Frozen state storage instability of a monoclonal antibody: aggregation as a consequence of trehalose crystallization and protein unfolding.

Purpose: To investigate the cause of unexpected and erratic increase in aggregation during long-term storage of an IgG2 monoclonal antibody in a trehalose formulation at -20°C.

Methods: Frozen matrix was sampled, stored frozen at various temperatures and analyzed by SEC over time.

Results: Aggregation increased with time at -20°C but not at -40°C or -10°C.