Technology Innovation Centres

Written evidence submitted by BIA Regenerative Medicine Industry Group (BIA RIG) (TIC 78)

Technology Innovation Centres

1. About BIA RIG

1.1. The BioIndustry Association is the trade association for innovative healthcare biotech companies in the UK with over 260 members involved in or supporting the development of new therapeutics. The BIA formed its Regenerative Medicine Industry Group Advisory Committee (RIGAC) to provide a voice for the emerging technologies that make up the field of regenerative medicine and in particular cell-based therapy. Overall there are around 50-60 companies engaged in developing therapeutics in the field of regenerative medicine in the UK. The BIA, through RIGAC, has taken an active role in the UK‟s regenerative medicine community since July 2008.

2. Introduction

2.1. The BIA supports the creation of Technology Innovation Centres (TIC) as a means to successfully translate research into commercial outputs. This paper aims to clearly highlight why a Technology Innovation Centre for regenerative medicine would be effective at bridging "the gap between universities and businesses, and helping to commercialise the outputs of Britain's world-class research base." [1] This perspective is then used to test the fit of the Fraunhofer model to the UK context.

2.2. A TIC for regenerative medicine must bring together all partners in the field including academia, business, clinicians and the NHS. Ultimately investment in regenerative medicine will not just benefit the UK economy, but also develop therapeutics for generations of NHS patients with presently unmet medical needs.

2.3. A TIC would reduce the risk of failure during the research phases for new innovative products as it would provide an environment that would be more conducive to use-inspired research than other institutions as it would combine fundamental and applied research as well as providing a stable funding mechanism for further investment.

2.4. Due to the word limit for this submission we have elected to include lists of examples of institutions to give the committee extra information on the assets the UK holds in the field of regenerative medicine.

3. Why Regenerative Medicine – the Business Case

3.1. The UK is currently a world leader in the science of regenerative medicine; we now need a model which will allow us to benefit from this advantage. Without a TIC the UK will be unable to capitalise on the competitive advantage this UK sector currently possesses. Herman Hauser identified regenerative medicine as a candidate for a TIC for this very reason. [2] Investment is currently accelerating the commercialisation of various regenerative medicine sectors around the world, this in-turn is attracting world class talent away from the UK. [3]

3.2. Estimates for the UK alone, suggest that regenerative medicine has the potential to materially improve the health of around 1 million people a year and generate around £5 billion of commercial activity, to achieve this would require around 15,000 highly skilled workers in the sector. [4] In addition to the economic growth the industry can generate from exports, regenerative medicines have the potential impact on national budgets through their potential to transform healthcare provisions. For example, the total annual cost of diabetes to the NHS has been estimated at between £1.3 billion in 2007. With an increasing number of people suffering from diabetes, the estimates for cost (both direct and indirect healthcare) and lost productivity are likely to increase. There is therefore the potential for over £1 billion in economic impact for the UK with a RM-based treatment for diabetes. [5]

3.3. While the UK currently excels at producing basic research in the field of stem cells and regenerative medicine there is still a significant shortfall in the amount of research being performed with the goal of commercial translation. The primary objective of a TIC would be to pursue use-inspired research. [6] This function is currently not being performed by any organisation in the UK to an extent which makes fully exploits our leading position in the regenerative medicine sector. To date the UK has produced more therapeutics than the rest of Europe together, this trend can continue into the future if investment is targeted wisely. [7]

3.4. The UK has a world class regenerative medicine science sector but it currently does not receive the appropriate level of translation funding. To date the Technology Strategy Board has invested £40-60 million in translation research in this sector compared to the $3 billion investment California is making in the sector. Bringing a new therapeutic to the clinic before the trial process begins costs at least £10 million, this figure demonstrates the need for innovative SMEs to find collaborators to share risks and investment.

3.5. Around the world regenerative medicine research is progressing at a rapid pace and the UK is not in an unassailable position. Globally over the past 10 years 2,765 trials involving cell-based regenerative medicine have taken place. [8] More significantly 51% of these trials were at phase II and III which begins to examine a therapeutics clinical effectiveness.

