In Vitro Diagnostics

Transcription

1 REVIEW 316/2015 In Vitro Diagnostics a Finnish Success Story A Review of the Finnish IVD Industry Development and Their Success in the Global Market Dr Paul Mundill

2 Tekes the Finnish Funding Agency for Innovation Tekes is the most important publicly funded expert organisation for financing research, development and innovation in Finland. We boost wide-ranging innovation activities in research communities, industry and service sectors. Tekes works with the top innovative companies and research units in Finland. Every year, Tekes finances some 1,500 business research and development projects, and almost 600 public research projects at universities, research institutes and universities of applied sciences. Copyright Tekes All rights reserved. This publication includes materials protected under copyright law, the copyright for which is held by Tekes or a third party. The materials appearing in publications may not be used for commercial purposes. The contents of publications are the opinion of the writers and do not represent the official position of Tekes. Tekes bears no responsibility for any possible damages arising from their use. The original source must be mentioned when quoting from the materials. ISSN ISBN Cover image: Tekes Page layout: Reflex Oy 2

3 Dr Paul Mundill In Vitro Diagnostics a Finnish Success Story Tekes Review 316/2015 Helsinki

4 Table of Contents Foreword... 5 In Vitro Diagnostics success through cooperation... 6 First immunoassay starts a new industry... 8 The first products evolve...9 Regulation in line with pharmaceuticals Towards personalised healthcare...10 Changing landscape Rapidly growing market...12 The Finnish IVD industry...13 Convergence on rapid tests & point-of-care...15 Tenacity and agility...15 Example: commercialising time resolved fluorescence...16 Turku IVD cluster is born...16 Strength in diversity...17 Innovation combined with existing technology...19 Finnish IVD industry looking forward Value chain drivers Strong B2B partnerships required...21 Bio-IT fusion Technology development through national initiatives and clusters Towards a more holistic view of development...24 Change gathers speed Business Cases Wallac Oy Abacus Diagnostica Oy Orion Diagnostica Oy SalWe Ltd Medix Biochemica Thermo Fisher University of Turku Author background & Abbreviations Tekes Reviews in English

5 Foreword Tekes has launched a series of studies describing how certain key technologies, competencies or basic scientific observations evolve into competitive businesses. The first of these development path reports was published in The previous reports have focused on business sectors like RFID technology, propulsors, software development, renewable diesel, enzymes, game industry and meteorological services. The development paths also illustrate the impact of Tekes innovation funding and services. The selected business sectors have been at the core of Tekes development programmes, with launches even to international markets revealing significant business potential. The entire set of studies build an intriguing picture not only of general industry trends, but also of the challenges and successes encountered by a supporting governmental entity. Everything starts from competitive advantage, but it is not enough. Competitive advantages must be translated into international success during the process of innovation. Achieving a strong competitive position has taken anything from a few years to decades. In hindsight, the successes have been the result of long-term hard work and a clear strategic vision. Typically the writers of these reports have personally been involved in the business sector in question. Development paths are described as they, active in the field, have seen it as insiders. The writer has selected the most relevant findings along the development path. This review is based on the development of in vitro diagnostics industry. The author, Dr Paul Mundill, has over 30 years of experience in the IVD industry and has interviewed several representatives of IVD sector for this review. Innovation policy goals have been realized in several ways in the IVD sector. It has been guided by usability and user experience in the global value networks. Sophisticated skills have supported the success in diverse innovation activities. Tekes funding has been targeted at forerunners aiming for significant renewal. Foreign companies with their sights on Finland were welcomed to collaborate with the Finnish innovation, organizational and business systems. These focuses are still valid today in the IVD sector. Tekes warmly thanks Dr Paul Mundill for his contribution. February

6 In Vitro Diagnostics Success Through Cooperation In the past ten years the diagnostics sector has been an exceptional success story in Finland, thanks to the strengths of the Finnish in vitro diagnostics industry in both equipments and reagents. Lately, the growth of the diagnostics exports has mainly relied on growth of reagent sales (11% in 2013), the export of equipments having stayed rather stable. In 2013, the diagnostics export totalled 411 million euros, about half of which was based on reagents and another half on equipments. In vitro diagnostics sector is part of the health technology industry, which currently is the largest and most important export sector of Finnish high technology. It accounted to 47% of Finnish high-tech exports which was 3.5 billion euros in Auli Pere, Tekes Source: FIHTA The diagnostics industry has a strong history in Finland, since the 1970s. Finnish exports in this area have long been larger than imports, and even in international comparison Finland has an exceptionally strong diagnostics sector in relation to the size of the nation. In vitro diagnostics is the second largest health technology segment right after medical equipments in Finland. International consolidation of the diagnostics business could be seen also in Finland towards the end of 1990s and the beginning of 2000s. The market was redistributed, and international competition was fierce. New strategic collaborations were born, and R&D knowhow became commodity. Small Finnish companies sought competitive edge from their strengths by focusing on niche markets. As a response to the increased activity of the in vitro diagnostics industry in Finland towards the end of 1990s, Tekes launched the four-year Diagnostics 2000 technology programme that invested comprehensively in diagnostics knowhow and business development. Diagnostics 2000 programme took place during a major turning point in technology. Genomics, proteomics and systems biology renewed research. Nucleic acid diagnostics was becoming part of daily life. Microtechniques and later nanotechnology paved the way towards miniaturised systems, which made it possible to develop equipments suitable for point-of-care testing. In Finland many companies started to invest in near patent testing. At the beginning of 2000s, the foundation for the new generation diagnostics business was built in Finland. At the same time, major steps were taken in development of fundamental technologies like antibody engineering, labelling techniques, surface chemistry and microtechnology. New detection and instrument technologies were developed. The Diagnostics 2000 programme emphasised multi-disciplinary collaboration necessary in the on-going global change. Sitra capitalised promising new companies whose R&D projects were funded by Tekes. During the course of the programme, the number of diagnostics companies grew from 20 to almost 30. 6

7 In addition to the Diagnostics 2000 programme, Tekes has supported the development of the diagnostics business in the following programmes among others: Drug 2000, Neobio, SymBio, Pharma, FinnWell, Functional materials, FinNano, Liideri and BioIT. Moreover, diagnostics companies have been able to tap into funding outside programmes. The national IVD graduate school coordinated by University of Turku has had an important role in training new experts for the industry. The school has embodied the spirit of collaboration typical to the diagnostics sector: cooperation between researchers and companies has been intense and networking has taken place in joint events. International networks with e.g. Canada and India have been built together with Tekes. The Strategic Centre for Science, Technology and Innovation Salwe, founded in 2009, also develops strategic expertise in the diagnostics field. Today we are again experiencing a major turning point. Digitalisation is changing our lives, especially healthcare and diagnostics. It enables having healthcare present almost everywhere, and we hope to be able to shift the focus from treatment towards prevention and health promotion. The rapid increase of data, ability to analyse it and change it into usable information transform diagnostics and treatment practices. Easy availability of information activates individuals. We can already buy diagnostics online and analyse our own health with various devices. Yet we are far from an ideal situation in which a patient can be monitored at the hospital without being tied to tubes and cables, a chronic can wear a monitoring device comfortably and unnoticed, or it is possible to do a test without penetrating the skin. Digitalisation means new opportunities for the diagnostics industry, but also challenges. The corporate world is undergoing major changes as new actors are entering the market from ICT sector in particular. There is again the need to change ways of working and to form new types of partnerships. One must be able to adapt and find a role in the changing ecosystem. Today, Tekes invests a great deal into digitalisation with the launch of three new programmes that have possible links to the diagnostics industry. The digital health programme Bits of Health offers funding, networking, partnering and internationalisation services to companies aiming at utilising digitalisation for renewal and international growth. The programme invites the diagnostics industry to join the work towards a strong Finnish digital health hub. What will diagnostics be like in years? How will it be done in the digital hospitals or virtual clinics of tomorrow? What will point-of-care testing be like in 10 years? Where and how will diagnostics be conducted? Where will the clients of our diagnostics industry be in the future? The Finnish diagnostics industry is in a good position to prosper even in the future and to grow to new heights. However, the change at hand may require better ability to envision the future, more courage to seize new ideas and ability to forge strategic partnerships wisely to aim for more than seems realistic today. 7

