Evaluation and Screening of Biopharmaceuticals using Multi-Angle Dynamic Light Scattering.

Area of Science:

• Biopharmaceutical analysis
• Protein characterization
• Analytical chemistry

Background:

• Biopharmaceuticals are complex molecules requiring stringent quality control during manufacturing.
• Instability and critical quality attributes (CQAs) like aggregation and particle size impact safety and efficacy.
• Established methods like Size Exclusion Chromatography (SEC) are used, but complementary techniques are valuable.

Purpose of the Study:

• To evaluate Multi-Angle Dynamic Light Scattering (MADLS) for biopharmaceutical characterization.
• To assess MADLS's capability in determining particle size, particle concentration, and aggregation.
• To explore MADLS as a streamlined analytical approach for product development.

Main Methods:

• Application of MADLS to three protein modalities: Bovine Serum Albumin (BSA), a monoclonal antibody (mAb), and an enzyme.
• Determination of particle number concentration using MADLS and correlation with known values.
• Comparison of MADLS results for aggregation analysis with gold-standard SEC.

Main Results:

• A reliable calibration curve (R² > 0.95) was established for particle number concentration across the tested proteins.
• MADLS demonstrated strong correlation (R² = 0.9938) with SEC for enzyme aggregation analysis.
• The study validated MADLS as a versatile tool for multiple biopharmaceutical quality attributes.

Conclusions:

• MADLS provides a comprehensive 3-in-1 approach for assessing particle size, concentration, and aggregation in biopharmaceuticals.
• This method can significantly reduce the number of samples and experiments needed during product screening and development.
• MADLS offers an efficient alternative/complementary technique to traditional methods, aiding in faster product realization.