Aggregation of a monoclonal antibody induced by adsorption to stainless steel
Article first published online: 1 SEP 2009
Copyright © 2009 Wiley Periodicals, Inc.
Biotechnology and Bioengineering
Volume 105, Issue 1, pages 121–129, 1 January 2010
How to Cite
Bee, J. S., Davis, M., Freund, E., Carpenter, J. F. and Randolph, T. W. (2010), Aggregation of a monoclonal antibody induced by adsorption to stainless steel. Biotechnol. Bioeng., 105: 121–129. doi: 10.1002/bit.22525
- Issue published online: 19 NOV 2009
- Article first published online: 1 SEP 2009
- Accepted manuscript online: 1 SEP 2009 12:00AM EST
- Manuscript Accepted: 25 AUG 2009
- Manuscript Revised: 22 AUG 2009
- Manuscript Received: 26 JUN 2009
- Graduate Assistantship in Areas of National Need (GAANN) Program
- NIH Leadership in Pharmaceutical Biotechnology Program (NIH). Grant Number: T32 GM008732
- NIH (NIH NIBIB). Grant Number: 1 R01 EB006006-01
- Amgen, Inc.
- protein aggregation;
- stainless steel;
- monoclonal antibody;
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.