Technoeconomic comparison of optimised bioreactor-filtration systems for mAb production.

• Integrated bioreactor-filtration (primary recovery) design is key in biopharmaceutical manufacturing. • Detailed mathematical modelling and parameterisation of rotational filter behaviour is completed. • Dynamic optimisation of fed-batch and perfusion bioreactors for mAb production is achieved. • Technoeconomic evaluation of optimal integrated designs vs. a variety of parameters is performed. • Fed-batch bioreactors combined with stacked membrane microfilters emerge as industrially optimal. Primary post-cultivation biomass recovery (cell culture removal from API-rich solutions) is essential in biopharmaceutical manufacturing. Centrifugation and depth filtration are dominant industrial primary recovery technologies, but mechanistic dynamic models suitable for performance evaluation are scarce. This paper uses established literature models to present and analyse optimal operation strategies for integrated process designs of fed-batch or perfusion CHO bioreactors (for mAb cultivation via CHO cultures), with an explicit rotational disk (dynamic crossflow) filtration model (for primary recovery). A rigorous DAE filter model (Marke et al., 2020) is employed here, to evaluate system performance. Dynamic optimisation of bioreactor-filter systems has been completed for different bioreactor types, filter arrangements and feed manipulations, considering the same annual mAb plant production target. A technoeconomic analysis of optimal designs addresses industrial viability, confirming a clear cost advantage of fed-batch reactors combined with stacked membrane microfilters. [ABSTRACT FROM AUTHOR]