A comparison of biophysical characterization techniques in predicting monoclonal antibody stability. Issue 6 (17th August 2016)

• Record Type: Journal Article
• Authors: Thiagarajan, Geetha; Semple, Andrew; James, Jose K.; Cheung, Jason K.; Shameem, Mohammed
• Is Part Of: MAbs. Volume 8:Issue 6(2016)
• Page Start: 1088
• Page End: 1097
• Publication Date: 2016-08-17
• Subjects: Aggregation -- colloidal stability -- diffusion interaction parameter -- fragmentation -- Immunoglobulin -- monoclonal antibody -- thermal stability -- zeta potential; Monoclonal antibodies -- Therapeutic use -- Periodicals; Monoclonal antibodies -- Periodicals; Antibodies, Monoclonal -- Periodicals; 616.0798
• DOI: 10.1080/19420862.2016.1189048
• Languages: English
• ISSNs: 1942-0862

Abstract

ABSTRACT: With the rapid growth of biopharmaceutical product development, knowledge of therapeutic protein stability has become increasingly important. We evaluated assays that measure solution-mediated interactions and key molecular characteristics of 9 formulated monoclonal antibody (mAb) therapeutics, to predict their stability behavior. Colloidal interactions, self-association propensity and conformational stability were measured using effective surface charge via zeta potential, diffusion interaction parameter (kD ) and differential scanning calorimetry (DSC), respectively. The molecular features of all 9 mAbs were compared to their stability at accelerated (25°C and 40°C) and long-term storage conditions (2–8°C) as measured by size exclusion chromatography. At accelerated storage conditions, the majority of the mAbs in this study degraded via fragmentation rather than aggregation. Our results show that colloidal stability, self-association propensity and conformational characteristics (exposed tryptophan) provide reasonable prediction of accelerated stability, with limited predictive value at 2–8°C stability. While no correlations to stability behavior were observed with onset-of-melting temperatures or domain unfolding temperatures, by DSC, melting of the Fab domain with the CH 2 domain suggests lower stability at stressed conditions. The relevance of identifying appropriate biophysical assays based on the primary degradation pathways is discussed.