Application of a High Throughput and Automated Workflow to Therapeutic Protein Formulation Development

Area of Science:

• Biopharmaceutical Formulation
• High Throughput Screening
• Protein Drug Development

Background:

• Efficient formulation development is crucial for competitive therapeutic protein markets.
• Conventional high throughput methods are limited to low protein concentrations, unsuitable for late-stage development.

Purpose of the Study:

• To present a high throughput (HT) formulation workflow for screening therapeutic proteins at representative concentrations.
• To demonstrate the workflow's efficiency and applicability in formulation design space expansion.

Main Methods:

• Integration of a micro-buffer exchange system with automated analytical instruments.
• Utilized size exclusion chromatography (SEC) and capillary electrophoresis (CEX) for stability profiling.
• Compared HT workflow results with traditional ultrafiltration/diafiltration methods.

Main Results:

• The HT workflow enables screening at representative protein concentrations.
• Achieved over 70% reduction in hands-on time and 30% in run time.
• HT workflow results showed good agreement with ultrafiltration/diafiltration methods.

Conclusions:

• The developed HT workflow is fit for purpose for biopharmaceutical formulation development.
• This approach accelerates the characterization of an expanded formulation design space.
• Successfully applied in case studies for viscosity and stability screening and mimic solution selection.