Ask any scientist in the know to name a few major biotech clusters in Great Britain and the geographical areas most likely to spring to mind include Oxford and Cambridge in England, and Edinburgh in Scotland. Bioscience clusters in Wales have traditionally remained very low profile, a fact that the Welsh Development Agency (WDA; www.wda.co.uk) is now working hard to reverse.
According to Bob Wallis, Ph.D., sector manager for bioscience at the WDA, the Welsh biotech industry is quietly thriving, with over 250 companies and a personnel base of some 15,000 people, out of a total population of only about three million.
In fact, he suggests, key Welsh regions have a highly successful biosciences industry, founded on a world-leading academic base, with diverse opportunities for collaboration, technology transfer, and investment. "Wales is probably one of the best kept bioscience secrets in the world."
The home-grown Welsh industry includes a broad mix of biotech companies operating in diverse fields, but primary sectors include medical devices and diagnostics, bio/pharmaceutical manufacturing, contract and clinical research, clinical trials, and contract service companies, Dr. Wallis explains.
In fact, there are over 100 medical device companies alone in Wales, and the country's diagnostics sector is believed to be responsible for producing a high percentage of all the diagnostic products sold in Europe today.
A significant pool of skilled research and technical staff, combined with complementary support companies, has also helped a number of multinational companies, including GE Healthcare, establish research and manufacturing operations in Wales.
The Huntleigh Diagnostics (www.huntleigh-diagnostics. com) division of multinational group Huntleigh Technology (Luton, U.K.) also originated in Cardiff, where it retains its manufacturing facility.
Clinical research is a particular strength, Dr. Wallis adds. Marix Drug Development (www.marix. co.uk), for example, is located on the dedicated Medi-Science Park near Cardiff, in a 30-bed clinical research facility built for the company by the WDA, adjacent to the 700-bed Royal Glamorgan Hospital.
Specializing in the provision of tailored early-phase clinical trials and clinical pharmacology services to clients worldwide, Marix also offers a full spectrum of consultancy and management expertise for drug development programs, their planning, and execution.
What sets Marix apart, claims commercial director John Roberts, is its ability to plan and execute complex Phase I/IIa trials. "Pharmaceutical and biotech companies want increasing amounts of pharmacodynamic and pharmacokinetic data from early volunteer trials, to help judge whether a new drug will be effective in its target disease.
"We have in-house expertise in the CNS, respiratory, and cardiovascular areas particularly with full-time clinicians in these fields and dedicated research laboratories. This combined expertise enables us to carry out highly detailed early trials, while keeping a focus on volunteer and patient safety."
Marix has also set up a network of Therapeutic Expert Partnerships (TEPs) to provide clients with any expertise not available in-house. "Each Marix TEP is a collaboration with experts in different therapeutic areas, who work with us to provide specialist advice or services in a range of therapeutic, clinical, or consultancy fields," Roberts points out.
"It's a unique set-up that has been so successful, we aim in the near future to double the capacity of our clinical research facility on the Medi-Science Park."
Marix' plans for expansion mirror those of a number of other clinical/contract research and services companies, Dr. Wallis suggests.
Thriving Service Industry
NuPharm Laboratories (www. newpharmlabs.com) is a pharmaceutical development service company offering clients expertise in areas from formulation development through to clinical and stability batch manufacturing and regulatory affairs.
In 2003, NuPharm doubled the size of its Deeside facilities, and in 2004 expanded overseas, with the commissioning of a purpose-built facility in Hamilton, New Zealand.
The company separately announced plans to set up a new business, NuPharm Manufacturing, focused on the contract manufacturing and packaging of pharmaceutical and healthcare products, to expand on its existing pilot-scale and process-development manufacturing capabilities. The new cGMP custom-built manufacturing and packaging facility is expected to come on-stream by mid-2005.
NuPharm is one of a number of companies offering pharmaceutical development services both locally and internationally. Penn Pharmaceuticals (www.pennpharm.co.uk) provides fully integrated formulation and analytical development services, along with clinical trials, manufacturing, packaging and supply management, contract manufacturing, CMC consultancy, and QP services.
Brecon Pharmaceuticals (www. brecon-pharm.co.uk) is an outsource packaging supplier to the global pharmaceutical industry, providing commercial packaging, analytical services, storage, distribution, and clinical trial services, while Biotec (www.biotec-uk. com) is a licensed clinical trials supply organization specializing in the import, QP release, storage, and distribution of temperature-sensitive biopharmaceuticals.
