Water loss from silicone tubing and effect on protein concentration during drug product manufacturing.

Silicone tubing is used in various unit operations during drug product (DP) manufacturing. Hold of protein formulations in silicone tubing over time may have an impact on product quality, particularly protein concentration. This study evaluated the change in protein concentration of a test monoclonal antibody (mAb) formulation over various hold times in silicone tubing as a function of tubing internal diameter (ID) and wall thickness. It was hypothesized that the rate of water diffusion through the semi-permeable membrane is a function of the tubing ID and wall thickness. The weight and protein concentration of various formulation-filled tubings over time was measured. The weight of water lost varied linearly with the change in protein concentration. It was observed to be independent of mAb type, formulation composition, and initial protein concentration for a given tubing ID and wall thickness. The effect of formulation water activity on the water loss rate was investigated. A mechanistic diffusion-based model was developed that predicts the change in tubing weight and therefore protein concentration over various hold times for a given formulation and tubing. Overall, this study suggests that water loss from silicone tubing affects protein concentration and should be monitored during DP process development and manufacturing.