EPSRC Fellowships in Manufacturing - Macromolecular Manufacturing

The bioprocess industry manufactures novel macromolecular drugs, proteins, to address a broad range of chronic and debilitating human diseases. The UK holds a leading position 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 cost reduction and waste minimisation are to be met, and populations are to benefit from the potent drugs becoming available. A sea change in manufacturing will be needed over the next decade or so if the potential of modern drugs are to make their way through to widespread distribution. It has been estimated that an economic return of 200-1000% can be gained by applying modelling and optimisation tools to bioprocessing.

In this fellowship I will address a series of related issues which will be necessary in order to achieve the transformation in manufacturing necessary for the UK to build a world lead. Broadly, there are two goals:-

i) to create mathematical models of complete manufacturing processes used for macromolecule production; and
ii) to use these mathematical descriptions as tools for the faster prediction of efficient and reliable operation so that industry can be more flexible in the way it runs intrinsically costly process plants.

Research to address this first goal will require collaborations with a range of scientists, mathematical, engineers and computer scientists in order to work out the most effective way to describe complex processes in mathematical equations. Of particular importance will be the need to devise methods which allow us to capture how the process for making a particular material actually changes the material properties. This "process memory" is a poorly understood phenomena but has a profound impact on manufacturing performance.

The second goal will be addressed via an industrial forum providing materials and data for testing of our work. The most crucial aspect will be the need to use the mathematical description of the process as a framework for setting up control strategies designed to be reliable even if the manufacturing process is perturbed. Such events are frequent in biological systems where inherent levels of variability mean that the processes are never truly identical.

The project, as a whole, will therefore lead to the rational development of robust processes that should work with minimal change during manufacturing. This, in turn, will lead to reductions in manufacturing costs; such reductions are critical to producing the next generation of protein and vaccine medicines in quantities sufficient to meet worldwide demand.

The benefits of the proposed EPSRC Manufacturing Fellowships will be significant. This is a radical new opportunity for the industry which suffers from a lack of joined up thinking and tends to operate in discrete silos of expertise whereas an integrated approach would pay high dividends.

UK-based companies will benefit from access to a research activities created by the fellowship. The research will allow UK companies to understand better the likely routes for manufacturing of their medicines and to have, for the first time, a genuine capacity to achieve robust control in spite of biological variability. Manufacturing efficiencies will be raised and waste reduced. The fellowship will create a network to provide a conduit for effective knowledge exchange. A key metric of success will be application in industrial practice and the adoption of the methods created. Industry will also gain from access to the skilled researchers who will form an integral part of the fellowship and who will each have benefited from a wide and interdisciplinary approach to their research and its application.

Potential patients will benefit because the fellowship innovations 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 and cardiovascular disease, as well as vaccines for previously unpreventable viral infections and cancers. By providing industry the capabilities and tools to achieve changes to manufacturing processes we shall, for the first time, 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 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 academic research 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 expand 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.

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 processes. Currently there is little scope to alter a manufacturing processes because we cannot readily predict the effects that such changes will have. This transformative research agenda will allow for the first time engineers to control directly the quality of output during manufacture. By creating and then testing manufacturing models for whole bioprocesses 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. These will together raise manufacturing efficiencies and reduce waste. 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 research will allow UK companies to gain a better prediction of the likely routes for manufacture of medicines. The tools will enable the UK biotechnology industry to design more efficient bioprocesses that fit to available as well as emerging manufacturing.