The Essential Role of Chromatographic Science in Column Modeling of Protein Separations

The mechanisms underlying chromatography of proteins span a multi-scale set of phenomena that have been modeled individually and collectively for the better part of a century. Modeling of molecular-level behavior is more recent but quantitative prediction of adsorption behavior is still not readily accomplished, due to factors such as the size and complexity of protein molecules and uncertainties regarding resin structure at high resolution. Even at a more coarse-grained level, column modeling has not yet matured into a tool that can be used routinely for detailed process design in biopharmaceutical manufacturing. Nevertheless, the availability of efficient and versatile modeling packages has facilitated more concerted efforts to refine chromatographic modeling of protein separations to a point where predictive modeling is becoming achievable. This has been enabled to a large extent by careful chromatography science studies, many of them from the Carta group, to elucidate the underlying particle-level behavior. This presentation will examine the interplay between such chromatography science findings and column-level modeling, with applications to downstream processing of monoclonal antibodies (mAbs). Examples include cation-exchange chromatography of single- and multi-component mAb systems, Protein A capture, and the exploitation of sample displacement to enhance purification.