Neves, Catarina; (2024) Decision-support tool for bioprocess economics and sustainability analysis of end-to-end continuous antibody manufacturing strategies. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The biopharmaceutical industry is navigating a dynamic landscape marked by heightened competition, cost pressures, and the pursuit of innovative manufacturing solutions. As a result, the sector is exploring new manufacturing avenues in continuous mode, with renewed interest in the potential of column-free capture alternatives for monoclonal antibody (mAb) production. This stems from a desire to reduce manufacturing costs and to align with global commitments to achieve net zero carbon emissions. In addition, concerted efforts are being directed to automate the control of continuous bioprocesses to enhance quality control and process performance levels. This thesis aims to create a decisional tool that facilitates an integrated evaluation of the economic and environmental aspects of end-to-end continuous antibody manufacturing routes, with a focus on column-free routes and automated control. A comprehensive framework for modelling the economic, environmental, and technological dimensions of end-to-end continuous manufacture was developed. The trade-offs of integrating the column-free options of precipitation or aqueous two-phase extraction in mAb capture on end-to-end continuous flowsheets were quantified with a process economics model. The assessment incorporated deterministic analysis, Monte Carlo simulations and multi-criteria decision making techniques and showed that continuous manufacturing was preferable over batch and that column-free based flowsheets could offer economic advantages for processes with intensified cell culture productivities and optimised yields. On the environmental front, a life cycle assessment of different manufacturing alternatives demonstrated that the key drivers of product carbon footprint were related to energy use and material supply. For batch processes, emissions were mostly related to a high energy consumption related to larger facilities, while for continuous processes the carbon footprint from reagents and consumables fabrication was a key driver. Carbon reduction strategies were identified and the flowsheet with product precipitation showed the most accentuated decrease in carbon emissions after process optimisation. Finally, the current state-of-the-art and vision for the implementation of process analytical technologies (PAT) in bioprocessing were investigated by conducting a survey and a series of interviews with global industrial and academic experts. The simulation tool also demonstrated the potential impact of PAT to decrease manufacturing costs, with a payback time of less than one year on the PAT investment. The work in this thesis showcased the added value of a simulation framework that provides an in-depth evaluation of different technologies, flowsheets and scenarios and streamlines the route to industrialisation for end-to-end continuous manufacture.

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