Retention Modeling to Accelerate & Optimize Method Development of Biomolecules

The growing interest in biopharmaceuticals is a trend consistent over the past few years. Biopharmaceuticals are structurally complex and pose numerous challenges in drug development. Globally, R&D companies are working to combat the complicated drug analysis necessary for large molecules, while trying to reduce laborious method development.

Retention modeling has proven to be a successful technique in accelerating method development and optimization. Pharmaceutical companies (like Novo Nordisk and Merck) are employing variations of this technique to integrate computer-assisted analysis with screening platforms for their chromatographic modeling.

Their method development strategy typically involves screening a wide range of columns and mobile phases that are known to generate large differences in selectivity. From these, the most promising column and mobile phase are selected, and a retention model is built by conducting a limited number of experiments. The retention model is then applied in silico to find the optimal temperature and gradient, assessing method robustness. In silico modeling is an effective tool to conduct fewer experiments and identify optimal conditions, improving the overall screening outcome and generating robust LC methods.

ACD/Labs’ LC Simulator functionality is used by Novo Nordisk and Merck, as part of their screening process to analyze the most comprehensive set of conditions. From there, they determine the best combinations of columns, stationary phases, and chromatographic techniques most suited for the sample. LC Simulator allows the user to define combined custom gradient and 2nd order temperature models (required for proteins) to find optimal selectivity and a suitable retention gradient. The results show the practicality and ease of use of the workflow and the modeling accuracy is shown to be the same for proteins and small molecules.

For more detailed insight about how Novo Nordisk and Merck use computer-assisted retention modeling to accelerate their method development please follow the links.

To learn more about ACD/Labs’ chromatography and method development solutions click here.