Monoclonal antibodies are protein molecules that are prone to aggregation, which is not acceptable for biopharmaceuticals, since it can increase the immunogenicity of the final product. Long-term protein stability can be assessed by measuring protein aggregation in samples exposed to elevated temperatures and subsequent extrapolation of data using different models. Due to different mechanisms of aggregate formation, aggregation kinetics and particle adhesion to the vial surface, higher particle concentrations in solution may occur under actual long-term storage conditions, which cannot be predicted from accelerated studies. We studied the effect of vial surface, temperature and presence of salt on the kinetics of aggregation process on multiple size ranges of aggregates for two monoclonal antibodies. Bimolecular collisions were found to be the limiting step of aggregation at concentrations specific to biologics. The rate of aggregation can be predicted at any temperature or concentration for only one of the tested monoclonal antibodies, while the other is likely to undergo an additional unknown process, which causes a deviation of prediction from the actual results. This poses an increased risk when selecting a formulation based on screening tests at elevated temperatures and low concentrations, which can be mitigated by additional temperature and concentration conditions.
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