Afraid of the wall of death? Considerations on monoclonal antibody characteristics that trigger aggregation during peristaltic pumping

Abstract

Protein aggregation is of major concern in manufacturing of biopharmaceutics. Protein aggregation upon peristaltic pumping for filtration, transfer or filling is triggered by protein adsorption to the tubing surface and subsequent film rupture during roller movement. While the impact of tubing type and formulation has been studied in more detail, the contribution of the protein characteristics is not fully resolved. We studied the aggregation propensity of six monoclonal antibodies during peristaltic pumping and characterized their colloidal and conformational stability, hydrophobicity, and surface activity. A high affinity to the surface resulting in faster adsorption and film renewal was key for the formation of protein particles ≥ 1 µm. Film formation and renewal were influenced by the antibody hydrophobicity, potential for electrostatic self-interaction and conformational stability. The initial interfacial pressure increase within the first minute can serve as a good predictor for antibody adsorption and particle formation propensity. Our results highlight the complexity of protein adsorption and emphasize the importance of formulation development to reduce protein particle formation by avoidance of adsorption to interfaces.

Keywords: Agglomeration; Bioprocess development; Filling; IgG antibody(s); Protein adsorption; Protein aggregation; Protein formulation; Pumping; Subvisible particles; Tubing.