Premium
Aggregation of a monoclonal antibody induced by adsorption to stainless steel
Author(s) -
Bee Jared S.,
Davis Michele,
Freund Erwin,
Carpenter John F.,
Randolph Theodore W.
Publication year - 2009
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.22525
Subject(s) - adsorption , monoclonal antibody , chemistry , protein aggregation , desorption , layer (electronics) , chemical engineering , chromatography , antibody , materials science , biophysics , organic chemistry , biochemistry , immunology , engineering , biology
Stainless steel is a ubiquitous surface in therapeutic protein production equipment and is also present as the needle in pre‐filled syringe biopharmaceutical products. Stainless steel microparticles can cause the aggregation of a monoclonal antibody (mAb). The initial rate of mAb aggregation was second order in steel surface area and zero order in mAb concentration, generally consistent with a bimolecular surface aggregation being the rate‐limiting step. Polysorbate 20 (PS20) suppressed the aggregation yet was unable to desorb the firmly bound first layer of protein that adsorbs to the stainless steel surface. Also, there was no exchange of mAb from the first adsorbed layer to the bulk phase, suggesting that the aggregation process actually occurs on subsequent adsorption layers. No oxidized Met residues were detected in the mass spectrum of a digest of a highly aggregated mAb, although there was a fourfold increase in carbonyl groups due to protein oxidation. Biotechnol. Bioeng. 2010;105: 121–129. © 2009 Wiley Periodicals, Inc.