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Accelerated Aggregation Studies of Monoclonal Antibodies: Considerations for Storage Stability

Journal Contribution - Journal Article

Aggregation of mAbs is a crucial concern with respect to their safety and efficacy. Among the variousproperties of protein aggregates, it is emerging that their size can potentially impact their immunogenicity.Therefore, stability studies of antibody formulations should not only evaluate the rate of monomer loss butalso determine the size distribution of the protein aggregates, which in turn depends on the aggregationmechanism. Here, we study the aggregation behavior of different formulations of 2 monoclonal immunoglobulins (IgGs) in the temperature range from 5 C to 50 C over 52 weeks of storage. We show that theaggregation kinetics of both antibodies follow non-Arrhenius behavior and that the aggregation mechanisms change between 40 C and 5 C, leading to different types of aggregates. Specifically, for a givenmonomer conversion, dimer formation dominates at low temperatures, while larger aggregates areformed at higher temperatures. We further show that the stability ranking of different molecules as well asof different formulations is drastically different at 40 C and 5 C while it correlates better between 30 C and5 C. Our findings have implications for the level of information provided by accelerated aggregationstudies with respect to protein stability under storage conditions
Journal: Journal of Pharmaceutical Sciences
ISSN: 0022-3549
Issue: 1
Volume: 109
Pages: 595 - 602
Publication year:2019
Keywords:Multidisciplinary chemistry, Organic & medicinal chemistry, Pharmacology & toxicology