The Innovative Manufacturing and Construction Research Centre (IMCRC) will undertake a wide variety of work in the Manufacturing, Construction and product design areas. The work will be contained within 5 programmes:1. Transforming Organisations / Providing individuals, organisations, sectors and regions with the dynamic and innovative capability to thrive in a complex and uncertain future2. High Value Assets / Delivering tools, techniques and designs to maximise the through-life value of high capital cost, long life physical assets3. Healthy & Secure Future / Meeting the growing need for products & environments that promote health, safety and security4. Next Generation Technologies / The future materials, processes, production and information systems to deliver products to the customer5. Customised Products / The design and optimisation techniques to deliver customer specific products.Academics within the Loughborough IMCRC have an internationally leading track record in these areas and a history of strong collaborations to gear IMCRC capabilities with the complementary strengths of external groups.Innovative activities are increasingly distributed across the value chain. The impressive scope of the IMCRC helps us mirror this industrial reality, and enhances knowledge transfer. This advantage of the size and diversity of activities within the IMCRC compared with other smaller UK centres gives the Loughborough IMCRC a leading role in this technology and value chain integration area. Loughborough IMCRC as by far the biggest IMRC (in terms of number of academics, researchers and in funding) can take a more holistic approach and has the skills to generate, identify and integrate expertise from elsewhere as required. Therefore, a large proportion of the Centre funding (approximately 50%) will be allocated to Integration projects or Grand Challenges that cover a spectrum of expertise.The Centre covers a wide range of activities from Concept to Creation.The activities of the Centre will take place in collaboration with the world's best researchers in the UK and abroad. The academics within the Centre will be organised into 3 Research Units so that they can be co-ordinated effectively and can cooperate on Programmes.

The broad theme of the research training addresses the most rapidly developing parts of the bio-centred pharmaceutical and healthcare biotech industry. It meets specific training needs defined by the industry-led bioProcessUK and the Association of British Pharmaceutical Industry. The Centre proposal aligns with the EPSRC Delivery Plan 2008/9 to 2010/11, which notes pharmaceuticals as one of the UK's most dynamic industries. The EPSRC Next-Generation Healthcare theme is to link appropriate engineering and physical science research to the work of healthcare partners for improved translation of research output into clinical products and services. We address this directly. The bio-centred pharmaceutical sector is composed of three parts which the Centre will address:- More selective small molecule drugs produced using biocatalysis integrated with chemistry;- Biopharmaceutical therapeutic proteins and vaccines;- Human cell-based therapies.In each case new bioprocessing challenges are now being posed by the use of extensive molecular engineering to enhance the clinical outcome and the training proposed addresses the new challenges. Though one of the UK's most research intensive industries, pharmaceuticals is under intense strain due to:- Increasing global competition from lower cost countries;- The greater difficulty of bringing through increasingly complex medicines, for many of which the process of production is more difficult; - Pressure by governments to reduce the price paid by easing entry of generic copies and reducing drug reimbursement levels. These developments demand constant innovation and the Industrial Doctorate Training Centre will address the intellectual development and rigorous training of those who will lead on bioprocessing aspects. The activity will be conducted alongside the EPSRC Innovative Manufacturing Research Centre for Bioprocessing which an international review concluded leads the world in its approach to an increasingly important area .

