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Biotechnology for the World – The Roche site Penzberg Kopfleiste zum ausfüllen 2 Biotechnology in Penzberg Research, development & production in Penzberg Penzberg Key site for biotech The Bavarian Roche site Penzberg is one of the largest biotechnology centers in Europe. For decades, scientists in Penzberg have researched, developed, and produced new biopharmaceutical ingredients (biologicals) as well as diagnostics. These areas are combined to provide increasingly personalized medical care. Penzberg is not only a “Center of Excellence for Therapeutic Proteins”, where all issues related to research and development of therapeutic proteins for the Roche Group converge, but also a “Center of Excellence for diagnostic reagents”. Biotechnology in Penzberg 3 photo: Hermann Rupp Roche in Penzberg Lasting visions Roche steadfastly pursues the vision of developing cutting-edge diagnostics and highly effective therapies. Patient well-being and corporate responsibility are the values that guide Roche. A focus on patient demand for high-quality diagnostic procedures and medications: at Roche, the development of innovative medical therapies adapted to patient needs is the basis for corporate success. Objective and vision Roche’s top priority is to develop innovative products for unsolved medical problems. This is the only way we can continue to make advances in the treatment of severe illness and disease. Improving people’s health as well as patients’ quality of life and life expectancy is the objective that drives everything we do. Being a responsible corporate citizen goes hand in hand with our commitment to improving people’s health worldwide through innovation made by Roche. A leader in biologics Innovation is the key to success in every sector of our business. This is why Roche has always been firmly committed to embracing unconventional ideas – a stance best shown by our early commitment to biotechnology, a long-underestimated field that has since become a very successful part of our operations. We set the stage with the acquisition of Boehringer Mannheim as well as partnerships with Chugai and Genentech. The investment has paid off: today, the pipeline is full of effective therapeutic proteins and extremely sensitive diagnostic tests. Roche is currently the world leader in the manufacture of monoclonal antibodies, in particular for both diagnostic and therapeutic applications. 4 Biotechnology in Penzberg Penzberg: the cooperation of pharma and diagnostics The Bavarian site in Penzberg is a major part of this success. Research, development and production for the pharmaceuticals and diagnostics divisions are combined under one roof in Penzberg, the only Roche site of its kind in the world. The vision is to develop efficient treatment methods by having these two separate disciplines working hand in hand. This allows the timely development of healthcare solutions – from early detection with diagnostics to appropriate medication selection. Thanks to intelligent diagnostics on the one hand and effective medications on the other, successful therapy in the sense of personalized medicine has become a tangible, feasible option. And Penzberg is the epicenter of this effort. More than 4,200 employees now work here, highly qualified, highly educated professionals. 34 percent hold a college degree, 54 percent have completed specialized vocational training, and eight percent have advanced training. Truly striking is the low turnover in Penzberg. Excluding retirees, only one percent of the workforce chooses to leave the Penzberg plant. Still, the average age of employees in Penzberg in 2006 was just 38.5 years. This is due in no small part to the company’s incredible commit- Research, development & production in Penzberg ment to training new workers. In 2006, 188 trainees, or 4.9 percent of the total Penzberg workforce, were employed at the Penzberg site. Site management forecasts that 90 percent of them will be offered a permanent job upon completion of their trainee period. Employees and functions C D A = 46% production B = 31% R&D C = 21% administration D = 2% management Lean management: Only one-fifth of Penzberg employees work in administration. More than three-quarters work in research, development, and production. 16,000 jobs in the region High global demand for therapeutic proteins will secure these jobs over the long term and ensure that yet more jobs are created in the area. Many in the region feel that Roche’s 1998 acquisition of the former Boehringer Mannheim plant was “a stroke of luck”. Every employee working directly for Roche indirectly creates another three to four jobs in the area, meaning that Germany’s largest biotech production site accounts for another 12,000 to 16,000 jobs in the beautiful countryside near Munich. It was no accident that this site was selected. The former mine site was spacious enough to accommodate the up-and-coming biotechnology company, and the company’s foresight paid off in the years after the facility opened. Pharmaceuticals production processes cannot tolerate interruptions. For example, twenty-four employees make sure that the site never runs out of pure water, steam, and process energy. The site also has its own water treatment facilitiy. Roche cares about preserving the environment for future generations and has had all of its processes