A New Approach to Study the Physical Stability of Monoclonal Antibody Formulations Dilution From a Denaturant

Svilenov, Hristo ; Gentiluomo, Lorenzo; Friess, Wolfgang; Roessner, Dierk und Winter, Gerhard (Dezember 2018): A New Approach to Study the Physical Stability of Monoclonal Antibody Formulations Dilution From a Denaturant. In: Journal of Pharmaceutical Sciences, Bd. 107, Nr. 12: S. 3007-3013

Abstract

The early-stage assessment of the physical stability of new monoclonal antibodies in different formulations is often based on high-throughput techniques that suffer from various drawbacks. Accordingly, new approaches that facilitate the protein formulation development can be of high value to the industry. In this study, a dynamic light scattering plate reader is used to measure the aggregation (by means of the increase in the hydrodynamic radius [Rh]) of monoclonal antibody samples that were subject to incubation and subsequent dilution from different concentrations of a denaturing agent, that is, guanidine hydrochloride. The increase in the Rh of the protein samples is dependent not only on the denaturant concentration used but also on the buffer in which the incubation/dilution was performed. We also compare the aggregation after dilution from a denaturant with other high-throughput stability-indicating methods and find good agreement between the techniques. The proposed approach to probe the physical stability of monoclonal antibodies in different formulation conditions offers a unique combination of features—it is isothermal, probes both the resistance to denaturant-induced unfolding and the colloidal protein stability, it is entirely label-free, does not rely on complex data evaluation, and requires very short instrument measurement time on standard equipment.

• Dokumententyp: Zeitschriftenartikel
• EU Funded Grant Agreement Number: 675074
• EU-Projekte: Horizon 2020 > Marie Skłodowska Curie Actions > Marie Skłodowska-Curie Innovative Training Networks > 675074: PIPPI - Protein-excipient Interactions and Protein-Protein Interactions in formulation
• Publikationsform: Postprint
• Keywords: protein aggregation; protein formulation; protein folding/refolding; light scattering (dynamic); stability; fluorescence spectroscopy
• Fakultät: Chemie und Pharmazie > Department für Pharmazie - Zentrum für Pharmaforschung
• Themengebiete: 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften; Biologie
• ISSN: 0022-3549
• Sprache: Englisch