Improved Stability of a Model IgG3 by DoE-Based Evaluation of Buffer Formulations

Area of Science:

• Biopharmaceutical formulation
• Protein stability
• Monoclonal antibody development

Background:

• Ensuring biopharmaceutical protein stability is critical for drug efficacy and safety.
• Challenging antibody formulations require careful optimization of storage conditions.
• Current methods for assessing protein stability inform formulation development.

Purpose of the Study:

• To optimize the formulation for a model murine IgG3 antibody.
• To identify storage conditions that enhance antibody stability and prevent degradation.
• To evaluate the effectiveness of design of experiments (DoE) in formulation screening.

Main Methods:

• Systematic exploration of formulation compositions using DoE.
• Assessment of antibody stability via UV/VIS absorbance and size exclusion high-performance liquid chromatography (SEC).
• Evaluation of solubility, opalescence, and aggregate formation.

Main Results:

• Acetate buffer was eliminated due to precipitate formation.
• A DoE combining arginine and histidine buffers was performed.
• An optimized formulation (200 mM arginine, 50 mM histidine, 100 mM NaCl, pH 6.5) significantly improved stability.

Conclusions:

• DoE is a powerful approach for optimizing challenging antibody formulations.
• The identified formulation enhances long-term storage stability and freeze-thaw resistance.
• This work provides a robust method for biopharmaceutical formulation development.