8 In Vitro Diagnostics a Finnish Success Story Over the last 16 years, the Finnish in vitro diagnostics (IVD) industry has delivered consistent year-on-year growth in line with global trends. This growth has proved to be resilient to economic and market changes. The Finnish IVD industry has been recognised for its technology development, the quality of its products and its commitment to the primary healthcare market segment. This reputation has been built on the creativity of individual researchers and entrepreneurs working with established business and developing new enterprises. Extensive research and education programmes as well as government initiatives enabling national and international collaboration have also provided support to the industry. This report outlines the IVD development process and charts the development of the industry, highlighting achievements of Finnish companies and identifying some of their main success drivers. First immunoassay starts a new industry The starting point for the IVD industry as a whole was the publication of the first immunoassay by Berson and Yalow in 1959, glucagon peptide hormone. The industry started to develop in the years following. The technology quickly grew in popularity and initiated a quiet revolution in clinical practice. It rapidly became an indispensable tool for disease diagnosis and treatment management. The industry has regularly introduced new technology and pioneered new testing protocols and locations. Evolving global regulations have supported these developments, aiming at improvements in both quality and product design. Glucagon peptide hormone, chemical structure. Glucagon is produced in the pancreas and has the opposite effect of insulin. Photo: Shutterstock / molekuul.be 8

9 Highlights of the IVD industry as it moved from research to a globally regulated industry FUTURE RESEARCH DIAGNOSIS THERAPY MANAGEMENT WELLBEING TECHNOLOGIES Radio and enzyme immunoassay Monoclonal antibodies and direct detection DNA & RNA micro arrays FUTURE VIEW Dedicated automated hospital labs Test types integrated for individuals and results seamlessly integrated across to personalised health care LOCATION Clinical research & hospitals Local health centres Home testing REGULATORY EVENTS USA Medical Device Amendments Act USA Clinical Improvement Amendments EU in vitro diagnostics medical device directive New regulations in development The first products evolve The first IVD products were a collection of reagents, requiring the users to assemble their own assay with local reference ranges and controls. The initial tests were developed and used in a research environment, where the skills and facilities required to handle the radioactive labels used for the detection of a substance were available. The early tests utilised the sensitivity of radioactivity and the specificity of antibodies establishing a lock and key format, which has remained the basis for these tests to this day. By the late 1970s, a multitude of new nonradioactive test formats was available as well as an expanding range of tests applications. This encouraged the wider use of the IVD tests in routine diagnosis. Gradually these tests were grouped into diagnostic families, and the focus moved from the technology to ease-of-use and test throughput. The use of radioactivity for detection waned with first enzyme, then direct label detection became more common. This drove an associated development in instrumentation, automation and data processing, establishing the conditions for fully automated clinical laboratories now common in hospitals. Overview of hybridoma technology and monoclonal antibody creation. Adapted from the original illustration: Wikimedia Commons / Adenosine (Mike Jones) 9

10 The antibody also went through a quantum development with the realisation of highly specific monoclonal antibodies. This would dramatically advance the performance of these tests and enable the creation of a consumer market for pregnancy and fertility tests. Regulation in line with pharmaceuticals The early IVD industry was extremely disruptive: challenging clinical practice, it introduced completely new tools to diagnose disease. Clinical history and symptoms were still important, but the use of IVD tests enabled the doctor to see what was happening in the patient s blood. The industry and the healthcare professionals soon recognised that the IVD industry was an indispensable part of the medical landscape. This led to regulation modelled after pharmaceutical regulations. The 1976 Medical Device Amendments act was the first specific legislation to cover the IVD industry requiring all devices on sale in the USA to be registered with the FDA and to follow quality control guidance. The subsequent Clinical Improvement Amendments (CLIA 88) passed in 1988 set the minimum requirements for doctors office testing and helped establish a new market segment. In Europe, the regulation was initially based on national laws. In 1998, the in vitro diagnostic medical device directive (98/79/EC) came into force to regulate IVD. The majority of tests were managed through the CE mark process. By the close of the 1990s, IVD was an essential component of the diagnostic process and, in some cases, the management of clinical interventions. The tests had moved from hospital laboratory to doctor s offices/points of care (POC) and even into homes, most notably for the management of diabetics and the confirmation of pregnancy. The industry was effectively regulated and was proving adept at integrating emerging technologies rapidly into new tests and services. Towards personalised healthcare During this phase, the ability to measure DNA and then RNA was becoming reliable enough to indicate the potential of what would become personalised medicine. Another revolution in biology, the human genome project, would be necessary to make this potential a real opportunity. At the same time, the exponential growth in the telecom industry was establishing new communication modes, which by 2010 would enable diabetics to use their mobile phones to manage their medication. Today, the industry is rapidly evolving integrated testing solutions, which can be delocalised and have scalable information distribution protocols. This is pushing the personalised health care agenda, providing the patient and health care professional with new tools and options for managing health needs. Photo: Shutterstock / italianestro 10

11 Changing landscape The essential requirements for successfully developing a new IVD test or system have changed considerably over the industry s history (see Table 1). Initially it was only necessary to develop reagents and estimate their performance. This rapidly gave way to a technology and reagent arms race to produce the most sensitive clinical test or system using the most advanced technology. By the 1990s, even the customer had changed. The buyer was no longer a clinical or medical expert, but the budget holder, whose purchase decisions were driven by cost efficiency. The regulatory measures soon established a level playing field for quality and standardisation, even though the FDA approach to clinical reliability and the EU emphasis on customer driven satisfaction were not always easy to accommodate. Just as these factors have changed, so have the location of the tests and the users of the information. Originally, tests were carried out only in hospitals by expert clinicians, who used the information. Today, the tests are more delocalised: they are performed in primary health care environments, the home and remote locations. They also provide information to a wider group of actors, from patients assessing or lobbying for particular health interventions to payers interested in the cost efficiency and outcome of individual treatments. Today, company developing a new test or test systems needs superb technology integration skills. In addition to this, the company needs to be able to incorporate the needs of disparate stakeholder groups into the product. Table 1 Requirements for developing IVD tests or systems have changed over the years. PERIOD CUSTOMERS VALUE DRIVERS pre 1979 Experts/professors/hospital based doctors New applications, quality reagents, sensitivity Primary health care doctors, laboratory managers Reliability, low test cost, regulatory compliance, automation Clinical, budget & quality managers, reimbursement groups, consumers Ease of use, delocalisation, clinical efficacy Primary care & hospital doctors, reimbursement groups, patients/consumers Quality and cost of healthcare Community health networking 11

