Rapid Development of High Concentration Protein Formulation Driven by High-Throughput Technologies

Area of Science:

• Biopharmaceutical Development
• Protein Formulation Science
• High-Throughput Screening

Background:

• Developing high concentration protein formulations (HCPF) requires balancing protein stability (conformational, colloidal, chemical) with solution properties (viscosity, osmolality).
• Traditional methods for optimizing these attributes can be time-consuming and resource-intensive.

Purpose of the Study:

• To establish and validate a rapid, multi-phase platform for the rational design and development of HCPF.
• To efficiently screen and select formulations that optimize both protein stability and desirable solution properties.

Main Methods:

• A three-phase approach was employed, starting with high-throughput (HT) biophysical and viscosity screening in 384-well plates.
• Phase 2 involved short-term stability studies in 96-well plates under stress conditions, with formulation selection based on stability-indicating assays and statistical analysis.
• Phase 3 confirmed the stability of lead formulations through a one-month accelerated stability study in glass vials.

Main Results:

• The HT screening platform was successfully established using a model antibody A (mAb-A).
• A lead formulation demonstrated a 30% reduction in mAb-A viscosity and an 80% decrease in subvisible particles post-thermal stress compared to a commercial control.
• Statistical analysis guided the selection of optimal formulations in Phase 2.

Conclusions:

• HT biophysical and viscosity screening effectively guides rational HCPF design.
• The developed platform enables rapid identification of HCPF balancing stability and solution properties within seven weeks (Phases 1 & 2).
• This strategy significantly accelerates the development timeline for high concentration protein formulations.