Leveraging high-throughput analytics and automation to rapidly develop high-concentration mAb formulations:...

Area of Science:

• Biopharmaceutical Formulation
• Protein Chemistry
• High-Throughput Screening

Background:

• Developing stable, low-viscosity high-concentration monoclonal antibody (mAb) formulations requires extensive experimental screening.
• Current methods are often time-consuming and material-intensive, hindering rapid optimization.
• A high-throughput approach is needed to efficiently assess excipient compatibility and viscosity.

Purpose of the Study:

• To develop and validate a high-throughput screening method for optimizing high-concentration mAb formulations.
• To identify key factors influencing stability (aggregation, fragmentation) and viscosity.
• To establish an integrated workflow for assessing excipient compatibility and biophysical properties.

Main Methods:

• Screened 96 formulations of a trastuzumab biosimilar using 8 excipient modifiers and 4 buffers across a pH range of 4.5-7.5.
• Assessed stability (high molecular weight aggregation, fragmentation) and viscosity at high concentrations.
• Employed multiple linear regression to identify critical formulation parameters and their interactions.

Main Results:

• Optimal pH range for the trastuzumab biosimilar was 5.0-6.5, balancing stability and viscosity.
• Buffer type significantly impacted high molecular weight (HMW) aggregation, with Na-acetate and histidine-HCl performing best.
• Excipient modifiers showed complex interactions with pH and buffer, influencing viscosity and stability; arginine-HCl and lysine-HCl reduced viscosity above pH 6.0, while glycine was effective below pH 6.0.

Conclusions:

• High-throughput screening enables rapid identification of optimal formulation design spaces for high-concentration mAbs.
• Careful optimization of excipient levels is crucial to balance benefits against potential incompatibilities.
• This integrated approach minimizes material requirements and accelerates the development of stable, low-viscosity antibody formulations.