Filling of High-Concentration Monoclonal Antibody Formulations: Investigating Underlying Mechanisms Impacting Precision of Low-Volume Fill by Peristaltic Pump

Wendy Shieu; Dax Lamar; Oliver Boris Stauch; Yuh-Fun Maa

doi:10.5731/pdajpst.2015.005926

Abstract

Filling of high-concentration/viscosity monoclonal antibody (mAb) formulations into vials or syringes by peristaltic pumps is an industrial standard. Control of the peristaltic pump on fill weight/volume accuracy/precision over time, however, has not been fully disclosed in the literature. This study systematically evaluated the impact of a broad range of system/pump parameters, from tubing set up to pump parameter settings to the filling nozzle, on filling precision using a bench-top system with fill weight readings from a high-precision balance. A low fill volume of 0.3 mL was targeted to fill liquids of various viscosities (including a high-concentration mAb formulation). Fill weight precision was reported via percent of fill weight data points (at least 100 consecutive points) falling within 3% of the target fill weight (e.g., within 0.009 g for a 0.3 g target fill weight). Experimental results suggested that the 3% precision target is challenging for filling high-viscosity liquids due to run-to-run and day-to-day variability. More importantly, none of the system/pump parameters seemed to directly correlate with fill weight precision. Photograph analysis revealed liquid suck-back height variations during fill, which correlated well with fill weight variability. Suck-back height variation was attributed to two possible root causes: (1) inconsistent liquid stream separation point and (2) pressure-induced variations upon suck-back. Liquid stream break-up was influenced by liquid properties as well as liquid/nozzle interactions, and pressure variations might be associated with tubing and overall mechanism of the peristaltic pump. A custom nozzle-tip design featuring a hydrophobic tip and a pressure-resistance barrier enabled consistent suck-back heights for each fill and approximately 90% of fill weight data within 3% precision for a high-concentration mAb formulation.

Received September 28, 2015.
Accepted December 22, 2015.

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