12 This has led to smaller companies focusing on individual aspects of the value chain. The larger companies, on the other hand, utilise their customer knowledge to identify emerging opportunities and focus on partner and supplier integration to deliver new products. Rapidly growing market The IVD market is currently estimated to be worth 42.5 billion US dollars. At Average Annual Growth Rate, it has been growing at about 16% over the last 10 years. The main markets are the USA, Japan and the EU. More recently, China has been a significant purchaser and is now a main production centre. While the traditional immunoassay format is still very important, the growth of polymerase chain reaction-based formats for detecting infectious diseases has been spectacular. In this area, China has invested considerably in technology and the integration of diagnostic results with health care decisions. While the industry has had strong growth, the last five years it has also seen considerable consolidation with new players emerging. Siemens and Philips have made significant acquisitions to promote their respective clinical and point of use market ambitions. At the same time, Alere has emerged out of the lateral flow niche to create a new global diagnostic company through acquisitions across the value chain. The integration of IT and telecommunications into pointof-care products starts to become the new paradigm Photo: Tekes New strategic partnerships between technology and marker groups are accelerating, as companion diagnostics becomes the leading edge for personalised medicine (see Overview of Companion Diagnostics in the Pharmaceutical Industry by Dr Stephen Naylor and Toby Cole). Furthermore, the integration of IT and telecommunications into point-of-care products starts to become the new paradigm. This can be clearly seen in the convergence of home use glucose monitors with mobile phone technology, e.g. My- GlucoHealth applications, and with IT health stations, which are able to link health centres with patients. An example is the HealthVault concept by Microsoft. 12

13 This foundation embraced all the key technologies necessary to develop IVD products These changes have necessitated the development of new business models, as some products have become commodities while others retain exclusivity. In more recent years, the period of exclusivity has shortened and there has been a noticeable shift from payment by test to payment for test result. This focus on information, its integration across knowledge bases and ubiquitous interpretation in professional and patient communication media are expected to drive the next phase of personalised healthcare. Photo: Medix Biochemica The Finnish IVD industry According to the Finnish In Vitro Diagnostic Cluster (FIVDIC), the Finnish IVD industry consists of about thirty companies employing some people and generating about 400 million euros in sales (2012). These sales are split between the main geographical areas: EU (37%), China (27%) and USA (20%), Average annual growth has been maintained at 16%. In 1995, sales were about 100 million euros and in 2009 about 330 million. The original companies were pioneers each in its own area of expertise: Wallac, now owned by PerkinElmer, in instrumentation, Medix Biochemica in antibody production, Orion Diagnostica in labelling chemistry and Labsystems, now owned by Thermo Fisher Scientific, in systems integration. This core technical understanding is still visible in their current product ranges. This foundation embraced all the key technologies necessary to develop IVD products, and it was to prove a boon for both the early companies and for the establishment of new companies. Table 2 summarises some of the key developments in the industry in Finland and highlights the growth in the range of products and number of companies producing them. Additionally we can see that foreign companies have been active in acquiring Finnish companies and have often widened the scope of operations in Finland to support global sales. 13

14 Table 2 Some of the key developments in the IVD industry in Finland COMPANIES ACTIVE Oy Medix Biochemica Ab Orion Diagnostica Oy Wallac Oy Labsystems Oy Nordiclab Oy Farmos Diagnostica Oy Ani Biotech Oy Innotrac Diagnostics Oy Finnzymes Oy Arctic Diagnostics Oy Biohit Oyj Labmaster Oy Hytest Oy Mobidiag Oy Abacus Diagnostica Oy PlexPress Oy Magnasense Technologies Oy Oy Reagena Ltd PURCHASES Wallac Oy purchased by PerkinElmer Labsystems purchased by Thermo Fisher Scientific Ani Biotech purchased a part of Labsystems Innotrac Diagnostics purchased by Radiometer (Danaher) Finnzymes purchased by Thermo Fisher Scientific Orgenium Laboratories Oy purchased by Ani Biotech SBA Sciences purchased by IDS KEY PRODUCTS AND INVENTIONS Dipslides [Orion Diagnostica] Steroid RIA [Nordiclab] thyroid RIA [Farmos Diagnostica] DELFIA [Wallac] QuickRead and bone markers [Orion Diagnostica] Actim [Medix Biochemica] Biocard [Ani Biotech ] Piko [Finnzymes] Prove-it [Mobidiag ] Clean Card PRO [Orion Diagnostica] ArcDia TPX [Arctic Diagnostics] Biocard Celiac [Ani Biotech] ReaScan [Reagena] Aio! [Innotrac Diagnostics] Actim PROM, Actim Partus [Medix Biochemica] GastroPanel [Biohit] TRAC technology [PlexPress] 14

15 Convergence of rapid tests & point-of-care During the 1980s and 1990s, there was a convergence of Finnish IVD companies on the rapid test and point-of-care market, which now represents a significant proportion of their business. Initially the products utilised traditional immunochemistry approaches, but more recently, new companies have emerged with DNA-based test formats. The focus on the rapid tests and point-of-care market can also be seen in the research organisations with supporting programmes, seeking to deliver new reagents, homogeneous test formats and low-cost production methods. The strong technical competencies within Finland in the electronic, optical and bioreagent areas have supported their success These latter areas have seen particular development in the microfluidic and printing areas to deliver new platforms. These are being incorporated into the new Finnish Strategic Centres for Science, Technology and Innovation (SHOK) programmes through Health and Well-being SHOK SalWe. Tenacity and agility The Finnish IVD industry has achieved consistent growth throughout the period with significant changes in the regulatory and reimbursement environment. At the same time, competition has increased. This growth has been achieved in part through tenacity and in part through agility. Companies have managed to maintain their customer base as well as adjust their geographical and customer focus, as circumstances necessitated. For example, the Finnish IVD companies were very early in China, and they have tailored their products for point-of-care use. The drive for export, control of supply chain costs, high quality reagents and creative technologies has enabled the relatively small Finnish companies to outperform global trends in their target sectors. Out of a strong reagent base, the Finnish IVD industry developed a worldwide business presence, integrating reagents and instrumentation into high quality products. Initially the focus was on hospital laboratory use. This was led by a collaboration between Wallac and Orion Diagnostica to develop a time resolved fluorescence platform and by Labsystems with their microtiter plate based instrumentation. As delocalised rapid testing emerged, Finnish companies successfully focused on this segment. Today this format is the common thread within the Finnish IVD companies. The strong technical competencies within Finland in the electronic, optical and bioreagent areas have supported their success in this segment. The backing provided by government organisations and funding agencies has also played an important part. These early foundations drove the development of new product platforms. They also gave rise to a close relationship between industry, universities and government research organisations aiming at commercial growth. 15

