Hessian Ministry of Economics, Transport, Urban and Regional Development www.hessen-biotech.de

Hessen – Your Gateway to the Diagnostics Market in Europe

A Practical Guide to Services and Technology for the Diagnostic Industry

Imprint

Publisher Hessian Ministry of Economics, Transport, Urban and Regional Development Project Management Hessen-Biotech Dr. Detlef Terzenbach HA Hessen Agentur GmbH Abraham-Lincoln-Str. 38-42 65189 Wiesbaden / Germany T: +49 611 7748 613 F: +49 611 7748 620 [email protected] www.hessen-biotech.de Editorial Office Genius GmbH, Darmstadt www.genius.de Layout ansicht kommunikationsagentur www.ansicht.com Print Werbedruck Schreckhase, Spangenberg Disclaimer Listing of a company profile within this publication is strictly voluntary, all Companies doing business in the field of in vitro diagnostics have the opportunity of being entered in this database. Fotographs committed by Abbott Diagnostics (pp 23-25) BIT Analytical Instruments (pp 20-22) Klaus Treude (pp 5-9) Paul-Ehrlich-Institute (pp 13-18) Philipps-University (pp 16-17) Sysmex (pp 10-12) targos (pp 18-19)

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Content

in vitro diagnostics in Hessen: Interdisciplinary and Attuned to Innovation

4

in vitro diagnostics in Hessen

5-9

in vitro diagnostics – a Future-Oriented Market in Movement

10-12

Regulatory View of in vitro diagnostics

13-15

Basis for Optimal Patient Care: Laboratory Diagnostics in Clinical Practise

16-17

Predicting the Response to the High-Value Medicines of Tomorrow

18-19

Efficiency through Integration: Development of Diagnostic Platforms

20-22

Bringing New Ideas into Life with a Big Partner

23-25

Company Profiles

26-42

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in vitro diagnostics in Hessen: Interdisciplinary and Attuned to Innovation

Prevention is better than cure. This is true not only for the benefit of patients and physicians but also for the healthcare system at large. A precise diagnosis at a very early stage greatly enhances the chances of curing or even preventing an upcoming disease and thereby reduces the costs to the healthcare system significantly. In this context, in vitro diagnostic (ivd) methods play a crucial role. Using these modern assays, diseases can be detected even in their earliest stages. Furthermore, in vitro diagnosis makes it possible to gain information on the cause of disease, the effect of medical treatment and the overall healing process. Although laboratory diagnostics account for only 2–3% of the total healthcare expenditures in Europe, they represent a large saving in the cost for treatments. Being the starting point of every medical treatment, innovation in diagnostics leads to innovation throughout the whole healthcare system. More precise, personalised and differentiated results open new ways of treatment for physicians and new targets for the pharmaceutical industry. The complete healthcare system therefore profits from diagnostic innovation. Driven by the insight of being a mainstay for the healthcare system, the diagnostic branch today is one of the most innovative industries.

Much of this innovation comes from Hessen, where many large, medium-sized and small diagnostic companies flourish in the productive environment of research-driven medtech, biotech, nanotech and IT companies and device manufacturers, to name only a few. Hessen offers a diverse life science landscape and thus represents a rich hotbed for in vitro diagnostics. Not least due to its long tradition as a location for chemistry and pharmaceuticals, a lively biotechnology and medical technology scene has evolved here. Another important feature of Hessen: The region offers a dense network of universities, universities of applied sciences and other research institutes, covering the complete spectrum of life sciences. Companies seeking access to the European ivd market will find a perfect base in Hessen. This brochure allows easy access to partners in technology, services and products. Therefore, I invite everyone to make use of the extraordinary opportunities of Hessen as a starting point for ivd business.

Dr. Alois Rhiel Hessian State Minister of Economics, Transport, Urban and Regional Development

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in vitro diagnostics in Hessen

Interdisciplinary and Geared to Innovation As a classical cross-section discipline, modern in vitro diagnostics (ivd) profit from the rapid advances in biotechnology, molecular biology, information and medical technology. Thus, ivds will undoubtedly become a leading sector within the healthcare system in the coming years. In 2006, the worldwide market for reagents, test systems, analytical equipment and services comprised around 30 billion Euros with an average growth of 7% per year. Europe has the second largest share, after North America, in the international ivd market, with Germany being the market leader in the European comparison.

This brochure presents the first comprehensive analysis of the in vitro diagnostics (ivd) industry in Hessen. Targeted surveys, intensive database research and comparison with national and international information on this sector have provided a reliable basis for the assessment of the ivd sector in Hessen. Complemented with contributions from Hessian experts in this field, this publication gives in-depth information on current market trends and ground-breaking technologies in ivd. The company profiles of the local ivd companies make this brochure a comprehensive reference guide for anyone interested in this emerging industry.

Hessen – The Gateway to the European Diagnostics Market

over 50 m. Û

up to 2 m. Û 17%

33%

20% 30%

up to 50 m. Û

Annual total turnover of ivd companies in Hessen

up to 10 m. Û

Hessen is a dynamic site for the ivd sector: Already 54 diagnostics companies are based here. In Hessen, these currently provide work for around 6,000 employees, of whom approximately 5,000 (83%) are employed directly in the ivd industry. Last year these Hessian companies achieved a total turnover of roughly 1.5 billion Euros. Of this, around 1.2 billion Euros (80%) was allotted straight to ivd. The significance of these figures emerges in the international comparison: For 2006, the German Diagnostics Industry Association (Verband der DiagnostikaIndustrie, VDGH) estimated a worldwide total turnover of 30 billion Euros in the field of ivd and the latest figures of the European umbrella organisation (European Diagnostic Manufacturers Association, EDMA, 2006) amount to 9.2 billion Euros for the European ivd market. 5

A Mix of Regional SMEs and International Players

Q up to 50 employees up to 250 employees more than 250 employees Frankfurt

Q Frankfurt Airport

The geographical distribution of ivd companies in Hessen shows a high density in the southern regions.

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in vitro diagnostics in Hessen

Of the 54 diagnostics companies, 36 (67%) are dynamic, highly innovative small and medium-sized enterprises (SMEs) and form the basis of the Hessian ivd industry. In general, these specialise in ivd, meaning that they achieve more than half of their total turnover with products and services in and around ivds. There are also the large and very large companies with headquarters in Hessen and global companies that have a branch in Hessen. With 1,700 employees Abbott is the largest ivd Company in Hessen. Abbott operates its entire diagnostics business for Europe, the Middle East and Africa from Wiesbaden, running large development and production facilities there. Another major player in this location is Siemens Healthcare Diagnostics, which – through the acquisition of Dade Behring, DPC Biermann and Bayer Diagnostics – has become one of the most important competitors in the European ivd market next to Abbott, Roche Diagnostics and Beckman Coulter. According to a Study by Frost & Sullivan from 2005, these companies have a turnover representing 60% of the European market.

A Center for the Diagnostic Industry

Innovative and Interdisciplinary

A distinct North-South-divide is apparent in the Hessian ivd landscape. The most active region in the business sector is southern Hessen, where more than 70% of all Hessian ivd companies are located, amongst which are the global players: Abbott, Biotest and Siemens Healthcare Diagnostics with several locations. Approximately 20% of the ivd companies are found in central Hessen. In addition to the Siemens subsidiary Dade Behring in Marburg, there are mainly small and mediumsized companies in the Giessen area. Only a few ivd companies are based in northern Hessen.

The entire value chain of the ivd industry – R&D, production and distribution – is represented in Hessen. Research is of high importance here. Of the companies questioned, 74% carry out R&D, in Hessen, and another 13% facilitates R&D outside of Hessen. This is a sign of the strength of innovation in Hessen. This impression is confirmed by the fact that a third of all companies undertaking research invest more than 10% of their turnover in R&D; a further 5% even more than 50%.

within and outside of Hessen 19%

outside of Hessen no research 13%

13%

up to 50% R&D

more than 50% R&D

up to 10% R&D

5% 33%

62%

55%

in Hessen

R&D locations

R&D share in the total turnover

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Laboratory Diagnostics in Focus – Focal Point Immune Diagnostics

Hessen: Germany’s economic powerhouse Among the 16 German States, Hessen is one of the most successful regions. Most of all, it has a long standing tradition as a center of the chemical and pharmaceutical industry, which is the largest industrial sector employing more than 86.000.

Within the product segments, the focus is clearly on laboratory diagnostics. More than 90% of the ivd companies work in this field; just under 40% are concerned with user-friendly Point of Care (POC) and rapid testing.

Hessen is home to Companies like EMD Serono, Fresenius, B. Braun, Siemens Diagnostics, Merz and Biotest, to name only a few. Global Players like Sanofi-Aventis, Novartis, Abbott, Clariant and Evonik run major parts of their businesses in Hessen.

Immune diagnostics play an important role. More than 60% of the Hessian ivd-companies offer products and services in this segment. Another Hessian strength ist the field of molecular diagnostics, which encompasses the development of biomarkers. 26% of the ivd-companies in Hessen work in this innovative area.

Frankfurt is home to Continental Europes largest Airport and to the European Central Bank. Population: 6.1 m Capitol: Wiesbaden (271,000) Largest City: Frankfurt (655,000) GDP per Capita: € 33.614 Information: www.invest-in-hessen.com

100 90 87

80

81

% lvD Companies

70 60

68

50

52

40 30 29

20

32

10 0

Production

R&D

Fields of Activity

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in vitro diagnostics in Hessen

Service/ Support

Contract Sales and Instruction/ Research Distribution Training

So the infant molecular diagnostics have gained an equal importance like the already established application fields – clinical chemistry, microbiology/ bacteriology, haematology/ histology/cytology – ranging between 25% and 29%.

IVD Definition • Lat. in vitro: in a test tube (Analyses of body fluids and tissue sections outside of the body). • Laboratory diagnostics • Point of Care Testing (POC) • Rapid Testing

Highest Marks for Infrastructure and Expertise What is it that makes the location Hessen so attractive to companies? This was also part of the survey, and the results show 80% of the interviewed companies are satisfied or highly satisfied with the local conditions in Hessen. Participants in the survey praised the outstanding traffic infrastructure, which was also rated as very good in an international context. In second and third place were the proximity to clinics and research facilities and the availability of skilled personnel. Here, the especially tight net of universities and research establishments in the field of life sciences and the good connection via the hub Frankfurt – Europe’s turnstile – pay off.

