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.

Wastewater-Based Epidemiology (WBE) requires relatively few resources compared to the systematic testing of populations. WBE is especially promising for novel infectious diseases, where asymptomatic cases might play a significant role in transmitting the virus. However, WBE is only now being used to monitor the spread of a pandemic infectious disease. Early studies by ourselves and others have shown that SARS-CoV-2 RNA can be recovered from wastewater, including from wastewater treatment plants (WWTP) preceding local COVID-19 hospitalisation activity. Given the challenge of making available diagnostic tests to the entire UK population, WBE represents a potentially low-cost and immediate mechanism for understanding levels of infection within large geographic areas. N-WESP aims to compare our methods with those of European & North American WBE teams in an inter-lab trial for understanding, supporting and improving the DEFRA COVID-19 measurements which will feed into the Joint Biosecurity Centre (JBC). We will also compare methods with DEFRA, the EA's and JBC whilst they explore options for finer geographical measurements. N-WESP will empower public health authorities with an optimised surveillance tool with maximal sensitivity and predictive power whose uncertainties have been well characterised. N-WESP will determine whether SARS-CoV-2 RNA in wastewater and sludge is infectious, and to what extent there might be downstream risks to human health. N-WESP will exploit catchment and, uniquely, sub-catchment-scale longitudinal surveillance to understand temporal and spatial heterogeneity, relationships to human disease burden distribution and whether there is potential outbreak 'hotspots' by surveilling sewer system nodes.