16 Example: Commercialising time resolved fluorescence The commercialisation of time resolved fluorescence (TRF) to IVD products exemplifies this cooperation. This led to the development of a global product brand called DELFIA. DELFIA s initial commercialisation was driven by a partnership between Wallac and Orion Diagnostica. Wallac developed the instrumentation and sales network and Orion Diagnostica some of the steroid bio reagents. While Wallac went on to establish a worldwide market based on TRF products, Orion Diagnostica established a strong position with IVD conjugates, which formed the foundation of their successful radio immunoassay and immunoturbidometric business. The TRF technology was revolutionary: it combined high sensitivity and dynamic range with stable end point, enabling stable and sensitive tests to be designed. Its radical nature combined with the limited launch test menu and the introduction of similar delivery systems by large diagnostic companies like Amersham and Abbot made TRF technology s initial take-up slow. Amersham launched their systems Amerlite using an existing global customer network, and even though the technology was radical, it was able to gain faster market traction by conversion of the large existing radio immunoassay customer base. However, Finnish companies initiated development of a fully automated system before the manual system was accepted. This proved a wise choice, as Ortho-Clinical Diagnostics Vitros automated clinical laboratory system utilises this technology. Despite the relatively slow uptake, the TRF technology was the basis for successfully establishing the global DELFIA brand. It was to become the technology of choice for commercial and governmental research organisations developing new markers or conducting benchmarking investigations. Turku IVD cluster is born One of the unintended outcomes of the success for TRF was the establishment of a significant IVD cluster in the Turku region. This cluster would support instrumentation and chemistry developments and establish spin out companies together with the university. These companies advanced the use of TRF. For example, Innotrac Diagnostics developed easyto-use critical applications and Abacus Diagnostica point-of-care applications. The development of fluorescence technology as a whole enabled new Photo: Hanna Oksanen / University of Turku (university communications) 16

17 fluorescence-based point-of-care systems to be developed by Arctic Diagnostic. The story continues today at Aqsens Oy, with further academic research on the integration of tiem resolved fluorescence with microfluidics and the utilisation of the underlying technology in new applications. These opportunities enable industrial and academic staff to network and collaborate Photo: Tekes With this continuous development and innovation, it is not surprising that a national IVD graduate school was established and coordinated by Turku University to provide teaching and research opportunities. These opportunities enable industrial and academic staff to network and collaborate over courses and research, providing a strong support for future generations entering this industry. Strength in diversity Even though the Finnish IVD industry has a shared technology competence, its strength lies also in the diversity of its enterprises. In the reagent development area, we can see this wider technical competence being a common root expressed differently in the diversity of companies. The establishment of antibody suppliers Medix Biochemica and Hytest exemplifies this translation of technical expertise into successful business. When Medix Biochemica started selling monoclonal antibodies, there was no market for them, as we understand it today. The IVD companies could not see the advantage of monoclonal antibodies, and the patent position was unclear, so originally the inertia to change was high. Today, monoclonal antibodies dominate the IVD reagent market. Early collaboration with Unipath plc, co-owner of key monoclonal patents related to IVD use, on the development of antibodies first for pregnancy and then for fertility tests proved an important milestone in the commercialisation of monoclonal antibodies in IVD tests. Medix Biochemica became established as a primary supplier of these reagents and cemented their reputation globally for high performance and quality reagents, which were cost effective and available in high volume. Hytest, another Finnish reagent company, is known for its cardiac market antigens and antibodies. A similar story plays out in a number of Finnish IVD companies, e.g. Orion Diagnostica with its early steroid reagents and antibody conjugates. This tradition for developing novel reagents can also be seen in Finnzymes application of heat stable enzymes in their flagship polymerase chain 17

18 reaction platform Piko. More recently, the emergence of chiral avidins as a result of university research exemplifies this Finnish tradition for pioneering new reagents. Once a core tradition in reagent chemistry has been built up and maintained, it is not too much of a step to expect some crossover into parallel areas. This crossover can be seen particularly with the development of novel nanoparticles, e.g. encapsulating europium for TRF applications, or their construction using recombinant technology. Another example is the ingenious manipulation of surfaces, using lipid-like self-assembled structures, by the VTT Technical Research Centre of Finland at Tampere to improve test performance, utilised in BioNavis Oy applications. These types of materials play an ever increasingly important role in the development of tests as companies optimise the triangle between cost, performance and ease of use to gain competitive advantage. Photo: Tekes There is one further area of reagents where Finnish IVD companies have been highly active: the introduction of new markers or combination of markers for clinical diagnosis. For these relatively small companies, it is a significant achievement to bring new markers to market These markers and reagents have often originated from university groups and have been taken up by Finnish companies, which often have been pioneers in their use. The markers cover a wide range of diseases. The ones with possibly the largest impact for the companies are UniQ bone markers for Orion Diagnostica and Suomen Bioanalytiikka services, celiac test and myeloperoxidase (MPO) test for Ani Biotech, Actim Partus preterm delivery test for Medix Biochemica and GastroPanel diagnostics for dyspepsia for Biohit. For these relatively small companies, it is a significant achievement to bring new markers to market, especially as it is becoming vastly more difficult with the changing regulation and reimbursement landscapes. However, the earlier collaborations within Finland between university and clinical researchers with local diagnostic companies enabled them to utilise the good healthcare information to develop and validate such markers locally. This is much harder today, yet it remains a critical area, where 18

19 government and business should be closely collaborating for both the economic health of the Finnish IVD industry and the well-being of the Finnish citizens. The recent establishment of the Finnish biobank creates an opportunity to develop such cooperation within the safety net of regulation to protect personal information while enabling cooperation programmes between commercial and medical groups. Innovation combined with existing technology As indicated earlier, Finnish IVD companies have maintained healthy growth and competitiveness. While local inventions have underpinned this growth, companies have shown remarkable ingenuity in co-opting existing technology. This is clearly exemplified in the use of lateral flow tests for point-of-care applications. The products from all the Finnish IVD companies which utilise this technology also incorporate key additional innovations, establishing a competitive advantage. This can be seen in the use of novel applications, like celiac or preterm delivery test by Ani Biotech and Medix Biochemica respectively, the use of a low cost reader format in Reagena s award winning platform, and the development of elegant and simple sampling methods by Medix Biochemica. These developments have helped the companies compete in the point-of-care market and establish strong positions in this rapidly expanding niche market. The products from all the Finnish IVD companies which utilise this technology also incorporate key additional innovations, establishing a competitive advantage In scanning across the Finnish IVD history, we can see high quality and novel reagents as core drivers, coupled with pragmatism to deliver easy-touse products. In addition, we can see a pioneering spirit, a willingness to take risks and to work hard to establish successful enterprises. Photo: Tekes 19