Definition: IVD Company According to the German Diagnostics Industry Association (Verband der Diagnostika-Industrie, VDGH) and European Diagnostic Manufacturers Association (EDMA): Suppliers of reagents, analytical equipment, consumable materials or software for the use in areas of IVD: • Clinical Chemistry, • Immune Chemistry, • Microbiology/Bacteriology, • Haematology/Histology/Cytology, • Infectious Immunology or • Molecular Biology

Definition of ivd Companies As the ivd industry does not officially represent an independent industrial sector, a definition was first decided upon to identify the ivd companies in Hessen. These are involved with products and services in and around the medical analysis of body fluids and tissues outside of the body (i.e. in vitro). The specific requirements of an ivd company are shown in the following box. 9

in vitro diagnostics – a Future-Oriented Market in Movement Jürgen Schulze, German Diagnostics Industry Association

Sales of in vitro diagnostic (ivd) products in Europe have been recently increasing by about 3–6% per year. This increase varies depending on the status of the healthcare system with respect to development and the corresponding regulatory activities within the European countries. There is a high demand for ivd products in the new member states of the EU; however, recent increments in turnover sales in Germany have been between 0 and 3% per year, showing restained growth. In 2007, the German diagnostics industry had a 2053.5 million Euro turnover for ivd products, an increase of 2% compared with 2006. The market for innovative products such as molecular diagnostic applications is developing, although that for routine diagnostics currently shows no expansion.

of which laboratory tests 1,84 Medicinal treatment 23,11

Hospital 50,80 17%

33%

Medicinal products 27,76

20% 30%

Dentists/prosthodonitcs 10,72 Specific remedies/adjuvants 8,62

Others 18,47

of which laboratory tests 1,51 Health insurance patient allowance 6,01

Administration 8,13

Early Recognition, Timely Treatment Laboratory diagnoses are often only seen as an expense factor. In actual fact, laboratory expenses amount to 3.35 billion Euro, which represents only 2.2% of the total expenditure of the compulsory health insurance fund. Compared with the minor portion of cost, the significance of modern laboratory diagnostics for the healthcare system is immense. Almost two thirds of all clinical diagnoses are based on laboratory analysis. Laboratory diagnostics make early recognition of disease and a timely treatment possible. Multifaceted tests improve the diagnosis, and eliminate differential diagnoses, so aiding prognosis and therapeutic measures. In this way, tests that often only cost a few cents or euros help to improve the quality of life of the patient and to achieve cost savings for the overall healthcare system. The German Diagnostics Industry Association (VDGH) is actively campaigning to show the benefits of modern laboratory diagnostics as a trigger for medical progress, demonstrating the savings for the overall system and the economical potential of this industrial sector. The VDGH is advocating an overall strategy for economical, technological and healthcare politics to use the potential of diagnostics development both for employment within the healthcare system and for the benefit of our economy.

In 2007, only 2,2 % (3.35 bn €) of the total expenditure of the German statutory health insurance funds (totalling € 153.62 billion) went into laboratory tests (source: VDGH, www.vdgh.de).

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in vitro diagnostics – A future-oriented market in movement

Chances for an Improved Prevention

Market in Motion

Laboratory diagnostics are of great significance in the area of prevention. Tumors that are identified at an early stage (such as prostate, cervical or bladder cancer) can be treated successfully. Early recognition of coronary heart disease can also contribute to successful therapy.

For several years now, there has been a strong consolidation of services for care providers, i.e., laboratories. Many hospital laboratories are being closed down and outsourcing is taking place. Other hospitals are building networks or are being taken over by private institutions. In the area of ambulant medical care the trend towards consolidation is even stronger. Only a few laboratory chains will survive in the medium term in Germany – experts expect less than 20 companies to survive. There is also a strong trend to internationalization of laboratory services. The ever-growing laboratory units demand optimized workflows with process cost as low as possible. All ivd providers have to adjust their portfolio accordingly. The market needs fully automated solutions that optimize the workflow and require little manual input. The optimization of the whole process under the standpoints of quality, time and cost are central to success. Chances for corporations that provide automated laboratory lines and platform technologies are opening up. In addition to performing analysis in laboratories, the demand for products for the so-called emergency or 24-hour diagnostics laboratory is increasing. For this purpose 'Point of Care' products are used to enable easy handling and reliable quality control.

The diagnostic industry provides innovative products for early diagnosis for various diseases. To take advantage of this progress, it is important that patients use the paid healthcare prevention programs of the compulsory healthcare providers, and that the healthcare systems take these innovative tests into the program they offer. As an example, colon cancer, if detected early enough, is curable in almost all cases. Yearly more than 70,000 people are diagnosed with colon cancer; the number of deaths is around 30,000. Only about 12% of qualified patients take advantage of the coloscopy prevention program that has been offered since October 2002. Many people avoid the presumed stressing and uncomfortable examination. As an alternative they can take advantage of the offered ivd blood stool examination. Until now, the only covered screening test is a so-called rapid diagnostic test strips. The significantly improved immunological test kit for occult blood using a one-enzyme system indicating metabolism products of a colon cancer, are not yet covered by the compulsory health insurance. Contrary to the current stool examinations, no special dietary instructions have to be followed with these modern tests and a significant more precise diagnosis is feasible.

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Industry in Flux The ivd industry is also changing. In addition to many small primarily research-oriented corporations, three trends are emerging: • The great synergic potential between pharmaceuticals and diagnostics is leading towards corporations that cover both areas. Diagnostics play a big role in research of new substances. The ‘personalized therapy’ (matching of a treatment to the individual through appropriate ivd) will become accepted in the medium or long term. • ‘In vitro laboratory diagnostics’ and ‘in vivo medical techniques’ (imaging diagnostics) branches of corporations are being merged. The aim is to optimize workflow with regards to the complete healthcare process (patients, diagnoses, therapies) and the development of new biomarkers and their combination with imaging techniques.

• Last, but not least, there are ‘pedigreed’ diagnostic corporations who operate very successfully. The product complexity in the area of diagnostics alone is already very demanding since providers have to be proficient not only in equipment technology, reagent development, production, etc., but also in areas such as software, application, automation, and workflow. The advantage of such corporations is that they can concentrate their resources on ‘their market’ – the laboratory. The trend to consolidation seen for laboratories will possibly extend to other corporation and network structures. All market participants envision the great potential for the field of ivd, and are ready to use their possibilities to exploit these potentials.

Dr Jürgen Schulze President of The German Diagnostics Industry Association (VDGH) Mainzer Landstraße 55 60329 Frankfurt am Main | Germany Managing Director of SYSMEX DEUTSCHLAND and SYSMEX EUROPE GMBH Bornbarch 1 22848 Norderstedt | Germany T: +49 40 534 102-280 [email protected]

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in vitro diagnostics – A future-oriented market in movement

Regulatory View of in vitro diagnostics Micha Nübling, Paul-Ehrlich-Institut

In Germany, in vitro diagnostics (ivds) were for a long time statutorily regulated like medicinal products. Today, they fall under the Act on Medical Devices. Manufacturers are thus allowed to bring new low risk category ivds or batches of such products onto the European market without governmental control or approval. However, statutory demands are stricter for ivds in higher categories. Private certification and testing institutes offer their expertise to manufacturers. An ivd testing laboratory at the Paul Ehrlich Institute (PEI) in Langen, near Frankfurt, may be subcontracted for some activities in this field. In line with the new European regulations that have been in place since the beginning of the new millennium, ivds no longer have to be governmentally approved, but only require a CE marking. By labeling a product with a CE mark, the manufacturer certifies that a product was manufactured in accordance with the existing German and European Union product safety regulations. The CE label does not automatically imply that the device was checked by an independent body to assure that these regulations were met.

The new regulations are based on the European ivd Directive (Directive 98/79/EC). This has been in effect since 1998, replacing the quite differing national regulations in various European member states with a unified European policy. In Germany, it was implemented into national law in 2002 through a second amendment to the Act on Medical Devices. Thus, in Germany, the former governmental control of ivds has been transferred to the responsibility of the manufacturer. The European regulations differentiate risk classes of ivds that have to meet different requirements. However, the majority of the ivds are under the sole responsibility of the manufacturer, and hence are only tested and assessed by him. Thus, the manufacturer can independently label the products with a CE mark, fulfilling the requirements for placing the product on the European market.

High Risk Level Demands External Assessment ivds of the highest risk category place higher demands on the manufacturers. These ivds include tests that detect dangerous viruses that may be transmitted by blood donations. Among those are primarily the AIDS virus HIV and the two hepatitis viruses B and C (HBV and HCV). ivds used to determine the most important blood groups (AB0 system, rhesus, Kell) also belong to the highest risk category of the ivd Directive, as well as detection systems for HTLV virus I and II and HDV.

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Paul Ehrlich was the first director of the Paul Ehrlich Institute and a Nobel Prize laureate in medicine in 1908. (Source: PEI)

Many of these ivds are manufactured using biological or biotechnological processes that are often not as easily standardized as chemical processes. Because of these biological production methods, some including use of cell cultures or bacteria, an extremely consistent, accurate and controlled production over many batches is necessary for a timely detection and prevention of any large variations in quality. The manufacturer has to have his internal quality control systems for all high-risk tests audited before placing the ivd on the market. This involves, for example, performing legally required studies for the ivd according to a particular plan. Also each production batch of these tests has to undergo specific controls. The producer commissions a private authority as “notified body” for both the evaluation of the studies and the batch testing. The notified bodies are neutral, independent and competent bodies that perform auditing or what is known as conformity assessments of products pursuant to the ivd Directive and ISO/IEG17000:2004. The participation of a notified body can be seen by the specific number below the CE mark, which identifies each notified body.

The PEI Reviews and Checks Important ivds The PEI, because of its long-standing experience in testing ivds, is in great demand as a partner by manufacturers and notified bodies. For several decades, when ivds still fell under the German Drug Law, the PEI was the central institute for evaluating the quality of tests for pathogenic agents, e.g., AIDS tests and diagnostics for hepatitis viruses. This forms the basis of PEI's expertise in the evaluation and batch release testing of ivds. In its new role as a testing laboratory, the institute offers to conduct studies to assess the quality of new ivds or to test new production batches before they arrive on the European market. The certificates of the PEI are acknowledged worldwide. Many countries in Asia or South America demand a certificate from the PEI before the ivds are allowed into their country.

Expertise is Growing with the Market Over the past decade, new technological procedures have found their way into diagnostics. Developments towards more sophisticated antibody tests [immunoassays, such as enzyme-linked immune assays (ELISAs)] as well as the introduction of new technologies have taken place. Here too, the PEI with its examinations is always at the cutting edge scientifically and technologically. The latest most important technologies include molecular tests for detecting tiny amounts of virus in blood that are only measurable by artificially

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Regulatory view of in vitro diagnostics

The buildings of the Paul Ehrlich Institute in Langen near Frankfurt am Main form a Y-like structure (when seen from above) – characteristic for antibodies. (Source: PEI)

multiplying the viral nucleic acid in vitro to a detectable concentration. One method for this is the polymerase chain reaction (PCR), an essential for today's modern research laboratories. The ivd industry now offers automated PCR systems that relieve laboratories and blood banks from many of the steps that were previously labor intensive and prone to error. At the PEI even the reagents developed for these modern analytical methods are continuously subject to quality control before new production batches are released on the European market. At this point we come back again to many biological medicinal products that are also handled at the PEI for regulatory purposes or in research projects. Biological materials from which these medicinal products are prepared (e.g., human blood plasma) are often tested for viruses and other pathogenic agents using these efficient molecular detection methods to guarantee effective and safe medicinal products.

nal products. These include, for example, vaccines and blood products as well as substances such as monoclonal antibodies or artificial nucleic acids for gene therapy. Unlike in Paul Ehrlich’s time, the authorization and control of medicines are increasingly performed at a European level today. The Paul Ehrlich Institute reports to the Federal Ministry of Health and employs over 700 staff. They primarily deal with questions on the safety and efficacy of biological medicinal products, are involved in approval and marketing authorization activities for these products and conduct internationally renowned experimental research in the field of life sciences.

