Lyle, Annabel;
(2024)
Decisional Tools for Optimising Process Economics, Capacity Sourcing and Portfolio Management for Biotherapeutics.
Doctoral thesis (Eng.D), UCL (University College London).
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Abstract
Biopharmaceutical industry portfolios have diversified from ones centred on protein therapeutics to inclusion of a myriad of novel modalities, such as cell and gene therapies (CGTs). These biotherapeutics have the ability to address unmet medical needs and potentially be curative. However, their nascency brings several complexities and uncertainties to their development, manufacturing and ultimately commercialisation. This thesis aims to create a decisional tool that integrates cost modelling with multi-objective optimisation to aid manufacturing and capacity decisions at the process, drug development and enterprise level for both protein and gene therapy modalities. This was approached by generating a decisional tool comprising the following key elements, (a) an adeno-associated virus (AAV) process economics model for the evaluation of AAV manufacturing options, (b) a drug development lifecycle cost model for the evaluation of overall research & development (R&D) budgets and (c) a stochastic multi-objective optimisation model for portfolio management and capacity planning of mixed-modality portfolios. Each component of the tool was used to approach industrially-relevant case studies. The first key novel contribution involved investigation of the cost-effectiveness and purity performance of AAV flowsheets, with a particular focus on the impact of traditional versus scalable alternatives. Secondly, the drug development cost model was used for the estimation of overall R&D budgets for protein and CGT products and to provide benchmark contributions for process development and manufacturing activities. Finally, the overall decisional tool provided a novel means to address a portfolio and capacity optimisation case study for mixed-modality drug pipelines. This reconciled both risk and reward as objective functions and provided the first study to consider the dynamic impact of clinical success rates on both portfolio composition and capacity. This initially focused on mAbs and ADCs, investigating the impact of batch versus continuous-next generation manufacturing on the profitability. The study was extended to evaluate the impact of CGT injection upon the portfolio characteristics. Overall, the decisional tool outlined within this thesis addressed both a novel set of computational methods and case studies, tackling some of the significant challenges biotherapeutic developers currently face.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Eng.D |
| Title: | Decisional Tools for Optimising Process Economics, Capacity Sourcing and Portfolio Management for Biotherapeutics |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2024. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10188992 |
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