Dynamic simulation, optimisation AND ECONOMIC ANALYSIS of FED-BATCH vs. perfusion bioreactors for advanced mAb manufacturing

Research output: Contribution to journalArticlepeer-review

Abstract

The variation of antigen binding sites on monoclonal antibodies (mAbs) enables manufacturing of the latter for targeted treatment of a variety of ailments, including cancer types and autoimmune diseases. Fed-batch operation of biochemical reactors used to manufacture mAbs grants the ability to manipulate cell dynamics via intermittent feeding of nutrients/substrates. Regulatory authority agendas (e.g. the U.S. Food & Drug Administration) consider the development of continuous technologies (e.g. perfusion reactors) as essential towards improved technoeconomic potential and biopharmaceuticals quality control. This paper presents dynamic simulations for multiple operational scenaria of a fed-batch and a perfusion reactor, in which a hybridoma cell culture is used to secrete mAb glycoforms. A novel dynamic optimisation of the fed-batch as well as perfusion reactors has also been conducted towards maximising the total mAb mass produced. Nonlinear Programming (NLP) formulations with the use of APOPT and IPOPT solvers have been employed to derive the manipulation, state and controlled variable trajectories, to achieve the mAb production maximisation objective. The detailed technoeconomic analysis clearly highlights strong benefits for the fed-batch bioreactor (especially over a plant-life time horizon), but also showcases a definite cost-related promise of perfusion bioreactor technologies, given the higher mAb yield.

Original languageEnglish
Article number107855
Pages (from-to)107855
JournalComputers and Chemical Engineering
Volume165
Early online date24 May 2022
DOIs
Publication statusE-pub ahead of print - 24 May 2022

Keywords

  • Biopharmaceutical manufacturing
  • Dynamic optimisation
  • Dynamic simulation

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