The next generation of monoclonal antibody (mAb) therapies are under increasing pressure from healthcare providers to offer cost effective treatments in the face of intensified competition from rival manufacturers and the looming loss of patent exclusivity for a number of blockbusters. To remain completive in such a challenging environment companies are looking to reduce R&D and manufacturing costs by improving their manufacturing platform processes whilst maintaining flexibility and product quality. As a result companies are now exploring whether they should choose conventional batch technologies or invest in novel continuous technologies, which may lead to lower production costs. This thesis explores the creation of a dynamic tool as part of a decision-support framework that is capable of simulating and optimising continuous monoclonal antibody manufacturing strategies to assist decision-making in this challenging environment. The decision-support framework is able to tackle the complex problem domain found in biopharmaceutical manufacturing, through holistic technology evaluations employing deterministic discrete-event simulation, Monte Carlo simulation and multi-attribute decision-making techniques. The hierarchal nature of the framework (including a unique sixth hierarchal layer; sub-batches) made it possible to simulate multiple continuous manufacturing scenarios on a number of levels of detail, ranging from high-level process performance metrics to low-level ancillary task estimates. The framework is therefore capable of capturing the impact of future titres, multiple scales of operation and key decisional drivers on manufacturing strategies linking multiple continuous unit operations (perfusion cell culture & semi-continuous chromatography). The work in this thesis demonstrates that the framework is a powerful test bed for assessing the potential of novel continuous technologies and manufacturing strategies, via integrated techno-economic evaluations that take proof-of-concept experimental evaluations to complete life-cycle performance evaluations
