i-PREDICT: Integrated adaPtive pRocEss DesIgn and ConTrol

The UK holds a leading position in the global life sciences scene. In this sector, biopharmaceuticals play a dominant role with almost £81bn in annual turnover (Life Sciences Competitiveness Indicators 2020, published: February 2021). Through the Life Sciences Vision 2021, the government is highlighting manufacturing innovation and ramp up as the UK's central aims. For the first time, Transition to Net Zero s brought at the centre of Life Sciences targets. For the UK to remain at the forefront of biopharmaceutical manufacturing, the Government is also encouraging digital innovation leading to time-/cost- efficient processes (Made Smarter, Review 2017). The crucial, positive health impact of (bio-) pharmaceutical processes may outweigh the environmental footprint of the sector that works with considerably lower volumes compared to other industries. Cumulatively, however, this remains to be an imminent challenge. Making those processes environmentally and economically sustainable is a complex task, involving conflicting objectives. For example, one would need to decide on the optimal number of separation cycles that meet both the target purity of the drug and create the least possible environmental footprint.
Computer modelling tools can be of great help, lending themselves to the design and solution of multifactorial problems for the identification of the most suitable process setup and operating mode. In this respect, the research question this project aims to answer is: "How can we use computer modelling tools to embed environmental and economical sustainability in bioprocesses, while meeting the purity constraints?". In essence, the goal is to employ Engineering thinking and tools for the development of a systematic framework and software platform that will assist: (a) quantification of the impurity content on the downstream separation performance, (b) identification of a feasible and optimal design space, within which process performance is deemed satisfactory with respect to the tracked key performance indicators (KPIs) and (c) design of optimisation and control policies to ensure optimal operation. The novelty of the proposed work lies in two main aspects. Firstly, environmental sustainability KPIs, such as buffer and energy consumption will be considered for the first time systematically in the design of a bioprocess. Secondly, Engineering innovation will be deployed through the development of a computer modelling framework and software platform (i-PREDICT), harnessing the power of different modelling methodologies. In the junction of Engineering, Manufacturing, Digitalisation and Bioprocessing, i-PREDICT will enable bioprocess digitalisation and integration via continuous monitoring. This is one of the first computational attempts realising "Pharma 4.0" through the development and experimental validation of Industry 4.0-aligned frameworks for upstream in-process monitoring, optimisation and control. This work will create a roadmap towards the integration of product quality in the design of the bioprocess. Endorsing process intensification, this project proposes to consider upstream/downstream interplay through the quantification of the impact that impurity propagation in downstream. This novel concept will allow the design of variability-robust separation processes, enabling seamless unit integration and downstream scale-up. The digital and mathematical tools developed here will be validated experimentally, closing the loop from in silico to in vitro. This highly ambitious, multi-disciplinary project will create a step change towards a revolutionary research area of integrated design, optimisation and control in (bio-) pharmaceutical processes.