Advances in Bioreactor Systems for the Production of Biologicals in Mammalian Cells

Abstract

With the steady advancement of medicine and the healthcare industry, the demand for recombinant biotherapeutics drugs and vaccines has increased in the last two decades. This has put substantial pressure on the biopharma industry to meet the increasing need for treatment of prevailing and new diseases. Different technologies and bioreactor designs have been developed over the years to ensure safe and economical manufacturing of biopharmaceutical products by attaining high cell densities and longevities for extended periods of time. Bioreactors are the backbone of the bioprocessing industry albeit each bioreactor design has its advantages and disadvantages. A comprehensive design suitable for wide varieties of cell lines to produce high‐yielding products with the lowest cost and risk in the shortest span of time is sought. This paper focuses on evaluating the engineering aspects of currently available bioreactor designs and their suitability for mammalian cell cultures.

Biomanufacturing Recombinantly Expressed Cripto-1 Protein in Anchorage-Dependent Mammalian Cells Growing in Suspension Bioreactors within a Three-Dimensional Hydrogel Microcarrier

“…Recent clinical progress in novel protein therapeutics has drawn renewed interest in establishing more robust methods for producing complex recombinant proteins in suspension bioreactors, particularly with mammalian cell lines. These efforts involve a range of mammalian cell types being engineered to overexpress the therapeutic protein, which is either secreted directly into the culture medium or retained within cells and extracted afterwards [ 21 , 52 , 53 , 54 ]. In this study, our aim was to optimize and validate a PF hydrogel 3D microcarrier for the production of large quantities of Cripto-1 protein by employing Cripto-overexpressing HEK293 cells grown in suspension bioreactors.…”

Advances in bioreactor control for production of biotherapeutic products

“…Single‐use bioreactor systems (SUBs) are being increasingly used for mass‐scale production (BioPlan Associates, 2019). Benefits that SUBs accrue are reduced capital investment (40%), lower operating costs (22%), flexibility to produce a lot of small batches, faster turnaround times, and a smaller environmental footprint (BioPlan Associates, 2019; Sharma et al, 2022). This is due to the reduction in cost by eliminating CIP and SIP steps, which lowers the usage of WFI and chemicals such as phosphoric acid and sodium hydroxide (utilized with conventional systems) (Sharma et al, 2022).…”

“…Benefits that SUBs accrue are reduced capital investment (40%), lower operating costs (22%), flexibility to produce a lot of small batches, faster turnaround times, and a smaller environmental footprint (BioPlan Associates, 2019; Sharma et al, 2022). This is due to the reduction in cost by eliminating CIP and SIP steps, which lowers the usage of WFI and chemicals such as phosphoric acid and sodium hydroxide (utilized with conventional systems) (Sharma et al, 2022). Also, a recent high surge in cell titer values and the perfusion technique of cell cultivation has urged the industry to embrace SUBs (BioPlan Associates, 2019).…”

“…Disposable sensors need to be cost‐efficient on a per‐use basis while long‐term stability can be neglected (Steinwedel et al, 2019). There is a need to customize conventional sensors so that they can be applied to SUBs (Sharma et al, 2022; Steinwedel et al, 2019). Attempts have been made to address these challenges.…”

Development and Scalable Production of Newcastle Disease Virus-Vectored Vaccines for Human and Veterinary Use

“…The processes also differ in terms of waste treatment: infected ECEs result in solid waste that is typically incinerated [ 104 ], while reusable bioreactors use methods such as cleaning/sterilization in place and chemical treatment of liquid waste, and single-use bioreactors are disposed of through chemical or physical treatments [ 105 ].…”