3.6. A commitment to the sector through the formation of a TIC would demonstrate the government‟s drive to supporting industry which in turn will attract greater inward investment. Pfizer has invested £10s of millions into the UK for regenerative medicine, a TIC will convince other large multinationals, who do not necessarily have the same experience with regenerative medicine, that the UK is serious about commercialising the technology and will provide the infrastructure to assist with this.

4. Specific Requirements for a TIC/Interventions in Regenerative Medicine

4.1. A TIC for regenerative medicine would have to cater to several unique aspects of the industry: including its resource intensive nature and lengthy timescales involved in the development of new therapeutics would mean the TIC would have to provide a model

for collaborative working. To ensure that a regenerative medicine TIC would fulfil this role it must:

· be formed out of a collaboration between academia, business, clinicians and the NHS;

· provide SMEs access to facilities and technologies which they would be unable to afford to own or operate otherwise; [9]

· have capabilities in Good Manufacturing Practice and Advanced Manufacturing in terms of human resources, facilities, quality systems and expertise in process design for new products. It must also be able to measure the quality of the new products produced. A centre would also provide a means for promoting and sharing best practice;

· the funding model must provide an effective means of delivering a therapeutic to phase III of the clinical trial process;

· have the in-house expertise to provide guidance and oversight for the clinical trials process in a broad range of therapeutic areas;

· have strong connections which will allow access to and from the NHS and clinicians enabling the UK to be the first to be benefit from mainstreamed regenerative medicine products;

· the centre should also work with the MHRA, EMA and NICE on appropriate regulation and reimbursement strategies for innovative new therapies;

· facilitate access to funding, by having the capacity to provide proposal writing expertise which would benefit both the TIC and its project partners; [10]

· be linked to existing distribution systems to form networks to distribute therapies, together with direct linkages to the cold supply chain;

4.2. There are also areas where the TIC should be able to work with other governmental and non-governmental entities to competitively position the UK‟s Regenerative Medicine industry by:

· facilitating access to international markets and understanding the reimbursement models of different healthcare systems. Also providing advice on international regulators such as the FDA in the United States and EMA in Europe. This could be done by the UKTI and trade bodies;

· meaningful mechanisms to allow the industry to network and speak with one voice. Also functions to ensure the work the TIC complements the other facilities and projects already successfully running in the UK – this can be, and is being, delivered by trade bodies such as the BIA RIG;

5. Questions:

What is the Fraunhofer model and would it be applicable to the UK?

5.1. Fraunhofer Institutes are physical facilities funded by government, academia and industry. The specific models for different Fraunhofer centres vary depending on the innovation systems they are a part of and the technology they are focused on. Fraunhofer-like Institutes are generally led by industry partnered with government and academia.

5.2. The traditional Fraunhofer model in Germany sees the institutes receive roughly equal funding from three sources: capability growth funding from the Fraunhofer Society, funding from single client projects directly funded by industry and funding from collaborative research grants won competitively. Fraunhofer Institutes rely on a sustained government funding stream to provide a stable platform to attract further investment and develop their technology capability for the future.

5.3. The start up costs of a UK „Fraunhofer‟ in an emerging industry such as regenerative medicine would require government to take on a greater share of the investment into the institute before becoming viable for other stakeholders. This is due to the unique aspects of medical technology such as extended development time-scales and the large investment required for research and development. In the case of regenerative medicine products, their manufacturing is an order of magnitude more complicated than the currently most advanced biopharmaceutical products. The UK would also differ from the German model significantly due to the funding and incentives individual Länder use to attract investment separately from the federal government. Therefore a UK TIC would have to work towards developing a new business model to fill the gap left by regional funding mechanisms.

