The UK government's support for the Life Sciences Industry Strategy (Bell Report, 2017) recognises the importance of developing new medicines to facilitate UK economic growth. Examples include new antibody therapies for the treatment of cancer, new vaccines to control the spread of infectious diseases and the emergence of cell and gene therapies to cure previously untreatable conditions such as blindness and dementia. Bioprocessing skills underpin the safe, cost-effective and environmentally friendly manufacture of this next generation of complex biological products. They facilitate the rapid translation of life science discoveries into the new medicines that will benefit the patients that need them. Recent reports, however, highlight specific skills shortages that constrain the UK's capacity to capitalise on opportunities for wealth and job creation in these areas. They emphasise the need for 'more individuals trained in advanced manufacturing' and for individuals with bioprocessing skills who can address the 'challenges with scaling-up production using biological materials'. The UCL EPSRC CDT in Bioprocess Engineering Leadership has a successful track record of equipping graduate scientists and engineers with the bioprocessing skills needed by industry. It will deliver a 'whole bioprocess' training theme based around the core fermentation and downstream processing skills underpinning medicines manufacture. The programme is designed to accelerate graduates into doctoral research and to build a multidisciplinary research cohort; this will be enhanced through a partnership with the Synthesis and Solid State Pharmaceutical Centre (SSPC) and the National Institute for Bioprocess Research and Training (NIBRT) in Ireland. Research projects will be carried out in partnership with leading UK and international companies. The continued need for the CDT is evidenced by the fact that 96% of previous graduates have progressed to relevant bioindustry careers and many are now in senior leadership positions. The next generation of molecular or cellular medicines will be increasingly complex and hence difficult to characterise. This means they will be considerably more difficult to manufacture at large scale making it harder to ensure they are not only safe but also cost-effective. This proposal will enable the CDT to train future bioindustry leaders who possess the theoretical knowledge and practical and commercial skills necessary to manufacture this next generation of complex biological medicines. This will be achieved by aligning each researcher with internationally leading research teams and developing individual training and career development programmes. In this way the CDT will contribute to the future success of the UK's bioprocess-using industries.

The UK government recognises that 'our economy is driven by high levels of skills and creativity' and has prioritised investment in skills as a means to recovery rapidly from the current economic downturn (HM Government: New Industry, New Jobs, 2009). Bioprocessing skills underpin the controlled culture of cells and microorganisms and the design of safe, environmentally friendly and cost-effective bio-manufacturing processes. Such skills are generic and are increasingly being applied in the chemical, pharmaceutical and regenerative medicine sectors. Recent reports, however, highlight specific skills shortages that constrain the UK's capacity to capitalise on opportunities for wealth and job creation in these areas. They emphasise the need for bioprocessing skills related to the application of 'mathematical skills... to biological sciences', in core bioprocess operations such as 'fermentation' and 'downstream processing' and, for many engineering graduates 'inadequate practical experience'. UK companies have reported specific problems in 'finding creative people to work in fermentation and downstream processing' (ABPI: Sustaining the Skills Pipeline, 2005 & 2008) and in finding individuals capable of addressing 'challenges that arise with scaling-up production using biological materials' (Industrial Biotechnology Innovation and Growth Team report: Maximising UK Opportunities from Industrial Biotechnology, 2009). Bioprocessing skills are also scarce internationally. Many UK companies have noted 'the difficulties experienced in recruiting post-graduates and graduates conversant with bioprocessing skills is widespread and is further exaggerated by the pull from overseas (Bioscience Innovation and Growth Team report: Bioscience 2015, 2003 & 2009 update). The EPSRC Industrial Doctorate Centre (IDC) in Bioprocess Engineering Leadership has a successful track record of equipping graduate scientists and engineers with the bioprocessing skills needed by UK industry. It will deliver a 'whole bioprocess' training theme based around fermentation and downstream processing skills which will benefit from access to a superbly equipped £25M bioprocess pilot plant. The programme is designed to accelerate graduates into doctoral research and to build a multidisciplinary research cohort. Many of the advanced bioprocessing modules will be delivered via our MBI Training Programme which benefits from input by some 70 industry experts annually (www.ucl.ac.uk/biochemeng/industry/mbi). Research projects will be carried out in collaboration with many of the leading UK chemical and pharmaceutical companies. The IDC will also play an important role supporting research activities within biotechnology-based small to medium size enterprises (SMEs). The need for the IDC is evidenced by the fact that the vast majority of EngD graduates progress to relevant bioindustry careers upon graduation. This proposal will enable the IDC to train the next generation of bioindustry leaders capable of exploiting rapid progress in the underpinning biological sciences. Advances in Synthetic Biology in particular now enable the rational design of biological systems to utilise sustainable sources of raw materials and for improved manufacturing efficiency. These will lead to benefits in the production of chemicals and biofuels, in the synthesis of chemical and biological pharmaceuticals and in the culture of cells for therapy. The next generation of IDC graduates will also possess a better understand of the global context in which UK companies must now operate. This will be achieved by providing each EngD researcher with international placement opportunities and new training pathways either in bioprocess enterprise and innovation or in manufacturing excellence. In this way we will provide the best UK science and engineering graduates with internationally leading research and training opportunities and so contribute to the future success of the UK bioprocess industries.

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.