Chromatography Process Development in the Quality by Design Paradigm I: Establishing a High-Throughput Process Development Platform as a Tool for Estimating 'Characterization Space' for an Ion Exchange Chromatography Step

摘要

This article describes the development of a high-throughput process development (HTPD) platform for developing chromatography steps. An assessment of the platform as a tool for establishing the "characterization space" for an ion exchange chromatography step has been performed by using design of experiments. Case studies involving use of a biotech therapeutic, granulocyte colony-stimulating factor have been used to demonstrate the performance of the platform. We discuss the various challenges that arise when working at such small volumes along with the solutions that we propose to alleviate these challenges to make the HTPD data suitable for empirical modeling. Further, we have also validated the scalability of this platform by comparing the results from the HTPD platform (2 and 6 pL resin volumes) against those obtained at the traditional laboratory scale (resin volume, 0.5 mL). We find that after integration of the proposed correction factors, the HTPD platform is capable of performing the process optimization studies at 170-fold higher productivity. The platform is capable of providing semi-quantitative assessment of the effects of the various input parameters under consideration. We think that platform such as the one presented is an excellent tool for examining the "characterization space" and reducing the extensive experimentation at the traditional lab scale that is otherwise required for establishing the "design space." Thus, this platform will specifically aid in successful implementation of quality by design in biotech process development. This is especially significant in view of the constraints with respect to time and resources that the biopharma industry faces today.