Principles and Applications of Selective Biophysical Methods for Characterization and Comparability Assessment of a Monoclonal Antibody

Haripada      Maity; Yin      Lai; Arvind      Srivastava; Joel      Goldstein

Abstract

The strategy for a comparability assessment is developed on a hierarchical risk-based approach. Critical analysis of physicochemical and biological characterization assays is essential for the development of a good comparability protocol. Therefore, selection and sensitivity of these assays is very important. This article discusses a case study to evaluate the sensitivity of various methods in a comparability assessment of three lots of an IgG1 monoclonal antibody (mAb). Analysis with eighteen methods demonstrated that only six of the methods were sensitive enough to show a measurable difference of comparability under accelerated conditions (40°C). Samples stored at 4°C were found to be comparable by all methods. A brief comparison of the results of biochemical and functional assays with biophysical analysis is discussed. Basic principles, applications, strength, and limitations of different biophysical methods are also discussed here.

Keywords: Comparability, aggregation, degradation, stability, differential scanning calorimetry, fluorescence, light scattering, IgG, monoclonal antibody (mAb), biophysical analysis, physicochemical characterization, in vivo, pharmacokinetic (PK), biophysical techniques, clinical trials.