environmentally certified. B Steady growth: After acquiring the Penzberg site, Roche has steadily increased the number of employees. More than 4,200 people make a living directly at Roche. More than 12,000 additional jobs depend indirectly on the site. A The Roche site Penzberg – employment trend 3,905 3,459 2,719 2,866 3,073 4,141 4,000 3,500 3,657 3,000 3,277 2,500 2,000 1,500 1,000 500 1999 2000 2001 2002 2003 2004 2005 2006 Biotechnology in Penzberg 0 5 Research, development & production in Penzberg A textbook total transformation From coal mining to high-tech In 1946, biotechnology was considered exotic. Today, biotechnology touches almost every area of people’s lives, a complete turnaround from the days when enzymes or microorganisms were confined to beer brewing and baking. The pioneering deeds of scientists relocated to Bavaria by the winds of war played a major role in this revolution. And this sleepy rural paradise that blossomed into a German biotech mecca can rightfully call itself the cradle of industrial biotechnology. The pioneers of Penzberg: the cradle of enzyme production A pioneering act in 1978: the first 75,000liter bioreactor is delivered to the Penzberg site for startup. Experts consider the founding of biotech pioneer Genentech in 1976 to be the advent of modern biotechnology. Today, the American company is part of the Roche Group. Some little-known facts: only two years later, in 1978, the first large-scale fermentation facilities were built in Penzberg, enabling the first industrial production of enzymes. The new production facilities opened the door to broad-scale use of enzymes and prepared the way for industrial applications of modern biotechnology. However, the technology was nothing new – fermenters with even larger tank capacities had already been used for many years to brew beer. With flexibility comes success What was new, however, was the fact that Penzberg researchers were flexible enough in their planning to enable the cultivation of more than 200 different microorganisms in the same stainless steel fermenters, allowing many different research and diagnostic products to be created at the same plant. Roche is still able to take on these demanding technological challenges. A unique feature of Penzberg’s facility is that bacterial cultures and mammalian cells can be cultivated with the same technologies – while upholding the highest purity and safety standards. As a result, the raw materials for six of Roche’s ten best-selling pharma and diagnostic products come from Penzberg plants. These products alone generate sales of more than ten billion euros annually, making Penzberg one of Roche’s most important production facilities in the world. 6 Biotechnology in Penzberg Kopfleiste zum ausfüllen An “exotic” idea takes flight The road to success began with the pioneering work on enzyme analysis led by Dr. Hans Ulrich Bergmeyer, who advanced biochemical production methods at the Tutzing site in Bavaria in the 1950s and 1960s and became the first Head of Research. The idea of producing medicines using biotechnology in an industrial setting was considered exotic at the time. Enzymes were initially produced solely for medical diagnostics. “Made in Penzberg”: Products that changed the world In the late 1960s, Bavaria was home to one of the most important production facilities for coenzymes, substrates, and metabolites extracted primarily from yeast fermentation products. Revolutionary new products such as the first urine test strip for measuring blood glucose were created here. With success came overcrowding – it soon became clear that Roche was quickly outgrowing the first site on the western shore of Lake Starnberg and needed to move to larger quarters. The closed coal mine on the outskirts of Penzberg turned out to be an ideal area. Shortly after the cornerstone for the new site was laid in 1972, biochemi- cal production moved to Penzberg. Success followed researchers to the new site: the 500 employees working in Penzberg in 1980 mushroomed to more than 4,100 at the end of 2006. By the end of 2006, Roche had invested more than 1.5 billion euros in the nearcontinuous expansion of the Bavarian site. Driven by the triumphant success of recombinant pharmaceuticals worldwide, the company has continued to enlarge the Penzberg site that is so important to the entire company. A 1954 photo of the coal mine in Penzberg – yesterday’s heavy industry has become today’s 350,000 m2 high-tech workplace in the country for more than 4,200 people. The Roche site in Penzberg – capital investment in millions of euros million euro 300 275 250 200 200 150 143 100 103 57 67 73 2000 2001 50 66 0 1999 2002 2003 2004 2005 2006 Biotechnology in Penzberg 7 Research, development & production in Penzberg Research in Penzberg Center for therapeutic proteins As a globally active healthcare company, Roche operates research sites around the world. These sites focus their efforts on the five therapeutic target areas of oncology, virology, inflammatory disease, metabolic disease, and disorders of the central nervous system. Many of the findings that emerge from Roche laboratories around the world eventually make their way to Penzberg, where the company’s central research lab for therapeutic proteins is located. Therapeutic protein initiative – success with biologics To continue its success with biologics, Roche established