title: Radar chart array analysis to visualize effects of formulation variables on IgG1 particle formation as measured by multiple analytical techniques.
abstract: This study presents a novel method to visualize protein aggregate and particle formation data to rapidly evaluate the effect of solution and stress conditions on the physical stability of an immunoglobulin G (IgG) 1 monoclonal antibody (mAb). Radar chart arrays were designed so that hundreds of microflow digital imaging (MFI) solution measurements, evaluating different mAb formulations under varying stresses, could be presented in a single figure with minimal loss of data resolution. These MFI radar charts show measured changes in subvisible particle number, size, and morphology distribution as a change in the shape of polygons. Radar charts were also created to visualize mAb aggregate and particle formation across a wide size range by combining data sets from size-exclusion chromatography, Archimedes resonant mass measurements, and MFI. We found that the environmental/mechanical stress condition (e.g., heat vs. agitation) was the most important factor in influencing the particle size and morphology distribution with this IgG1 mAb. Additionally, the presence of NaCl exhibited a pH and stress-dependent behavior resulting in promotion or inhibition mAb particle formation. This data visualization technique provides a comprehensive analysis of the aggregation tendencies of this IgG1 mAb in different formulations with varying stresses as measured by different analytical techniques.
authors.affiliation: Department of Pharmaceutical Chemistry, Macromolecule and Vaccine Stabilization Center, University of Kansas, Lawrence, Kansas, 66047.
authors.forename: Cavan
authors.initials: C
authors.lastname: Kalonia
authors.forename: Ozan S
authors.initials: OS
authors.lastname: Kumru
authors.forename: Jae Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: C Russell
authors.initials: CR
authors.lastname: Middaugh
authors.forename: David B
authors.initials: DB
authors.lastname: Volkin
mesh_terms: D002152:Calorimetry, Differential Scanning; D002850:Chromatography, Gel; D007091:Image Processing, Computer-Assisted / Q000379:methods; D007074:Immunoglobulin G / Q000737:chemistry*; D008853:Microscopy / Q000379:methods; D010316:Particle Size; D011487:Protein Conformation; D055550:Protein Stability; D012965:Sodium Chloride / Q000737:chemistry; D013050:Spectrometry, Fluorescence
chemical_list: D007074:Immunoglobulin G; D012965:Sodium Chloride
keywords: Archimedes; data visualization; formulation; microflow imaging; monoclonal antibody; morphology; particle size; protein aggregation; stability