Surfaces Affect Screening Reliability in Formulation Development of Biologics

Area of Science:

• Biopharmaceutical development
• Protein aggregation science

Background:

• Predicting antibody aggregation is crucial for therapeutic quality and safety.
• Container surfaces can influence protein aggregation kinetics.

Purpose of the Study:

• To investigate the role of container surfaces on monoclonal antibody (mAb) aggregation.
• To assess aggregation under elevated temperature and long-term storage conditions without mechanical stress.

Main Methods:

• Systematic study of aggregation across different proteins, vial materials, and storage temperatures.
• Utilized size exclusion chromatography and micro-flow imaging for aggregate quantification.
• Employed optical and atomic force microscopy to analyze vial surface interactions.

Main Results:

• Protein particles adhere to vial surfaces at elevated temperatures, leading to underestimated aggregation.
• At 5°C, particles do not adhere, increasing bulk concentration unpredictably by standard methods.
• Identified specific protein-surface interactions driving nanoscale oligomer formation.

Conclusions:

• Interpretations of stability data require careful consideration of temperature and vial type.
• A combined approach analyzing vial surfaces and bulk solution is proposed for comprehensive understanding of protein aggregation.