20 Finnish IVD industry looking forward In this section, we look at the Finnish IVD industry through the prisms of value chain, competencies and attributes as well as national structures. In this way, we explore the various key features driving the business, and then look at its strengths and speculate on new opportunities. Value chain drivers The value chain concept has been a central tool for companies to evaluate their business strengths and identify key opportunities. Here, however, the more recent Value Reference Model approach is applied, utilising the original value chain principles but more suited to technology-dependent industries. The Value Reference Model utilises both planning and implementation governance modes and can be used as a review window as well as for tracking implementation process. Here we are using the review mode. Table 3 identifies some very general points reflecting the present situation within Finnish IVD companies and also indicating some relevant global trends. Most of the Finnish IVD companies are technology driven and tend to focus on research and development, design and production, while marketing and, to a great extent, sales are delivered through distributors. The drivers for the products have often been technical, and in many cases, they can be traced to Table 3 Finnish IVD companies today and trends affecting them. R&D DESIGN COMMON SITUATION TODAY Individual driven and key product driver Often focus of 2nd generation product GLOBAL TREND Increased B2B activity with networks Earlier prototyping and shortening product life cycle PRODUCTION Internally managed Outsourcing becoming available MARKETING & SALES DISTRIBU- TION CUSTOMER SERVICE Partially outsourced to distributors Largely through distributors Often channelled through distributors Distributor acquisition becoming disruptive Increasingly important to achieve direct contact with users 20

21 key individuals. This approach was particularly successful where topic based inventions could drive an entire product line, for example TRF driving the DELFIA system. Strong B2B partnerships required Now the trend is to integrate several technologies and materials in order to achieve product differentiation. This often requires B2B partnerships and the use of both localised and virtual teams to bring the product to fruition. It is interesting that this trend was foreseen in a survey of Finnish companies in 2009, where they indicated that they expected new products to evolve from B2B relationships. In the same survey, there was also a strong expectation that new products would come from platforms, which were multiplexed and could be achieved at low cost. In addition to the development of multiplexed platforms, the companies placed strong emphasis on infectious disease tests, the use of printing technology to deliver low cost products and improved access to financing to help start-up companies productise their technology. The use of distributors has worked well for Finnish IVD companies enabling them rapid and relatively low cost access to global markets. Strong relationships are often forged with the distributors and co-dependency can develop giving both parties stability and access to expert knowledge. However, for the IVD producer this type of relationship can become a trap as they can lose direct contact with the product user, as their customer becomes the distributor. This can make it more challenging to identify new market opportunities and understand the relevance of emerging trends. As the speed of change in the IVD market has accelerated, being in direct touch with end users and healthcare providers has become increasingly important. This is often recognised within the Finnish IVD sector, although moving outside niche areas has proved difficult and often has only been achieved by being acquired but a larger multinational. Within their niche areas the Finnish IVD companies have balanced these conflicting issues successfully and have been able to maintain their customer base during challenging economic times, while also being able to use their marketing knowledge to develop customer loyalty. The challenge is to translate the Finnish invention strengths into global innovations at the technical and commercial level. Photo: Shutterstock/ Phase4Studios 21

22 Since 2005, there has been considerable consolidation in the global industry, creating new entities as well as extending ownership of the value chain for existing companies. This can be seen in the acquisition of distributor companies, private central testing laboratories and private health centres. The increased use of outsourcing by public health services to deliver chronic and rehabilitative care services with a focus on home management has provided a focus for the larger global IVD and IT companies to form partnerships and establish new markets. Bio-IT fusion The industry appears to be entering a new phase where IT technology is becoming a gatekeeper, opening many opportunities in this sector. This suggests that more extensive ownership of the value chain coupled with crossover partnerships could become more common. By combining the inherently disruptive nature of IT with diagnostics to manage healthcare processes, we can expect to see new opportunities emerge These partnerships can be expected to create new business pathways and new product opportunities, effectively expanding the actors in the value chain. This can be seen in the surge of partnerships to develop companion diagnostics, where fusions between marker and delivery actors are being reported. The suggestions that IT and IVD companies will work closer together is potentially much more disruptive. By combining the inherently disruptive nature of IT with diagnostics to manage healthcare processes, we can expect to see new opportunities emerge. As the information processing aspects develop, it is entirely feasible that the simple static marker diagnosis model will come under challenge from more dynamic and personalised approaches. This potential Bio-IT fusion, which has been extensively discussed in the Finnish IVD circles, has the potential to redefine some of the value chain channels and provide good opportunities for Finnish companies. Programmes which could address this type of opportunity appear to be fragmented and perhaps it will be necessary to find a vehicle to bring together the technology developments and healthcare management issues with citizens desires and expectations to realise such opportunities. MODZ blood glucose meter sends test results automatically as a text message to a mobile phone and wirelessly to MODZweb. MODZweb is a service on the Internet, where all test results and the carbohydrate contents of meals as well as sports exercises logged in the meter will be stored. Photo: Modz Oy 22

23 The past has proven that Finnish technology and national partnerships can deliver successful IVD companies It will also be necessary to maintain blue sky programmes to develop Bio-IT technologies and integrate them into the personalised medicine sector. Such programmes will be essential to take full advantage of the cloud based healthcare data banks, which are being established, but are so potentially disruptive that they will be seen as incompatible with normal product life cycles. The past has proven that Finnish technology and national partnerships can deliver successful IVD companies. Yet despite this, the industry has not produced a large global player. The elements are in place and perhaps the Bio-IT opportunity will see such a company emerge over this next exciting phase in the Finnish IVD story. Technology development through national initiatives and clusters The Finnish government through Tekes has regularly engaged with the Finnish IVD companies through workshops and funding initiatives to help strengthen links with researchers and support companies introducing new technology. During the 1990s and in the early 2000s, Sitra also had an active role as an investor in IVD. The Diagnostic 2000 programme of Tekes effectively combined company programmes and themed public programmes, which were networked through local reviews and national presentations. These activities helped to widen understanding in the commercial sectors of the skill clusters, which were available, and provided the researchers with a better understanding of the key industry players needs. It is interesting that in the time covering this programme and in the years shortly after, there has been considerable activity in new product forms and release of new products, such as Provite It and Clean Card Pro. It is very evident that the national support activities have contributed to new products and enabled companies to take higher levels of risk to translate new technology into product forms. Additionally there have been initiatives within the national research groups, such as VTT Technical Research Centre of Finland, to develop substantial skill centres, suitable for enabling the IVD industry. These activities have covered such areas as sensors, bioactive paper, recombinant proteins and low-cost microfluidic structures. Photo: Tekes 23

24 The outcome has been the establishment of technology clusters combining university and national research organisations (see table 4 for examples) While it is clear that these structures have a real and direct impact on the technical development of products, they have tended to target the areas of the value chain where the companies were already strong. Networking opportunities have been developed and good workshops held to widen understanding of the global opportunities, but they have not really addressed the global issues consistently. Two new funding schemes managed by Tekes address some of these points today: the funding scheme for new innovative young companies (NIY) and the concept of Strategic Centres for Science, Technology and Innovation (SHOK). The NIY programme is putting substantially more emphasis on progress through commercial roadmaps and has the potential to enable the establishment of more robust start-up companies. In SalWe, the SHOK for Health and Well-being, companies have more freedom to construct Sal- We s research programmes; here there is an increased focus on both new platforms and product design activities which has good potential for new products. It has the potential to form the nucleus for development across business and research groups. In both programmes, there may be insufficient promotion of open innovation methods to support rapid global solutions as well as accessing global talent. Also the issues of funding start-up/ spin-off companies and the injection of experienced business development to them are not being directly addressed. Towards a more holistic view of development Future products will need more global networking, B2B cooperation and the development of functional prototypes to help define new business opportunities. Table 4 Examples of university and national research organisations in Finland. LOCATION ACTIVITIES OULU Printed intelligence, opto-electronics, cardiac and bone disease. HELSINKI/ ESPOO Recombinant protein, microfluidics, sensors, low cost diagnostic devices, bioactive materials. TAMPERE Surface chemistry, microfluidics, detection methods, smart avidins. TURKU Time resolved fluorescence, bio marker discovery, test formatting, printing, training/education. 24

