This proposal will establish a national multidisciplinary centre for research into crystals and powders and the challenges presented by their industrial manufacture, properties and use. Powders, particles, crystals and the molecules they are made of are important in the chemical and pharmaceutical industries as intermediate stages and final products in the manufacture of a range of materials from drugs to inks and pigments to paints to computer screens. Crucially, the structure and properties of crystals, particles and powders control the ease of manufacture, function and performance of the final product and it is therefore important to be able to make these materials reproducibly. Firstly, by understanding the ways in which the molecules, which make up the crystal pack together. Many molecules can adopt several distinct crystal forms by packing together in different ways, which can dramatically affect physical properties despite the fact the same molecule is present. It is vital to control this during crystal formation since the wrong form could for example, affect the amount of drug released by a tablet into the body after it is swallowed. Secondly as the crystal grows its size (micrometres or millimetres), shape, or morphology (flat or round) is critical for some applications especially when many crystal particles come together in a powder and impact on the ease with which the material is subsequently manufactured into a paint or ink for example. These challenges are critical as currently manufacturers struggle with crystal formation and control of their particle and powder properties due to the traditional batch methods they employ. To tackle these problems the Centre aims to revolutionise current processes by researching exciting new continuous methods of crystal formation and particle and powder production applicable to current but importantly also future products such as nanomaterials. In addition the Centre will explore how established methods for molecule synthesis are best integrated with continuous crystallisation processes and how continuously manufactured crystals are isolated, dried and transferred into subsequent formulation and final product manufacturing stages whilst preserving their carefully optimised properties. To maximize these technology changes the Centre must also understand the impact that such a transformation will have on the way companies approach this aspect of their business. This will ensure that the maximum economic potential is effectively exploited. To achieve this the Centre consists of a multidisciplinary team of 14 outstanding researchers from 7 leading Universities covering the country from Glasgow, to Edinburgh, to Cambridge, to Bath. In addition industrial support, interest and input (2 million) will be provided from 3 major pharmaceutical companies and many small technology driven companies within the UK. This provides a combination of academic and industrial expertise ranging from chemistry and chemical engineering to pharmacy and systems management capable of powerfully attacking the issues from many angles. The Centre's aim is to deliver new continuous manufacturing technologies with improved performance in a range of areas. Control of crystal formation and particle and powder properties is critical, however a key goal will also be the development of simpler and faster technologies. Such a combination will permit quicker product development and cheaper, cleaner and greener manufacturing processes. The Centre will deliver these technologies to the UK chemical and pharmaceutical industry thus maintaining this sector at the international forefront of product development and manufacture with obvious national economic benefits in terms of jobs and income. National and international benefits will also arise through better and new medicines and improved and new consumer products, which will assist the global community.

This proposal is to establish a Doctoral Training Centre embedded within the EPSRC Centre for Innovative Manufacturing in Continuous Manufacturing and Crystallisation. The Centre tackles a core issue in the manufacture of fine chemicals and pharmaceuticals - an important sector for the UK - and has strong support from industry including major companies from the Pharma sector (GSK, AstraZeneca, Novartis). We will enable manufacturers to shift their production processes from traditional batch methods, which can be expensive, inefficient and limited in their control, to continuous methods that offer solutions to each of these issues. The Centre can potentially make a huge impact on the UK's manufacturing efficiency in a £multi-billion sector. Although the EPSRC Centre does have a limited cohort of PhD students at the moment, there is no provision for 2012 onwards. As the largest of the current EPSRC Centres, achieving a critical mass of researchers across the core disciplines is a key goal as we establish a world class research activity. It is also important for our industry partners that the UK can meet their needs for trained people in this area and embed continuous processing in their manufacturing plants. We will establish a unique and tailored training and research programme that meets these needs. The proposed DTC will add an extra dimension to the EPSRC Centre, training 3 cohorts of PhD students with the skills, knowledge and understanding to help meet the challenges of continuous manufacturing. Recruiting 45 students over 3 intakes in 2012/13/14 the DTC will mark a step change in activity in this field. We will attract the very best PGR students and equip them to become future leaders who will be influential in implementing this transformational change. The research will contribute to opportunites for new products that can be brought more quickly to market, using more reliable, energy-efficient and profitable manufacturing routes. The Centre involves a multidisciplinary team across 7 universities who will contribute to the DTC including expertise in pharmaceutical sciences, chemical engineering, chemistry, operations management and manufacturing. Thus, the embedded DTC will provide students with a unique programme of training across disciplines, using a combination of modules and research activities. . Students will register in a host institution and will follow a 1+3 year model. Year 1 will comprise intensive formal training delivered in 10 residential courses across the universities, including transferable skills and group project work, allowing the cohort to gain identity and build team spirit and fellowship. Elective specialist elements will then develop knowledge in preparation for PhD research, along with exploratory cross-disciplinary mini-projects. Assessment of modules and projects will be by a combination of presentations and reports. Years 2-4 will focus on multidisciplinary, co-supervised PhD research projects, allowing the student to work with academics from across the Centre. Further transferable skills training and cohort building activities will include an annual two-week Summer School, and networking opportunities with other cohorts. The proposed DTC has captured the imagination of our industrial collaborators with 5 additional companies having added their support to the creation of this DTC. In addition to substantial cash contributions they are offering training, site visits, project input, mentoring and short-term industrial placements. We will create a national community of highly skilled researchers in continuous manufacturing and crystallisation, building the scale and quality of research to enhance the international reputation of our Centre and make a real difference to the manufacture of high-value products, such as pharmaceuticals. The training of 45 high quality DTC PhD students will make a major contribution towards this goal.

