Physicochemical Stability of Monoclonal Antibodies: A Review.

ABSTRACT

Monoclonal antibodies (mAbs) are subject to instability issues linked to their protein nature. In this work, we review the different mechanisms that can be linked to monoclonal antibodies instability, the parameters, and conditions affecting their stability (protein structure and concentration, temperature, interfaces, light exposure, excipients and contaminants, and agitation) and the different analytical methods used for appropriate physicochemical stability studies physical stability assays (aggregation, fragmentation, and primary, secondary, and tertiary structure analysis), chemical stability assays and quantitative assays. Finally, data from different published stability studies of mAbs formulations, either in their reconstituted form, or in diluted ready to administer solutions, was compiled. Overall, the physicochemical stability of mAbs is linked to numerous factors such as formulation, environment, and manipulations, and must be thoroughly investigated using several complementary analytical techniques, each of which allowing specific characterization information to be harvested. Several stability studies have been published, some of them showing possibilities of extended stability. However, those data should be questioned due to potential lacks in study methodology.