Characterization of Opalescence in low Volume Monoclonal Antibody Solutions Enabled by Microscale Nephelometry

Monoclonal antibody (mAb)-based drugs are often prone to unfavorable solution behaviors including high viscosity, opalescence, phase separation, and aggregation at the high concentrations needed to enable patient-centric subcutaneous dosage forms. Given that these can have a detrimental impact on manufacturability, stability, and delivery, approaches to identifying, monitoring, and controlling these behaviors during drug development are critical. Opalescence presents a significant challenge due to its relationship to liquid-liquid phase separation. Quantitative characterization of opalescence via turbidimetry is often restrictive due to large volume requirements (>2 mL) and alternative microscale approaches based on light transmittance (Eckhardt et al., J Pharm Sci Technol. 1994, 48: 64–70) may pose challenging with respect to accuracy. To address the need for accurate and quantitative microscale opalescence measurements, we have evaluated the use of a ‘de-tuned’ static light scattering detector which requires