Frozen storage of mAbs at elevated temperatures: Balancing stability and sustainability

Protein bulk drug substance (DS) is conventionally kept at -70 to -80 °C to reduce risks such as microbial growth, agitation-related stress, and degradation. This study investigates the long-term physical stability of four IgG-type monoclonal antibodies (mAbs) at -70 and -40 °C under unformulated and fully formulated conditions to probe the broader applicability of -40 °C storage across different antibody formats. For one representative mAb, we further screened minimal formulations and assessed stability at -10 °C. Across all mAbs, -40 °C preserved physical stability comparably to -70 °C. Minimal excipient formulations enabled reliable preservation even above Tg' at -10 °C. The glass transition temperature (Tg') serves as a useful guideline, but the difference between the storage temperature and Tg' is not predictive of stability. Our findings support the adoption of higher frozen-storage temperatures and help guide the optimization of formulations for frozen storage. With this, the study lays the foundation for sustainability, reducing energy consumption without compromising DS quality.