History of the Paul Ehrlich Institute The PEI, originally established in 1896 as an institution for serum research and serum testing in Steglitz, Berlin, is today still active in the industrial area of Langen south of Frankfurt. It was named after its first director – the physician and later Nobel Prize laureate Paul Ehrlich. He had the assignment to develop and implement the basic principles of governmental control of medicinal products.

Dr. Micha Nübling Paul-Ehrlich-Institut Molecular Virology Paul-Ehrlich-Str. 51-59 63225 Langen | Germany T: +49 6103 77 3304 [email protected]

Today the tasks of the PEI still concentrate on testing and research in the area of biological medici-

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Basis for Optimal Patient Care: Laboratory Diagnostics in Clinical Practise Harald Renz, Philipps-University, Marburg

During the last decade laboratory medicine has developed into a medical discipline that is indispensable for daily clinical routine. About 80% of all medical diagnoses are made through or confirmed by laboratory examinations. Laboratory medicine is an extremely inexpensive facility, constituting only 1.5% of the hospital budget. Besides the wideranging skills of the laboratory medicine specialists, acquired during 5 years of extended vocational training, the field is also distinguished by a broad methodological competence. Recently, this aspect has gained in importance through the introduction of a multitude of complex and innovative methods, for example automated immunoassays, nephelometry, turbidimetry, mass spectroscopy, atom absorption and flame photometry, which have developed to maturity out of basic biomedical research. In day-to-day laboratory operation, quality management is essential. And this high quality of medical diagnostics has to be ensured 24 h a day, 365 days a year. Laboratory medicine was one of the first medical disciplines that established comprehensive quality management in form of ‘round robin proficiency test’ that is embedded in law and therefore binding for all users of laboratory diagnostics.

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The latest developments in quality management concern accrediting medical laboratories according to ISO/DIN norms. In Germany, the Marburg University Institute was the second University institution that has reached this highest standard of quality assurance. From this it is clear that laboratory medicine possesses a particular competence for optimising complex process procedures. The time between arrival of the sample in the laboratory and the delivery of diagnostic findings to the sender, the so-called turnaround time, has to be kept as short as possible. In this short time, high complex analytics, quality assurance and medical diagnosis have to take place.

Trend towards Automation and Specialisation With the latest developments, the field is moving between the two antipodes of an increasing automation on the one hand and specialisation on the other. Today about 2,000 different laboratory tests are routinely available worldwide, of which 600 are offered in the central laboratory at the University Hospital Gießen (Gießen, Germany) and Marburg GmbH (Marburg, Germany). Of these, 120 are socalled vital parameters requiring a basic laboratory turnaround time of about 30 min. This area makes up nearly 70% of the analyses of the central laboratory. So, the last 30% of analyses require one of ~480 laboratory tests, which are performed in different areas of specialty within the Marburg Institute.

Basis for optimal patient care: Laboratory diagnostics in clinical practise

Among the most important are allergy diagnostics, diagnostics of autoimmune diseases, hormonal imbalances, measuring of metabolic performance, analysis of functions in body defence, diagnostics of infectious diseases, coagulation disorder, toxicology, analysis of vitamins and trace elements.

Individualized Allergy Therapy With increasing cost pressure, setting up laboratory networks and laboratory co-operations is extremely important to maintain high medical and technical performance. With its special medical competence in the research on inflammation, the Marburg institute is optimally integrated into these network structures. Today, this is the only way to guarantee efficiency in this tremendously fast developing field. In the Marburg institute, several internationally accredited research groups are working in the area of chronic inflammations that in the last decade have become widespread diseases. Among these are asthma, atopic dermatitis, food allergies, rheumatism and other autoimmune diseases. These complex diseases develop through interactions between genes and the environment that are not yet fully understood. Since standard therapies are not applicable for every patient, these diseases demand a complex and individualised therapy. In the coming years this will lead to an increasing development of subtyping – subcategories of a disease – that will provide the basis for a specialised and personalised therapy.

This again will directly effect the definition of laboratory medicine since the entire chain of risk assessment, prevention, diagnoses of diseases, monitoring of treated patients and assessment of the prognosis significantly relies on laboratory tests. The latest developments bring laboratory medicine very close to the diagnostic industry that can only develop, verify and market new tests in cooperation with the users of medical diagnostics. With its high standard of laboratory performance as well as its expertise in basic research, the Department of Clinical Chemistry and Molecular Diagnostics at the University Hospital Gießen and Marburg can significantly contribute to the development of innovative diagnostic tests and associated technologies.

Harald Renz, MD Chairman and Professor Head of the Department Clinical Chemistry and Molecular Diagnostics - Central Laboratory - Hospital of the University Baldingerstr. 35033 Marburg | Germany T: +49 6421 58-66234 [email protected]

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Predicting the Response to the High-Value Medicines of Tomorrow Thomas Henkel, targos molecular pathology gmbh

Based on the current assumptions, the majority of drug treatments are ineffective because the decision for a drug prescription is mainly driven by statistical results for a patient population rather than a diagnostic result for an individual patient. In many cases the decision is not evidence based at all. This situation is becoming increasingly unacceptable, and hence addressing the challenge of predicting the response to a specific drug treatment is an imperative for three main reasons: First, selecting patients likely to benefit most from a drug from those who predictably will have no benefit is highly ethical. Second, healthcare professionals and healthcare providers worldwide need diagnostic guidance on how to handle the mismatch between innovative high-value medicines and limited financial resources. Third, it is of economic advantage for the pharmaceutical industry to stratify patient populations in clinical drug development and stratification thus helps to increase medical innovation. For these reasons, in March 2005, the U.S. Food and Drug Administration (FDA) issued a guidance that requests the submission of all available validated biomarker data for any application for a new drug. The European Medicines Agency (EMEA) has its own regulations, which are sometimes even stricter than those of the FDA, as seen with the recent approval of the anti-cancer drug panitumab (Amgen Inc.), for which a diagnostic test ruling out therapy resistance is required in Europe but not in the US.

Predictive Biomarkers Optimize Prescription The instruments to address these challenges are validated predictive biomarkers. Unfortunately only few of these biomarkers have made their way to clinical practice, e.g., Her2 testing by immunohistochemistry or by in situ hybridization for the selection of breast cancer patients eligible for trastuzumab (Herceptin, Roche) treatment; HLA B*5701 genotyping for the identification of HIV-infected patients most at risk for abacavir-related hypersensitivity reactions (Ziagen, GSK); the immunohistochemistry testing for the presence of estrogen receptors and progesterone receptors as prerequisite for antihormonal therapy in breast cancer patients; or the above-mentioned analysis of K-ras mutations by RT-PCR to identify therapy resistance to panitumab in colon cancer patients. To improve this situation, many drug development companies have dramatically increased their efforts to co-develop predictive biomarkers together with new targeted therapies. Some pharmaceutical companies have joined forces with diagnostic companies, such as Eli Lilly Co. and GE Healthcare; in some cases the pharmaceutical and diagnostic branches of one company have started joint activities (e.g., Roche Pharma and Roche Diagnostics) with a clear focus on predictive pathology. The pharmaceutical industry’s fear of fragmented markets due to patient stratification is diminishing, with more success stories such as Gleevec (Novartis) for small selected patient collectives. Finally, healthcare providers in California, USA and Quebec, Canada have started to analyze life-cycle

18

Predicting the response to the high-value medicines of tomorrow

costs for a given disease. This will allow calculating the impact of improved therapy prediction using novel diagnostic tests on the overall costs of disease treatment. In general, the costs for selecting suitable patients for a targeted drug treatment are less than 10% of the costs for the drug itself.

Validation in Close Collaboration with Clinical Pathology Predictive biomarker testing in oncology is mostly performed using molecular pathology – a tight interdisciplinary cooperation between molecular biology providing the test platforms and clinical pathology providing the knowledge about tumor cells, tissue and disease. targos molecular pathology gmbh was founded to meet the increasing international demand by applying highly standardized biomarker analysis. The company’s core business is to discover, apply and validate highly standardized predictive biomarkers in human medicine. Founded in 2005 in Kassel, targos’s (currently 38) employees offer a clinical and scientific biomarker service to the international pharmaceutical and diagnostic industries under strict quality and project management. More than 40,000 patient tissue samples from over 60 countries have been analyzed in the targos labs since its inception. targos collaborates closely with the large, experienced pathologist team of the Pathology Nordhessen, a private pathology institute in Kassel, with its focus on tumor pathology and predictive pathology, an expertise that the institute also provides to the hospitals and physicians in the region. In addition,

targos collaborates with the Institute of Pathology at the University Hospital in Bonn to extend its expertise and capacities in pathology. Due to its strategic position, targos can act as a bridge between the pharmaceutical and diagnostic industries developing the new high-value drug treatments and diagnostic tests, and the diagnostic institutions that have the task to provide patients with novel predictive tests under the increasing financial constraints of the healthcare systems. In the next decade we will see an increasing importance of predictive biomarkers. Once more tests have been validated and approved, and more healthcare providers have calculated the benefit of patient stratification to the healthcare budget, predictive biomarker testing will not be primarily offered to patients within clinical trials but will be part of daily clinical routine. targos has taken up the challenge of the internationally growing demand and aims to thrive and to remain a high-quality partner for the pharmaceutical and diagnostic industries as well as for the diagnostic institutions.

Dr Thomas Henkel Chief Executive Officer targos molecular pathology gmbh Mönchebergstrasse 41-43 34125 Kassel | Germany T: +49 561 980-4100 [email protected]

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Efficiency through Integration: Development of Diagnostic Platforms Alfred Lang, BIT Analytical Instruments GmbH

In modern medicine, diagnosis and therapeutic monitoring relies extensively on in vitro diagnostic (ivd) systems. Such systems are capable of determining a variety of different parameters, mostly from blood but also from urine, liquor or saliva. A broad range of different diagnostic assays are available ranging from mass tests like glucose, various panels such as infectious diseases to very specific DNA based determinations. Such ivd systems are now used in hospitals, blood banks and forensic science, as well as research laboratories or centralized laboratories, which sometimes process many thousand samples a day. The increasing economic pressure drives the need for highly reliable, highthroughput automated ivd analysers, which represent the most cost-efficient processes.

