Principles and applications of selective biophysical methods for characterization and comparability assessment of a monoclonal antibody.
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.
ImClone Systems, Eli Lilly and company, 59-61 ImClone Drive, Branchburg, NJ 08876, USA. haripada.maity@imclone.com
Haripada
H
Maity
Yin
Y
Lai
Arvind
A
Srivastava
Joel
J
Goldstein
D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000032:analysis / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002850:Chromatography, Gel; D002942:Circular Dichroism; D004355:Drug Stability; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis / Q000737:chemistry*; D008027:Light; D011487:Protein Conformation; D012542:Scattering, Radiation; D013050:Spectrometry, Fluorescence; D017550:Spectroscopy, Fourier Transform Infrared
D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G