Trends in Monoclonal Antibody Production Using Various Bioreactor Syst

Abstract

Monoclonal antibodies are widely used as diagnostic reagents and for therapeutic purposes, and their demand is increasing extensively. To produce these proteins in sufficient quantities for commercial use, it is necessary to raise the output by scaling up the production processes. This review describes recent trends in high-density cell culture systems established for monoclonal antibody production that are excellent methods to scale up from the lab-scale cell culture. Among the reactors, hollow fiber bioreactors contribute to a major part of high-density cell culture as they can provide a tremendous amount of surface area in a small volume for cell growth. As an alternative to hollow fiber reactors, a novel disposable bioreactor has been developed, which consists of a polymer-based supermacroporous material, cryogel, as a matrix for cell growth. Packed bed systems and disposable wave bioreactors have also been introduced for high cell density culture. These developments in high-density cell culture systems have led to the monoclonal antibody production in an economically favourable manner and made monoclonal antibodies one of the dominant therapeutic and diagnostic proteins in biopharmaceutical industry.

SHTXTHHly, an extracellular secretion platform for the preparation of bioactive peptides and proteins in Escherichia coli

“…Currently, most mAbs approved for therapeutic applications are produced in mammalian cells since their function relies heavily on correct folding and proper glycosylation, which cannot be supplied by the prokaryotic system [ 30 ]. However, E. coli , on the other hand, remains a choice for mAb fragments such as Fab, single-chain Fv (scFv), and scFv-Fc fusion [ 31 ].…”

Bioengineering Outlook on Cultivated Meat Production

“…The construction of the wave bioreactor consists of a flexible polymeric bag (usually made of polyethylene) placed on the rocking platform, with special ports allowing us to introduce air, oxygen or medium or to withdraw samples under sterile conditions. The chamber of the bioreactor is partially filled with medium and cultivated cells, while the rest of the space is filled with air which is being continuously passaged through the bioreactor headspace, in order to keep the bioreactor bag completely inflated [ 169 ]. Medium exchange through the bioreactor bag is also allowed; hence, different operation modes could be applied, including perfusion [ 170 ].…”

“…The material used for manufacturing of hollow fibers could be customized, mostly in terms of pore size, to pre-determine which compounds or particles should be retained or pass through the semipermeable membrane [ 145 ]. The most commonly used materials are cellulose and polyethersulfone, which are hydrophilic and have a high-percentage porosity [ 169 ]. Knazek et al [ 208 ] were the first to describe the HFR for animal cell culture, which proved a thesis that mammalian cells could attach to hollow fibers and grow in vitro.…”

“…Considering that the first option has already been used to mimic blood vessels in TE [ 202 ] with nutrients, oxygen and metabolites exchange through the diffusion between the intra-capillary and extra-capillary spaces [ 145 ], CM production could have more benefits from this solution where the hollow fibers are used for nutrient delivery and removal of undesired metabolites. This system provides a cell density similar to the one in the solid tissues, as well as the similar physiological state of the cells regarding nutrient supply, waste removal and pH control [ 169 ]. Hence, the HFRs in the context of CM production are usually considered as the perfusion systems based on the principle of compartmentalization, where cells in high density are retained inside the bioreactor compartment, while the medium is perfused through the hollow fibers placed within the cell compartment, i.e., this system could be considered as intra-capillary inoculation with extra-capillary perfusion [ 144 , 145 ].…”

CDMOs Play a Critical Role in the Biopharmaceutical Ecosystem

“…High-density culture or continuous culture methods have attracted attention as another technology in the upstream process to reduce capital costs and improve productivity ( Jyothilekshmi and Jayaprakash, 2021 ). Continuous production allows for large quantities of culture in small facilities.…”