Meeting Customer Requirements

BIT Analytical Instruments, a member of the Messer group, has been involved in the design and manufacturing of medical analytical instruments for more than 30 years. Recently BIT has expanded its market position in the US by introducing Source Scientific, based in Irvine, CA, as a new member of the now global BIT Group.

• transfer of developments into manufacturing

BIT Group offers its customers a comprehensive One Stop Solution service with respect to development, manufacturing and after-sale services for ivd analysers and biochemical or pharmaceutical instruments. Such instrumentation is marketed by BIT's customers together with their own reagents, disposables and reagent–related software and sold under their brand. Consequently, in such cases, IP's for ivd systems are retained by BIT`s customers and the cooperation functions within long-term partnerships.

20

Both parties bring their know-how into the partnership – BIT from the technical and the customer from the application side – to develop tailor-made solutions. At the beginning of a cooperation, requirements regarding services around medical automation as well as instrumentation are clarified. Such services may comprise: • feasibility studies • comprehensive “turn-key” instrument- or moduledevelopments • provision of prototype batches for system evaluation or field trials

• system integration of instrument, software, reagents and disposables • shipping and logistics services • after-sale services. Experience and use of FDA- and ISO-compliant processes is essential. BIT is FDA registered and certified according to ISO 13485 and 9001. The customers' main requirements are besides BIT`s technical capabilities a short “time to market” as well as very competitive development and manufacturing costs. To achieve this, an appropriate platform strategy is employed.

Efficiency through integration: Development of diagnostic platforms

IVD Ð Analyzers Types of instruments and platform modules required Clin. Chem. / enzymatic

Coagulation

Immunology

DNA Analytics

Customer specific software

Customer specific software

Customer specific software

Customer specific software

Ion Selective Electrodes

Clot detection

Photomultipliers

2ÐD - Imaging

Photometer, Turbidimetric, Nephelometric

Turbidimetric, Luminescence, Fluorescence

Washunits

Washunits, Solid phase seperation

Needle modules, Agitation

Needle modules, One way tips, Agitation Dilutors

Temperature and climate control (cooling, heating, cycling) Sample Ð and Reagent Ð Rotors xy-, xyz-, z, -Robotics Electronics, Microcomputers and embedded control software

Such platforms are applicable to ivd analysers for: • clinical chemistry, employing enzymatic and homogeneous immunoassays as well as electrolytes. • coagulation • immunology, using antibodies or antigens bound on solid phases such as tubes or (magnetic) beads. • DNA, generally using chip-based technologies in conjunction with temperature cycling.

Challenges and Solutions Obviously some modules are common and often used either in different types of analysers (such as rotor drives, robotic units, temperature controls, etc.) or within one type of analyser (such as detection units or user software modules). Thus, a set of platform modules providing standard and off-the-shelf solutions is available. However, typically, there are different requirements even within one type of analyser. For example, rotor sizes vary due to different assay packaging dimen21

sions (different bottles, reagent packs) or variable throughput or “walk away time” requirements. Therefore, just employing a single module for different customer projects will not usually be an option. Typically a high level of modularisation usually leads to some over-engineering, with features being included to maintain modularity that are not always required. Such unnecessarily increased module costs may be caused.

engineering skills and an outer team integrating customers activities (assay development, cartridges, reagent packaging, barcodes, user–software, system integration, etc.). Once in manufacture, a product life cycle support is provided.

The BIT Group has therefore gone “one step back” and has developed autonomous sub modules (ASM) that are independent of such varying requirements. Examples of such ASM are:

For BIT, access to universities and institutes as well as to engineering and rapid prototyping partners in close vicinity is vital. Local universities also provide professionally educated staff with a broad range of skills. Generally, the innovative and high-tech environment within the area is of notable benefit for BIT's business. In addition, there are several customers in close vicinity to BIT Analytical Instruments in Schwalbach. With BIT Group having local as well as international customers and with its daughter company in California, quick access to the local air, rail and motorway services is essential. The public transport and motorway complexes available represent a very considerable advantage of the Hessen Rhine-Main area.

• linear drive • z,α drive • rotor drive • diluter • needle + liquid level detection

• wash unit • agitation unit • photometer unit • microcomputer unit • microcomputer basic control shell

System Development in Cooperation with Customers

Rhine-Main Area – an Ideal Location

The BIT Group provides the system and engineering skills necessary for such analysers. This includes development of the mechanical, optical, and liquid flow processes as well as the electronics and software. Specific focus is given to manufacturability within robust and reliable procedures. Projects are run by a System Project Manager who is the contact person for the customer. An integrated product development team is established, comprising a core team with the appropriate instrument 22

Efficiency through integration: Development of diagnostic platforms

Alfred Lang CTO BIT Analytical Instruments GmbH Am Kronberger Hang 3 65824 Schwalbach am Taunus | Germany T: +49 6196 806 101 [email protected]

Bringing New Ideas into Life with a Big Partner Michael Hausmann, Abbott Diagnostics

External Innovation Management is becoming a core expertise in building a differentiated product portfolio, and companies rely increasingly on collaborations with external partners, from new lead identification to market introduction of new products. At Abbott Diagnostics Division, a leader in in-vitro Diagnostics, the New Product Development process is separated into two phases: the Research phase with discovery, concept definition and feasibility activities, and the Development phase with formal Design Transfer, Verification and Validation and market launch. Abbott has established two strategic and comprehensive concepts for external R&D partnerships that are aligned with these two phases.

Abbott Diagnostics has created a network of strategic multi-year and multi-project alliances with leading academic institutions in the USA, Europe and Japan, called Centers of Excellence (COE), that supports internal R&D teams during the Research phase in ensuring technical and commercial success of product development efforts. Three of Abbott´s nine COE´s are located in Germany and focus on markers for cancer, cardiovascular and infectious diseases. They support the identification and assessment of new leads as well as the definition of user needs and product requirements to ensure development of differentiated, best-in-class products. Moreover, they evaluate performance characteristics of prototypes and provide early, “real world” feedback to help determine whether a design concept is ready to move forward into Development and Design Control. As a result, development cycle times and launch dates have become more predictable. In support of the development phase activities, Abbott Diagnostics has established co-development joint ventures with established ivd companies worldwide. Abbott forms partnerships with these original equipment manufacturing (OEM) companies to expand development and manufacturing capacity and to access certain novel biomarkers. Co-development partnerships have proven to be a key concept to accelerate the expansion of the product portfolio and to help executing commercial and regulatory strategies for new products.

23

How to Start a Partnership Development & Manufacturing partnerships need to be carefully selected and managed. Selection criteria - apart from financial terms – typically include technology capabilities and product offering of the potential partner, size and resource complementarity, and its track record of collaborations with other firms. Also, cultural fit, a common understanding of quality system requirements and the level of general project execution, manufacturing and supply chain capabilities turn out to be key success factors in maintaining an effective relationship. Even more than with internal development efforts, an early and joint definition of timeline expectations and deliverables for the different project milestones, product requirements, roles and responsibilities and decision making processes, intellectual property management, and communication plans is essential. At Abbott Diagnostics, contracts, project plans as well as quality agreements outline expectations and responsibilities between Abbott and its OEM partners. Roles and responsibilities differ from project to project and depend on the individual capabilities and the capacity of the partner. In many cases, new product concepts are defined by the internal (Abbott) R&D department and the prototype is transferred to the partner for development and manufacturing. Abbott provides technical and operational know-how, labeling and translations,

24

Bringing new ideas into life with a big partner

as well as Marketing, Clinical Research, Quality Assurance, Regulatory Affairs, and Supply Chain management support. Abbott will market and distribute the new product worldwide. Formal and informal communication prevents relationship issues, which are a common cause for alliance failures. Both partners should assign Project Managers as key contacts and interface between the companies, who coordinate project activities, establish and monitor timelines and arrange for regular conference calls and face-to-face team meetings. In addition, Abbott Diagnostics usually establishes Steering Committees that include R&D and other management from both firms that help resolving issues and facilitate decision making, and provides dedicated Relationship Managers, who handle business and contractual aspects of the partnership and ensure that financial issues do not interfere with the daily interaction of the R&D project teams.

Benefits for Both Sides External innovation is an opportunity for all parties involved, an opportunity for the smaller partner to commercialize new products, to learn from the larger partner in terms of new product development, quality, regulatory and manufacturing processes and systems, and an opportunity for the larger partner to expand development capacity and to provide differentiated new products.

However, R&D partnerships require enduring commitment from all partners and relationships need to be carefully managed. Maintaining trust in the partnership and resolving issues quickly and mutually are the basis for an effective long-term cooperation.

Abbott is a Big Partner Abbott Laboratories is a broad-based health care company that discovers, develops, manufactures and markets products and services that span the continuum of care – from prevention and diagnosis to treatment and cure. Abbott's principal businesses are global pharmaceuticals, nutritional and medical products, including diagnostics and cardiovascular devices. Headquartered in north suburban Chicago, Abbott serves customers in more than 130 countries, with an employee base of more than 68,000 at more than 100 manufacturing, distribution, research and development, and other locations around the world. The headquarter of Abbott's Diagnostics Division for Europe, the Middle-East, Africa and India has been established in Wiesbaden-Delkenheim in the early 80s and employs more than 500 people in manufacturing, quality assurance, supply chain and R&D. The site manufactures reagent kits and components equivalent to 3 Million tests per day for the fully automated PRISM, AxSYM and ARCHITECT analyzers, with a focus on Immunoassays for the prevention, diagnosis and monitoring of infectious diseases.

