Monoclonal antibodies (mAbs) are attractive forms of therapeutic agents due to their high specificity with antigens. The successful development of a new therapeutic mAb product needs to meet many requirements, such as marketability, safety, administration routes and stability. The stability of mAbs is of critical importance to the end product’s marketability and safety, and research into understanding their stability is ongoing in both industrial and academic environments.[1-2] It is well established that the formation of irreversible mAb aggregates can occur due to surface adsorption and desorption, which is a common occurrence during drug manufacture, shipping, and long-term storage. Further factors that impact formulation stability include the interfacial stresses due to selective adsorption of mAbs at the air-water interface, which is attributed with causing instabilities and aggregation. In industrial formulations, surfactants are regularly incorporated into mAb formulations where they play the role of stabilizer, either by forming mAb-surfactant complexes or through preferential adsorption to hydrophobic interfaces.
In our work, we have selected two complementary mAbs with very different long-term (3 year) stabilities determined by visible particle count in bulk solution. These mAbs are dispersed in buffer with and without non-ionic surfactants (polysorbate 80 and poloxamer 188) and their interfacial dynamics at the air-water interface studied by dynamic surface tension, interfacial shear rheology, interfacial dilatational rheology, Brewster angle microscopy (BAM) as well as X-ray reflectivity (XRR). The mAbs absorb irreversibly and form a gel-like phase that cannot be displaced by surfactant, while both surfactants are capable of protecting against mAb adsorption. Differences in behavior at the air-water interface are compared with long-term stability in bulk solution to better understand mAb formulation.
Roberts, C. J. (2014). Protein aggregation and its impact on product quality. Current Opinion in Biotechnology, 30, 211–217.
Amin, S., Barnett, G. v, Pathak, J. A., Roberts, C. J., & Sarangapani, P. S. (2014). Protein aggregation, particle formation, characterization & rheology. Current Opinion in Colloid & Interface Science, 19 (5), 438–449.

Ken Qian

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