EPSRC Centre for Doctoral Training in Emergent Macromolecular Therapies (EMT): A National CDT linked to an EPSRC Centre for Innovative Manufacturing

The bioprocess industry manufactures novel macromolecular drugs, proteins, to address a broad range of chronic and debilitating human diseases. The complexity of these protein-based drugs brings them significant potential in terms of potency against disease, but they are also much more labile and challenging to manufacture than traditional chemical drugs. This challenge is continuing to increase rapidly as novel technologies emerge and make their way into new therapies, such as proteins conjugated to chemical drug entities, DNA, RNA or lipids, or fusions of multiple proteins, which increase their potency and targeted delivery in patients. The UK holds a leading position in developing and manufacturing new therapies by virtue of its science base and has unique university capabilities underpinning the sector. Whilst revenues are large, ~£110bn in 2009 on a worldwide basis, there are huge pressures on the industry for change if demands for healthcare cost reduction and waste minimisation are to be met, and populations are to benefit from the most potent drugs becoming available. A sea change in manufacturing will be needed over the next decade if the potential of modern drugs are to make their way through to widespread distribution. Moreover there is a widely accepted skills shortage of individuals with fundamental "blue-skies" thinking capability, yet also with the manufacturing research training needed for the sector.

The proposed EPSRC CDT will deliver a national capability for training the next generation of highly skilled future leaders and bioprocess manufacturing researchers for the UK biopharmaceutical sector. They will be capable of translating new scientific advances both in manufacturing technologies and new classes of macromolecular products into safely produced, more selective, therapies for currently intractable conditions at affordable costs. This is seen as essential where the rapid evolution of biopharmaceuticals and their manufacturing will have major implications for future medicine. The CDT will be a national resource linked to the EPSRC Centre for Innovative Manufacturing (CIM) in Emergent Macromolecular Therapies (EP/I033270/1), which aims to tackle new process engineering, product stability, and product analysis challenges that arise when manufacturing complex therapies based on radically new chemistry and molecular biology. The CDT will embed PhD students into the vibrant research community of the top UK Institutions, with collaborations overseen by the EPSRC CIM, to enable exploration of new process engineering, modelling, analysis, formulation and drug delivery techniques, and novel therapies (e.g. fusion proteins, and chemical drugs conjugated to antibodies), as they emerge from the international science and engineering community. Alignment to the EPSRC CIM will ensure projects strategically address key bioprocess manufacturing challenges identified by the industrial user group, while providing a cohort-based training environment that draws on the research excellence of the ESPRC CIM to maximise impact and knowledge transfer from collaborative partners to research led companies.

The benefits of the proposed EPSRC Centre for Doctoral Training (CDT) aligned to the EPSRC Centre for Innovative Manufacture of Emergent Macromolecular Therapies will be significant. The CDT will address an acute skills storage of trained manpower, needed to take this industry forward for the benefit of the UK, and ultimately to improve the levels of healthcare provision nationally. This is a radical new opportunity for the industry which suffers from a lack of joined up thinking and hence tends to operate in discrete silos of expertise. The integrated approach offered by the CDT would pay high dividends. UK companies will benefit from access to highly skilled doctorates who will each have benefited from a wide and interdisciplinary research approach created by the CDT. Macromolecular medicines are complex and labile so that bioprocess development times and costs tend to be high due to unforeseen issues that occur during scale-up of the manufacturing process. Currently there is little scope to alter a manufacturing process because the effect of changes cannot be readily predicted. This is compounded by lack of individuals skilled in the methods needed. Our transformative CDT research training agenda will allow for the first time engineers and scientists to create the methods and approaches needed for UK companies to genuinely understand and control directly, for the first time, the quality of output during manufacture, in spite of biological variability. By creating and then testing manufacturing models and methods for whole bioprocesses using the resources of a national EPSRC Centre we shall gain fundamental engineering insights crucial for the more effective direction of acquisitions of experimental data and also the improved design and operation of whole bioprocesses. Manufacturing efficiencies will be raised and waste reduced. Such a vision is consistent with recent efforts by the regulatory authorities, and in particular the Quality by Design (QbD) initiative of the International Committee on Harmonisation (ICH), to develop science-based regulatory submissions for approval to manufacture new biological products. The CDT will create a network to provide a conduit for effective knowledge exchange from the very best academic groups in the UK. A key metric of success will be retention of CDT graduates within the industry where they will be effective in the application of Centre concepts with industrial practice and the adoption of the methods created. Potential patients will benefit as the innovations created by the CDT research will significantly aid reduction in development times of macromolecular medicines, which is particularly crucial for those addressing previously unmet clinical needs and the treatment of severe conditions such as arthritis, cardiovascular disease, viral infections and cancers. By providing industry the capabilities and tools to achieve changes to manufacturing processes we shall open up possibilities for major improvements to processes during production and hence reduce costs to the NHS. The capacity to treat conditions such as rheumatoid arthritis much more effectively in ageing populations is vital but it still poses a problem with respect to stretched NHS budgets. A significantly greater number of drugs will be capable of meeting NICE's thresholds and thus benefit extended patient populations. The UK economy will benefit because the academic research and training offered by the CDT will complement the country's strength in bioscience discovery. Collaboration between bioprocess engineers, process modellers manufacturing experts, regulators and physical scientists will ensure effective knowledge and skills transfer between the science and engineering base and UK industry and the regulating agencies. This will strengthen the UK position in the global healthcare market and attract further R&D investment from global business which recognises the UK as a good place to conduct these activities.