Regenerative medicine (RM) is a convergence of conventional pharmaceutical sciences, medical devices and surgical intervention employing novel cell and biomaterial based therapies. RM products replace or regenerate damaged or defective tissues such as skin, bone, and even more complex organs, to restore or establish normal function. They can also be used to improve drug testing and disease modelling. RM is an emerging industry with a unique opportunity to contribute to the health and wealth of the UK. It is a high value science-based manufacturing industry whose products will reduce the economic and social impact of an aging population and increasing chronic disease.The clinical and product opportunities for RM have become clear and a broad portfolio of products have now entered the translational pipeline from the science bench to commercialisation and clinical application. The primary current focus for firms introducing these products is first in man studies; however, success at this stage is followed by a requirement for a rapid expansion of delivery capability - the 'one-to-many' translation process. This demands increasing attention to regulatory pathways, product reimbursement and refinement of the business model, a point emphasised by recent regulatory decisions demanding more clarity in the criteria that define product performance, and regulator initiatives to improve control of manufacturing quality. The IMRC will reduce the attrition of businesses at this critical point in product development through an industry facing portfolio of business driven research activities focussed on these translational challenges. The IMRC will consist of a platform activity and two related research themes. The platform activity will incorporate studies designed to influence public policy, regulation and the value system; to explore highly speculative and high value ideas (particularly clinically driven studies); and manufacturing-led feasibility and pilot studies using state of the art production platforms and control. The research themes will focus on areas identified as particular bottlenecks in RM product translation. The first theme will explore the delivery, manufacturing and supply processes i.e. the end to end production of an RM product. Specifically this theme will explore using novel pharmaceutical technology to control the packaged environment of a living RM product during shipping, and the design of a modular solution for manufacturing different cell based therapies to the required quality in a clinical setting. The second research theme will apply quality by design methods to characterise the quality of highly complex RM products incorporating cells and carrier materials. In particular it will consider optical methods for non-invasive process and product quality control and physicochemical methods for process monitoring.The IMRC will be proactively managed under the direction of a Board and Liaison Group consisting of leading industrialists to ensure that the Centre delivers maximum value to the requirements of the business model and assisting the growth of this emerging industry.

It is now widely accepted that up to ten years are needed to take a drug from discovery to availability for general healthcare treatment. This means that only a limited time is available where a company is able to recover its very high investment costs in making a drug available via exclusivity in the market and via patents. The next generation drugs will be even more complex and difficult to manufacture. If these are going to be available at affordable costs via commercially viable processes then the speed of drug development has to be increased while ensuring robustness and safety in manufacture. The research in this proposal addresses the challenging transition from bench to large scale where the considerable changes in the way materials are handled can severely affect the properties and ways of manufacture of the drug. The research will combine novel approaches to scale down with automated robotic methods to acquire data at a very early stage of new drug development. Such data will be relatable to production at scale, a major deliverable of this programme. Computer-based bioprocess modelling methods will bring together this data with process design methods to explore rapidly the best options for the manufacture of a new biopharmaceutical. By this means those involved in new drug development will, even at the early discovery stage, be able to define the scale up challenges. The relatively small amounts of precious discovery material needed for such studies means they must be of low cost and that automation of the studies means they will be applicable rapidly to a wide range of drug candidates. Hence even though a substantial number of these candidates may ultimately fail clinical trials it will still be feasible to explore process scale up challenges as safety and efficency studies are proceeding. For those drugs which prove to be effective healthcare treatments it will be possible then to go much faster to full scale operation and hence recoup the high investment costs.As society moves towards posing even greater demands for effective long-term healthcare, such as personalised medicines, these radical solutions are needed to make it possible to provide the new treatments which are going to be increasingly demanding to manufature.

SummaryContinued improvement in the nation's health depends upon the efficient development of affordable replacement human tissue and related therapies; an acute shortage of willing organ donors and the shortcomings of conventional therapies leads to the preventable death of many patients each year. The next healthcare revolution will apply regenerative medicines, creating biological therapies or substitutes for the replacement or restoration of tissue function lost through failure or disease. However, whilst science has revealed the potential, and early products have shown the power of such therapies, there is now a need for the long term supply of people properly trained with the necessary skills to face the engineering and life science challenges before the predicted benefits in human healthcare can be realised. Because the products arising from this technology differ significantly from those made by mainstream pharmaceutical companies, training programmes currently available are poorly equipped to meet the demand for increasing numbers of appropriately trained personnel. We estimate that the number of engineers with the necessary skills to interact `on the same level' with cutting edge bioscientists and clinicians is very small, perhaps no more than 100 nationally; in such a small community 50 newly trained PhD's will have a very large impact. Here we propose a new UK based DTC in Regenerative Medicine integrated across three Universities with highly complementary expertise where students will be trained in the core skills needed to work at the life science/engineering interface and then engaged in strategic research programmes designed to address the major challenges in the field. This will ensure that the necessary people and enabling technologies are developed for the UK to lead in this rapidly growing worldwide marketplace.