5.4. Primarily the main industry projects Fraunhofer Institutes undertake are either on behalf of SMEs commercialising new technology or large companies looking to headquarter themselves close to communities of similar business and academia focused on their sector. Fraunhofer Institutes also add value to institutions through their brand‟s strong association with innovation. Institutes have to win the Fraunhofer brand before attracting the supporting finance model.

5.5. In Germany there are currently several institutes working in regenerative medicine which provide examples of the different forms the collaboration between different sectors can take. Appendix A outlines the work Germany‟s Fraunhofers perform in the regenerative medicine sector.

5.6. In terms of what would be suitable for the UK, several studies of intermediate institute models have produced, most notably Herman Hauser‟s The Current and Future Role of Technology Innovation Centres in the UK and James Dyson‟s Ingenious Britain. [11] [12]

5.7. Additionally we recommend that the committee requests evidence from Erik Arnold of Technopolis [13] who is a specialist in the design and evaluation of the effectiveness of applied research programmes and has already been involved with regenerative medicine associated activities e.g. cord blood banking. [14]

5.8. The UK needs a regenerative medicine TIC which is a physical hub and possesses the equipment and capabilities to fully commercialise regenerative medicine research. A TIC will create a critical mass for the regenerative medicine industry in the UK to become self sustaining and to add value to the nation overall.

Are there existing Fraunhofer-type research centres within the UK, and if so, are they effective?

5.9. There are currently no alternative models present in the UK that would fulfil the work of a Fraunhofer Institute in the regenerative medicine sector.

5.10. The UK does possess significant private and public assets that would complement the formation of a TIC and ensure that it worked effectively within existing systems and structures. While these centres and institutes are useful they do not provide the direct means to fully translate a promising piece of regenerative medicine research produced by academia/industry into a marketed therapeutic. These assets listed in Appendix B currently put the UK‟s regenerative medicine sector on a par with other countries, without further investment in a translation centre we will fail to benefit from the £100 million plus tax-payer investment to date in stem cell research.

5.11. The UK assets and complementary centres have provided the nation with a significant comparative advantage in the field of regenerative medicine. However even with the wealth of assets the UK possess there is still a critical gap which exists in translating new technology into commercial products.

5.12. Funding for academic research and grants by the Medical Research Council and the Wellcome Trust has meant that the upstream science for regenerative medicine has given us a world leading research base and this must continue in order to produce the basic science to advance the sector as a whole. Several other bodies such as the EPSRC, BBSCR, NIHR and NIBSC provide additional funding to basic research before it begins to be commercialised. Centres such as the MRC CRM have the goal to translate research into therapeutics but as yet have limited resources to engage with the commercial sector plus they are not fully commited to regenerative medicine. The TSB has invested £40-60 million into the regenerative medicine translation space, however it does not provide companies with direct access to expertise and crucial equipment that is required to fully commercialise regenerative medicine products.

What other models are there for research centres orientated towards applications and results?

5.13. Other countries have developed significant infrastructures to facilitate the translation of research. In regenerative medicine/translational medicine there are some key international Academic, Business and Clinical (ABC) centres:

· The McGowan Institute at the University of Pittsburgh has contributed significantly to the growth of the regenerative medicine sector in the USA. It has a focus on upstream science, clinical trials and application. Its parent, the UPMC, is now one of the largest medical systems in the North America (22 hospitals) and reinvests a portion of its income into McGowan. As a consequence McGowan is able to partner with industry and business – it therefore can make advantageous „deals‟ rather than behaving as a pure for-service sub-contractor. [15]

· Wake Forest Institute for Regenerative Medicine (Winston-Salem, NC, USA) is a several hundred million dollar funded centre that runs collaborative programmes with industry and academia. It has a guiding philosophy to form research alliances and identify strategic partners that are critical to the continued growth and success of their research enterprise. [16] The institute has achieved significant milestones in the field of regenerative medicine such as the first laboratory grown bladder. [17]

· California Institute for Regenerative Medicine. This does not have a physical presence instead it operates as a virtual model or as a „banker‟ for research on a large scale. The Institute receives around $3 billion of funding through California State Proposition 71. [18]

