A Systematic Multitechnique Approach for Detection and Characterization of Reversible Self-Association during Formulation Development of Therapeutic Antibodies

Hydrogen-Deuterium Exchange Mass Spectrometry as an Emerging Analytical Tool for Stabilization and Formulation Development of Therapeutic Monoclonal Antibodies

“…Changes in local dynamics may better correlate with the short‐term or long‐term pharmaceutical stability of some or perhaps many different mAbs than data obtained from other biophysical measurements. Alterations in mAb local dynamics can therefore be of interest during many aspects of pharmaceutical development including elucidating degradation pathways, designing stable formulations, assessing biopharmaceutical comparability due to process or product changes, and potentially assessing mechanisms of self‐association and high viscosity in certain mAbs . Here, we review the application of H/D‐MS to formulation development of mAbs by exploring the effects of chemical modifications, environmental stresses, and formulation additives on the local dynamics of IgG1 mAbs and their interrelationships with conformational and pharmaceutical stability.…”

Recent applications of light scattering measurement in the biological and biopharmaceutical sciences

“…The resolution and range of this method of analysis are not as great as those afforded by CG-SLS, but may be entirely satisfactory for characterization of simple associations, such as a monomer-dimer equilibrium within a limited range of interaction strength, as illustrated in Figure 7 [14]) . In addition, the very low quantity of sample required to measure DLS and the rapidity of data acquisition make this an attractive option for detection of interactions over a broad range of experimental conditions or within a panel of candidate binding partners, to be followed by more detailed study of the system under selected conditions or binding partners via CG-SLS [35]. …”

“…CG-DLS, CG-MALS and sedimentation equilibrium measurements were used to quantitatively characterize reversible self-association of a monoclonal antibody [35]. The data obtained from all three types of measurements were quantitatively accounted for by a model in which the antibody could reversibly self-associate to form a trimer, and the trimers so formed could weakly self-associate at higher concentration to form oligomers of indefinite size according to an isodesmic scheme.…”

High-throughput screening for developability during early-stage antibody discovery using self-interaction nanoparticle spectroscopy

“…This is problematic because weak antibody self-and cross-interactions are often responsible for aggregation and polyreactivity, respectively. 6,7,12,[14][15][16][17][18][19] Nevertheless, numerous assays such as self-interaction chromatography (SIC) [20][21][22][23][24][25] and cross-interaction chromatography (CIC) [26][27][28] have been designed to identify these possibly troublesome antibodies early in the discovery program to avoid downstream issues. In these chromatography assays, increased retention of mAbs passing through a column conjugated with identical mAbs or a pool of polyclonal serum antibodies is indicative of attractive self-or cross-interactions, respectively.…”