the Therapeutic Protein Initiative (TPI), a global, internal company network to develop new drugs, in 2001. The idea for the TPI was born in Penzberg, but it soon garnered strong support from all Roche research sites. The Bavarian site has a major hand in the development of every biologic – the roads from the world’s largest research sites all lead to Penzberg. And activities that lead to new findings in Basel, Nutley or Palo Alto are coordinated in Penzberg. This is true of technical research and development as well as the generation, production, and engiResearch, development, and production of biologics in Penzberg 1000 employees in the pharmaceutical division Research Development Production Therapeutic Protein Initiative – Technical development – Process development and optimization of fermentation and downstream processing – EPO and CERA – Trastuzumab – Interferon α-2a – Reteplase Drug development for proteins/antibodies for all Roche indication groups Oncology proteins/antibodies 8 e. g. provision of clinical test material Biotechnology in Penzberg neering of therapeutic proteins such as antibodies. Penzberg is where production processes are developed and optimized before the active pharmaceutical ingredient is produced. It is not surprising that the Penzberg site was recently awarded the prestigious title of “Center of Excellence for Therapeutic Proteins”. A global network with Bavarian hub in Penzberg In addition to working closely with internal Roche research labs, the scientists also work within a global network of more than 70 universities and biotech companies. Integrating their technologies makes it possible to keep Roche’s own products up to date. Recent advances have significantly boosted the quality of earlier biotech agents such as pegylated interferon and erythropoietin (EPO). Interferon alpha-2a, which is also manufactured in Penzberg, is another success story; the older version suppressed viral infection over the long term in about ten percent of hepatitis C patients. A chemically modified version has boosted the response rate to a remarkable 40 percent. And now an even more effective variant of the compound has been developed by Roche in cooperation with two network partners. Kopfleiste zum ausfüllen Joining forces to annihilate Alzheimer’s In addition to refining and improving existing drugs, Roche developers focus their energies on finding completely new treatment options using proteins. More than 200 Penzberg pharmaceutical researchers are currently working on about 40 projects. There is no shortage of up-and-coming treatments: new suggestions constantly flow in from all corners of the world. Researchers work on projects in all five indication groups for which Roche develops medications. These include inflammatory and viral diseases, disorders of the central nervous system (CNS), vascular diseases, and oncology, where Roche wants to consolidate its leadership position with new antibodies (see photos). However, CNS disorders such as Alzheimer’s are rapidly becoming a stronger area of focus. Working hand in hand with the company’s Basel headquarters, Penzberg researchers are developing a concept for a new antibody to attack the destructive beta-amyloid plaques found in the brains of Alzheimer’s patients. The first step is to develop an antibody prototype. One option is to have special mice produce the protein. These genetically modified animals can immediately produce agents that will work in humans. Roche is successfully working with external partners in this area. In the specific case of the Alzheimer’s an- tibody, Roche and a network partner decided to take a different track and develop the protein completely in the laboratory. Prototype quality was tested in Basel. When a therapeutic antibody proves effective, several modification stages of fine-tuning ensue. If the fine-tuned antibody has the right characteristics, pilot cell lines can be developed in Penzberg. These will be used for later production. After initial pilot studies are complete, production steps in 100-liter and 1,000-liter bioreactors follow, and the material is used in worldwide clinical studies. If the product is approved, it can be produced on an industrial scale. Successful healing in mice: Roche is developing new antibodies to fight cancer. A promising candidate inhibited tumor growth (yellow/green) in mice. The differences between the untreated mouse (left) and the treated mouse (right) are clearly visible. Biotechnology in Penzberg 9 Research, development & production in Penzberg Production in Penzberg Medicine for mankind Biologics have been available for a quarter-century. While the first biopharmaceuticals were copies of human hormones such as insulin or EPO, the mechanisms of effect are becoming increasingly sophisticated. Antibodies in particular have recently become the remedies of choice, especially in oncology. Today, no large pharmaceutical company can afford to ignore biotech research. More than half of research projects have their origins in biotechnology. Biopharmaceuticals becoming the new standard Biopharmaceutical production: About 29,000 employees currently work in Germany’s biotech industry. In 1982, the first biotechnologically produced medication went on the market in the United States: insulin. Since then, biopharmacy has moved forward at light speed. According to AS Insights, an industry information