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Protein Adsorption and Layer Formation at the Stainless Steel - Solution Interface Mediates Shear-Induced Particle Formation for an IgG1 Monoclonal Antibody

Published

Author(s)

Cavan K. Kalonia, Frank Heinrich, Joseph E. Curtis, Sid Raman, Maria A. Miller, Steven Hudson

Abstract

Passage of specific protein solutions through certain pumps, tubing, and/or filling nozzles can result in the production of unwanted subvisible protein particles (SVP). In this work, surface mediated SVP formation was investigated. Specifically, the effects of different solid interface materials, interfacial shear rates, and protein concentrations on SVP formation were measured for the National Institute of Standards and Technology monoclonal antibody (NISTmAb), a reference IgG1 monoclonal antibody (mAb). A stainless steel rotary piston pump was used to identify formulation and process parameters which affect aggregation, and a flow cell (alumina or stainless steel interface) was used to further investigate the effect of different interface materials and/or interfacial shear rates. SVP particles produced were monitored using flow microscopy or flow cytometry. Neutron reflectometry and a quartz crystal microbalance with dissipation monitoring were used to characterize adsorption and properties of NISTmAb at the stainless steel interface. Pump/shear cell experiments showed that NISTmAb concentration and interface material had a significant effect on SVP formation, while the effects of interfacial shear rate and passage number were less important. At the higher NISTmAb concentrations, the adsorbed protein became structurally altered at the stainless steel interface. The primary adsorbed layer remained largely undisturbed during flow, suggesting that SVP formation at high NISTmAb concentration was caused by the disruption of patches and/or secondary interactions.
Citation
Molecular Pharmaceutics
Volume
15
Issue
3

Keywords

biomanufacturing, NIST mAb, antibody reference material, protein particle formation, protein sorption at solids, quartz crystal microbalance, neutron reflectivity

Citation

Kalonia, C. , Heinrich, F. , Curtis, J. , Raman, S. , Miller, M. and Hudson, S. (2018), Protein Adsorption and Layer Formation at the Stainless Steel - Solution Interface Mediates Shear-Induced Particle Formation for an IgG1 Monoclonal Antibody, Molecular Pharmaceutics, [online], https://doi.org/10.1021/acs.molpharmaceut.7b01127, https://tsapps.nist.gov/publication/get_pdf.cfm?pub_id=924050 (Accessed June 16, 2024)

Issues

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Created February 8, 2018, Updated October 12, 2021