title: Improved Comparative Signature Diagrams to Evaluate Similarity of Storage Stability Profiles of Different IgG1 mAbs.
abstract: For therapeutic protein analytical studies related to evaluating lot-to-lot variability, different processes and/or formulations, or biosimilars, there is growing interest in applying novel data visualization tools for fingerprint analysis to identify statistically significant differences between 2 samples. Comparative Signature Diagrams (CSDs) were previously developed to display such differences as colored contour plots using a variety of biophysical data sets. In this study, several improvements are proposed to enhance readability and quantitative determinations of CSDs using protein stability data from more commonly used analytical methods such as size exclusion chromatography and capillary isoelectric focusing. To demonstrate the effectiveness of improved CSDs for data visualization, an accelerated and real-time stability study was set up for an IgG1 mAb (mAb A) and its corresponding triple mutant (mAb E). The stability profiles of both mAbs were compared for differences in aggregation (size exclusion chromatography) and charge heterogeneity (capillary isoelectric focusing) profiles over time. Both traditional data analysis and the improved CSDs conclude that the triple mutant mAb E is more susceptible to physicochemical degradation than mAb A under accelerated conditions. The current abilities and limitations of CSDs to provide fingerprint analysis of protein stability profiles to facilitate the determination of similarity versus nonsimilarity between samples is discussed.
authors.affiliation: Department of Pharmaceutical Chemistry, Macromolecule and Vaccine Stabilization Center, University of Kansas, Lawrence, Kansas 66047.
authors.forename: Jae Hyun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Pharmaceutical Chemistry, Macromolecule and Vaccine Stabilization Center, University of Kansas, Lawrence, Kansas 66047.
authors.forename: Sangeeta B
authors.initials: SB
authors.lastname: Joshi
authors.affiliation: MedImmune, One MedImmune Way, Gaithersburg, Maryland 20878.
authors.forename: Reza
authors.initials: R
authors.lastname: Esfandiary
authors.affiliation: MedImmune, One MedImmune Way, Gaithersburg, Maryland 20878.
authors.forename: Vidyashankara
authors.initials: V
authors.lastname: Iyer
authors.affiliation: MedImmune, One MedImmune Way, Gaithersburg, Maryland 20878.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Bishop
authors.affiliation: Department of Pharmaceutical Chemistry, Macromolecule and Vaccine Stabilization Center, University of Kansas, Lawrence, Kansas 66047.
authors.forename: David B
authors.initials: DB
authors.lastname: Volkin
authors.affiliation: Department of Pharmaceutical Chemistry, Macromolecule and Vaccine Stabilization Center, University of Kansas, Lawrence, Kansas 66047. Electronic address: middaugh@ku.edu.
authors.forename: Charles Russell
authors.initials: CR
authors.lastname: Middaugh
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry*; D059451:Biosimilar Pharmaceuticals / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002850:Chromatography, Gel / Q000379:methods; D004355:Drug Stability; D004356:Drug Storage; D007074:Immunoglobulin G / Q000737:chemistry*; D055550:Protein Stability
chemical_list: D000911:Antibodies, Monoclonal; D059451:Biosimilar Pharmaceuticals; D007074:Immunoglobulin G
keywords: Comparative Signature Diagram; IgG1; SEC; aggregation; biosimilarity; capillary isoelectric focusing; comparability; deamidation; mAbs