The future of industrial bioprocessing: Batch or continuous?

Abstract

For over 75 years, continuous bioprocessing has been investigated in both academia and industry as an alternative to batch bioprocessing. Many classic textbooks have major sections on continuous bioprocessing (e.g., Aiba et al

Optimization of Bioethanol In Silico Production Process in a Fed-Batch Bioreactor Using Non-Linear Model Predictive Control and Evolutionary Computation Techniques

“…Another notorious question is that many times the costs for upgrade the production structure to continuous production are prohibitive [36,37]. Thus, several large-scale reactors still operated under a fed-batch configuration, and it is important to ensure an adequate control methodology for the feed rate [23,35], as aforementioned.…”

Tailoring recombinant protein quality by rational media design

“…Several parameters including the biology of the production cell line, product quality and stability, manufacturing capacity, process scalability, volumetric productivity, and unit cost determine the selection of the production process, namely fed-batch or perfusion 31 . Due to product stability issues, many recombinant proteins, such as insulin and interferons, were produced in perfusion in the early stages of the biotechnology industry 32 . Product residence times are low in perfusion mode and thus the recombinant drug is less exposed to various Chapter 1.…”

“…The productivity of newly developed perfusion processes is much greater than what those developed in the 80's achieved, and more importantly, volume exchanges are low (1-2 reactor volumes per day), which potentially drives cost of goods down 35,37,38 . Furthermore, the continuous mode can be extended to the purification platform, thus reducing the total processing time and the risks associated with degradation pathways 32 .…”

Catalytic Pseudomonas taiwanensis VLB120ΔC Biofilms Thrive in a Continuous Pure Styrene Generated by Multiphasic Segmented Flow in a Capillary Microreactor

“…Despite these features, reported industrial whole-cell continuous processes are rare and are mainly applied in the treatment of wastewater or in the production of unstable biopharmaceuticals [1,2]. The main issues concerning continuous operations occur from the inhomogeneity of nutrient storage and biomass accumulation, poor flexibility in handling multiple products, and high cost for process development from laboratory to technical scale [2].…”

“…Despite these features, reported industrial whole-cell continuous processes are rare and are mainly applied in the treatment of wastewater or in the production of unstable biopharmaceuticals [1,2]. The main issues concerning continuous operations occur from the inhomogeneity of nutrient storage and biomass accumulation, poor flexibility in handling multiple products, and high cost for process development from laboratory to technical scale [2]. In recent years, the development of miniaturization concepts has offered technological answers to overcome issues regarding nutrient inhomogeneity owing to good mixing and high mass transfer rates, reduction in costs due to the lower amount of reactants needed, and easy scale-up principles using parallelization concepts [3,4].…”