25 Photos: Tekes This will require a shift away from technical focus to a more holistic view of the company as well as the creation of funding vehicles which companies can use to focus on these complex issues to help develop new products. The past programmes have tended to look at technology in partial isolation from the business environment, focusing on new technology rather than its use. The rationale was that application is the responsibility of companies and the funding programmes should support underpinning technology. Company involvement in public programmes is seen as a steering element to shepherd the technology towards commercial application. Unfortunately, the result has been to emphasise new technology as a driver rather than as a tool to deliver new product opportunities. Thus, the development of technology to support alternate product form factors or to improve the user experience has been understated. Yet it is in these areas where technology integration is having some of the biggest impacts in the healthcare markets. The utilisation of wireless technologies and cloud data management are already opening new possibilities and can be expected to drive new product Patients are looking for more individual treatment and more elective choices forms. This, in turn, can be expected to refocus reagent types and product packages. Such developments will most likely require either new, de novo technologies or the integration of existing platforms to create new solutions. It appears that there is some morphing of the familiar model of research prototype development into a more Venn diagram type of approach, where the boundaries between these three activities have points of coalescence. These points are overlapped with customer/user assessment activities to prioritise product development activities. Change gathers speed The rate of change continues to increase, shortening the product and business life cycles and pressuring the industry to increase its product range. While the overall market continues to expand, the customer/user base is changing, product features have a much shorter strategic advantage and health care budgets are focusing on the test value as much as its clinical reliability. Coupled with this, patients are looking for more individual treatment and more elective choices about how and where the treatment is administered. 25

26 It is becoming feasible to gather individual, distributed health information The new sector of wellness is emerging and is expected to take over some of the traditional healthcare activities. However, this sector is being driven by consumer-oriented companies and is bringing new approaches, which can be expected to flow into the healthcare sector. In both sectors, IT-based products are proving to be very attractive, allowing patients more influence over their treatment as well as enabling them to manage their healthcare information. Where electronic health cards are operational, patients are starting to act like consumers shopping for treatment and care facilities. The biggest area of this impact is in the delivery of recuperative and chronic care; here home services are blooming and are popular with both patients and providers. Alongside these changes, there are shifts in the way IVD information is being used and is planned to be used. Already mentioned is the significant rise in the development of companion diagnostics, which, when used with patient profiles, can be used to opt individuals in or out of treatment programmes. A current active area can be seen in some of the national bio-banks where programmes are providing participants with access to their own diagnostic results. These programmes can be very large: one recent programme in Sweden plans to enrol 500,000 participants and provide each of them with access to their results via a web-based personal health page. Suddenly it is becoming feasible to gather individual, distributed health information and to utilise it via a cloud database to manage a specific treatment. Additionally, patients are able to obtain a personal health fingerprint during their healthy years, which offers the potential of more data driven risk assessment of an individual who may need an intervention in the future. The possibility of providing individual predictive, dynamic assessments is starting to open up. The third area starting to develop rapidly is the way in which the disease state is monitored. For all of the IVD history, the lock and key test format has been used, incorporating unique reagents for the quantisation of a specific disease. The underlying principle is that a unique biomarker or small number of such markers (2 or 3) are sufficient to significantly aid diagnosis. Recently researchers (see Professor Christer Wigren at Lund University, and products developed by Immunovia) have been utilising principle component analysis of antibody arrays to generate biochemical signatures, which can be used to identify disease stages and risk groups. Photo: Shutterstock/ Sergey Nivens 26

27 This proteomic approach uses antibody arrays, which are not specific for the disease, but are used to identify differences in a disease s lifecycle and so enable the disease to be staged through the changes in the biochemical signature. More radically, researchers at Turku University (Professor Pekka Hänninen and Dr Harri Härmä) have demonstrated that TRF could be combined with surface modulators to generate liquid fingerprints. These fingerprints are generated through non-specific interactions that are mediated by a very wide range of chemical modulators. The technology can be used to identify changes in complex solutions, and while it has only been applied in industrial situations (see Aqsens Oy) it has significant potential for monitoring an individual health status. These approaches offer a novel way to investigate the progression of disease and the well-being of an individual. When combined with the temporal health information from national bio-banks, it may be that more selective treatments can be realised and they will form an important development route for the realisation of personalised health care. Looking across the industry drivers can be categorised as either established or developing or emerging and are indicated in table 5. The established category is highly visible in the Finnish IVD industry, whereas the emerging category looks at industry drivers from a more global perspective. It is quite possible that some level of translation from established to emerging drivers will occur or is occurring within the Finnish IVD industry. This translation can be expected to be company dependent, and in that sense each company will have its own programme. Table 5 Industry drivers now and tomorrow. ESTABLISHED DEVELOPING EMERGING BUSINESS Early engagement with foreign markets Excellent cost control Early product design processes Low cost production Branding Product development partnerships ORGANI- SATIONAL Adaptable Close networks Education & research facilities Translating inventions into new profit streams Outsourcing Integrating global partners Open innovation Bio-IT driven organisation TECHNICAL Individual inventors Protein and materials chemistry Optics/fluorescence Printing technologies Smart surfaces Technology integration Customer solution based technology integration Computational driven diagnostics 27

28 FROM HYGROMETERS TO MARKET LEADER IN NEONATAL SCREENING Wallac Oy Wallac Oy, part of PerkinElmer s Diagnostics business, was a pioneer of IVD diagnostics in Finland and across the world. In 1950, Wallac started as an instrument company its first instruments were cloth hygrometers. The Company soon branched out to providing gamma counters, and after the development of a time-resolved fluorescence (TRF) method lead by Erkki Soini in 1975, product development for the diagnostics industry began. Wallac s patented TRF method is still the basis for the technology used today. According to Pekka Peltonen, PerkinElmer, Diagnostics, R&D Director, Tekes has been involved in the funding of most projects for developing the technology and applications further. Over the years, we have developed from an instrument manufacturer to a provider of systems that include instruments, reagents and software, says Peltonen. In addition to R&D, Wallac has manufacturing, sales and marketing functions located in Turku, where approximately 510 of PerkinElmer s employees are employed. The Turku site employs other technological expertise beyond the original TRF and maintains an up-to-date manufacturing infrastructure. The PerkinElmer products originating from Wallac are used in both prenatal and neonatal screening and need to meet the highest regulatory and quality requirements. In the USA, the products, their development and manufacturing are under the regulation of the Food and Drug Administration. FINNISH KNOWHOW IN A GLOBAL GROUP In the beginning of the 1990s, Wallac was acquired by EG&G, now known as Perkin- Elmer, for its expertise and state-of-the-art technology. 28