Michael Hausmann, PhD Director R&D Abbott Diagnostics Division Abbott GmbH & Co. KG Max-Planck-Ring 2 65205 Wiesbaden | Germany T: +49 6122 581764

25

Overview

Abbott GmbH & Co.KG ANALYTICON BIOTECHNOLOGIES AG BAG Health Care GmbH Biaffin GmbH & Co KG Biohit Deutschland GmbH BIOTEC-FISCHER GmbH BIT Analytical Instruments GmbH CYTO Labor- und Vertriebs-GmbH Dade Behring Marburg GmbH A Siemens Company DiaSorin Deutschland GmbH Döll + Co. Medizintechnik GmbH DRG Instruments GmbH Elté Sensoric GmbH Genzyme Virotech GmbH HUMATRIX AG Immucor Medizinische Diagnostik GmbH IMMUNDIAGNOSTIK AG Immunodiagnostic Systems (IDS) GmbH Immunolab GmbH INNO-TRAIN Diagnostik GmbH Keller Medical GmbH LABCON GmbH Milenia Biotec GmbH mti-diagnostics Gesellschaft für medizin. + techn. Investitionsprojekte mbH NatuTec GmbH R-Biopharm AG RCC Cytotest Cell Research GmbH ScheBo Biotech AG targos molecular pathology GmbH Viro-Immun Labor-Diagnostika GmbH Zedira GmbH

26

Company Profiles

Abbott GmbH & Co. KG

ANALYTICON BIOTECHNOLOGIES AG

Max-Planck-Ring 2 65205 Wiesbaden | Germany T: +49 6122 58 0 F: +49 6122 58 1244 www.abbottdiagnostik.de www.abbottdiagnostics.com

Am Mühlenberg 10 35104 Lichtenfels I Germany T: +49 6454 79 91 35 [email protected] www.analyticon.de Contact: Andreas Busching

Year of Foundation: Number of Employees:

Year of Foundation: Number of Employees:

Core Activities:

Core Activities:

✓ ✓ ✓ ✓

✓ ✓ ✓ ✓

✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓

27

1888 (in Chicago / USA) 4100 (in Germany)

Laboratory Diagnostics Rapid Diagnostic Tests/POCTs Clinical Chemistry Immunochemistry Microbiology/Bacteriology Haematology/Histology/Cytology Infectious Immunology Molecular Biology Analytical Instruments/Testing Equipment Software (Operation, Data Management, Automation) Consumables Manufacturing Research & Development Service Contract Research Sales and Distribution Trainings and Education

✓ ✓ ✓ ✓

✓

1980 87

Laboratory Diagnostics Rapid Diagnostic Tests/POCTs Clinical Chemistry Immunochemistry Microbiology/Bacteriology Haematology/Histology/Cytology Infectious Immunology Molecular Biology Analytical Instruments/Testing Equipment Software (Operation, Data Management, Automation) Consumables Manufacturing Research & Development Service Contract Research Sales and Distribution Trainings and Education

Company Profile:

Company Profile:

Abbott is represented in Germany with locations in Wiesbaden, Ludwigshafen, Wetzlar, and Rangendingen. Approximately 1,700 employees work in Wiesbaden and the executive board for all commercial activities in the fields of pharmaceuticals (AI), lab diagnostics (ADD), blood glucose monitoring (ADC) and nutritionals (ANI) also is located here. Wiesbaden is one of the most important sites worldwide in the field of lab diagnostics. Since headquarters for the entire diagnostics industry in Europe, the Middle East and Africa are here at home, this means that the entire region is serviced by scientific staff from the Wiesbaden hub in marketing, support, regulatory affairs and quality processes. Furthermore, the second largest location worldwide for diagnostics production and development is situated in Wiesbaden. From here, the European logistics centre for diagnostics makes deliveries every day to 140 countries worldwide. German sales in the field of blood glucose monitoring as well as in lab diagnostics are controlled from Wiesbaden. This includes marketing, support and training with regard to products and equipment, as well as scientific support. In the field of nutrition, the medical-scientific division as well as the marketing and sales division may be found in Wiesbaden, where the German logistic centre also is located.

Analyticon® Biotechnologies AG, with currently 87 employees, manufactures diagnostic tests for human medicine at two locations in north Hessen. The company distributes its products via a worldwide network of dealers and branch offices in currently 89 countries. In the first quarter 2008 a subsidiary in the US was established. Analyticon Biotechnologies AG fulfils the requirements of the German law on medical products and the Guidelines of the German Medical Association, also the requirements of the US Food and Drug Administration (FDA) and the Chinese State Food and Drug Administration (SFDA). All products are manufactured in compliance with GMP regulations and DIN EN ISO 13485. The company guarantees complete quality control from development through production to distribution. Analyticon® Biotechnologies AG carries out continual research and development to improve and extend its ivd portfolio and to maintain quality at the highest level. The core competencies of Analyticon® are in the field of quick tests – including point of care tests (POCTs) and self-tests for home use. The proposed biomarkers cover a wide range of clinical uses.

Company Profiles

BAG Health Care GmbH

Biaffin GmbH & Co KG

Amtsgerichtsstr. 1-5 35423 Lich I Germany T: +49 6404 92 50 [email protected] www.bag-healthcare.com

Heinrich-Plett-Str. 40 34132 Kassel I Germany T: +49 561 80 44 662 F: +49 561 80 44 665 [email protected] www.biaffin.de

Contact: Dr. Nicolas Sachsenberg Contact: Dr. Stephan Drewianka

Year of Foundation: Number of Employees:

28

1947 150

Year of Foundation: Number of Employees:

2001 7

Core Activities:

Core Activities:

✓ Laboratory Diagnostics ✓ Rapid Diagnostic Tests/POCTs Clinical Chemistry Immunochemistry ✓ Microbiology/Bacteriology ✓ Haematology/Histology/Cytology ✓ Infectious Immunology ✓ Molecular Biology Analytical Instruments/Testing Equipment Software (Operation, Data Management, Automation) Consumables ✓ Manufacturing ✓ Research & Development Service Contract Research ✓ Sales and Distribution ✓ Trainings and Education

✓ Laboratory Diagnostics Rapid Diagnostic Tests/POCTs Clinical Chemistry ✓ Immunochemistry Microbiology/Bacteriology Haematology/Histology/Cytology Infectious Immunology Molecular Biology Analytical Instruments/Testing Equipment Software (Operation, Data Management, Automation) Consumables Manufacturing ✓ Research & Development ✓ Service ✓ Contract Research ✓ Sales and Distribution Trainings and Education

Company Profile:

Company Profile:

BAG Health Care GmbH is a medium-sized company located at the outskirts of the Rhine-Main area, engaged in the development, production and distribution of in vitro diagnostics and sterilisation indicators. A further company emphasis is on contract manufacturing of pharmaceutical products. BAG GmbH is committed to fair and offensive competition. The qualification, enthusiasm and performance of its staff are decisive factors for the success of BAG. The importance of these factors is reflected in the company’s obligations towards its customers and employees. The company develops, produces and distributes human diagnostics and indicators for the monitoring of sterilisation processes. It also offers contract production of solutions for aseptic filling and, more particularly, for freeze drying.

Biaffin specialises in biomolecular interaction analysis (BIA) with modern SPR biosensors and in applications of BIA technology for customers from the pharmaceutical, biotechnological and diagnostics industries. Biaffin has acquired long experience and expert knowledge in the application of biosensors based on surface plasmon resonance (SPR) and is known as a reliable partner for the performance of biomolecular interaction analyses and functional assays. The range of services offered also includes the performance of phosphorylation assays and the development of medium to high throughput functional in vitro assays. Biaffin's products are bioluminescent assays, recombinant proteins (protein kinases), inhibitors of protein kinases as well as a novel fusion tag technology for combining rapid purification of recombinant proteins with capturing on surfaces for subsequent interaction assays.

Company Profiles

Biohit Deutschland GmbH

BIOTEC-FISCHER GmbH

Raiffeisenstr. 1 61191 Rosbach I Germany T: +49 6003 82 82 15 [email protected] www.biohit.com

Daimlerstr. 6 35447 Reiskirchen I Germany T: +49 6408 60 72 [email protected] www.biotec-fischer.de

Contact: Dipl.-Ing. Uwe Thönges

Contact: Markus Fischer

Year of Foundation: Number of Employees:

Year of Foundation:

1988 10

Core Activities: ✓ Laboratory Diagnostics ✓ Rapid Diagnostic Tests/POCTs ✓ Clinical Chemistry Immunochemistry Microbiology/Bacteriology Haematology/Histology/Cytology Infectious Immunology ✓ Molecular Biology ✓ Analytical Instruments/Testing Equipment Software (Operation, Data Management, Automation) Consumables Manufacturing ✓ Research & Development Service Contract Research ✓ Sales and Distribution Trainings and Education

1974

Core Activities: ✓ Laboratory Diagnostics Rapid Diagnostic Tests/POCTs Clinical Chemistry Immunochemistry Microbiology/Bacteriology ✓ Haematology/Histology/Cytology Infectious Immunology Molecular Biology ✓ Analytical Instruments/Testing Equipment Software (Operation, Data Management, Automation) ✓ Consumables ✓ Manufacturing ✓ Research & Development Service Contract Research ✓ Sales and Distribution ✓ Trainings and Education Company Profile:

Company Profile: Since its foundation in 1988, Biohit has established itself on the global market with innovative high-tech products for liquid handling. During the last ten years the company has invested in the launching of countless new products, new production technologies, automation and quality control. During this process, an extensive international sales and marketing network came into being. Our research and development profited from cooperation with leading researchers at universities and research institutes. In the early nineties, Biohit started out on the development of new diagnostic tests and laboratory appliances for further business areas. Today the company supplies three different top quality product groups – liquid handling products, diagnostic tests and laboratory appliances. Biohit has been certified in accordance with the following international standards: ISO 9001: 2000, Quality System Standard, ISO 13485: 2003, Quality Systems, ivd / Medical Devices, ISO 14001: 2004, Environmental Systems, and IS0 17025, Accreditation of Calibration Laboratory.

29

Company Profiles

BIOTEC-FISCHER GmbH manufactures and distributes products in the fields of densitometry and electrophoresis, together with the chemicals and disposables needed for their use. The company also offers advice and assistance on all problems in connection with these themes. BIOTEC-FISCHER guarantees its customers maximum care in production and quality control. Customers can be confident of receiving only the best high-end products at extremely favourable prices. On top of this, BIOTEC-FISCHER guarantees the simplest possible handling of its products in practical use. BIOTEC-FISCHER has been in the market for over 30 years and has developed into a specialist in electrophoresis.

BIT Analytical Instruments GmbH

CYTO Labor- und Vertriebs-GmbH

Am Kronberger Hang 3 65824 Schwalbach I Germany T: +49 6196 80 61 01 [email protected] www.BIT-Instruments.com

Ortsstr. 22 35423 Ober-Bessingen (Lich) I Germany T: +49 6404 90 43 7 [email protected] www.cytolabor.de

Contact: Dipl.-Ing. Alfred Lang

Contact: Inka Petzelt

Year of Foundation: Number of Employees:

Year of Foundation: Number of Employees:

Core Activities:

Core Activities:

✓ ✓ ✓ ✓

✓ ✓ ✓ ✓

✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓

30

1977 130

Laboratory Diagnostics Rapid Diagnostic Tests/POCTs Clinical Chemistry Immunochemistry Microbiology/Bacteriology Haematology/Histology/Cytology Infectious Immunology Molecular Biology Analytical Instruments/Testing Equipment Software (Operation, Data Management, Automation) Consumables Manufacturing Research & Development Service Contract Research Sales and Distribution Trainings and Education

✓ ✓ ✓ ✓ ✓ ✓ ✓

1982 6

Laboratory Diagnostics Rapid Diagnostic Tests/POCTs Clinical Chemistry Immunochemistry Microbiology/Bacteriology Haematology/Histology/Cytology Infectious Immunology Molecular Biology Analytical Instruments/Testing Equipment Software (Operation, Data Management, Automation) Consumables Manufacturing Research & Development Service Contract Research Sales and Distribution Trainings and Education

Company Profile:

Company Profile:

BIT Analytical Instruments offers all-round services in contract development and manufacturing, also aftersales service for appliances used by OEMs in the medical, diagnostic and industrial sectors. The company is an independent market leader in Europe for high-end ivd analytical instruments in the high-end OEM market. BIT’s core competencies: · Individual contract manufacturing of medium to highly complex instrumentations, assemblies and custom-built production facilities. · One Stop Solution – a partner for your product development, manufacturing and after-sales service. Always with the highest quality standards according to ISO13485 / ISO 9001, FDA-compliant.