service, more than 130 biopharmaceutical medications are currently approved for use and marketed around the world. And the percentage of biopharmaceuticals continues to grow. According to BioPharm Insight, one-fourth of newly approved drugs are produced biotechnologically. If one goes back to earlier stages of develop- ment, the share of biopharmaceuticals rises; in 2006, biologics projects accounted for about 53 percent of total worldwide research projects that were not yet at the clinical or pre-clinical stages. If this large group of agents makes it to market in a few years, it would probably give biologics sales a further boost. In numbers, this means that sales volume, currently at 60 billion US dollars a year, could skyrocket by 15 to 19 percent a year. Sales could crack the 100 billion dollar mark by the end of the decade. Biopharmaceuticals racking up impressive sales: 10 percent of total pharmaceutical sales According to the German Association of ResearchBased Pharmaceutical Companies (VfA), 2006 sales of biotechnologically produced drugs topped 3.1 billion euros in Germany alone, accounting for more than ten percent of total drug sales. “Older” drugs like insulin and immune modulators accounted for about two-thirds of that total. In addition to insulin, growth factors such as EPO, monoclonal antibodies, and vaccines are also major sellers. About 29,000 people worked in the commercial biotechnology sector in Germany in 2006, according to the information portal at www.biotechnologie.de. Roche is the largest employer in this group in Germany. 10 Biotechnology in Penzberg Kopfleiste zum ausfüllen Biologics IV: Largest ever individual investment completed in record time The success of Roche’s biotech medications, coupled with ceaseless advances in technology, require constant expansions of and upgrades to production facilities. Roche’s fourth pharmaceutical production building on the Penzberg campus, Biologics IV, was the company’s biggest single investment to date. The groundbreaking ceremony for the new building took place in September 2004. Building construction began in July 2005 and proceeded in record time. Just two years later, the high-tech production facility for the trastuzumab antibody, used to treat breast cancer, was complete. The validation phase that precedes the actual start of production will take approximately two more years. The facility will then be inspected and approved for use by regulatory authorities. A highly automated plant Roche has good reason to be proud. It has incorporated the latest state-of-the-art technology into antibody production at its new Biologics IV pharmaceutical production building. The level of automation at the new building is particularly impressive. At night, the facility literally runs all by itself. The ceaseless stream of technical innovation means that employees must constantly change and adapt, whether they are chemists, biotech researchers, or even trained dairy workers or brewmasters. As a result, the ever-growing body of technical expertise requires continuous training of the production employees. Many of them have worked with “their” systems for years, becoming highly specialized employees who keep production running smoothly around the clock, 365 days a year. Biologics IV: The fourth and newest production building at the Penzberg campus was dedicated in summer 2007. Costing 290 million euros, the building represents Roche’s largest single investment. Production of erythropoietin in bioreactors at the Penzberg site: Keeping up with advances in technology is a constant challenge Brisk demand for breast cancer treatment trastuzumab worldwide Once the plant passes inspection, 150 employees can begin producing trastuzumab, an antibody produced with mammalian cells. The time until production begins is pressing, as the demand for this drug is enormous. Worldwide, about a half-million women are diagnosed with breast cancer every year; trastuzumab treatment during the early or advanced stages of the disease is an option for roughly one-fourth of these patients. Demand is brisk, so Penzberg is not the only facility that produces the medication. Genentech, a Roche subsidiary, runs its own production facility to supply the important US market. Biotechnology in Penzberg 11 Research, development & production in Penzberg Diagnostics – new tests Personalized medicine People often underestimate the importance of diagnostics, but they are the basis for the doctor’s choice of treatment. Decoding the genome and proteome for humans as well as viruses and bacteria opens up new options for the field of diagnostics. As a result, the next generation of new, more sensitive tests that are also often faster are in development. Experience shows that closely interlinked therapy and diagnostics can not only be extremely helpful to the patient, but also a way to relieve pressure on the healthcare system. Diagnostics: a critical stepping-stone to safety and efficiency Diagnostics account for only five percent of worldwide healthcare spending, but they are the basis for more than two-thirds of all treatment decisions. 