Aggregation Kinetics for Monoclonal Antibody Products

Abstract

Monoclonal antibodies have emerged as a valuable class of therapeutic products. However, the industry still faces pertinent challenges with respect to product stability, particularly product aggregation that leads to toxicity and immunogenicity. The present project is an attempt to propose a kinetic model for the aggregation of monoclonal antibodies using the analysis of experiments that were performed for several different combinations of buffer type, temperature, pH and salt concentration pertaining to three types of chromatography - protein A chromatography, cation exchange chromatography and anion exchange chromatography. Modified Lumry Eyring model has been employed by taking into account the reversibility of each step in the aggregation process. MATLAB R2011b has been used to find the optimum values of the kinetic rate constants for the different cases. The model can go a long way in reducing the extent of aggregation by helping to accurately choose the experimental conditions with the minimum number of experiments.