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Increasing parvovirus filter throughput of monoclonal antibodies using ion exchange membrane adsorptive pre‐filtration
Author(s) -
Brown Arick,
Bechtel Charity,
Bill Jerome,
Liu Hui,
Liu Jun,
McDonald Dan,
Pai Satyan,
Radhamohan Asha,
Renslow Ryan,
Thayer Brooke,
Yohe Stefan,
Dowd Chris
Publication year - 2010
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.22729
Subject(s) - membrane , chromatography , chemistry , filtration (mathematics) , monoclonal antibody , adsorption , ion exchange , parvovirus , elution , size exclusion chromatography , ion , antibody , biochemistry , organic chemistry , biology , virology , virus , statistics , mathematics , immunology , enzyme
Pre‐filtration using ion exchange membrane adsorbers can improve parvovirus filter throughput of monoclonal antibodies (mAbs). The membranes work by binding trace foulants, and although some antibody product also binds, yields ≥99% are easily achieved by overloading. Results show that foulant adsorption is dependent on pH and conductivity, but independent of scale and adsorber brand. The ability to use ion exchange membranes as pre‐filters is significant because it provides a clean, well defined, chemically stable option for enhancing throughput. Additionally, ion exchange membranes facilitate characterization of parvovirus filter foulants. Examination of adsorber elution samples using sedimentation velocity analysis and SEC‐MALS/QELS revealed the presence of high molecular weight species ranging from 8 to 13 nm in hydrodynamic radius, which are similar in size to parvoviruses and thus would be expected to plug the pores of a parvovirus filter. A study of two identical membranes in‐series supports the hypothesis that the foulants are soluble, trace level aggregates in the feed. This study's significance lies in a previously undiscovered application of membrane chromatography, leading to a more cost effective and robust approach to parvovirus filtration for the production of monoclonal antibodies. Biotechnol. Bioeng. 2010;106: 627–637. © 2010 Wiley Periodicals, Inc.