Use of Raman and Raman optical activity for the structural characterization of a therapeutic monoclonal antibody formulation subjected to heat stress

Structural complexity of biological drug products presents an analytical challenge in terms of early detection of aggregation and/or degradation. In the present study, Raman and Raman optical activity (ROA) were evaluated for their sensitivity to detect heat-induced molecular instability in an Immunoglobulin G4 subclass therapeutic monoclonal antibody present in its formulation matrix. The therapeutic antibody was subjected to heat stress at 50 °C and was analyzed at various time points up to 1 month. The current results suggest that Raman and ROA are sensitive to early-stage detection of heat-induced instability of the antibody, in which significant changes could be observed at 1 week of stress. ROA could provide early detection of the subtle differences at the tertiary structure level in a heat-stressed monoclonal antibody and Raman/ROA spectra could provide early detection in secondary structural changes as well.