Factors influencing antibody stability at solid–liquid interfaces in a high shear environment
- 1 September 2009
- journal article
- formulation and-engineering-of-biomaterials
- Published by Wiley in Biotechnology Progress
- Vol. 25 (5) , 1499-1507
- https://doi.org/10.1002/btpr.211
Abstract
A rotating disk shear device was used to study the effect of interfacial shear on the structural integrity of human monoclonal antibodies of IgG4 isotype. Factors associated with the solution conditions (pH, ionic strength, surfactant concentration, temperature) and the interface (surface roughness) were studied for their effect on the rate of IgG4 monomer loss under high shear conditions. The structural integrity of the IgG4 was probed after exposure to interfacial shear effects by SDS-PAGE, IEF, dynamic light scattering, and peptide mapping by LC-MS. This analysis revealed that the main denaturation pathway of IgG4 exposed to these effects was the formation of large insoluble aggregates. Soluble aggregation, breakdown in primary structure, and chemical modifications were not detected. The dominant factors found to affect the rate of IgG4 monomer loss under interfacial shear conditions were found to be pH and the nanometer-scale surface roughness associated with the solid-liquid interface. Interestingly, temperature was not found to be a significant factor in the range tested (15–45°C). The addition of surfactant was found to have a significant stabilizing effect at concentrations up to 0.02% (w/v). Implications of these findings for the bioprocessing of this class of therapeutic protein are briefly discussed. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009Keywords
This publication has 50 references indexed in Scilit:
- Current Perspectives on Stability of Protein Drug Products during Formulation, Fill and Finish OperationsBiotechnology Progress, 2008
- Determining Antibody Stability: Creation of Solid-Liquid Interfacial Effects within a High Shear EnvironmentBiotechnology Progress, 2007
- Role of hydrodynamic shear on activity and structure of proteinsPublished by Springer Nature ,2006
- Protein aggregation and bioprocessingThe AAPS Journal, 2006
- Induction and analysis of aggregates in a liquid IgG1-antibody formulationEuropean Journal of Pharmaceutics and Biopharmaceutics, 2005
- Protein aggregation and its inhibition in biopharmaceuticsPublished by Elsevier ,2005
- Monoclonal antibodies marketNature Reviews Drug Discovery, 2004
- Bioequivalence and the immunogenicity of biopharmaceuticalsNature Reviews Drug Discovery, 2002
- Stabilisation of biopharmaceutical products and finished product formulationsPublished by Springer Nature ,1999
- The kinetics and mechanism of shear inactivation of lipase from Candida cylindraceaBiotechnology & Bioengineering, 1989