Evaluating facility design and capacity planning decisions for clinical and commercial supply with hybrid continuous processes
Assessing the value potential of alternative process and facility design strategies will be critical to the successful management of continuous processes. UCL’s Decisional Tools team have developed advanced decision-support tools that effectively integrate concepts from bioprocess economics, dynamic simulation, risk analysis, combinatorial optimization and operations research to address such challenges (e.g. 1-5). This presentation will show our latest practical applications of such models to industrially-relevant problems related to facility design and capacity sourcing for long-term commercial supply when dealing with processes with either continuous upstream or downstream processes. The results can be translated across a range of products such as mammalian cell-derived monoclonal antibodies, E.coli-derived antibody fragments and labile blood factors.
The first case study explores the economic feasibility of different configurations of continuous chromatography for clinical and commercial manufacture. It will address questions such as: How do the feed characteristics and resin properties impact the optimal number of columns to have in a continuous chromatography system? Does the adoption of pre-packed disposable columns change the feasibility of continuous chromatography? How does the feasibility of continuous chromatography combined with pre-packed disposable columns change across different feed characteristics, resin properties, development phases and commercial production scales? What is the optimal design of integrated continuous downstream process configurations?
The second case study addresses the challenge of long-term production planning for a portfolio of commercial candidates with different product stabilities and hence requiring capacity for both fed-batch and perfusion cell culture modes. Questions that will be addressed include: How best can installed multi-site capacity be used to meet commercial demands of a portfolio containing perfusion and fed-batch based therapeutics? What is the trade-off between retrofitting existing facilities to cope with fed-batch and perfusion candidates versus sourcing capacity through CMOs or a new build? What is the impact of changeovers between perfusion and fed-batch campaigns on capacity plans across a network of multiproduct facilities?