12 Even after years of extremely intensive research, many types of cancer cannot be vanquished. However, it is now possible to detect them much earlier, classify them more accurately, and often do a far better job treating them. We have diagnostics to thank for that. Many experts see great promise in “preventive medicine”. It can help with early detection not just of cancer, but also of more common diseases such as rheumatism; it can also predict the success of chemotherapy much earlier. According to the World Health Organization (WHO), global expenditures for healthcare in 2005 totaled 2.5 trillion US dollars. Only five percent of that total was spent on diagnostics, while 16 percent went for medications. According to a Lewin Group analysis, more Biotechnology in Penzberg than two-thirds of treatment decisions are made on the basis of clinical laboratory tests. Therefore, diagnostics are a key instrument to make a positive impact on both patient benefit (safety and efficacy of therapy) and cost (for follow-up medical care). Diagnostics development: looking for the needle in the haystack The path to a successful diagnostic tool is simpler than the path to an effective medication, but it is still a long lasting puzzle. It costs about 10 million euros to develop a completely new instrument. Research and development take two and a half to three years. However, modern sequencing and proteomics technologies have dramatically accelerated development. Today, researchers in Penzberg’s laboratories routinely compare approximately 40 samples of diseased Research, development & production in Penzberg tissue with healthy samples. From this material, they identify five to six thousand interesting genetic differences that could lead to the development of a new test. However, finding that needle in the haystack – that key biological difference that marks the beginning of a disease – is no easy task. These so-called biomarkers must be more than just reliable indicators. Ideally, they should also appear in blood or urine so that a test can access them. Initial raw data are subjected to a few tests, and only the most promising marker candidates are pursued further. About 50 make the initial cut, and initial pilot tests are developed for these hopefuls. However, this is nowhere near the end of the road. Routine testing of large numbers of samples in the lab and in clinical studies is used to review marker candidates until suitable ones are pinpointed. Personalized medicine: just a vision, or a dream come true? Many new methods have become established via these procedures in recent years. Personalized medicine is the guiding principle. Diagnostics experts use this term to denote the ability to offer patient groups an individually tailored treatment plan. Pre-existing conditions as well as the patient’s gender, genotype, habits and lifestyle can all play a role. The current mantra of “same symptoms, same disease, same treatment” will soon be a thing of the past. Physicians’ improved understanding of the molecular causes of illness has spurred many new concrete approaches. The goal is to achieve better specific effectiveness with fewer side effects, and thus a better cost-benefit ratio for all patient groups needing treatment. These are the true benefits of personalized medicine. Role of diagnostics: think again to re-think their approach to healthcare because diagnostics are an essential part of modern medical treatment. However, their value has not yet been recognized here in Germany. Experts believe that all roads will necessarily lead to personalized medicine. They also assume that innovative therapies will become the norm and that broad acting and non-specific medications will be pushed out of the market. Germany should be at the forefront of this trend. Personalized medicine or customized therapies: They reflect the fact that every individual’s body chemistry is just that – individual. Both patient benefit and efficiency in the healthcare system can be improved with such methods. Companion diagnostics: Breast cancer therapy provides inspiration Regulatory authorities are pressuring the industry to develop appropriate diagnostic instruments to complement new drug therapies, in part due to costcutting campaigns, but with a primary focus on the benefit to patients. This strategy has already proven successful for aggressive breast cancer. A simple test can single out women with fast-growing tumors, enabling them to receive specially tailored treatment. Tumor cells in these women test positive for a growth factor called human epidermal growth factor receptor 2, or HER2. German scientists carried out important basic research on this receptor. They discovered that cells that produce high levels of this surface molecule receive especially strong growth impulses. As a result, the tumors are especially aggressive, making post-operative treatment a matter of life or death for many patients. Thanks to the HER2 genetic test developed in parallel with the medication, response rates to treatment with trastuzumab are extraordinarily high. Efforts to significantly extend survival of HER2positive patients with metastases were ultimately successful. Experts consider this the most significant advance in treatment of metastasized breast cancer in more than 40 years. However, despite promising possibilities, only a few new laboratory tests have received their own reimbursement codes. Insurance companies need Biotechnology in Penzberg 13 Kopfleiste zum ausfüllen Targeted therapy From genes to diagnosis Same disease, same treatment – that’s a mantra from the past. Modern treatments combine diagnostic tests and targeted therapies with the goal of achieving better specific effectiveness and fewer side effects. Maggie Duke, breast cancer patient: “Before I was diagnosed with cancer, I didn’t know that there were different kinds of breast cancer. And I had no idea that there are different therapies depending on the kind of cancer you have. In my case, the HER2 test and the subsequent treatment with trastuzumab saved my life.” Thanks to passionate political activism by patients, the medication was approved for use in the United States in a recordbreaking six months. 