Anion exchange membrane adsorbers for flow‐through polishing steps: Part II. Virus, host cell protein, DNA clearance, and antibody recovery

Abstract

Anion exchange membrane adsorbers are used for contaminant removal in flow-through polishing steps in the manufacture of biopharmaceuticals. This contribution describes the clearance of minute virus of mice, DNA, and host cell proteins by three commercially available anion-exchange membranes: Sartobind Q, Mustang Q, and ChromaSorb. The Sartobind Q and Mustang Q products contain quaternary amine ligands; whereas, ChromaSorb contains primary amine based ligands. Performance was evaluated over a range of solution conditions: 0-200 mM NaCl, pH 6.0-9.0, and flow rates of 4-20 membrane volumes/min in the presence and absence of up to 50 mM phosphate and acetate. In addition contaminant clearance was determined in the presence and absence of 5 g/L monoclonal antibody. The quaternary amine based ligands depend mainly on Coulombic interactions for removal of negatively charged contaminants. Consequently, performance of Sartobind Q and Mustang Q was compromised at high ionic strength. Primary amine based ligands in ChromaSorb enable high capacities at high ionic strength due to the presence of secondary, hydrogen bonding interactions. However, the presence of hydrogen phosphate ions leads to reduced capacity. Monoclonal antibody recovery using primary amine based anion-exchange ligands may be lower if significant binding occurs due to secondary interactions. The removal of a specific contaminant is affected by the level of removal of the other contaminants. The results of this study may be used to help guide selection of commercially available membrane absorbers for flow-through polishing steps.

Adapting viral safety assurance strategies to continuous processing of biological products

“…Of the possible membrane adsorber moieties available, AEX membrane adsorbers are already known to efficiently clear mammalian viruses (Miesegaes et al, ; Phillips et al, ) across wide pH ranges (Strauss et al, ), and viral pIs (Miesegaes et al, , ; Valera et al, ). However, technological gaps have been identified as some buffer conditions required for a lower pI monoclonal antibody product can reduce clearance efficiency when product is present (Weaver et al, ,). For CP, AEX membrane adsorbers are the most attractive/cost‐effective resin for continuous flow‐through operation, since they can easily be exchanged when they are clogged.…”

Standardized large-scale H-1PV production process with efficient quality and quantity monitoring

“…Chromatography and chromatofocusing are of special interest for large-scale production (Okada et al, 2009), since empty and full particles can be separated by chromatography, as shown for AAV (Qu et al, 2007). The use of membrane absorbers to capture the protoparvovirus MVM has also been described recently (Weaver et al, 2013).…”

Suitability of a generic virus safety evaluation for monoclonal antibody investigational new drug applications

“…AEX membranes have become widely utilized in the industry due to their high load capacities, greater flow rates, reduced processing time, disposability, and lower buffer consumption . Several authors have demonstrated robust membrane‐based clearance at neutral pH and low salt buffer conditions . Resin‐based AEX columns are also effective and can be reused dozens of times, as long as proper cleaning and regeneration procedures are followed, but have the disadvantage of increased operational complexity.…”