRT might now be operating, but where's its physical manifestation?"
In contrast, Kelly points to Singapore's Biopolis, where private research labs for companies such as GlaxoSmithKline, Novartis, and Takeda sit alongside five of Singapore's health and biomedical public research centers. "What you see on the ground is very impressive. It's very integrated. We don't have an equivalent."
Indeed, the threat posed by the Far East economic hot-spot was flagged back in 2003 by a government-sponsored analysis. The report argued that Ireland had many of the positive attributes necessary to attract significant investments in biologics, but it warned that the country faced competition from other locations: not only Singapore, but also Scotland and Scandinavia's Medicon valley, a cross-border biotech cluster comprising greater Copenhagen in Denmark and Skane in southern Sweden.
Moran does acknowledge that the right building blocks are now being put in place in areas such as research and training. "To be fair to the IDA, they are actually doing a good job," he says, noting that Ireland is still attracting investments in biologics. "There's lots of scope there for Ireland to become a center for manufacturing excellence globally," says Moran. "It's critical that we build good alliances between industry and the research community. It's all going in the right direction. We just need to keep doing it."
Biologics Investments
In April 2008 Eli Lilly and Company began construction of what could ultimately become a €403 million ($630 million US) development and manufacturing operation, focused on monoclonal antibody therapies for cancer, diabetes, and Alzheimer disease. Genzyme, meanwhile, announced a €130 million ($200 million US) investment to expand its sterile fill/finish manufacturing operation in Waterford.
In November 2007, Merck & Co unveiled plans to establish a new €180 million ($280 million US) vaccine facility in Carlow Town. The year 2007 also saw the completion of a 10,000-m2 facility for Centocor in Cork, which is due to commence production of Remicade, the monoclonal antibody therapy, later this year.
Wyeth's 90-acre campus in Grange Castle, Dublin, dwarfs all these investments. This mammoth operation is the largest biopharmaceutical facilities anywhere in the world, coming in at an investment of close to €1.3 billion ($2 billion US). The operation, which commenced production in 2005, currently employs 1,270 people, a figure set to rise to 1,350 later this year.