Effect of Different Buffer Components on IgG4 Stability

This study investigated the impact of four buffer systems (sodium citrate, citrate phosphate, histidine, and acetate) and various excipients on the stability of an IgG4 monoclonal antibody, employing Design of Experiments methodologies and advanced analytical techniques (SEC, IEX, HIC, DSF). While sodium citrate buffer showed superior performance compared to citrate phosphate, an additional peak observed in both systems necessitated further optimization. Histidine buffer formulations with alternative stabilizers (trehalose, sorbitol) demonstrated stability comparable to the approved IgG4 formulation. Acetate buffer emerged as a promising alternative, outperforming citrate-based buffers in some aspects. The study revealed complex buffer-pH-excipient interactions, with pH critically influencing protein stability, particularly in the acetate system. This comprehensive research provides a foundation for rational IgG4 formulation design, highlighting the potential of acetate and histidine buffers, and emphasizing the need for long-term stability and forced degradation studies to fully understand excipient behaviors.