High Throughput Prediction Approach for Monoclonal Antibody Aggregation at High Concentration

Area of Science:

• Biopharmaceutical Development
• Protein Aggregation Science

Background:

• Monoclonal antibodies (mAbs) are crucial biopharmaceuticals.
• Understanding and preventing mAb aggregation is vital for drug efficacy and safety.
• Aggregation can occur during development, storage, and administration.

Purpose of the Study:

• To characterize monoclonal antibody aggregation.
• To identify stability factors predicting aggregation propensity.
• To develop a high-throughput, low-resource screening method for aggregation.

Main Methods:

• Used differential scanning calorimetry, dynamic light scattering, and size exclusion chromatography.
• Assessed conformational and colloidal stability and aggregation kinetics.
• Induced aggregation in two IgG mAb subclasses at varying concentrations (1-50 mg/mL) and high temperatures (55°C for 3 weeks).

Main Results:

• Monoclonal antibodies exhibited first-order aggregation kinetics, indicating a unimolecular rate-limiting step.
• Conformational stability was measured by denaturation temperature.
• The dynamic interaction parameter (kD) emerged as a promising predictor of mAb aggregation propensity.

Conclusions:

• Evaluated the significance of various aggregation predictors at high concentrations.
• The dynamic interaction parameter (kD) is a valuable tool for predicting mAb aggregation.
• Contributes to understanding protein aggregation in biopharmaceutical development and production.