Monoclonal antibodies are complex molecules that typically require high concentration formulation for subcutaneous injection and drug substance storage, and low concentration formulation for intravenous administration. Stability is a common concern in both high and low concentration formulations. However, high concentration formulations are further complicated with an increase in viscosity, leading to manufacturing and administration challenges. This presentation will discuss new excipients modified to provide functional properties that minimize the increase in formulation viscosity and decrease the rate of degradation of the monoclonal antibody by minimizing protein-protein interactions and deamidation. They are suitable for use across the antibody concentration range. The excipients were able to reduce the viscosity of a monoclonal at 300 mg/ml antibody concentration by 80 % when compared to a buffer control formulation. Stabilization of the antibody by the excipients was also tested at accelerated temperature conditions at 250 mg/ml and 10 mg/ml antibody concentrations. The stability samples were analyzed by SEC-HPLC, IEC-HPLC and LC-MS/MS. The stability data has demonstrated that the excipients were able to minimize changes in both size and charge variance. The percent monomer remaining following 4 weeks of storage at 40°C was about 14% higher, while the precents aggregate and degradant were about 12% and 2% lower, respectively in formulations containing excipient compared to buffer control. The change in acidic peak group (APG) was about 38% lower in the formulations containing the excipients compared to the buffer control following 4 weeks of storage at 40°C. Similar results were observed for 10 mg/ml antibody formulation as well. The 10 mg/ml antibody concentration formulations were further analyzed by LC-MS/MS for post transitional modifications following 8 weeks of storage at 40°C. The deamidation of asparagine increased from 8% to 23% following 8 weeks of storage at 40°C in the formulation lacking excipient; however, it remained unchanged in the formulations containing excipient.

An approach to enhancing the versatility and stability of an antibody formulation by minimizing protein-protein interactions and deamidation

ACS Fall 2021

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