5.14. There are also alternative models in the UK which could be investigated:

· Research and Technology Organisations (RTOs) - RTOs are organisations which as their predominant activity provide research and development, technology and innovation services to enterprises, governments and other clients. This definition distinguishes RTOs from universities, the predominant activity of which is education, and from enterprises, the predominant activity of which is the production and sale of goods and services. [19]

· Knowledge Transfer Networks - The HTM KTN is dedicated to accelerating innovation and technology exploitation in the broad health industries sector. [20]

· Technology Strategy Board managed Innovation Platforms - The TSB has run successful Innovation Platform programmes in areas such as stratified medicines. While these are successful at targeting funding at particular areas it cannot provide the physical equipment and other resources that are essential to commercialise research or the permanent expertise to guide new businesses.

· OSCHR - see appendix B

5.15. There are also instances of alliances, trade associations and lobby groups in the UK and other locations the BIA RIG in the UK, ARM in the US and RMIG in Germany. (See appendix C for more info)

Whose role should it be to coordinate research in a UK-wide network of innovation centres?

5.16. The Technology Strategy Board has continually demonstrated its leadership, excellence and impact as a body that successfully oversees the translational of research into commercial activity. We therefore most highly recommend the TSB co-ordinates UK-wide network of TICs.

5.17. For the governance of a specific TIC in regenerative medicine, the BIA supports the recommendation by Herman Hauser for centres to be industry led. An advisory committee consisting of stakeholders formed of academia, business, clinicians, the NHS and patient organisations would provide significant input into the governance of the centre and ensure the collaborative functions of the centre worked effectively.

What effect would the introduction of Fraunhofer-type institutes have on the work of Public Sector Research Establishments and other existing research centres that undertake Government sponsored research?

5.18. A TIC must complement current UK assets and existing NHS centres as outlined in the answer to Question 2 (above).

5.19. The UK research institutes are currently primarily academically based with research funding up to TRL4 stage (research which seeks to evaluate the „real world‟ health outcomes application of basic research in practice) - this still leaves a significant funding gap before the research technologies become viable for business. A TIC‟s primary objective would be to successful cross this gap and thus provide a secure means to commercialise research.

5.20. The work of a TIC would primarily be focused on the commercialisation aspects of TRL 4-6 but with elements working to TRL 9 and beyond.

5.21. Currently the TSB funds translational activities up to TRL 7 as this is the point where traditionally technology businesses become commercially viable. However, due to the need to new cell-based therapeutics to be tested and evaluated up until it receives full marketing approval the centre would also need expertise and to provide support for the later stages of product development and early manufacturing. With this joined-up multidisciplinary support, regenerative medicine SMEs will become more attractive to larger companies looking for partnerships or acquisitions.

5.22. Crucially for the emerging regenerative medicine sector ,a TIC would provide a focal point for many of the discussions and issues which the sector still has to address including appropriate regulation, scalable manufacture and reimbursement. It would also provide a central approach to engaging with the NHS and patients. Importantly as well, it would provide a means to look at models to capture the value of cell-based therapies and to develop the market models which will be crucial to the sectors commercial future. These will include both patient specific (NHS-embedded) and universal therapies (conventional pharma/biotech-based model).

5.23. A regenerative medicine TIC would enable the world-class stem cell and regenerative medicine science that is produced by the UK to be turned into safe, efficacious cell-based therapies that are capable of being scalably manufactured at a price that is affordable. The result will be a sustainable and competitive new UK healthcare sector – a win for patients, the NHS and UK plc.

