(673i) Role of the Air-Solution Interface on the Mechanism of Subvisible Particle Formation in  an IgG1 Mab Solution

Mechanical agitation of monoclonal antibody (mAb) solutions often leads to protein particle formation. Using a Langmuir trough, controlled interfacial stresses were applied to various IgG1 mAb formulations, and the resulting protein particles formed at the interface and in the bulk solution were characterized using atomic force microscopy and flow digital imaging. Bulk protein particle formation after being subjected to interfacial stresses was also compared to mAb solutions agitated in glass vials and unstressed controls. mAb samples subjected to 750-1000 interfacial compression-expansion cycles in six hours, contained high particles numbers in bulk solution, and displayed similar particulation trends when agitated in vials. At compression rates of 50 cycles in six hours, however, particle levels in mAb solutions were comparable to unstressed controls, despite protein aggregates being present at the air-solution interface. Our results together suggest that while the air-solution interface serves as a nucleation site for initiating protein aggregation, the number of protein particles measured in bulk mAb solutions depend on the total number of compression cycles that proteins at the air-solution interface are subjected to within a fixed time.