Mahal, Hanna CK; (2025) Decisional tools to evaluate the business case of end-to-end continuous antibody manufacture: from development to market. Doctoral thesis (Eng.D), UCL (University College London).

Text Hanna Mahal EngD thesis post viva final submission.pdf - Accepted Version Access restricted to UCL open access staff until 1 October 2025. Download (5MB)

Abstract

Monoclonal antibodies (mAbs) are a class of well-established and important therapeutics in healthcare. There are currently high demands for these products that the industry may struggle to meet in an efficient and cost-effective way while continuing to use platform batch manufacturing processes. For this reason, there are industry-wide goals to achieve process intensification to enable improved manufacturing costs and access to these medicines. Companies are looking to adopt novel continuous processing for its ability to increase productivities over platform batch methods. The high productivities achieved with continuous processing can provide significant increases in production capacity whilst reducing manufacturing costs, capital investment, and facility footprints. This thesis aims to develop advanced process economic decisional tools to evaluate the business case of end-to-end continuous antibody manufacture compared with traditional batch methods, considering a therapeutic’s lifecycle from development to market and integrating financial, scale, and operational considerations. The decisional tools developed in this work comprise and integrate the following: new design equations tailored to end-to-end continuous processes as well as new methods to calculate fixed capital investment costs (FCI), facility footprints, the cost of goods (COG), and the cost of development. This has made it possible to perform a holistic business case analysis for the adoption of new continuous processes, taking into account the impact on process economics from initial drug development up to and including commercialisation. The decisional tools were applied to industrially-relevant case studies, providing insights into the costs associated with batch, continuous, and hybrid manufacturing, including the use of single-use unit operations. The analysis first assessed the economic trade-offs between continuous and batch processing in mAb production, focusing on COG versus development costs across different scales and scenarios. It explored whether the COG savings from continuous processing could be outweighed by the higher costs of developing non-platform processes. Secondly, shortcut methods were developed to estimate the footprint, fixed capital investment (FCI), and COG per gram for single-use batch and continuous mAb facilities. These methods, supported by a validated dataset from a revised economic model, produced easy-to-use lookup tables for rapid economic evaluations in facility design. Additionally, process change scenarios were analysed to identify the most cost-effective points for transitioning to continuous processing, incorporating evaluations of out-of-pocket costs and net present value to assess time-to-market impacts. Sensitivity analyses were also performed to determine under which conditions the preferred manufacturing method might vary. Together, these studies provide a comprehensive framework for biopharmaceutical companies to align manufacturing strategies with business objectives. More specifically, with the wide range of scenarios investigated, this work provides an extensive analysis on where continuous manufacturing fits best in the production of mAbs and the future objectives that need to be met for target cost reductions to be realised.

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