BioIndustry Association (BIA)

02 December 2010

Appendix A: Regenerative Medicine Fraunhofers

1.1. The Fraunhofer Institute for Immunology and Cell Therapy IZI Leipzig

The Institute was created to find solutions to specific problems at the interfaces between medicine, life sciences and engineering. The Institute’s core competencies are to be found in regenerative medicine

1.2. The Institute works especially closely with hospitals, performing quality tests and clinical studies on their behalf. Additionally it also provides assistance in obtaining manufacturing licenses and certifications. [21] The table below gives an overview of the projects the institute was involved in for 2009:

1.3. Fraunhofer-Gesellschaft : FhG-IGB Stuttgart, FhG-ISC Würzburg, FhG-IBMT Berlin

The FhG-IGB Stuttgart, FhG-ISC Würzburg, FhG-IBMT Berlin make up part of the Fraunhofer-Gesellschaft, Europe’s largest application-oriented research organization. [22] Unlike Leipzig, none of these Fraunhofers focus solely on regenerative medicine, instead they contribute to the sector through the development and optimization of processes and products which end up benefiting a variety of business sectors. [23]

1.4. Each centre has a particular focus. Würzburg targets developing supporting implant materials for the regeneration of skin, bone and cartilage. Stuttgart specialises in the development and optimization of processes and products for the business areas of medicine, pharmacy, chemistry, the environment and energy. The Berlin campus works in close collaboration with industry offering solutions in the areas of biomedical and medical engineering as well as industrial process automation and in-line/on-line process control, in particular for the food, chemical and pharmaceutical industry. [24] It is the only institute in Germany which has permission to import human embryonic stem cells.

Appendix B: UK Complimentary Centres and National Assets

1.1. Complimentary Centres

UK Centre for Medical Research and Innovation (UKCMRI):

· This £600 million collaboration between the Medical Research Council, Cancer Research UK, Wellcome Trust and UCL will be an interdisciplinary medical research institute. UKCMRI will encourage ground-breaking research across a range of scientific disciplines and facilitate the translation of discoveries into treatments as quickly as possible. [25] However it is not currently known whether UKCMRI will have any major involvement with the regenerative medicine community plus the centre itself will not be completed until 2015.

1.2. Scottish Centre for Regenerative Medicine incorporating the MRC Centre for Regenerative Medicine (MRC CRM). [26]

· Brings together world-leading basic stem cell research and established clinical excellence to deliver a ‘bench-to-bedside’ approach in addressing the challenges posed by degenerative diseases.

· The MRC Centre in Cambridge brings together leading researchers in two Cambridge faculties (School of Biological Sciences and School of Clinical Medicine) and enables them to translate their individual research into clinical use by providing them with dedicated stem cell research resources and a forum for collaborative interactions, including state-of-the-art stem cell culture facilities, seminars and a training programme.

· EPSRC has made significant investment in research infrastructure in regenerative medicine including the EPSRC Centre for Innovative Manufacturing in Regenerative Medicine. This Loughborough University led partnership including Nottingham and Keele universities, has focuses on upstream (TRL1-4) industry collaborative research to enable the regulated manufacturing and supply of regenerative medicine products.

· The EPSRC and TSB funded Innovation and Knowledge Transfer Centre in Regenerative Therapies and Devices in Leeds facilitates collaboration between companies, engineers, scientists and clinicians to develop innovative biomaterial-focussed technologies that help the body repair and restore function. The IKC invests resources in TRL 3 and 4 to bridge the specific gap in proof of concept studies.

1.3. Other UK national assets

National Institute for Biological Standards and Control (NIBSC)

· The NIBSC role is to play a major national and international role in assuring the quality of biological medicines through product testing, developing standards and reference materials and carrying out applied research. It supports health policy development and implementation through provision of expert evidence-based advice and technical support and is an important component of the Department of Health’s risk management strategy for public health. [27]

1.4. UK Stem Cell Bank

· The UK Stem Cell Bank was established within NIBSC to provide a repository of human embryonic, foetal and adult stem cell lines as part of the UK’s governance for the use of human embryos for research. Its role is to provide quality controlled stocks of these cells that researchers worldwide can rely on to facilitate high quality and standardised research.

