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Correlating Surface Activity with Interface-Induced Aggregation in a High-Concentration mAb Solution.
Estephanie L N Escobar1, Valerie P Griffin1, Prajnaparamita Dhar1
1Department of Chemical and Petroleum Engineering, The University of Kansas, 1530W 15th Street, Lawrence, Kansas 66045, United States.
Molecular Pharmaceutics
|February 22, 2024
Summary
Interface-induced protein aggregation is a problem for high-concentration antibody (mAb) therapeutics. Surfactant addition may not prevent particle formation at high concentrations, highlighting the importance of the surfactant-to-mAb ratio.
Area of Science:
- Biopharmaceutical Manufacturing
- Protein Aggregation Science
- Formulation Development
Background:
- Interface-induced aggregation is a critical issue in manufacturing and storing protein therapeutics, especially at high concentrations.
- Understanding the relationship between protein concentration and interface-induced particle formation is crucial.
- The precise mechanisms by which polysorbate surfactants prevent protein aggregation at high concentrations are not fully understood.
Purpose of the Study:
- To investigate the dependence of interface-induced protein particle formation on bulk protein concentration.
- To elucidate the role of polysorbate 20 (PS20) in mitigating protein aggregation at the air-water interface.
- To determine the critical factors influencing surfactant efficacy in high-concentration monoclonal antibody (mAb) formulations.
Main Methods:
- Utilized a tensiometer technique to measure surface pressure of a mAb at varying concentrations, with and without PS20.
- Employed microflow imaging to correlate adsorption kinetics with subvisible protein particle formation at the air-water interface and in bulk solutions.
- Analyzed protein and surfactant adsorption behavior at the air-water interface.
Main Results:
- Subvisible particle formation in bulk increased linearly with mAb concentration without surfactant.
- Interface particle formation showed a logarithmic dependence on mAb concentration.
- At low mAb concentrations (10 mg/mL), PS20 addition above CMC reduced particle formation.
- At high mAb concentrations (170 mg/mL), coadsorption of mAb and PS20 occurred, and PS20 failed to prevent particle formation.
Conclusions:
- The ratio of surfactant to mAb molecules is a critical parameter for preventing protein particle formation in high-concentration mAb therapeutics.
- Surfactant efficacy in mitigating aggregation is concentration-dependent and influenced by coadsorption phenomena.
- These findings provide essential insights for optimizing formulations of high-concentration protein-based drugs.
