Schlaeppi, Jean-Marc and Lavoisier, Alexandra (2014) Early developability screen of therapeutic antibody candidates using Taylor dispersion analysis and UV area imaging detection. MAbs , 7 (1). pp. 77-83. ISSN 1942-0870 (Print), 1942-0862 (Online)

Abstract

Therapeutic antibodies represent one of the fastest growing segments in the pharmaceutical market. They are used in a whole range of disease fields, such as autoimmune diseases, cancer, inflammation and infectious diseases. These developments called for new analytical platforms for faster and better antibody selection and characterization. Early quality control and risk assessment of biophysical parameters help to prevent late stage failure in antibody development thus reducing costs and time. Critical parameters such as aggregation, conformational stability, colloidal stability and hydrophilicity, are measured during the early phase of antibody generation and guide the selection process of the best lead candidates in terms of technical developability. We report on the use of a novel instrument (Actipix/Viscosizer) for measuring both the hydrodynamic radius and the absolute viscosity of antibodies based on Taylor dispersion analysis and UV area imaging. The looped microcapillary-based method combines low sample consumption, fast throughput and high precision as compared to other conventional methods. From a random panel of 130 mAbs in the early selection process, we identified a few antibodies with larger hydrodynamic radius outside the normal distribution and a few others with non-Gaussian Taylor dispersion profiles. These antibodies with such abnormal properties were confirmed later in the selection process to show poor developability profiles. Moreover, combining these results with the viscosity measurements at high antibody concentrations as usually required for sub-cutaneous injection, allows screening with limited amounts of materials, candidates with potential issues in pre-formulation development.

Item Type:	Article
Keywords:	monoclonal antibodies, hydrodynamic radius, viscosity, Taylor dispersion, UV array imaging detection, developability assessment
Date Deposited:	13 Oct 2015 13:12
Last Modified:	13 Oct 2015 13:12
URI:	https://oak.novartis.com/id/eprint/23112