1.5. NHS Blood and Transfusion Service

· NHSBT manages the consent, collection, and delivery to patients of over 2,000 adult heamopoetic (blood) stem cell transplants and 13,000 human tissue allograft p.a; giving it a unique position to support the growing regenerative medicine market. The delivery of viable treatments is supported by a strong research function, including driving innovative technology development in collaboration with universities. Utilising its knowledge and facilities it also provides contract manufacture services to SMEs and clinicians.

1.6. Office for Strategic Co-ordinated Health Research

· OSCHR’s mission is to facilitate more efficient translation of health research into health and economic benefits in the UK through better coordination of health research and more coherent funding arrangements. [28]

1.7. NHS

· The greatest potential asset the UK has for any form of medical research is the NHS. The ability to access a centralised patient population with the potential to work with a single centralised system would provide researchers with ability to recruit and monitor patients easily.

Appendix C Best practice models for translational research centres in medical technologies

A Joint Loughborough University - University Hospitals of Leicester MRC IDBA International Innovation Workshop, ABHI, London 23 January 2008

Introduction

It is becoming recognised that there is an international requirement to create translational research centres in medical technologies. Such centres of excellence will work by integrating clinical professionals, industry and academia and are targeted at generating practical improvements in human health and business opportunities. This will be achieved by enabling the systematic research needed to translate inventions into practical technology platforms which have the potential to be exploited to the benefit of patients and the businesses which can produce them. This in turn will further enhance national and regional economic activity progressing national and regional innovation agendas and enhancing the role of healthcare provider organisations as an engine for regional economic growth.

The purpose of the workshop was to share best practice nationally and internationally to explore the essential strategies for success in the development of such centres of excellence and to have a timely influence on UK policy.

The workshop formed part of the work of the innovation strand of the Joint Loughborough University/University Hospitals of Leicester NHS Trust MRC funded Interdisciplinary Bridging Award (IDBA).

The core of the meeting was formed from presentations by Dr Mark Beggs, Programme Manager of the Wyeth Translational Medicine Research Collaboration (TMRC), Dundee, and Dr Alan Russell, Director of the McGowan Institute for Regenerative Medicine, University of Pittsburgh Medical Centre, and the ensuing discussion. This note summarises the presentations and discussion, including some subsequent to the meeting. Attendees are shown in the appendix.

During the meeting Jill Dhell gave an update on the status of the National Institutes for Health Research (NIHR) stemming from "Best Research for Best Health" and of the two pilot Healthcare Technology Co-operatives (HTC) linking academia, business and clinicians, indicating that they were to be announced in the next few weeks. Each HTC is to be provided with core funding of £275k p.a for two years and is aimed to prime infrastructure for medical technology research in areas of unmet clinical need, centred on the patient. The role of the topic-specific research networks, and the UK Clinical Research Collaboration and associated networks was also noted.

Data on two other examples of significant internationally recognised translational medicine centres, The Langer Lab at MIT and the Translational Centre for Regenerative Medicine in Leipzig, were also tabled.

Translational Medicine Research Centre at Dundee, Mark Beggs, Wyeth

Mark’s presentation began with an explanation of the motivation for the Dundee Centre. A major problem for the pharmaceutical industry is the very high level of product attrition rates that occur within Phase 2 clinical trials, which continues to worsen. Wyeth believe that the development and application of bio-markers which can be used for drug discovery and development will decrease attrition rates through the product pipeline. They see the key to success in the creation of TRMC as being an appropriate combination of academic research, NHS involvement and industrial collaboration. All parties bring different sets of attributes, which when combined help overcome the major impediments to the development of new bio-markers.

The TMRC model involves four universities (Dundee, Aberdeen, Glasgow and Edinburgh) as well as 4 NHS Trusts, Scottish Enterprise and Wyeth each with complementary skills. The latter contributes $8m via operational funding and $45m via research contracts and Scottish Enterprise provide $35m; half as an R&D grant on the basis of a 5-year renewable award and half as a loan. Having a defined time limit focuses minds upon successful delivery. The TMRC acts as a hub for the translational community.

