As product titers continue to increase in upstream cell culture processes, so too the demand for enhanced capacity in downstream purification steps. MabSelect SuRe LX chromatography medium (resin) is specially developed for monoclonal antibody (MAb) capture from high-titer feeds. To help ensure good process economy, the medium can withstand hundreds of rigorous cleaning cycles with NaOH, with retained dynamic binding capacity (DBC) and MAb yield.

High Dynamic Binding Capacity (DBC)

FIGURE 1: MabSelect SuRe LX exhibits significantly higher DBC compared with MabSelect SuRe medium at 6 min residence time.

Large-scale purification of MAbs usually consists of two or three chromatographic steps, where protein A is the ligand of choice for the initial capture step. MabSelect SuRe LX is based on the same rigid high-flow agarose base matrix and alkali-stabilized ligand as its precursor MabSelect SuRe medium. When compared with MabSelect SuRe, however, MabSelect SuRe LX provides up to 45% higher DBC at 6 min residence time (Figure 1). The ligand can withstand rigorous cleaning in place (CIP) using NaOH. In a lifetime study, MabSelect SuRe LX retained a high DBC over more CIP cycles, using 0.5 M NaOH as cleaning agent, compared with MabSelect SuRe medium (Figure 2).

Window of Operation

FIGURE 2: MabSelect SuRe LX retained 80% DBC after 150 CIP cycles using 0.5 M NaOH as cleaning agent, compared with 125 cycles for MabSelect SuRe medium.

MabSelect SuRe LX is based on a high-flow agarose base matrix that allows for high flow rates at low pressure drop, meaning that MabSelect SuRe LX has a large window of operation in terms of both bed heights and flow velocities. At 20-cm bed height, MabSelect SuRe LX can be run at linear velocities as high as 500 cm/h at a pressure of 1 bar.

Conclusion

Although suitable also for lower MAb titers, the benefits of MabSelect SuRe LX are especially apparent in MAb captures from high-titer feeds. The protein A ligand of MabSelect SuRe LX is very stable and withstands repeated and effective CIP procedures using NaOH without loss in function. Compared with MabSelect SuRe medium, the high capacity of MabSelect SuRe LX can increase downstream productivity (in gram MAb processed per hour) or enable the use of smaller columns. More details can be found in the application notes Dynamic Binding Capacity Study on MabSelect SuRe LX for Capturing High-Titer Monoclonal Antibodies (GE Healthcare 28-9875-25, edition AA, 2011) and Lifetime Performance Study of MabSelect SuRe LX During Repeated Cleaning-in-Place (GE Healthcare 28-9872-96, edition AA, 2011).

Jonathan Royce is BioProcess senior product manager for antibody affinity media at GE Healthcare Life Sciences, Bjrkgatan 30, SE-751 84 Uppsala, Sweden; [email protected]; www.gelifesciences.com.

GE and GE monogram are trademarks of General Electric Company. MabSelect SuRe is a trademark of General Electric Company or one of its subsidiaries. 2014 General Electric Company All rights reserved. First published in July 2014.