Impact of Surface Tension, Viscosity, Pump Settings, and Nozzle Size on Filling Process Capability and Accuracy in High-Concentration Biopharmaceuticals.

Abstract

Filling is the final critical unit operation in the manufacturing process of liquid biological drug products. This paper thoroughly investigates the influence and mechanisms of peristaltic pump settings, nozzle size, product surface tension and viscosity on the biopharmaceutical filling processes based on the established filling process model of surrogates. Our study highlights the significant role of pump settings in influencing filling process capability indexes, in addition to their primary function of regulating flow rate. Surface tension minimally impacts flow behavior but significantly regulates the final drop's behavior, with lower surface tension increasing dripping tendencies. Viscosity proves crucial; higher viscosity intensifies friction and head loss of filling flow in tube/nozzle, causing pressure and flow rate losses, more pronounced dripping, and worse filling accuracy. Furthermore, nozzle size moderates the impact of pump settings, surface tension, and viscosity on filling performance. Larger nozzles help mitigate these effects, contributing to enhanced stability in filling performance under challenging conditions. For high-concentration biopharmaceuticals with elevated viscosity during filling, utilizing larger nozzles and reducing pump speed could achieve enhanced Cpk values and improved filling accuracy. Understanding the complex interactions among these factors is vital for optimizing the biopharmaceutical industry, promoting cost-effective practices, and enhancing production efficiency.