Abstract

Formulation Optimization of Biologics:  Rapid Assessment of Long Term Stability

Ernesto Freire, Professor, Johns Hopkins University

Predicting the long term stability of biologics is a major goal in the development and formulation of protein therapeutics. In this presentation I will show that isothermal chemical denaturation (ICD) combined with standard techniques like size exclusion chromatography (SEC) or light scattering, have the ability to predict the formation of protein aggregates for over one year. ICD data identifies the protein conformation that exhibits the highest tendency to aggregate and the concentration of that species at time zero, i.e. at the time the protein solution is made. SEC or light scattering data provide the required kinetic parameters and aggregate size. Both sets of data are integrated using a novel algorithm. The approach quantitatively predicts the amount of high molecular weight aggregates and can be applied to the early selection of the best formulation conditions.