by Maria A. Croyle, PhD, Katie Gerding, and Kayla S. Quick, Pharm.D.
Volume 2, Issue 5 (September/October 2003)
The biologic activity of protein therapeutics is often compromised by the formation of soluble aggregates and protein precipitates. While the detailed molecular mechanism of protein aggregation remains unclear, substantial evidence suggests that factors that promote protein unfolding and exposure of hydrophobic residues play a significant role in aggregate formation. These can vary according to the particular protein of interest, the solvent system, and storage conditions. Slight changes in temperature, pH, and ionic strength have been documented to have a significant effect on the aggregation phenomena of numerous proteins. Freezing and subsequent thawing of a preparation (whether by design or accident) during processing, shipping, and storage can induce subtle changes in the ionic strength, solute concentration, and pH of a given preparation and induce aggregate formation…
Citation:
Croyle MA, Gerding K, Quick KS. Role of the Container/Closure System and Formulation on Agitation-Induced Aggregation Phenomena in Recombinant Adenoviral Products. BioProcess J, 2003; 2(5): 35-41.