Governance of the collaboration is important as this is not a grant funding scheme nor is it as rigid as contract research. Full economic costs are paid to academia and any resulting IP is assigned across the collaboration partners depending on its application. The initiative represents a balanced middle road to collaboration where all parties receive mutual benefit.

The mechanics of the scheme involve ideas being jointly generated by the company and the Principal Investigator (PI), which are then peer reviewed by the PI and his or her opposite number in Wyeth – to ensure strategic business fit – followed by further review by the TMRC. Project costs are paid for by Wyeth and infrastructure support by Scottish Enterprise. To allow for flexibility, research plans may be modified to the mutual agreement of all parties. IP is jointly owned via a complex model which permits academic publication subject to prior protection.

The dedicated Core Laboratory base in Dundee acts as an analytical centre of excellence for the four Universities and is run as a central service with the extremely high quality standards required for exploitation. The Core Laboratory is also responsible for all ethics and governance control as well as ensuring that all base data are collected and handed over at the end of a project. It focuses on the development of platform tools and technologies including genomics, proteomics, assay development, bio-statistics and informatics. By 2011 deliverables expected include, from the commercial perspective: IP development, economic growth, new diagnostic tests, earlier diagnosis of disease and an increase in the number of novel therapies. From a research perspective, highly cited publications and the development of new research areas and topics will be key outputs.

Immediate discussion that followed centred on the issue of state aid, and the reasons why Wyeth had chosen Scotland. Responses to the latter included the readiness of the Scottish network and its geographic concentration, the historic familiarity with clinical trial work in Scotland due to certain disease prevalence, the relative simplicity in progressing discussions and the availability of electronic patient identification in Scotland.

McGowan Institute for Regenerative Medicine, University of Pittsburgh Medical Centre, UPMC, Alan Russell

The presentation began with the background to the development of the UPMC and the economic regeneration of the former steel town. A great deal of the city’s wealth is now generated as a direct consequence of the prowess of its universities (Duquesne, Pittsburgh and Carnegie-Mellon) including their interaction with the health industry. The UPMC has undergone significant growth since its foundation as an academic medical centre in the early 90’s. It is now one of the largest medical systems in the US (22 hospitals) and has an operating margin of around 5% on a revenue of more than $6bn. As a consequence it is able to partner with industry and business – it makes deals rather than behaving as a mere sub-contractor. UPMC is now the sixth largest recipient of NIH funding ($375.8m) and has some 1,800 faculty members. It has been working in regenerative medicine for twelve years and in 2000 it visibly established its focus via the McGowan Institute with the sole passion to bring new regenerative technologies to its patients as quickly and as safely as possible – clinical translation. Importantly, McGowan will apply other peoples work too. UMPC pump primed McGowan at a significant level ($3-5m). It is important to recognise that this focus has also enabled significant success in for example spin out (14) and job creation (~470) for the region. It also has 10-15 clinical trials in progress and significant Department of Defence funding. While McGowan includes 215 faculty across the region, one third of whom are clinicians, the core of McGowan is 35 faculty located in two new buildings – income to the core faculty is around $15m per year with $73m to the wider organisation.

The success of the UPMC and the McGowan Institute can be directly attributed to the level of its interdisciplinary research, many of the successes would not have been achieved without different disciplines learning how to effectively work together whilst remaining focused on a common goal. This requires a critical mass of individuals/expertise and getting people to work together. Consequently a focus on clustered teams has been a priority from "day one". It was emphasised that interdisciplinary work is unnatural and that traditionally academics are happy to work in their individual silos, it requires behavioural change and the resetting of clinical ambitions (by buy-outs for research). Alan emphasised the work of McGowan was sited in Pasteur’s Quadrant – that of value laden use inspired basic research (see Donald Stokes, Pasteur’s Quadrant: Basic Science and Technological Innovation, Washington DC: The Brookings Institution, 1997) – in effect representing the journey from bench to bedside and back, translational medicine.