The Welsh biotech sector also has a longer history than many realize, the WDA adds. Molecular Light Technology (MLT; www.mltresearch.com) was spun out of the University of Wales College of Medicine (UWCM; now merged with Cardiff University) in the 1980s to commercialize an acridinium ester-based chemiluminescence technology, initially for the development of clinical diagnostics.
Although the company had little access to venture capital or other financial support during a time when the region's biotech industry was still in its infancy, MLT built a licensee base for its technology to fund in-house product development.
The company now offers a proprietary range of products, including diabetes research assays, gene-based assays for aquatic toxicology, and biomonitoring assays. The chemiluminescence technology also forms the basis of clinical diagnostic assays marketed worldwide by MLT's two major U.S. licensees.
In 2003, the company was acquired by Gen-Probe (San Diego), in a move that will both give the Welsh company a firm base from which to expand further, and provide Gen-Probe with new opportunities to diversify, points out MLT vice chairman, Stuart Woodhead, Ph.D.
"Our aim is to expand through the development of our technologies in nonclinical, industrial diagnostic applications," he explains. "To this end, our research programs are greatly aided by ongoing collaborations with the School of Biosciences at Cardiff University, the University's Molecular Recognition Research Unit, and the Centre for Clean Chemistry at the University of Swansea."
Aber Instruments (www.aber-instruments.co.uk) was also established in the 1980s to commercialize an approach to biomass monitoring developed by researchers at the University of Wales, Aberystwyth, with the help of local electronic engineering company, Dulas Engineering.
Based on a patented radio frequency impedance technology, Aber's high specification online instruments are now used as standard by breweries worldwide, and the company's Biomass Monitor, developed for viable cell mass monitoring in biotechnology applications, represents Aber Instruments' major revenues driver.
Designed for real-time, accurate measurement and control of biomass in fermentors at both laboratory and industrial scale, the Biomass Monitor is widely recognized as the optimum online instrument for viable cell mass, according to John Carvell, Ph.D., Aber Instruments' sales and marketing director. Improvements in the company's basic technology has also broadened the applications of the Biomass Monitor, he points out.
"Our initial instruments were designed primarily as biotech research tools, but following extensive market research in the U.S. we developed a new product, launched a couple of years ago, which is suitable for cGMP applications in mammalian cell culture and prokaryotic fermentations.
"This platform conforms to FDA requirements and is more sensitive, enabling us to move into new markets, including the large-scale amino acid manufacturing fermentation industry. As demonstrated by our largest client, the system can also be used as a critical step in control loops, rather than just for monitoring/recording applications. The success of our technology means we are currently expanding our manufacturing facilities by some 85 percent."
Data Mining with a Difference
Douglas Kell, Ph.D., co-inventor of the technology on which Aber Instruments was founded, is also a director of Predictive Solutions (www.predictivesolutions.co.uk), which markets a data mining and analysis tool, Gmax-bio, based on an evolutionary computation approach known as Genomic Computing.
Gmax-bio is designed for tackling complex data processing problems in biotechnology, pharmaceutical, and other natural science applications, Dr. Kell explains. "The genetic programming technology exploited through Gmax-bio is based on a sophisticated form of supervised learning.'
In essence, Gmax-bio applies user-selected properties from one dataset to determine solutions from new data. It discovers relationships specifically relevant to the query in hand, rather than just highlighting all obvious patterns in data."
There are two desirable features of a data mining technology, Dr. Kell continues. One is that it should give you the right answer, and the other is that it provides an understanding of how it got there.
"Typically there has been no one product that can achieve both these features, but the Gmax-bio genetic programming technology represents a superset that combines the best elements of other approaches, without the requirement for specialized computing expertise."
The Welsh biosciences industry benefits enormously from the academic and technology transfer expertise of the country's universities, including Cardiff, Swansea, Aberystwyth, and Bangor, which also support dedicated incubator facilities and research centers of excellence in bioscience fields as diverse as tissue engineering and optical biochips.
In January 2005, the Welsh Assembly Government announced significant investment in the construction of a state-of-the-art Institute of Life Sciences (ILS) at Swansea University.
Scheduled for completion by the end of 2006, the ILS represents a unique partnership between the University and IBM (www.ibm. com), which will build a dedicated supercomputer within the ILS' Deep Computing Visualization Centre for Medical Applications.
With ongoing technical and life-science applications support by IBM, the supercomputer will represent one of the fastest in the world dedicated to life science research.
The ILS will join a number of dedicated research-based academic facilities in Wales. The Institute of Grassland and Environmental Research (IGER) at Aberystwyth represents the largest U.K. center for independent research in grassland-based livestock agriculture and agri-environmental science.