14 Stories of hope: Maggie Duke Regaining control over the disease When Maggie Duke mentioned a small lump in her breast to her doctor following a regular mammogram, he wasn’t concerned at all. However, the lump became increasingly noticeable and painful, so Duke, an avid sportswoman, insisted on additional testing. This is how she came to be diagnosed with breast cancer in the summer of 1997. Duke, an American hygiene expert living in Switzerland, was initially in a total state of shock and couldn’t believe her diagnosis – breast cancer. Despite her fears, she tried to stay positive and hoped that her life would return to normal after surgical removal of the tumor. However, this was not to be. Within a week, she had to undergo another operation to remove more tissue from the tumor site and a lymph node under her arm. Although the rest of the breast seemed to be healthy, the cancer quickly metastasized to another lymph node. Despite ongoing hormone treatment as well as chemotherapy and radiation, Duke forced herself to keep going to work every day. In the summer of 1998, exactly one year after her initial diagnosis, she was told she had bone cancer. By the end of the year, it had spread to her liver. By this point, no one gave Maggie Duke any real chance of survival. Her friends kept Maggie’s spirits up and worked with her to find a solution. One of them told her about a doctor who had obtained good results with a new type of therapy – trastuzumab. Maggie had a diagnostic test done that showed her tumor produced a great deal of HER2. She learned that such tumors are extremely aggressive, grow quickly, and are very likely to reoccur. She was accepted into a clinical study that combined trastuzumab with chemotherapy. The results surpassed her wildest dreams. Within two and a half months after beginning treatment, images of Maggie’s liver showed that the metastases had shrunk to just one-quarter of their previous size. Maggie once again felt as though she could get control of her cancer. After two and a half years, Maggie was able to discontinue chemotherapy and has been treated solely with trastuzumab ever since. Maggie, who is now 59, was able to return to a normal life and go back to her hobbies – including competitive cycling. Biotechnology in Penzberg Research, development & production in Penzberg The Roche Group Success by innovating It all started with the hormone erythropoietin in the early 1990s, when Roche realized the benefits of biopharmaceuticals. EPO products are still among the company’s top 10 sellers today. But Roche has also had enormous success with diagnostics: its product line for measuring blood sugar levels is number three on the sales list. The Penzberg site plays a major role in six of the ten best-selling Roche products. 2006 – another record year for Roche New biotech therapies and diagnostics The Roche Group of Switzerland once again posted record results for fiscal year 2006. The Group boosted sales by 17 percent to 26 billion euros, and its profits of almost 4 billion euros constituted the largest jump in profits in company history. The Group’s Pharmaceutical Division grew 21 percent in 2006, three times the growth of the world market. Diagnostics was able to increase its sales by five percent, maintaining and consolidating its position as the global market leader. The market rollout of a new product line for measuring blood glucose levels was one of the Diagnostics highlights of 2006. Last year, Roche had a total of 14 medications approved for sale and rolled out many new diagnostic tools, including a new product line for high-throughput routine tests. Cancer drugs were also successful. The bevacizumab antibody to treat lung cancer, trastzumab for early-stage breast cancer, and rituximab for rheumatoid arthritis were approved for additional indications. This allowed the Roche Group to further consolidate its global leadership in the production of biopharmaceuticals. Blockbusters – the 10 top-selling biotech drugs worldwide In billions of US dollars 4.4 4.1 4,000 3.9 3.6 3.2 3.1 3,000 2.9 2.7 2.5 2.4 2,000 1,000 0 Etanercept Darbepoetin-α Rituximab Infliximab Epoietin-α Trastuzumab Epoietin-α Pegfilgrastim Human insulins Sales of most of the ten biggest-selling biotech drugs worldwide posted doubledigit sales increases. Three of the ten bestsellers, rituximab, trastuzumab, and bevacizumab, come from Roche (violet). (Source: Nature 2007) Bevacizumab Biotechnology in Penzberg 15 Imprint Publisher: Roche Diagnostics GmbH Communications Nonnenwald 2 82377 Penzberg, Germany www.roche.de www.roche.com www.gesundheitspioniere.de © 2007 Editor / Realization: Dr. Patrick Dieckhoff BIOCOM AG, Berlin www.biocom.de Design: Oliver-Sven Reblin, Berlin Pictures: Roche tourismus & sport oberstdorf BIOCOM AG Printed at: enka-druck, Berlin Item: 05141206-990 09-07