Production of High-Value Proteins under Stringent Cost Constraints—The Case of Hollow Fiber Technology for Cell Culture

Abstract

For decades, the benefits of utilizing hollow fiber bioreactors for continuous cell culture to produce monoclonal antibodies have been widely recognized. However, the suitability of this technology for laboratories or centers with limited resources and expertise seeking to expand their production capacity is uncertain, mainly due to unknown cost-effectiveness. In this study, a hollow fiber bioreactor with a 4.7-mL culture volume was used to culture a hybridoma clone producing immunoglobulin G antibody specific to hemoglobin F (HbF). The antibody reached a maximum concentration of 1.22 g/L and totaled 21 mg over a 44-day culture period. This preliminary production data was used to estimate the cost of consumables required for using the hollow fiber bioreactor to produce 130 mg of monoclonal antibodies, which was found to be THB35.8k (£880). The cost was slightly more expensive than batch cultivation in typical culture dishes, which ranged from THB27.8 to 30.2k (£680 to 740). Despite the advantages in terms of reduced hands-on time, shorter production duration, and highly concentrated products, the primary challenges associated with using hollow fiber bioreactors were the cost and availability of the cartridges.

Extracellular Vesicles as Next-Generation Diagnostics and Advanced Therapy Medicinal Products

“…This unique construction and operation allow for the production of a large cell mass and high number of EVs [ 71 ]. The optimal production of a large cell mass in hollow-fiber bioreactors should take into account the quality control of parameters such as the pH; temperature; osmolarity; hypoxia; and nutrients added to the medium, including glucose and ion contents [ 72 ]. Therefore, the upscaling of hollow-fiber bioreactors from preclinical studies to manufacturing scale requires numerous iterative tests to keep the cell mass phenotype acceptable while producing EV batches on a large scale ( Supplementary Figure S1 ).…”