Opalescence of an IgG1 Monoclonal Antibody Formulation is Mediated by Ionic Strength and Excipients

Opalescence is a phenomenon that has been observed in several commercially available monoclonal antibodies, both in liquid and reconstituted lyophilized formulations. In this article, we demonstrated that an increase in the ionic strength of a monoclonal antibody formulation (MAb1) led to opalescence and higher viscosity. When the ionic strength was reduced, no opalescence in the MAb1 formulation was observed. The removal of polysorbate-80 (PS-80) from the formulation resulted in an increase in opalescence in NaCl-containing formulations, whereas it had no effect on formulations lacking NaCI. Differential scanning calorimetry with MAb1 formulations containing increasing amounts of NaCI indicated that formulations with higher ionic strength present a lower apparent melting temperature. Opalescent MAb1 formulations placed on stability remained unchanged after four weeks at 4 °C, whereas at 45 °C, an increase in dimers was observed. Using multi-angle light scattering, the MAb11 formulation was found to have a negative second virial coefficient.