Determining antibody stability: Creation of solid-liquid interfacial effects within a high shear environment
Date
2007
Authors
Biddlecombe, J.
Craig, A.
Zhang, H.
Uddin, S.
Mulot, S.
Fish, B.
Bracewell, D.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Biotechnology Progress, 2007; 23(5):1218-1222
Statement of Responsibility
James G. Biddlecombe, Alan V. Craig, Hu Zhang, Shahid Uddin, Sandrine Mulot, Brendan C. Fish and Daniel G. Bracewell
Conference Name
Abstract
The purpose of this study was to assess the stability of protein formulations using a device designed to generate defined, quantifiable levels of shear in the presence of a solid-liquid interface. The device, based on a rotating disk, produced shear strain rates of up to 3.4 × 104 s-1 (at 250 rps) and was designed to exclude air-liquid interfaces and enable temperature to be controlled. Computational fluid dynamics (CFD) was used to study the fluid flow patterns within the device and to determine the shear strain rate (s-1) at a range of disk speeds. The device was then used to study the effect on a monoclonal IgG4 of high levels of shear at the solid-liquid interface. Monomeric antibody concentration and aggregation of the protein in solution were monitored by gel permeation HPLC and turbidity at 350 nm. High shear strain rates were found to cause significant levels of protein aggregation and precipitation with reduction of protein monomer following first-order kinetics. Monomer reduction rate was determined for a range of disk speeds and found to have a nonlinear relationship with shear strain rate, indicating the importance of identifying and minimizing such environments during processing.