An Empirical Quantitative Model Describing Simultaneously Temperature and Concentration Effects on Protein Solution...

Area of Science:

• Biopharmaceutical Manufacturing
• Physical Chemistry
• Drug Product Development

Background:

• High-concentration protein solutions, common in biologics, present manufacturing and administration challenges due to viscosity.
• Accurate viscosity modeling for biologics is critical for formulation development and process optimization but remains challenging.

Purpose of the Study:

• To develop and validate a practical model for predicting the viscosity of therapeutic protein solutions.
• To assess the model's effectiveness across various antibody types, formulations, concentrations, and temperatures.

Main Methods:

• Developed a viscosity model combining Ross-Minton for concentration dependence and modified Arrhenius for temperature dependence.
• Experimentally measured viscosity of four therapeutic antibodies across a range of concentrations and temperatures in clinical formulations.

Main Results:

• The developed viscosity model demonstrated broad applicability across different antibodies and formulations.
• The model accurately predicted viscosity over more than two orders of magnitude.
• The model effectively captured the influence of temperature and protein concentration on solution viscosity.

Conclusions:

• The proposed viscosity model offers a practical and generalizable approach for predicting the behavior of therapeutic protein solutions.
• This modeling capability can help mitigate challenges in biopharmaceutical drug manufacturing and improve process control.