Since 1982, CYTO Labor- und Vertriebs GmbH has been providing in vitro diagnostics for the analysis of immune reactions to foods. The managing directors Dina and Hartmut Tulaszewski see their company primarily as an institute for clinical nutritional therapy, with nutritional counselling as one of the main pillars of its range of services. From the very outset, the company’s diagnostics have been aimed at advising and assisting persons who wish to alter their eating habits or are forced by illness to adapt their diet. With its Cytolisa® test, the company was the first on the German market to provide a blood test for analysing IgG-mediated immune reactions to food antigens. Since the end of 2005, the company has been certified in accordance with DIN EN ISO 9001 and DIN EN ISO 13485 for “production, development and distribution of in vitro diagnostics”. The company is based in Lich/OberBessingen in Hessen, 60 km north of Frankfurt.

Company Profiles

Dade Behring Marburg GmbH A Siemens Company

DiaSorin Deutschland GmbH

Emil-von-Behring-Str. 76 35041 Marburg I Germany T: +49 6421 39 13 F: +49 6421 66064 www.siemens.com/diagnostics

Von-Hevesy-Str. 3 63128 Dietzenbach I Germany Phone +49 6074 401 0 Fax +49 6074 401 209 [email protected] www.DiaSorin.com Contact: Dr. Thorsten Hilbich

Core Activities: ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓

Laboratory Diagnostics Rapid Diagnostic Tests/POCTs Clinical Chemistry Immunochemistry Microbiology/Bacteriology Haematology/Histology/Cytology Infectious Immunology Molecular Biology Analytical Instruments/Testing Equipment Software (Operation, Data Management, Automation) Consumables Manufacturing Research & Development Service Contract Research ✓ Sales and Distribution Trainings and Education Company Profile: Dade Behring Marburg GmbH with its locations in Marburg, Schwalbach, and Duisburg became part of Siemens Healthcare Diagnostics in November 2007. At these locations, the approximately 1,200 employees of the company produce top-quality diagnostic systems and reagents for clotting, infection and plasma protein testing and ensure prompt delivery to customers. Siemens Healthcare Diagnostics, one of the leading in-vitro diagnostics in the world, is committed to providing clinicians with the vital information they need for the accurate diagnosis, treatment and monitoring of patients. Our comprehensive portfolio of performancedriven systems, unmatched menu offering, and IT solutions, in conjunction with highly responsive service, is designed to streamline workflow, enhance operational efficiency and support improved patient care. Siemens Healthcare Diagnostics employs more than 14,000 people worldwide and operates in over 110 countries. In the fiscal year 2007 (Sept. 30), Siemens Healthcare Diagnostics reported sales of €3.3 billion. The products of Dade Behring Marburg GmbH include a broad range of diagnostic systems for immunoassays, chemistry, hematology, molecular biology, urinalysis, diabetes, blood gas, clotting, plasma proteins and infection testing as well as automation, IT and consulting solutions to meet the demands of laboratories of all sizes.

31

Company Profiles

Year of Foundation: Number of Employees:

2001 121

Core Activities: ✓ Laboratory Diagnostics Rapid Diagnostic Tests/POCTs Clinical Chemistry ✓ Immunochemistry Microbiology/Bacteriology Haematology/Histology/Cytology ✓ Infectious Immunology Molecular Biology ✓ Analytical Instruments/Testing Equipment Software (Operation, Data Management, Automation) ✓ Consumables ✓ Manufacturing ✓ Research & Development ✓ Service Contract Research ✓ Sales and Distribution Trainings and Education Company Profile: DiaSorin is the embodiment of a tradition of growth and excellence focused on the improvement of human health. The DiaSorin Group develops, produces, and distributes immunoreagent kits for clinical diagnostics. Thanks to its well-established expertise, specifically in the immunodiagnostics market, DiaSorin has become “the” in vitro diagnostics specialist. Over the years, by making available to the medical profession tests that can provide optimum guidance for reaching clinical decisions, DiaSorin has contributed to improving the provision of health care and reducing its cost. In Germany the Group operates a production facility in Dietzenbach.

Döll + Co. Medizintechnik GmbH

DRG Instruments GmbH

Im Langgewann 7 65719 Hofheim I Germany T: +49 6192 20 90 30 F: +49 6192 20 90 35 [email protected] www.doell-med.de

Frauenbergstr. 18 35039 Marburg I Germany T: +49 6421 17 00 0 [email protected] www.drg-diagnostics.de Contact: Wilhelm Sänger

Contact: Christa Schleich

Year of Foundation: Number of Employees:

1961 50

Year of Foundation: Number of Employees:

1973 41

Core Activities:

Core Activities:

✓ Laboratory Diagnostics ✓ Rapid Diagnostic Tests/POCTs ✓ Clinical Chemistry Immunochemistry ✓ Microbiology/Bacteriology ✓ Haematology/Histology/Cytology Infectious Immunology Molecular Biology ✓ Analytical Instruments/Testing Equipment ✓ Software (Operation, Data Management, Automation) ✓ Consumables Manufacturing Research & Development ✓ Service Contract Research ✓ Sales and Distribution Trainings and Education

✓ Laboratory Diagnostics ✓ Rapid Diagnostic Tests/POCTs Clinical Chemistry ✓ Immunochemistry Microbiology/Bacteriology Haematology/Histology/Cytology ✓ Infectious Immunology Molecular Biology Analytical Instruments/Testing Equipment Software (Operation, Data Management, Automation) Consumables ✓ Manufacturing ✓ Research & Development Service ✓ Contract Research ✓ Sales and Distribution Trainings and Education Company Profile: DRG, founded in 1973, is specialized in the development, production and global distribution of ELISA and RIA test kits, principally for clinical diagnostics and research. In our production facilities, high-quality and economical products are developed in adaptable formats – OEM included – which can be fully tailored to individual customer or market requirements. A complete line of laboratory instruments and equipment is also provided. Products include ELISAs such as Hepcidin, Estrone, DHEA, Corticosterone, PLGF, the tumour markers CA 72-4, CA 125, CA 19-9, CA 15-3, CYFRA 21-1, Saliva diagnostics and Chemiluminescence assays.

32

Company Profiles

Elté Sensoric GmbH

Genzyme Virotech GmbH

Wilhelm-Schöffer-Str. 33 63571 Gelnhausen I Germany T: +49 173 94 39 33 5 [email protected]

Löwenplatz 5 65428 Rüsselsheim I Germany T: +49 6142 69 09-0 [email protected] www.virotech.de

Contact: Dr. Andreas Haenel Contact: Dr. Klaus Ackermann

Year of Foundation:

2003

Core Activities: ✓ Laboratory Diagnostics ✓ Rapid Diagnostic Tests/POCTs Clinical Chemistry Immunochemistry Microbiology/Bacteriology Haematology/Histology/Cytology Infectious Immunology Molecular Biology ✓ Analytical Instruments/Testing Equipment Software (Operation, Data Management, Automation) Consumables Manufacturing ✓ Research & Development Service Contract Research Sales and Distribution Trainings and Education

Year of Foundation: Number of Employees:

1986 130

Core Activities: ✓ Laboratory Diagnostics ✓ Rapid Diagnostic Tests/POCTs Clinical Chemistry Immunochemistry ✓ Microbiology/Bacteriology Haematology/Histology/Cytology ✓ Infectious Immunology ✓ Molecular Biology ✓ Analytical Instruments/Testing Equipment ✓ Software (Operation, Data Management, Automation) Consumables ✓ Manufacturing ✓ Research & Development ✓ Service ✓ Contract Research ✓ Sales and Distribution ✓ Trainings and Education Company Profile: Genzyme Virotech develops, produces and distributes medical diagnostic products. Since the foundation (1986) the product range has continuously been extended and new product lines have been added. We interact the co-operation with universities and research institutes and continuously invest in the product development and improvement. Our 100 qualified employees are anxious to always provide customers with a high product quality and excellent service. With more than 50 distributors we distribute our own products worldwide. For the German market we are exclusive distributors for a broad number of immunological and microbiological detection systems that we purchase from international companies. Our growth strategy is to enter new co-operations, to be able to increase research, development and sales and to fill existing gaps of our portfolio. Furthermore we are interested in new technologies and product lines that might be interesting for the German respectively the international market. We currently search/offer co-operations in the field of research, development, contract manufacturing, distribution of new dia- gnostic and microbiological products and technologies. A corresponding certification in accordance with DIN EN ISO 9001: 1994 was already awarded in 1998.

33

Company Profiles

HUMATRIX AG

Immucor Medizinische Diagnostik GmbH

Carl-Benz-Str. 21 60386 Frankfurt/Main I Germany T: +49 69 42 08 86 16 [email protected] www.humatrix.de Contact: Tobias Gerlinger

Adam-Opel-Str. 26a 63322 Rödermark I Germany T: +49 6074 84 20 26 [email protected] www.immucor.com Contact: Heidi Sommer

Year of Foundation: Number of Employees:

34

2001 8

Year of Foundation: Number of Employees:

1982 53

Core Activities:

Core Activities:

✓ Laboratory Diagnostics Rapid Diagnostic Tests/POCTs Clinical Chemistry Immunochemistry Microbiology/Bacteriology Haematology/Histology/Cytology Infectious Immunology ✓ Molecular Biology Analytical Instruments/Testing Equipment Software (Operation, Data Management, Automation) Consumables Manufacturing Research & Development ✓ Service Contract Research ✓ Sales and Distribution Trainings and Education

✓ Laboratory Diagnostics Rapid Diagnostic Tests/POCTs Clinical Chemistry Immunochemistry Microbiology/Bacteriology ✓ Haematology/Histology/Cytology Infectious Immunology Molecular Biology ✓ Analytical Instruments/Testing Equipment Software (Operation, Data Management, Automation) ✓ Consumables ✓ Manufacturing ✓ Research & Development ✓ Service Contract Research ✓ Sales and Distribution ✓ Trainings and Education

Company Profile:

Company Profile:

humatrix AG is a biotech company in Frankfurt specializing in analyses of human DNA. Founded in February 2001 by four young scientists and a young entrepreneur, it is the first public listed company to offer products throughout Germany for the analysis and determination of paternity tests and ancestry determinations for both private and judicial purposes. A high-precision method testing up to 50 identifying characteristics (or “loci”) guarantees as a rule up to 99.9999% certainty for the customers of humatrix AG. The product range of humatrix AG also includes a newborn screening for several health risks (Lactose-Intolerance, Gluten-Intolerance, Multidrug-Resistance, Antibiotics-Intolerance and AAT-deficiency), risk assessments for genetically induced diseases (Parodontitis, Osteoporosis, Hemochromatosis etc.), identifications of DNA fingerprints, e.g. of suspects or victims, or for bone marrow donor databases, etc.