Alan highlighted the key lessons learnt in successfully establishing the Institute. These included: the need to secure commitment from individual academics and groups of academics which then enables these to be linked together; the activity must take place on a large scale ($10m is a minimum to make an impact, in reality >$50m is required); individuals need to be 100% committed to the concept of interdisciplinary working and "fakers", non-collaborators just in it for the funding, are rooted out early; the focus has been objective driven (patient-focused). Additionally, the whole working environment and related "hygiene factors" need to be excellent, there has to be sufficient "foundations and scaffolds" for individual groups to build their "castles". He reinforced the need for bottom up buy-in, empowered leadership top down facilitation and management, clear management structures, the need for a mixture of central dedicated facilities and the ability to offer appropriate incentives to staff to facilitate their participation. A common barrier to facilitating interdisciplinary research is an existing negative culture and overly complex tiers of bureaucracy/hierarchy. Some level of project failure is to be expected and encouraged if internationally leading and valuable work is to be carried out. Inter-institutional collaborations are also not without problems: for example, an attempt to use common IP terms and conditions in contracts between institutions have not worked in Pittsburgh.

He closed by saying that the Institute and the UPMC wish to export their model and are establishing some other worldwide translational science centres, including one in Palermo, Sicily at a cost of EURO 350M. They also have aspirations to perhaps establish similar centres in Ireland and the UK. UPMC will undertake management, under contract, of a hospital facility in the UK in the near future.

Following the presentation, discussion began with questions on the McGowan model but subsequently broadened to other areas. In summary it included the following:

· Research on a large scale is essential because of critical mass requirements and a pragmatic recognition that at least 30% of activity will never generate the anticipated outcomes. True solutions only tend to be found where a significant level of activity is duplicated between competing groups. The $50m threshold for work of value requires identified leadership, the scientific and business/economic case for the particular field and influencing at the right level of government. The evidence for the business/economic case is both the hardest to generate and to evaluate. Any business case is likely to be phased.

· It would be of value to have a more extensive survey of the different models of translational research centre to assist in the preparation of business cases for any UK initiatives.

· The importance of physical/regional co-location and joint working of a core was also emphasised as evidenced by both models – being there must be part of the daily work of the people. Choosing the full time team is also critical. This challenges some of the current UK emphasis on networks and committees of involved but not committed stakeholders.

· Often the initial ideas for such institutes occur bottom-up in an informal setting and are usually only taken forward successfully where a charismatic leader exists. The leader must build a persuasive scientific and business/economic case and give directional leadership to the emerging enterprise. The operational details then follow. The theme of such an institute, the "big idea", will inevitably match a local need but resonate at a larger scale, embrace risk and probably "change the rules".

· It was acknowledged that within the UK there is a growing national and regional recognition of the need to think bigger, as has been evidenced in recent aerospace and energy initiatives. Large institute models are under consideration for a national nanomedicine initiative. The importance of developing national and regional "joined up thinking" between individual RDAs, the Research Councils, the Technology Strategy Board, industry, the NHS and universities was emphasised.

David Williams, Oliver Wells and Peter Townsend, February 2008

Attendees at IDBA Innovation Workshop ABHI, London 23 January 2008

Appendix D: Regenerative Medicine Trade Representatives

BIA-RIG, UK - Regenerative Medicine Industry Group represents the UK cell-based therapy industry – currently over 50-60 small and medium size entities (SMEs) in the UK plus growing interest from big pharma. BIA-RIG embraces every option for regenerative medicine including tissue engineering, adult and embryonic stem cells.

ARM, US - The Alliance for Regenerative Medicine (ARM) is a Washington, based non-profit organization whose mission is to educate key policy makers about the potential of regenerative medicine and to advocate for favourable public policies.

RMIG, Germany - The Regenerative Medicine Initiative Germany has been established to act as a cross-sectional, multidisciplinary network within a broad spectrum of biological material research concerning stem cell biology.