Building bioscience in Wales?

Once famous for coal and steel, Wales now aims to make its mark in the life sciences sector. The recent BioWales 2008 (UK) conference demonstrated how much the region has progressed, thanks to the support of the Welsh Assembly government, the EU and the enthusiasm of the Welsh biotech community. The country's bioscience sector, which comprises approximately 200 companies, grew by 18% last year and is now worth £1.3 billion (€1.6 billion) in annual turnover, employing 15–20000 people.

Susan Aldridge

Addressing more than 400 delegates at the conference, Dr John Patterson, Executive Director for the development of AstraZeneca's new medicines, spoke of the patents that are expected to expire on many of the world's best-selling drugs by 2011, the increasing frequency of patent challenges and the limits of data exclusivity. "Generic erosion is steeper and faster each year," he said. Added to this, the public is increasingly critical of the pharmaceutical industry, while having ever higher expectations. People seem to have bought into an instant gratification mentality; as soon as a gene is discovered, a cancer cure is expected to swiftly follow.

"So why do we bother?" Patterson asked. The answer is that there are so many unmet medical needs — some of them clearly related to aspects of modern life, such as stress, pollution and obesity. Then there is the problem of antibiotic resistance and the demands of an ageing population. Pharma must try to grab these opportunities, but how can the industry boost its flagging success rate?

Patterson noted that academia and small companies are very good at discovering new therapeutic molecules, but they are unable to turn them into medicines. Biotech companies are flexible and innovative but, unlike big pharma, they cannot fund failure or scale-up. Pharma has the global reach, the manufacturing standards, the track record and the ability to withstand failure, but it is just too big?

"You are now seeing the whole of the pharmaceutical industry undergoing a revolution," Patterson said. In the future, he believes the winners will be the companies who access both big and small molecules — a blend of biotech and traditional pharma, although where the balance between the two will lie is debatable. The winners will be those who use translational medicine, meaning closer collaboration between the research and clinical sides, and those who leverage emerging markets.

Many of these lessons are being put into practice in one of Wales's leading biopharmaceutical companies, Ipsen BioPharma, which is headquartered in France, but has a manufacturing facility in Wrexham that opened in 2000. Ipsen has five products in oncology, endocrinology and neuromuscular disorders, including Dysport, which competes with Botox, and Decapeptyl, a GnRH analogue. The Wrexham facility is dedicated to the manufacture of these therapeutic proteins and others that are moving through Ipsen's pipeline.

According to Mike Harvey, VP of Manufacturing Supply Operations for Ipsen, design is the key to pharma success. "We so often hear of a discovery being stillborn because of a factor like dosage or distribution," he says. "Design must be thought through right at the beginning if you are to be successful in this industry." Although neither easy nor cheap, earlier commitment and decision making are needed to assure product quality in its broadest sense. "Product form and presentation must be thought of early, and early analytical development is vital for biologics," he adds. "Quality by design is here to stay and it is important for proteins too. It must be used."

Design is what keeps a company competitive as 85% of the cost of goods is set by how a product or process is designed. Harvey believes that the key to Ipsen's manufacturing success in Wales is "a constant drive, a burning desire to improve, with focused teams in manufacturing with a mixture of skills, including those with commercial awareness." This is particularly important when products are manufactured far from the site where they were developed; for example, by a contract manufacturer.

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Wales is famous for its sheep — so maybe it is suitable that it is also home to two companies that make therapeutic antibodies raised in sheep (even if one of them uses Australian sheep). Protherics, a leading biopharmaceutical company, has its main manufacturing operations in Llandysul, where it produces three commercial products: CroFab, ViperaT and DigiFab, as well as a new product in clinical development. These are all polyclonal antibody fragments (also known as Fab fragments) for the critical care market, based on antibodies raised in sheep sourced from Australia. CroFab and ViperaT are for treating poisonous bites from North American rattlesnakes and European vipers, respectively, while DigiFab treats overdoses of digoxin, a heart drug with a narrow therapeutic index. CytoFab, also a Fab fragment for severe sepsis is being groomed for blockbuster status with AstraZeneca.

Meanwhile MicroPharm, which is located in Newcastle-Emyln in West Wales, uses local sheep to raise a range of antisera and antivenoms for contract manufacture, and offers Wales's only contract sterile filling service. The company has a deal with the Nigerian government to supply antivenom against the Carpet Viper, which is responsible for approximately 2000 bites a year, meaning that the MicroPharm product has likely saved hundreds of lives. The company also helps Nigeria save money because it has a liquid rather than freeze-dried formulation contained in cheaper vials. They also reduce cleaning costs by using disposables in their manufacturing plant.

Meanwhile, Wrexham is the location of one of India's leading generic companies, Wockhardt UK, which is the second largest producer of hospital generics in the UK. "The Welsh experience encouraged us to grow our business in Europe," says Sirjiwan Singh, Managing Director of the company. "When we located here, people thought we were fools for not going East."

But Wockhardt has earned $450 million (€284 million) in Europe, mainly through mergers and acquisitions, since moving. Currently, Europe accounts for 60% of revenues of the companies, while those from India have declined. In Wales, Singh says he likes: the good infrastructure, a supportive business environment and a good support structure. "We are now moving to value-added niche products. We want to build an entrepreneurial and risk-taking ability in our managers."

It seems to work, for Wockhardt is now growing at a rate of 14%, which is twice the rate of UK pharma. "I've learned that we must improve at a rate greater than the competition," he concludes. "What has happened in the computer industry in the last 15 years will happen to pharma in the next 15." There is going to be a lot of change and evolution, and only those companies that can keep up will survive.

Meanwhile, Ortho-Diagnostics, which is part of Johnson & Johnson, will open a facility for the manufacture of diagnostic kits for heart disease, HIV and hepatitis B virus in the new Pencoed Industrial Park in July. In the UK, locations outside of London, Cambridge and Oxford struggle to get the attention they deserve from the rest of the world, but Wales is developing connections with Israel. For instance, MaimoniDex RA of Tel Aviv, which develops monoclonal antibodies for rheumatoid arthritis, is intending to establish a facility in Swansea. Addressing BioWales, Gil Erez, Minister for Commercial Affairs at the Embassy of Israel in London, commented that Israel and Wales are actually the same size. His country is a fast growing, high-tech economy, which scored high on the Global Competitiveness Report. It is an EU partner in Framework Programme 7 and has 50 ongoing projects with the UK. Israel has 466 life science start-ups and is fourth in the world for molecular patents and second for medical device patents. The UK is seen as an expensive place to locate a biopharma facility, and Israeli companies still do not know enough about life beyond London. However, Erez believes Wales is going in the right direction, by sending delegates to BioIsrael, for example, and encouraging companies to come here.