Immucor is a global in vitro diagnostics company specializing in the area of pre-transfusion diagnostics. The company develops, manufactures, and sells products used by hospital blood banks, clinical laboratories, and blood donor centers to detect and identify certain properties of human blood prior to patient transfusion. Immucor has revolutionized the industry through our dedication to automating manual processes in the blood bank laboratory. The German subsidiary – Immucor Medizinische Diagnostik GmbH – is located in Rödermark.

Company Profiles

IMMUNDIAGNOSTIK AG

Immunodiagnostic Systems (IDS) GmbH

Stubenwaldallee 8a 64625 Bensheim I Germany [email protected] www.immundiagnostik.com

Mainzer Landstr. 49 60329 Frankfurt/Main I Germany T: +49 69 30 85 50 25 [email protected] www.ids-de.com

Contact: Dr. F. P. Armbruster Contact: Anke Snethkamp

Year of Foundation: Number of Employees:

35

1986 50

Year of Foundation: Number of Employees:

1977 8

Core Activities:

Core Activities:

✓ Laboratory Diagnostics Rapid Diagnostic Tests/POCTs ✓ Clinical Chemistry ✓ Immunochemistry Microbiology/Bacteriology Haematology/Histology/Cytology Infectious Immunology ✓ Molecular Biology Analytical Instruments/Testing Equipment Software (Operation, Data Management, Automation) Consumables ✓ Manufacturing ✓ Research & Development Service Contract Research ✓ Sales and Distribution Trainings and Education

✓ Laboratory Diagnostics Rapid Diagnostic Tests/POCTs ✓ Clinical Chemistry Immunochemistry Microbiology/Bacteriology Haematology/Histology/Cytology Infectious Immunology Molecular Biology ✓ Analytical Instruments/Testing Equipment Software (Operation, Data Management, Automation) Consumables ✓ Manufacturing ✓ Research & Development Service Contract Research ✓ Sales and Distribution Trainings and Education

Company Profile:

Company Profile:

Immundiagnostik specialises in developing and producing detection methods for use in the laboratory and in medical research. Our main customers are involved in routine clinical diagnostics in hospitals and private laboratories, as well as in pharmaceutical companies and in basic clinical research. The company maintains an active R & D programme and continuously develops new and innovative assays. The product range has recently been extended by a range of new enzyme immunoassays for stool diagnostics and the production of our own polyclonal and monoclonal antibodies. We hold a continuously expanding portfolio of products addressing major disease areas as well as highly specialised niche markets. Our core activities include calcium and bone metabolism, cardiovascular and renal systems, oxidative stress and gastroenterology. In addition, we provide kits for HPLC applications and molecular biology (PCR). Parameters of special interest: 25-OH-Vitamin D3, OPG, total sRANKL, BSP, ADMA, oxLDL, RBP4, Calprotectin, Norovirus, and Thymus Peptides.

Immunodiagnostic Systems Limited (IDS) is an innovative, dynamic biotech company specializing in the development and provision of high-end assays for clinical and research purposes worldwide. The company is represented in Germany by a branch office in Frankfurt am Main. Increasingly exacting requirements in the laboratory landscape call for constant improvements in efficiency, quality, costs and clinical differentiation. These factors are the key to optimum patient care, therapies and disease management. With these aims in mind, IDS has developed a special robot system with its own panel for the fields of bone metabolism, growth and high blood pressure. The panel comprises 25-hydroxy vitamin D, intact and bioactive PTH, BAP, osteocalcin, CTX-I, HGH, IGF-I, IGFBP-3, renin and aldosteron. IDS works together with opinion leaders throughout the world to optimize the panel with highly specific nextgeneration disease markers.

Company Profiles

Immunolab GmbH

INNO-TRAIN Diagnostik GmbH

Otto-Hahn-Str. 16 34123 Kassel I Germany T: +49 561 49 17 42 0 [email protected] www.immunolab.de

Niederhöchstädter Str. 62 61476 Kronberg I Germany T: +49 6173 60 79 30 F: +49 6173 60 79 50 [email protected] www.inno-train.de

Contact: Dr. Hans J. Jacobsen Contact: Dr. Rainer Frank

Year of Foundation: Number of Employees:

36

1992 21

Year of Foundation: Number of Employees:

1998 22

Core Activities:

Core Activities:

✓ Laboratory Diagnostics ✓ Rapid Diagnostic Tests/POCTs Clinical Chemistry ✓ Immunochemistry ✓ Microbiology/Bacteriology Haematology/Histology/Cytology ✓ Infectious Immunology Molecular Biology ✓ Analytical Instruments/Testing Equipment ✓ Software (Operation, Data Management, Automation) Consumables ✓ Manufacturing ✓ Research & Development Service ✓ Contract Research ✓ Sales and Distribution Trainings and Education

✓ Laboratory Diagnostics Rapid Diagnostic Tests/POCTs Clinical Chemistry ✓ Immunochemistry Microbiology/Bacteriology ✓ Haematology/Histology/Cytology Infectious Immunology ✓ Molecular Biology ✓ Analytical Instruments/Testing Equipment ✓ Software (Operation, Data Management, Automation) ✓ Consumables ✓ Manufacturing ✓ Research & Development ✓ Service Contract Research ✓ Sales and Distribution ✓ Trainings and Education

Company Profile:

Company Profile:

Immunolab GmbH was founded in February 1992 in Kassel as routine laboratory closely associated with the immune diagnostics producer MELJA. The company possesses the legally required authorizations for import and export, handling of radioactive materials in compliance with the German law on medical products. Immunolab manufactures immunological test kits for applications in the food, environmental and medical sectors. The company operations are concentrated primarily on producing immune diagnostic test kits to determine antibodies (IgG, IgA, IgM and IgE) against a number of diseasetriggering substances, antigens and allergens. In the food testing field, Immunolab supplies a range of ELISA kits, including histamine, aflatoxins, gliadin, listeria and chloramphenicol. These parameters are determined in many different matrices (meat, fruit juices, nuts, cereals, vitamin tablets, milk).

Inno-Train Diagnostik GmbH is a company set up in Frankfurt am Main in 1998, with its head offices in Kronberg/Taunus. Its range includes self-produced goods, distribution products and laboratory services. Inno-Train Diagnostik GmbH engages in international competition with the aim of integrating new, innovative products into the trade with goods in the areas of transfusion medicine and immune haematology. Its product range includes diagnostics and detection systems for specific analyses at genome level, together with HLA diagnostic products. International contacts enable the InnoTrain team to present its products worldwide and at the same time to establish foreign products on the German market. As the company name suggests, Inno-Train Diagnostik GmbH is a competent partner in the area of training and consultancy. It offers long-term assistance on DNA technologies in the form of consultancy contracts, or on-site training courses over periods of several days.

Company Profiles

Keller Medical GmbH

LABCON GmbH

Wiesbadener Weg 2a 65812 Bad Soden I Germany T: +49 6196 76 46 51 5 [email protected] www.keller-medical.de

Benzstr. 4 64646 Heppenheim I Germany T: +49 6252 94 2510 [email protected] www.labcon.de

Contact: Isabell Henke

Contact: Dipl.Ing. Albert Sax

Year of Foundation: Number of Employees:

2003 10

Core Activities: ✓ ✓

✓

✓ ✓ ✓

✓ ✓ ✓

Laboratory Diagnostics Rapid Diagnostic Tests/POCTs Clinical Chemistry Immunochemistry Microbiology/Bacteriology Haematology/Histology/Cytology Infectious Immunology Molecular Biology Analytical Instruments/Testing Equipment Software (Operation, Data Management, Automation) Consumables Manufacturing Research & Development Service Contract Research Sales and Distribution Trainings and Education

Company Profile: Keller Medical is a partner for intelligent point-of-care solutions. The company offers solutions for independent measurements in all matters concerning blood gases, electrolytes, coagulation and cardiac markers, using high-performance, maintenance-free appliances. Keller Medical was started up in 2003 as an exclusive distribution partner in Germany for the formerly Linde Medical Sensors AG. The company established itself rapidly as a competent partner for transcutaneous blood gas measurement. Keller Medical was equally quick in adding point-ofcare tests (POCT) to its product portfolio and making them an important second mainstay of the company. The company sees itself as a competent partner for its customers, offering them flexible solutions with innovative products and a wide range of services. Keller Medical also understands itself as a competent, partner-like mediator between clinics and manufacturers for the benefit of patients at the POC.

37

Company Profiles

Year of Foundation: Number of Employees:

1996 6

Core Activities: ✓ Laboratory Diagnostics Rapid Diagnostic Tests/POCTs ✓ Clinical Chemistry ✓ Immunochemistry Microbiology/Bacteriology ✓ Haematology/Histology/Cytology Infectious Immunology Molecular Biology ✓ Analytical Instruments/Testing Equipment Software (Operation, Data Management, Automation) ✓ Consumables Manufacturing Research & Development ✓ Service Contract Research ✓ Sales and Distribution Trainings and Education .

Milenia Biotec GmbH

mti-diagnostics Gesellschaft für medizin. + techn. Investitionsprojekte mbH

Versailler Str. 1 35394 Giessen I Germany T: +49 641 94 888 3-0 F: +49 641 94 888 3-80 [email protected] www.milenia-biotec.de

Oberemser Str. 15 65510 Idstein I Germany T: +49 6082 93 05 02 1 [email protected] www.mti-diagnostics.de Contact: Robert Dinges

Contact: Dr. Ralf Dostatni

Year of Foundation: Number of Employees:

38

2000 10

Year of Foundation: Number of Employees:

1999 11

Core Activities:

Core Activities:

Laboratory Diagnostics ✓ Rapid Diagnostic Tests/POCTs Clinical Chemistry ✓ Immunochemistry Microbiology/Bacteriology Haematology/Histology/Cytology Infectious Immunology Molecular Biology ✓ Analytical Instruments/Testing Equipment Software (Operation, Data Management, Automation) Consumables ✓ Manufacturing ✓ Research & Development ✓ Service ✓ Contract Research ✓ Sales and Distribution Trainings and Education

✓ ✓ ✓ ✓

Company Profile:

Company Profile:

Milenia Biotec GmbH develops, produces and markets immune diagnostics worldwide. The company was founded in 2000 as a spin-off from DPC Biermann GmbH in Bad Nauheim. Its core products are point-of-care tests for diagnosing allergies and infections and measuring immune mediators. The company markets its products in Germany through a qualified field staff and abroad via independent distributors.

mti-diagnostics Gesellschaft für medizin. + techn. Investitionsprojekte mbH is a small, highly innovative entrepreneur network which, in addition to producing standard and system reagents (complete with barcode and ready for use) in the field of clinical chemistry, also engages in the development of new reagents, tailored to customer requirements and made available in the shortest possible time. The resulting test kits are packaged, labelled and designed in accordance with customer wishes. mti-diagnostics is also a specialist for cleaning, rinsing, separating and disinfection solutions for automated analytical systems, pipetting robots and the cell culture facilities in the laboratory. One year ago, reagents for foodstuffs and wine laboratories were added to the company’s core competence. mti-diagnostics has developed a series of new tests for this area.

