Impact of bulking agents on the stability of a lyophilized monoclonal antibody.

The impact of the bulking agents on the stability of lyophilized protein pharmaceuticals is not typically considered, as they usually crystallize, preventing them from stabilizing the protein. In this study, combinations of sucrose with mannitol or glycine were evaluated for their effects on antibody stability (deamidation and aggregation) and solid-state properties (water content, residual antibody structure, and T(g) values). While sucrose remains the primary stabilizing agent for the antibody in the solid state, inclusion of some amorphous glycine leads to a significant increase in stability. Mannitol displays little, if any, stabilizing ability in this system. In formulations where infrared spectroscopy could be applied, maintenance of secondary structure is an important factor in predicting storage stability. This study demonstrates that bulking agents can impact protein stability in the solid state. By remaining partially amorphous, bulking agents can sometimes lower degradation rates, while at the same time, providing a crystalline matrix producing elegant cakes. It appears that bulking agents may belong to a larger class of low molecular weight plasticizers, which appears to be able to increase solid-state stability of proteins despite lowering the glass transition temperature.