Earning $30 million annually in research income, including $6 million in commercial research, IGER promotes an active technology transfer program to exploit new innovations in a range of fields, including animal feeds, antimicrobials, and plant breeding.
The 2004 merger of the University of Wales College of Medicine with Cardiff University generated one of the largest research-based universities in the U.K.
Cardiff is a major force in supporting research and clinical initiatives, and is home to the Cardiff University Brain and Repair Imaging Centre, the Cardiff Institute of Tissue Engineering and Repair, and the Optical Biochip project, a collaboration established in 2003 between the then UWCM, Cardiff University, and the University of Wales Bangor.
Cardiff is also involved in the All Wales Biobank (www.wellcome.ac.uk/doc_WTD002901. html), one of six U.K. government-funded Biobanks that aim to harness population genetics to gain new insights into the roles of genes in disease.
Wales Gene Park
The Wales Gene Park (www. walesgenepark.co.uk), funded by the Welsh Assembly Government and the U.K. Department of Trade and Industry (DTI), is a Cardiff University-led partnership that brings together academic and clinical expertise in genetics from across the country.
Currently a virtual network, the Wales Gene Park is one of six U.K. government-funded genetic knowledge networks (the other five are in the Oxford, Cambridge, London, Newcastle, and Manchester regions of England).
Focused on expediting genetic research and innovation, the network aims to help generate and transfer genetic knowledge and new technologies into the healthcare sector, while sponsoring and encouraging education and discussion for and by the public and health professionals.
The Wales Gene Park network actually has a broad remit, explains director Nick Lench, Ph.D. "It's about translating research into clinical practice, from improving genetic counselling services to developing new gene-based diagnostics, discovering new drug targets or therapeutic approaches, and sponsoring education for both healthcare professionals and the general public."
Technology transfer is also high on the list of priorities, he continues. "Promising new technologies or IP developed through the Gene Park research are partnered with or licensed out to biotech and pharma companies, both generating revenues and accelerating their development into clinically relevant products and services."
All six U.K. genetic knowledge parks have their own clinical research focus. "The Wales Gene Park research focus is in the areas of cancer and neurosciences," Dr. Lench adds. "We work closely with the Wales Cancer Bank (www.walescancerbank.com), an initiative that eventually aims to collect clinical data and biopsy samples from every new cancer patient in Wales.
"We also have links with the Wales Cancer Trials Network (www.wctn.org.uk ), and benefit from specialized resources in neuropsychiatric genetics. Our large patient cohorts in diseases such as Alzheimer's, schizophrenia, and depression, along with the associated clinical and genetic data, are already being exploited through collaborations with pharma companies such as GlaxoSmithKline (www.gsk.com)."
Commercializing Academic Innovation
Welsh academia has significant expertise in technology transfer, aided by initiatives such as the Wales spin-out program (www. spinoutwales.com). Based in Aberystwyth, the drug discovery company MNLpharma (formerly MolecularNature; www.mnlpharma.com) was spun out of IGER in 1999.
MNL has an in-house research program focused on the development of naturally occurring small molecule immunomodulators as potential treatments for diseases such as cancer, immune disorders, and viral infections, including HIV. The company claims its lead compounds, expected to enter clinical testing in 2006, are the first small molecular immunomodulators of their kind.
Dedicated Bioscience Technium
The WDA plays a key role in providing funding, along with advice and business and networking support for young life science companies and international companies looking to set up a European operation.
To complement existing life- and bioscience incubators and science parks linked with the country's Universities, the WDA is expecting to start construction of a dedicated bioscience Technium in Cardiff Bay, during 2006.
Part of a residential, recreational and industrial development spanning six miles of waterfront, the 50,000-sq-ft bioscience Technium will represent the first phase of a bioincubator facility that can be expanded to encompass another one million sq ft.
"The new Technium for bioscience will represent a major asset to the Welsh biosciences industry," concludes Paul Landricombe, sector marketing manager for biosciences at the WDA.
So Why So Quiet?
"Wales supports a closely networked biosciences industry underpinned by outstanding academic expertise. It has traditionally been low profile partly because its major strengths are not in the sexier, news-grabbing fields of breakthrough science, such as Dolly the Sheep or high-profile drug development."
Moreover, Landricombe points out, industry sectors like medical devices and diagnostics, clinical research, and manufacturing, generally require far less equity capital.
"They are characterized by a much faster time to market and lower risks, and as a result Wales has a relatively small dedicated venture capital community. Nevertheless, with a highly qualified workforce and a wealth of supporting technologies and service companies, Wales does represent an ideal base for relocation, expansion and investment."