29 SCREENING FOR CONGENITAL DISORDERS Today, PerkinElmer Wallac s main markets are neonatal and prenatal screening for congenital disorders. Prenatal screening is used to determine the well-being of the mother and the fetus. In neonatal screening, the Company is the world market leader. Wallac has clients in about 100 countries with 32 million babies tested each year. If these disorders are found soon after birth or even before it, the chances of ensuring the normal development of the child improve significantly, says Peltonen. A good example is hypothyroidism, i.e. insufficient production of thyroid hormones, which is the most common disorder found in neonatal screening. Found early, it is easily treated, but left untreated can lead to delayed physical and mental growth. Wallac s competitive advantage is its wide offering in both systems and applications. Moreover, the Company s products are often tailored to meet the customer s specific needs. GROWTH FROM OLD AND NEW MARKETS PerkinElmer diagnostics operations in Turku have more than doubled from 1990 through 2000, and since then continued to grow steadily. And there is no end in sight for the businesses rapid growth. The current main markets will continue to grow as new countries begin screening mothers and newborn babies and new tests are developed. When newborn screening began in the 1960s, only two or three tests were performed per baby. Now, babies are tested for multiple disorders at birth. Prenatal screening is also expected to expand in the future. For example, Perkin- Elmer has recently developed a test for measuring the risk of developing preeclampsia. When detected in the early stages of pregnancy, the mother can be treated and/or monitored more closely. To find new areas of growth, the Company has invested in developing new molecular diagnostics, supported by Tekes funding. This work started in 2006 with the acquisition of Spectral Genomic s DNA arrays; the products, manufacturing and R&D were transferred from the United States to Turku. The current technology is called BACs-on- Beads for fast, precise and cost-effective targeted molecular karyotyping. In recent years, we have been developing the first molecular application for neonatal screening. We expect significant growth in this area. Photos: Wallac Oy 29

30 RAPID DNA TESTING SPIN-OFF TAKES WING Abacus Diagnostica Oy Abacus Diagnostica Oy is a classic example of a university spin-off. The roots of the company were established in Tekes-funded Diagnostics 2000 research project at the University of Turku. The research led to patent applications, and when the companies involved in Diagnostics 2000 indicated they were not interested in taking them further, the inventors decided to start Abacus, says Tom Palenius, CEO of Abacus. The atmosphere at the UTU biotechnology department was very supportive of establishing a company. People there have commercial mindset and spin-offs are not uncommon. Three of the seven patents currently in Abacus IPR portfolio stem from the research done at the University of Turku. The company was founded in 2004 to further develop and commercialise the now patented Genom Era technology for rapid DNA testing. Abacus proprietary technology platform is a powerful tool for DNA based testing. The technology combines a rapid assay principle employing Time Resolved Fluorescence detection with a simple-to-use reagent concept on a low-cost plastic test chip. Compared to other solutions on the market, GenomEra is fast, safe, compact and inexpensive and still offers very high performance. Our solution is so easy to use that is can be applied in routine applications, where molecular diagnostics methods often are challenging due to the specific skills needed. Moreover, it does not require dedicated laboratory facilities. Originally, GenomEra was developed for food safety applications. Due to changes in the strategy of Abacus partners, in 2008 the company found itself with an almost finished product but no partner and no funding. 30

31 A quick change of direction was required. Abacus decided to focus on human clinical applications, and two venture capitalists invested one million euros in the company. In 2009, all the pieces of the puzzle started to fall into place, and at the end of 2010, the system was finished and CE-marked. The first GenomEra test systems and MRSA test products were sold in For Abacus, the year was financially challenging, as it built up its logistics systems and sales network with hardly any revenue. Then things started looking up. In September 2011, we sold about five systems; in March 2012, this has increased to 30. Now we are expanding our market area constantly. Throughout its history, Abacus has been involved in public research projects and company projects funded by Tekes. Tekes-funded projects have been very important for us, not just for the funding but also for their networking possibilities. Tekes has also been very flexible, which was critical during the 2008 change of direction, Tom Palenius points out. Now we are seeing our long-term research and development work beginning to pay off. Our goal is to expand our test selection and further expand our sales to Europe and maybe at a later stage to the US. Photos: Abacus Diagnostica Oy 31

32 HIGH-END PRODUCT OPENS DOORS TO NEW MARKETS Orion Diagnostica Oy Orion Diagnostica Oy is one of Finland s biggest IVD technology companies. Over the years, Orion Diagnostica has experienced a change in focus. Earlier, Orion Diagnostica s main products were reagents for large laboratory analysers, but today its product portfolio also includes test systems developed and manufactured in cooperation with instrument companies. From the beginning of 1990s, Orion Diagnostica has focused on point of care tests and test systems, which allow rapid diagnostic and adequate treatment decisions during patient consultation. The use of printing technology in the production of diagnostic tests is also our strength. We have carried our different projects with VTT Technical Research Centre of Finland and Tekes in this area, says Orion Diagnostica s President Jaakko Rissanen. These printing technology projects have resulted in the Orion Clear Card PRO test, which is the only printed diagnostic rapid protein test for monitoring surface cleanliness e.g. in hospitals and the foodstuff industry. The simple wipe test shows whether there are any protein residues on the surface for bacteria to grow on. The Orion Clean Card PRO test has several advantages: it is very easy to use, it does not require any special user training, and the result is ready in only 30 seconds, says Rissanen. Orion Clean Card PRO received the Innovation Award of the Chemical Industry Federation in Finland in The product combines expertise in different fields of technology and science material sciences, printing technology, and protein chemistry in a new and innovative way. Orion Clean Card PRO is a typical product of a networking development project, which took approximately six years to complete. This type of a pioneering product opens up new possibilities in international sales. We are currently in discussions with different companies to map out all the possible applications of this product. These discussions may result in Orion Clean Card PRO 32

33 becoming a platform for developing also other products, based on similar printing technology, points out Rissanen. Another example of Orion Diagnostica s innovations are the UniQ PINP and ICTP collagen tests that measure bone metabolism from a blood sample. The UniQ PINP test detects increased bone turnover, which helps identify patients at risk of fracture, and UniQ ICTP indicates pathological bone degradation specifically, without being influenced by physiological bone turnover. In Japan, for instance, the innovative UniQ ICTP test is used widely to detect bone metastases in breast cancer patients. The UniQ PINP test provides a means for monitoring the efficacy of osteoporosis medication. Tekes was essential in the creation of this development path and competitive advantage, says Rissanen. As a company, we are relatively small and active in a field where special expertise is required. It is natural for us to network, learn and develop together with our partners. Tekes facilitated the creation of this network for us. Photo: Orion Diagnostica Oy Health with top knowhow SalWe is a Strategic Centre for Science, Technology and Innovation (SHOK) in the field of health and wellbeing. Through the operations of this centre, Finnish companies build knowhow and international business together with research centres. This collaboration produces researchbased products, services and practices that aim at maintaining and improving the functional capabilities of individuals. The goal is to prevent, detect and treat socially significant diseases. The research programmes aim also at accelerating the transfer of research findings to product development and to improve competitiveness as well as to prepare for a launch on larger markets. Our asset in the competition in global networks is our speed and agility, points out Programme Director Jouko Haapalahti, SalWe Ltd. Up till now, Salwe s research programmes have included Intelligent Monitoring for Health and Well-being (IMO) and Mind and Body

