Exploration of fiber-based cation exchange adsorbents for the removal of monoclonal antibody aggregates.

Cation exchange chromatography (CEX) is a widely used technique for the removal of monoclonal antibody (mAb) aggregates. At present, resins are mainly used for this purpose, as convective types of adsorbents such as membrane adsorbers (MAs) have often not demonstrated overall comparable performance for this particular application. Fiber-based adsorbents can overcome the current limitations of MAs with respect to permeability, binding capacity, and adsorbent cost, and could therefore be a viable alternative to resins for the removal of mAb aggregates. It has not been evaluated, however, whether and under which conditions the use of such adsorbents is feasible for this purpose. In the present study, the use of fiber-based CEX adsorbents for mAb aggregate removal was examined. Two types of fiber-based adsorbents, an uncontrolled grafted and a controlled grafted fiber-based adsorbent, were evaluated with respect to permeability, dynamic mAb binding capacity (DBC), resolution capabilities, and the performance in bind and elute (B/E) and frontal chromatography mode with respect to typical performance indicators. The permeabilities of the fiber-based adsorbents ranged from 200 to 1700 mD, making it possible to use the fiber-based adsorbents at larger bed heights than membrane adsorbers with fast mobile phase velocities. Antibody DBCs ranged from 20 to 41 g/L at 150 cm/h, and at higher mobile phase velocities exceeded the DBC of an existing resin material, Poros 50 HS, which has frequently been used for aggregate removal. Both fiber types showed good resolution capabilities of monomer and aggregates, and provided better resolution per column length than Poros 50 HS. Typical purity and yield constraints were fulfilled for both fiber types in both B/E and frontal chromatography mode for mobile phase velocities ranging up to 480 cm/h and 1060 cm/h. The overall performance of the controlled grafted fibers was found to be superior to the performance of uncontrolled grafted fiber-based adsorbents due to higher productivity and lower buffer consumption. The overall performance of the fiber-based adsorbents was found to be comparable to the performance of Poros 50 HS at typical operating conditions. The results in this study indicate that the use of fiber-based adsorbents for mAb aggregate removal is feasible with a performance that is comparable to the performance of an existing resin material. Depending on the cost of the adsorbents and the use scenario, the usage of such adsorbents could be beneficial.

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Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.