Strategies for maximizing the clearance of impurities across an anion exchange flow through step in the context of an integrated antibody purification process

BIOT 198

Amitava Kundu, amitava.kundu@pdl.com1, Amy Miller1, Jerrod Einerwold, jerrod.einerwold@pdl.com1, Michelle Xia2, Robert Duffy2, and Weichang Zhou3. (1) Purification Process Engineering, PDL BioPharma, 9450 Winnetka Ave N, Brooklyn Park, MN 55445, (2) Purification Process Development, PDL BioPharma, 34801 Campus Dr, Fremont, CA 94555, (3) Process Sciences Engineering, PDL BioPharma, 34801 Campus Dr, Fremont, CA 94555
A commonly used platform process for purification of monoclonal antibodies involves the use of Protein A affinity chromatography as an initial capture step. This is typically followed by a couple of ion exchange steps as polishing steps. In this case study, we present a purification process that comprises of an anion exchange flow through (non binding) followed by a bind and elute cation exchange as polishing steps. While clearance of DNA and virus can be easily accomplished under a wide range of operating conditions, clearance of other process related impurities such as host cell proteins and leached Protein A is relatively more sensitive to operating conditions. This presentation will focus on obtaining an understanding of how different salt counter ions, in addition to pH and conductivity of the mobile phase impacts the clearance of these process related impurities. The robustness of the anion exchange flow through step with respect to the process parameters will be presented. Finally, the implications of an optimized anion exchange process in the context of a three-step versus a two-step purification process will be discussed.