As the field of analytics continues to evolve, methods guided by regulatory general chapters are increasingly seen as outdated due to their limited resolving power and speed. These compendial methods were originally written when larger particle sizes and systems with larger system dispersion were the norm. In response, regulatory agencies have lifted restrictions on method parameters such as flow rate, column dimensions, and particle size. This allows scientists using compendial methods to leverage modern instruments and particle sizes for a significant enhancement in performance. In this study, a HPLC system and several columns were constructed with bio-inert materials for modernizing biotherapeutic compendial methods. To assess the benefits of this next-generation HPLC instrument platform, the modernized methods were compared to the regulatory general chapter method analysed on a legacy HPLC system.

In this work, two different compendial methods outlined in USP General Chapters <129> and <121.1> were scaled and analysed on the next-generation HPLC instrument and evaluated on speed and recovery. By leveraging columns with a smaller particle size and bio-inert column and system hardware, these compendial methods generate equivalent chromatographic separations while significantly reducing analysis time, sample, and mobile phase consumption. This poster will demonstrate the benefits of modernizing compendial methods to yield more accurate results.