Predicting, characterizing, and controlling interfacial antibody adsorption and aggregation
July 14-17, 2019
Exposure to interfaces can accelerate aggregation of antibody therapeutics, particularly under stresses encountered during manufacture, transportation, and administration. Controlling interfacial antibody adsorption is critical to limiting aggregation. A panel of monoclonal antibody therapeutics was characterized by multiple surface-sensitive techniques to predict their risk of interfacially mediated aggregation. The antibodies with the highest interfacial aggregation propensity exhibited more than a five-fold faster rate of surface pressure increase and rapidly formed hydrophobic films upon adsorption, which indicated these molecules unfolded rapidly at the interface. Strong, essentially irreversible protein-protein interactions, likely dominated by hydrophobic interactions, resulted in high levels of aggregation for these antibodies. In contrast, the antibodies with a low propensity to aggregate at the interface required many minutes of interfacial exposure to form hydrophobic films and did not develop strong, irreversible interactions. Overall, characterization of the interfacial properties of the antibodies allowed us to predict their extent of interfacial aggregation.
The risk of interfacial aggregation measured using surface-sensitive techniques was then related to the level of surfactant required in a formulation to stabilize against aggregation. Specifically, a small-scale IV bag agitation model was used to assess aggregation after simulated handling and transportation in the clinic. The level of surfactant required to stabilize against the agitation stress correlated directly with the risk of interfacial aggregation of the antibody, suggesting that surface-sensitive techniques can be used to enable rapid surfactant screening during formulation development.
Ian Shieh, "Predicting, characterizing, and controlling interfacial antibody adsorption and aggregation" in "Biological and Pharmaceutical Complex Fluids III: Protein Self-Assembly, Rheology and Interfacial Properties", Samiul Amin, Manhattan College, USA Miguel Rodrigues, University of Lisbon, Portugal Paolo Arosio, ETHZ, Switzerland Eds, ECI Symposium Series, (2019). https://dc.engconfintl.org/bpcf_iii/8