Investigating and Addressing Challenges Associated with Filling Protein Drug Products

Area of Science:

• Biopharmaceutical Manufacturing
• Process Engineering
• Drug Product Development

Background:

• The fill-finish process is critical for biopharmaceutical products.
• High-concentration formulations introduce unique manufacturing challenges.
• Standard filling technologies face difficulties with viscous biopharmaceutical products.

Purpose of the Study:

• To investigate operational challenges in the fill-finish unit operation for high-concentration biopharmaceutical products.
• To evaluate three common filling technologies: piston pump, time-over-pressure pump, and peristaltic pump.
• To identify key factors causing filling line stoppages and propose mitigation strategies.

Main Methods:

• Case studies were conducted on bench-scale and manufacturing operations.
• Analysis of product-related parameters (protein concentration, viscosity, surface tension) for piston pump filling.
• Characterization of fluid flow and pump parameters for peristaltic pump filling, including failure mode analysis.
• Examination of time-pressure filling operations and associated challenges.

Main Results:

• Piston pump filling was impacted by protein concentration, viscosity, and surface tension.
• Peristaltic pump filling showed issues related to fluid dynamics and product drying.
• Time-pressure filling presented its own set of operational difficulties.
• Common challenges included drug product-nozzle interactions, inadequate pump clearances, and suboptimal control parameters.

Conclusions:

• High-concentration product manufacturing requires careful consideration of filling technology.
• Drug product properties significantly influence the performance of piston pumps.
• Optimizing pump parameters and addressing product-nozzle interactions are crucial for preventing stoppages in peristaltic and time-pressure filling.