Subcutaneous delivery of protein therapeutics presents unique challenges to formulation development and ensuring physical stability at high protein concentrations.  A correlation was found between the concentration of an IgG1 antibody and aggregate formation over time stored at -20�C with significant worsening stability at high protein concentrations (e.g. 150 mg/mL).  Degradation trends for a 200 mg/mL mAb formulated in arginine succinate show a generally linear rate of 0.5 � 0.1 % monomer loss per month up to 9 months then decreases to 0.3% for the subsequent 9 months.  In addition, freeze-thaw stress had notable adverse impact at = 200 mg/mL mAb and degradation species were characterized by SEC.  Parameters investigated for determining the mechanism of action included freezing rate, storage container, glass transition temperature (Tg'), and storage temperature. The results can then inform development of a robust formulation to address this kind of degradation during frozen storage.

Evaluation of physical stability during frozen storage of a high concentration liquid formulation for a monoclonal antibody

245th National Meeting (2013)

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