In September 1978, the American biotech company Genentech, which had only been established a few months previously, made a sensational scientific announcement. A group of researchers led by David Goeddel, who was only 27 years old at the time, had managed to produce recombinant insulin totally identical to human insulin. Just four years later, the drug - the first to be produced with genetically modified microorganisms - was approved for sale in the US market.

It became soon obvious that the blood-sugar reducing drug, which was marketed under the name Humulin, was far superior to the insulin originating from pigs and cattle. First, it works at lower doses; second, it is associated with far fewer undesirable allergic reactions. It was not long before all animal-based insulin products disappeared from the market, heralding the era of modern biopharmaceuticals.

Numerous other recombinant drugs rapidly entered the market, including the growth hormone somatotropin, immunomodulating interferon and several factors involved in the blood coagulation cascade. The latter represented major progress for the treatment of haemophilia sufferers, because the drugs greatly obviated the need for high risk treatment with donor blood. Another milestone was achieved at the end of the 1980s by the Californian company Amgen who used a special method to produce erythropoietin, a hormone used in the treatment of anaemias. Virtually overnight, the hormone, which stimulates the production of red blood cells in the bone marrow, led to a dramatic improvement in the quality of life of countless cancer and dialysis patients.

Success stories like this led to the worldwide triumph of biopharmaceuticals. According to the German Association of Research-Based Pharmaceutical Companies (VFA), a total of 134 drugs involving 98 genetically engineered substances were on sale in Germany in 2008. Many of these drugs have become indispensable for the treatment of diseases such as multiple sclerosis, rheumatoid arthritis and many other genetic metabolic diseases. Biopharmaceuticals have also become an integral form of treatment for tumour diseases. An example is the antibody trastuzumab (trade name Herceptin), a monoclonal antibody used for the treatment of specific mamma carcinomas. The antibody, which is directed against the surface receptor HER2/neu, can considerably increase life expectancy and a few years ago had already become part of standard mamma carcinoma treatment.

In future, genetically engineered drugs will remain one of the strongest growth sectors in the pharmaceuticals market as a whole. The proportion of biopharmaceuticals among newly approved drugs has already reached 35 percent - and is continuing to grow. In Germany alone, biopharmaceuticals generate more than 3 billion euros of revenue; globally, the sale of biopharmaceuticals accounts for as much as 45 billion euros. At present, this is only about 15 percent of total sales revenues in the pharmaceutical industry. However, some experts believe that in the near future one out of every three prescribed drugs will be of biotechnological origin.

Biopharmaceuticals are a lucrative business, and more and more pharmaceutical companies that previously focused on the production of chemically synthesised drugs are interested in being part of it. The fact that the patent protection of many first-generation biopharmaceuticals has already expired, opens up additional options. However, biotechnological production methods are extremely complex, lengthy and expensive because the materials are produced by living cells – simple proteins by bacteria or yeasts and more complex ones such as erythropoietin by recombinant DNA technology in mammalian cell culture. The smallest aberrations in the production process can have a huge effect on the quality and biological activity of the final product.

The European Drug Agency, EMEA, has already reacted to these issues by regarding all biopharmaceutical follow-up products (biosimilars) as discrete drugs. Under EMEA guidelines, biosimilars have to be tested in the same way as the original product with numerous preclinical and clinical tests. This makes the production of biosimilars far more expensive than the production of traditional generic products, but at the same time guarantees the user the highest degree of product safety possible. The European Union is an important step ahead of the USA in this respect. The American FDA, which is responsible for the approval of new drugs, has so far not been able to come to a decision, thereby preventing access to the American market of many EU-approved biosimilars. This is clearly to the disappointment of American insurance companies who would like to switch to cheaper products sooner rather than later.

With more helpful regulations, the Europeans, and especially the Germans, have shown that they have learnt from previous mistakes. Back in the 1980s, the research and production of all genetically engineered drugs in Germany was greatly hindered by draconian regulations, which made many pharmaceutical companies take their production abroad. This had long-term consequences for the German economy: today, more than 50% of all biopharmaceuticals are produced in the USA while only 15% are produced in Germany.

However, in the meantime, the importance of biotechnology for the German pharmaceutical sector has been recognised and the changed socio-political environment is now bearing its first fruits. Germany has caught up spectacularly and now has the largest number of biopharmaceutical companies in Europe. Several hundred companies focus on the development of innovative, genetically engineered drugs – a large number of these are located in Baden-Württemberg. In order to better exploit this huge melting pot of ideas, the BMBF has recently restructured its funding policy. One goal of the Pharmaceuticals Initiative for Germany that was initiated in 2007, is to give new impetus to Germany’s biotechnology and pharmaceuticals industry by bringing all relevant players in the biopharmaceutical value creation chain closer together in order to advance the development of new therapies more effectively in future.

sb - 12 January 2009
© BIOPRO Baden-Württemberg GmbH