Effects of ultra-/diafiltration conditions on present aggregates in human immunoglobulin G preparations

Small traces of aggregates may cause reduced stability of human immunoglobulin G preparations. Ultra-/diafiltration as last step before formulation could also contribute to aggregate formation or depletion. One of the key challenges is to find a sensitive analytical method for the early detection of initial aggregation. Dynamic light scattering was applied to detect differences in the aggregate pattern during cross-flow filtration of human immunoglobulin preparations. The change of ionic strength of the process solution during diafiltration significantly influenced the aggregate pattern. Other causes for aggregation, such as flow induced shear stress or high local protein concentrations due to the build-up of a gel layer, did not significantly influence the formation of aggregates. The use of weak buffered solutions suppressed aggregate formation and as a positive effect permeate flux was increased during diafiltration.