Company Profiles

✓ ✓ ✓ ✓

Laboratory Diagnostics Rapid Diagnostic Tests/POCTs Clinical Chemistry Immunochemistry Microbiology/Bacteriology Haematology/Histology/Cytology Infectious Immunology Molecular Biology Analytical Instruments/Testing Equipment Software (Operation, Data Management, Automation) Consumables Manufacturing Research & Development Service Contract Research Sales and Distribution Trainings and Education

NatuTec GmbH

R-Biopharm AG

Königslacher Str. 15-21 60528 Frankfurt/Main I Germany T: +49 69 67 73 78 0 [email protected] www.natutec.de

Landwehrstr. 54 64297 Darmstadt I Germany T: +49 6151 81 02 11 [email protected] www.r-biopharm.de

Contact: Eva-Brigitte León

Contact: Ralf Dreher

Year of Foundation: Number of Employees:

39

1993 10

Year of Foundation: Number of Employees:

1988 180

Core Activities:

Core Activities:

✓ Laboratory Diagnostics Rapid Diagnostic Tests/POCTs Clinical Chemistry ✓ Immunochemistry ✓ Microbiology/Bacteriology ✓ Haematology/Histology/Cytology ✓ Infectious Immunology ✓ Molecular Biology✓ Analytical Instruments/Testing Equipment Software (Operation, Data Management, Automation) ✓ Consumables Manufacturing Research & Development Service Contract Research ✓ Sales and Distribution Trainings and Education

✓ Laboratory Diagnostics Rapid Diagnostic Tests/POCTs Clinical Chemistry ✓ Immunochemistry ✓ Microbiology/Bacteriology Haematology/Histology/Cytology ✓ Infectious Immunology Molecular Biology Analytical Instruments/Testing Equipment Software (Operation, Data Management, Automation) Consumables ✓ Manufacturing ✓ Research & Development Service Contract Research ✓ Sales and Distribution Trainings and Education

Company Profile:

Company Profile:

NatuTec GmbH is a young German company, founded in 1994, with its head office in Frankfurt am Main. The company supplies a wide range of high-end quality reagents for scientists in the fields of immunology and molecular biology, metabolism and cell biology. A constantly expanding product range ensures plenty of dynamism and promotes the development of completely new and innovative products at NatuTec.

R-Biopharm AG develops pioneering solutions in the areas of clinical diagnostics and food and animal feed analysis. The company was founded in 1988 as a subsidiary of Röhm GmbH in Darmstadt and is certified in accordance with DIN EN ISO 9001 and quality management standard ISO 13485. In clinical diagnostics, R-Biopharm possesses many years of sound and proven experience not only in the area of infectiological stool evaluation but also in serological infection diagnostics and allergies. The company also supplies innovative tests for tumour diagnostics and gastroenterology. Since January 2000, R-Biopharm AG has held worldwide exclusive distribution rights for the Enzymatic BioAnalysis of Roche Diagnostics. The acquisition of Rhône Diagnostics Technologies in Scotland in 2002 enabled the company to expand its position in the field of food and animal feed analysis. This field now comprises products with widely acknowledged immunological, enzymatic and microbiological test kits for the detection of residues, ingredients or microbiological contaminations.

Company Profiles

RCC Cytotest Cell Research GmbH

ScheBo Biotech AG

In den Leppsteinswiesen 19 64380 Roßdorf I Germany T: +49 6154 80 72 11 [email protected] www.rcc.ch www.rcc-ccr.de

Netanyastr. 3 35394 Gießen I Germany T: +49 641 49 96 0 [email protected] www.schebo.com Contact: Dr. Ursula Scheefers-Borchel

Contact: Dr. Völkner

Year of Foundation: Number of Employees:

40

1986 138

Year of Foundation: Number of Employees:

1989 33

Core Activities:

Core Activities:

Laboratory Diagnostics Rapid Diagnostic Tests/POCTs Clinical Chemistry Immunochemistry Microbiology/Bacteriology Haematology/Histology/Cytology Infectious Immunology Molecular Biology Analytical Instruments/Testing Equipment Software (Operation, Data Management, Automation) Consumables Manufacturing Research & Development Service ✓ Contract Research Sales and Distribution Trainings and Education

✓ Laboratory Diagnostics ✓ Rapid Diagnostic Tests/POCTs Clinical Chemistry ✓ Immunochemistry Microbiology/Bacteriology Haematology/Histology/Cytology Infectious Immunology Molecular Biology Analytical Instruments/Testing Equipment Software (Operation, Data Management, Automation) ✓ Consumables ✓ Manufacturing ✓ Research & Development Service Contract Research ✓ Sales and Distribution Trainings and Education

Company Profile:

Company Profile:

RCC Cytotest Cell Research GmbH, ever since its foundation in 1986, has provided contract research work in the areas of genetic toxicology, cell biology and biocompatibility testing. The institute, an operational unit for Genetic Toxicology and Cell Biology, belongs to the Research and Consulting Company Ltd (RCC), based in Itingen/ Basel (Switzerland). It originated from the Laboratory for Mutagenicity Testing (LMP) of the Technical University in Darmstadt, which was set up as the first laboratory of this kind in Germany in 1981. RCC Cytotest Cell Research GmbH has certifications for GLP (since 1986) and GMP (2008).

ScheBo®• Biotech AG, founded in 1989, is a biotech company specializing in the development, production and marketing of in vitro diagnostics and the business areas of active substance research and drug development. All products possess high innovation potential and were developed with a view to market requirements. The company was founded by the molecular biologists and biochemists Dr. Ursula Scheefers-Borchel and Dr. Hans Scheefers. ScheBo®• Biotech AG operates distributor companies in the USA (ScheBo®• Biotech AG USA, Inc.) and England (ScheBo®• Biotech UK Ltd). The company is independently managed and keyed to both national and international markets. All products have unique USPs in the field of clinical diagnostics. Consistent orientation to R&D activities, constant optimization of production processes and close focus on market requirements form the basis for successful launching and marketing of a wide range of innovative products. .

Company Profiles

targos molecular pathology GmbH

Viro-Immun Labor-Diagnostika GmbH

Mönchebergstr. 41-43 34125 Kassel I Germany T: +49 561 98 04 10 0 [email protected] www.targos-gmbh.de

In der Au 29 61440 Oberursel I Germany T: +49 6171 62 81-00 F: +49 6171 62 81-12 [email protected] www.viro-immun.de

Contact: Dr. Thomas Henkel Contact: Alexander Bücker-Flürenbrock

Year of Foundation: Number of Employees:

2005 35

Core Activities: ✓ Laboratory Diagnostics Rapid Diagnostic Tests/POCTs Clinical Chemistry ✓ Immunochemistry Microbiology/Bacteriology ✓ Haematology/Histology/Cytology Infectious Immunology ✓ Molecular Biology Analytical Instruments/Testing Equipment Software (Operation, Data Management, Automation) Consumables Manufacturing ✓ Research & Development ✓ Service ✓ Contract Research Sales and Distribution ✓ Trainings and Education

Year of Foundation:

1985

Core Activities: ✓ Laboratory Diagnostics Rapid Diagnostic Tests/POCTs Clinical Chemistry ✓ Immunochemistry ✓ Microbiology/Bacteriology Haematology/Histology/Cytology ✓ Infectious Immunology Molecular Biology Analytical Instruments/Testing Equipment Software (Operation, Data Management, Automation) Consumables ✓ Manufacturing ✓ Research & Development Service Contract Research ✓ Sales and Distribution Trainings and Education Company Profile:

Company Profile: targos molecular pathology GmbH was founded in 2005 to meet the increasing need for standardized analyses in the area of clinical biomarkers. The company cooperates with many international pharmaceutical and diagnostics companies to undertake, for instance, patient selection on the basis of existing predictive biomarkers in clinical studies with new, targeted oncological therapies. A further goal of targos is to establish new predictive biomarkers for the identification of suitable patients for specific therapies. Since this service was introduced, more than 40,000 patient samples from 60 countries and 700 clinical centres have been tested. One of the largest clinical studies supervised by targos was the HERA study with more than 10,000 patients to investigate herceptin in the adjuvant treatment of mamma carcinoma. The company is currently supervising 30 studies in which a wide variety of targeted therapies are being investigated in seven different tumour indications. At the present time, the company has a staff of 38 and is collaborating closely with the private institution Pathologie Nordhessen in Kassel and the Institute of Pathology of the University of Bonn.

41

Company Profiles

Viro-Immun Labor-Diagnostika GmbH is the diagnostic specialist for infectious and autoimmune diseases within Biotest Group and one of the leading international producers of ELISAs, IFAs and Western Blot kits. We develop and produce diagnostics for the serological diagnosis of viral, bacterial and mycotic infections and autoimmune diseases. Key to our success for over 20 years is the proprietary production of antigens, conjugates and other criticial reagents combined with the utmost adaption of our kits to specific customer/distributor/OEM specifications.

Zedira GmbH Roesslerstr. 83 64293 Darmstadt I Germany T: +49 6151 32 51 10 F: +49 6151 32 51 19 [email protected] www.zedira.com Contact: Dr. Martin Hils

Year of Foundation: Number of Employees:

2007 15

Core Activities:: ✓ Laboratory Diagnostics Rapid Diagnostic Tests/POCTs Clinical Chemistry ✓ Immunochemistry Microbiology/Bacteriology Haematology/Histology/Cytology Infectious Immunology ✓ Molecular Biology Analytical Instruments/Testing Equipment Software (Operation, Data Management, Automation) Consumables ✓ Manufacturing ✓ Research & Development Service Contract Research ✓ Sales and Distribution Trainings and Education Company Profile: Zedira has made a commitment to Celiac Disease and Transglutaminase. Our approach to the disorder is multifaceted. Research & Development: In order to assist investigators studying Celiac Disease and other Transglutaminase related physiological processes and disorders, Zedira offers a unique portfolio of specialty reagents for basic research and development. Diagnosis: About 1% of the population is affected by Celiac Disease. Unfortunately, only about one out of ten of these individuals is aware of suffering from the autoimmun disease, which if undiagnosed can lead to serious medical complications. In co-operation with leading European scientists Zedira has succeeded in identifying a new marker (Neuronal Transglutaminase, TG6) for Celiac Disease which can be used to detect neurological disorders caused by gluten. Further, Zedira produces standard antigens for Celiac Disease diagnostics (TG2, TG3, gliadin peptides etc.) Therapy: At present, Celiac Disease cannot be treated by pharmacological intervention. The only treatment available to patients is strict adherence to a gluten-free diet. For that reason Zedira develops a drug to treat Celiac Disease.

42

Company Profiles

www.hessen-biotech.de

Executing organisation of Hessen-Biotech, a project of the Hessian Ministry of Economics, Transport, Urban and Regional Development