Process and economic evaluation for monoclonal antibody purification using a membrane‐only process

Abstract

In recent years, the market for therapeutic monoclonal antibodies (mAb) has grown exponentially, and with this there has been a desire to reduce the costs associated with production and purification of these high-value biological products. A typical mAb purification process involves three adsorption/chromatography steps [protein A, ion exchange (IEX), and hydrophobic interaction (HIC)], along with ultrafiltration, nanofiltration, and microfiltration. With the development of membrane adsorption/chromatography as a viable alternative to traditional pack bed systems, the opportunity exists to complete the entire downstream purification process using only membrane operations. In this study, the process simulation tool SuperPro Designer was used to evaluate the application of recently developed ultra-high capacity electrospun nanofibrous adsorption membranes as a replacement for conventional chromatographic media in the downstream mAb production process. The simulation showed that nanofibrous adsorption membranes in place of the three packed bed chromatography steps reduced the required volume of protein A, IEX, and HIC adsorptive medium by 25, 80, and 80%, respectively. In addition, the membrane-only process reduced the downstream processing time by 50%, decreased the number of labor hours associated with the purification steps by 40%, generated 40% less aqueous waste, and reduced the overall downstream process operating expenses per unit product by 23%. There were also significant savings in facility construction costs and the price of fixed equipment required for separations. With these savings not only is the membrane-only process economically competitive with the traditional packed bed operations, but it offers the possibility of moving toward more disposable process.

Purification process of recombinant monoclonal antibodies with mixed mode chromatography

“…flow distribution, flow rate limitations and cleaning validation, membrane chromatography was developed, and anion-exchange membrane adsorbers are already being used as an alternative to column chromatography in some mAb manufacturing processes [19]. In light of this advantage, protocols have been developed for the use of membrane adsorbers for all purification steps [20].…”

In situ cross-linked and highly carboxylated poly(vinyl alcohol) nanofibrous membranes for efficient adsorption of proteins

“…[1][2][3][4] Conventional methods such as sedimentation, dialysis, ultracentrifugation, and chromatography have been applied to purify proteins. [1][2][3][4] Conventional methods such as sedimentation, dialysis, ultracentrifugation, and chromatography have been applied to purify proteins.…”

Novel natural and biomimetic ligands to enhance selectivity of membrane processes for solute‐solute separations: beyond nature's logistic legacy

“…It has indeed been suggested that the cost of the ligand is the main impediment to the widespread application of immuno‐ultrafiltration or affinity ultrafiltration in general . And it is exactly the use of chromatographic processes that drives the cost of potential ligands up due to the low throughput and limited economies of scale . Aptamers could be one of the keys to breaking this powerful catch‐22 for several reasons.…”

“…In this case also the size requirement to ensure membrane high rejection would vanish. Parallel with the development of affinity ultrafiltration, membrane adsorbers have evolved tremendously over the last decade . From designs where the membrane merely constitutes a porous structured packing for classical diffusion‐controlled chromatographic beads, hence appropriately termed membrane chromatography, to true membrane adsorbers where a variety of ligands can be covalently attached to new highly porous and as a result convection‐controlled, fouling resistant polymers (Fig.…”