Reaching the breaking point: Effect of tubing characteristics on protein particle formation during peristaltic pumping.

Peristaltic pumping has been identified as a cause for protein particle formation during manufacturing of biopharmaceuticals. To give advice on tubing selection, we evaluated the physicochemical parameters and the propensity for tubing and protein particle formation using a monoclonal antibody (mAb) for five different tubings. After pumping, particle levels originating from tubing and protein differed substantially between the tubing types. An overall low shedding of tubing particles by wear was linked to low surface roughness and high abrasion resistance. The formation of mAb particles upon pumping was dependent on the tubing hardness and surface chemistry. Defined stretching of tubing filled with mAb solution revealed that aggregation increased with higher strain beyond the breaking point of the protein film adsorbed to the tubing wall. This is in line with the decrease in protein particle concentration with increasing tubing hardness. Furthermore, material composition influenced particle formation propensity. Faster adsorption to materials with higher hydrophobicity is suspected to lead to a higher protein film renewal rate resulting in higher protein particle counts. Overall, silicone tubing with high hardness led to least protein particles during peristaltic pumping. Results from this study emphasize the need of proper tubing selection to minimize protein particle generation upon pumping.