Biopharmaceutical manufacturing continues to evolve with an increased emphasis on underpinning science and engineering. Effective deployment of contemporary knowledge in science and engineering throughout the product life cycle will facilitate manufacturing efficiencies and regulatory adherence for biopharmaceuticals. Fundamental to this paradigm shift has been the drive to adopt an integrated systems approach based on science and engineering principles for assessing and mitigating risks related to poor product and process quality. Changes have been enabled as a consequence of the regulatory authorities introducing a new risk-based pharmaceutical quality assurance system. The traditional approach to manufacture has been to accommodate product variability into the specifications and fix operational strategies to ensure repeatability. Developments in measurement technology have invited changes in operational strategy. This revised approach is based on the application of Quality by Design (QbD), underpinned by process analytical technology (PAT) to yield products of tighter quality and more assured safety. QbD is defined as the means by which product and process performance characteristics are scientifically designed to meet specific objectives. Practical improvements therefore demand a knowledge base of science and engineering understanding to identify the interrelationship between variables and integrate the learning into different manufacturing scenarios. The focus of the Centre is to address the challenges emerging from this paradigm shift and to train a new generation of students with competencies in all stages of commercial biopharmaceutical process development. Critical to this is to ensure they have the skills to work at the discipline interfaces in the areas of biosystem development, upscaled upstream process engineering, and the engineering and development of downstream processing. The training will be formulated around three elements that form the backbone of achieving an enhanced understanding of the process. The three elements are (i) Measurement, Data and Knowledge Management, (ii) Enhance Available Knowledge and (iii) Use Knowledge More Effectively. The power of the approach being adopted is that it is equally applicable to established bioprocesses based on microbial and animal cell culture, as well as emerging areas including stem cells, marine biotechnology and bio-nanotechnology. The rationale for proposing a Centre in this area is to address a well recognised problem, a lack of appropriately trained personnel, who will deliver the next generation of biopharmaceutical development. These issues have been clearly articulated in a series of reports. SEMTA reported that over a quarter of bioscience companies do not have sufficient science skills. 39% of bioscience/pharmaceutical companies have long-term vacancies; with 22% having skill shortages in the science arena (five times that for other sectors). Lord Sainsbury, concerned at the rapidly changing nature of the bioscience business, set up the BIGT and commissioned Bioscience 2015. One of the strong messages raised was the serious shortfall in trained staff. Furthermore a quantitative assessment of the increase needed of trained people entering the sector was made by bioProcessUK. They estimated an increase of 100 trained personnel was required on top of the current 150 doctoral level candidates graduating per year. It is not simply a matter of increasing the number of trained persons. The Centre will also address the limitations of the current UG training of engineers, chemists and biologists which does not prepare them for the challenge of working in process development distinguished by disciplinary interfaces. The proposed programme will address a strategic shortfall and produce a new generation of graduates with the appropriate inter-disciplinary skills to drive both the research agenda and knowledge transfer of underlying concepts into industry.

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.