The UK chemical sector has an annual turnover of over £32 billion with 99,000 direct jobs in 2016. The Centre's vision is to transform the UK's chemical industry into a fossil-independent, climate-positive and environmentally-friendly circular chemical economy. The overall novelty of our programme is the development of a sector-wide solution with deep circularity interventions, by creating a circular resources flow of olefin-the raw material for 70% of all organic chemical production. Our whole system approach will include key sectors of production, transportation/distribution, refinery/downstream, use and waste recycling, to reduce fossil reliance and improve productivity and sustainability of the whole process industry. The Centre will generate a cross-disciplinary platform combining synergistic innovations in science/engineering with social scientists to comprehend the whole system industrial symbiosis and market/policy/incentive design. The Core Research Programme is organised around three interconnected themes: (1) Key technologies to enable olefin production from alternative/recycling wastes streams and design more reusable chemicals via advanced catalytic processes; (2) Process integration, whole system analysis and value chain evaluation, and (3) Policy, society and finance. Through detailed process modelling, economic analysis and environmental assessment of technology solutions along the supply chain, accelerated understanding, opportunities and optimum solutions to achieve circularity of olefin-derived resources flow will be attained. These activities are embedded with stakeholders involving all affected groups, including local SMEs and downstream users, and will provide evidence and data for policymakers. The Centre will engage with users through social studies and organised events, and exploit consumer/business behavioural change related to chemical systems enabling a sustainable community and society with innovative technologies.

The UK chemical sector has an annual turnover of over £32 billion with 99,000 direct jobs in 2016. The Centre's vision is to transform the UK's chemical industry into a fossil-independent, climate-positive and environmentally-friendly circular chemical economy. The overall novelty of our programme is the development of a sector-wide solution with deep circularity interventions, by creating a circular resources flow of olefin-the raw material for 70% of all organic chemical production. Our whole system approach will include key sectors of production, transportation/distribution, refinery/downstream, use and waste recycling, to reduce fossil reliance and improve productivity and sustainability of the whole process industry. The Centre will generate a cross-disciplinary platform combining synergistic innovations in science/engineering with social scientists to comprehend the whole system industrial symbiosis and market/policy/incentive design. The Core Research Programme is organised around three interconnected themes: (1) Key technologies to enable olefin production from alternative/recycling wastes streams and design more reusable chemicals via advanced catalytic processes; (2) Process integration, whole system analysis and value chain evaluation, and (3) Policy, society and finance. Through detailed process modelling, economic analysis and environmental assessment of technology solutions along the supply chain, accelerated understanding, opportunities and optimum solutions to achieve circularity of olefin-derived resources flow will be attained. These activities are embedded with stakeholders involving all affected groups, including local SMEs and downstream users, and will provide evidence and data for policymakers. The Centre will engage with users through social studies and organised events, and exploit consumer/business behavioural change related to chemical systems enabling a sustainable community and society with innovative technologies.

Our Hub research is driven by the societal need to produce medicines and materials for modern living through novel manufacturing processes. The enormous value of the industries manufacturing these high value products is estimated to generate £50 billion p.a. in the UK economy. To ensure international competitiveness for this huge UK industry we must urgently create new approaches for the rapid design of these systems, controlling how molecules self-assemble into small crystals, in order to best formulate and deliver these for patient and customer. We must also develop the engineering tools, process operations and control methods to manufacture these products in a resource-efficient way, while delivering the highest quality materials. Changing the way in which these materials are made, from what is called "batch" crystallisation (using large volume tanks) to "continuous" crystallisation (a more dynamic, "flowing" process), gives many advantages, including smaller facilities, more efficient use of expensive ingredients such as solvents, reducing energy requirements, capital investment, working capital, minimising risk and variation and, crucially, improving control over the quality and performance of the particles making them more suitable for formulation into final products. The vision is to quickly and reliably design a process to manufacture a given material into the ideal particle using an efficient continuous process, and ensure its effective delivery to the consumer. This will bring precision medicines and other highly customisable projects to market more quickly. An exemplar is the hubs exciting innovation partnership with Cancer Research UK. Our research will develop robust design procedures for rapid development of new particulate products and innovative processes, integrate crystallisation and formulation to eliminate processing steps and develop reconfiguration strategies for flexible production. This will accelerate innovation towards redistributed manufacturing, more personalisation of products, and manufacturing closer to the patient/customer. We will develop a modular MicroFactory for integrated particle engineering, coupled with a fully integrated, computer-modelling approach to guide the design of processes and materials at molecule, particle and formulation levels. This will help optimise what we call the patient-centric supply chain and provide customisable products. We will make greater use of targeted experimental design, prediction and advanced computer simulation of new formulated materials, to control and optimise the processes to manufacture them. Our talented team of scientists will use the outstanding capabilities in the award winning £34m CMAC National Facility at Strathclyde and across our 6 leading university spokes (Bath, Cambridge, Imperial, Leeds, Loughborough, Sheffield). This builds on existing foundations independently recognised by global industry as 'exemplary collaboration between industry, academia and government which represents the future of pharmaceutical manufacturing and supply chain R&D framework'. Our vision will be translated from research into industry through partnership and co-investment of £31m. This includes 10 of world's largest pharmaceutical companies (eg AstraZeneca, GSK), chemicals and food companies (Syngenta, Croda, Mars) and 19 key technology companies (Siemens, 15 SMEs) Together, with innovation spokes eg Catapult (CPI) we aim to provide the UK with the most advanced, integrated capabilities to deliver continuous manufacture, leading to better materials, better value, more sustainable and flexible processes and better health and well-being for the people of the UK and worldwide. CMAC will create future competitive advantage for the UK in medicines manufacturing and chemicals sector and is strongly supported by industry / government bodies, positioning the UK as the investment location choice for future investments in research and manufacturing.