34 The IMO programme has benefited not only from medical knowhow but also top Finnish expertise in bio-, IT- and nanotechnology as well as materials technology. The research conducted within this programme has produced for example a technology platform used in the research of celiac disease and biomarkers. Research has also been conducted on the diagnostics of prostate cancer. The business value of the PSA test currently used to diagnose the disease goes up to approximately a billion dollars. The Mind and Body programme combines nutrition, sport, biomedicine, neuro and behavioural sciences to information technology, medical technology and consumer research in a unique way. The programmes bring together a multidisciplinary group of companies and research teams focused on health and wellbeing. The collaboration results in new types of solutions that may have a positive effect on both public health and national economy, when successful. Research cooperation continues in Sal- We s new programme Personalised diagnostics and care The overall objective of the programme is to enhance the use of personalized diagnostics and care. The programme focuses on the efficient utilization of personal health records, patient records and genomic information including new technologies in point-of-care testing. The ICT solutions to be developed, including genetic and other laboratory data, support the effective use of patient data both in the prevention and treatment. For the first time public and private health care, occupational health, multidisciplinary research and industry develop together new approaches for personalized diagnostics and care. Subcontracting or following public research are no longer the only options to pursue in the cooperation between companies and universities. Fruitful work can be done side by side, also in international collaboration networks, says Saara Hassinen, Managing Director of SalWe Ltd. Photo: SalWe Ltd. 34

35 STATE-OF-THE-ART PREGNANCY MONITORING FROM FINLAND Medix Biochemica Oy Medix Biochemica Ab was the first company in the world to develop a reliable and accurate method, based on monoclonal antibodies, to detect premature rupture of fetal membranes. Actim PROM is the fastest test on the market, which reacts to the presence of amniotic fluid in vaginal samples. Of all fetal deaths, approximately 10% are related to ruptures in fetal membranes. Detecting even minor ruptures is important, as they make both the fetus and the mother prone to infections. Actim is a line of rapid test products for various applications. At the moment, there are eight different Actim products on the market and two of them are specifically used for pregnancy monitoring. Actim PROM and Actim Partus, for identifying patients with a risk of preterm delivery, are extremely simple to use and require no laboratory processing. Dipstick tests are easy to apply and take just a few minutes to perform. Thanks to the cutting-edge characteristics of the products and Medix Biochemica s successful commercialisation of them, the tests have been widely accepted and adopted worldwide. Actim PROM is a case example of a Finnish diagnostics invention for a niche market that has acquired considerable market share on the global market. Medix Biochemica s distribution network includes now over 60 countries. With Tekes support, we had the courage to invest in our product development sufficiently, and we got the new products developed, produced and launched on the market, says Ismo Råman, CEO of Medix Biochemica. Actim PROM and Actim Partus were patented in the early 1990s, and the patents are about to expire soon, so competition will be much tougher when similar types of tests will enter the market. So far, we have been able to utilise the protection provided by our patents and to develop the market to gain a strong foothold on it, he continues. 35

36 Medix Biochemica s main sales area is Europe, where Germany and France are the biggest markets. Japan and China are growth areas, and this year, the company will also enter the US market. The other mainstay of Medic Biochemica, in addition to rapid test products, is antibodies used in diagnostics. The company s antibodies stand out in the competition due to their high and constant quality. We are expanding into a new area of the development and production service of recombinant antibodies, in other words, we tailor the antibody to the customer s needs. Antibodies are optimised in the laboratory to include the desired characteristics. This technology is already commonly used in therapy, but new to diagnostics applications, says Råman. In Finland, the new antibody technology knowhow resides in the VTT Technical Research Centre of Finland and in the University of Turku, which are both partners to Medix Biochemica. From Tekes point of view, this is a natural development path, as Tekes has been involved in supporting the development of this new technology. Photos: Medix Biochemica 36

37 NETWORKING WITHIN Thermo Fisher Thermo Fisher Scientific Oy of today has been formed through acquisitions and mergers. In Finland, the three main branches in company s history are Labsystems, Konelab and Finnzymes. Labsystems Oy started with pipettes and Konelab Oy with clinical chemistry analyzers in the early of the seventies. Finnzymes Oy, specialising in molecular diagnostic products, was founded in mid of the eighties. All the Finnish companies merged into Thermo Fisher Scientific had set their sights on international markets from the start. This meant that from the very beginning, the companies planned their operations to meet the needs of the global market. Now the extensive product range includes not only pipettes and clinical chemistry analyzers but also microplate instruments, magnetic particle processing systems, laboratory automation solutions and quantitative real-time polymerase chain reaction and RNA technologies. Businesses are integrated into different divisions of US-based Thermo Fisher Scientific Corporation, a New York Stock Exchange listed company, with revenues of $12 billion and approximately employees. Finnish knowhow is highly valued in our global group: we have been given then opportunity to expand our research and development work, even though originally some suspected the opposite. Now we can network within the company and share in the expertise of our colleagues in other countries, says Bill Östman, Vice President and General Manager, Clinical Diagnostics. Of the 650 employees in Finland, over one hundred work in R&D, and 10 percent of turnover is invested in product development. The long standing collaboration with Tekes has been an important factor when networking with the Finnish research communities and especially when growing the R&D investment in Finland. We produce integrated solutions for healthcare. Product development focuses now on in vitro diagnostics tests and systems based on polymerase chain reaction amplification of DNA and molecular biology. Thermo Scientific innovations have made the company s reagents and services exceptionally sensitive, fast and robust. Focus is on sample purification, reagents and equipment, says Östman. Photos: Thermo Fisher Scientific 37

38 RESEARCH SERVING BUSINESS Department of Biochemistry University of Turku The cooperation between the academia and business focusing on in-vitro diagnostics in the Turku area is exceptionally close. Since its start in 1992 our department has concentrated solely on IVD related research, which makes us unique in the academic world, says Professor Kim Pettersson, Department of Biotechnology, University of Turku (DBUT). Even though DBUT is not involved in product development, the research it carries out in terms of novel technologies, new platform concepts applied to timely application areas is geared towards promoting the diagnostics industry in Finland, its international reputation and success. If companies do not adopt and utilise our knowledge, we have failed. Everything we do must eventually become part of implemented diagnostics either in the short or long term, Pettersson sums up. With the philosophy prevalent at DBUT, it is not unusual for the researchers to employ themselves. Spin-offs are an important part of the Turku IVD community and Tekes has been a central facilitator of this development. Pettersson lists three samples of spin-offs at different stages of maturity: Innotrac Diagnostics Oy was founded in 1996 on the diagnostics principle developed at the University of Turku. The first products were launched in 2001, and in 2006, the company was acquired by Danish Radiometer. Today the growing business employs about 70 people in Finland. RESEARCH TURNED INTO BUSINESS This attitude is reflected in the placing of graduates: since 1996 almost 40 doctors have graduated from Turku, and of these two thirds have found central positions in diagnostics businesses. Photo: University of Turku 38