Impurity Profiling in Chromatographic Purification of Monoclonal Antibodies

University Of Delaware, Newark DE

Investigators

Abstract

0966644 Lenhoff This NSF award by the Chemical and Biological Separations program supports work to characterize the principal impurities to be removed in the purification of monoclonal antibodies (mAbs) produced in cell culture by Chinese hamster ovary (CHO) cells, which are used ubiquitously in industrial practice. We will identify the impurity proteins that persist in the product stream, with the main source being proteins produced by the cells that make the mAbs, hence the name host cell protein (HCP). An additional class of impurities to be characterized are product-associated impurities, i.e., proteins that bind to the mAb product and are therefore difficult to remove from the process stream during the purification steps. These analyses to identify the principal impurities to be removed in a given mAb process and can serve as the basis for optimizing the strategies for separating them from the mAb product. Complementary to characterizing these two classes of impurities is characterization of their behavior in the important class of separations involving liquid chromatography. Knowledge of the chromatographic behavior of the different proteins, both mAb product and impurity, under different conditions will allow identification of the conditions most suitable for removing the impurities from the product stream. The results will be applied to representative efforts to optimize particular mAb separations. Capabilities such as those to be developed in this project can be instrumental in streamlining industrial process development methods for the large and growing class of mAb therapeutics. The research will also serve as an effective vehicle for student education and research training, via the students who will perform most of the research.