Increasing parvovirus filter throughput of monoclonal antibodies using ion exchange membrane adsorptive pre-filtration.
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 > or =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.
Brown
Arick
A
Process Research & Development, Genentech, 1 DNA Way, South San Francisco, California 94080, USA. abrown@gene.com
Bechtel
Charity
C
Bill
Jerome
J
Liu
Hui
H
Liu
Jun
J
McDonald
Dan
D
Pai
Satyan
S
Radhamohan
Asha
A
Renslow
Ryan
R
Thayer
Brooke
B
Yohe
Stefan
S
Dowd
Chris
C
D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000302:isolation & purification*; D003470:Culture Media / Q000737:chemistry; D004553:Electric Conductivity; D005374:Filtration / Q000379:methods*; D006863:Hydrogen-Ion Concentration; D007474:Ion Exchange; D008566:Membranes; D017992:Parvovirus / Q000302:isolation & purification*
D000911:Antibodies, Monoclonal; D003470:Culture Media