Membrane technology for purification of therapeutic proteins

Abstract

Membrane systems are used throughout the downstream purification in the commercial production of high value therapeutic proteins. Over the last two decades, new membranes, modules, and systems have been developed specifically to meet the requirements of the biotechnology industry. These developments have been facilitated by an improved fundamental understanding of: (1) the effects of electrostatic interactions and concentration polarization on protein transmission during ultrafiltration and (2) the role of membrane morphology on protein fouling during both sterile and virus filtration. This perspective highlights some of the key work in this area and provides insights into possible future improvements in membrane technology for the purification of recombinant therapeutic proteins.

Increasing parvovirus filter throughput of monoclonal antibodies using ion exchange membrane adsorptive pre‐filtration

“…An improved understanding of fouling and advances in membrane casting have resulted in the development of superior composite membranes for sterile filtration (Zydney, 2009). Many of the same lessons have likely been applied to the development of new virus filters including the Viresolve 1 Pro.…”

Simultaneous clarification of Escherichia coli culture and purification of extracellularly produced penicillin G acylase using tangential flow filtration and anion-exchange membrane chromatography (TFF-AEMC)

“…from 1.07 U/mL at 0 min to 1.56 U/mL at 280 min. Such concentration polarization is not unusual for ultrafiltration and is indicative of membrane fouling [1,19] though the flow rate of the permeate was not fully stopped. If necessary, the fouling can be relieved by reversing the retentate flow direction or increasing the tangential flow rate to improve the flux of the permeate [1].…”

Role of electrostatic interactions during protein ultrafiltration

“…It is also possible to exploit electrostatic interactions for high resolution protein separations through the use of high performance tangential flow filtration (HPTFF) [1][2][3][4][5]. As originally described, HPTFF provided high selectivity by operating in the pressure-dependent regime at or below the "transition point" in a plot of filtrate flux versus transmembrane pressure [47].…”

“…However, it is now well established that the rate of protein transmission is determined by both steric and long-range interactions, with the latter dominated by electrostatic interactions associated with the electrical charge on the protein and/ or membrane [1,2]. Electrostatic interactions have been exploited to develop high performance ultrafiltration membranes with significantly better selectivity (for a given value of the permeability) than conventional UF membranes [2][3][4][5][6]. Electrostatic effects have also been used to achieve high resolution protein separations, with the charged membranes providing high retention of like-charged proteins while allowing relatively uncharged solutes to pass into the permeate [1,5].…”

“…UF was originally viewed as a purely size-based separation process with the macromolecular species retained by the membrane due to steric exclusion from the small pores. However, it is now well established that the rate of protein transmission is determined by both steric and long-range interactions, with the latter dominated by electrostatic interactions associated with the electrical charge on the protein and/ or membrane [1,2]. Electrostatic interactions have been exploited to develop high performance ultrafiltration membranes with significantly better selectivity (for a given value of the permeability) than conventional UF membranes [2][3][4][5][6].…”