N-Rich

Summary

Introduction to N-Rich

Impurities are a critical factor to consider in the development of therapeutic drug candidates, as they can affect the safety and efficacy of the drug. To identify and characterize impurities, they must first be isolated in sufficient quantities. This is frequently achieved by pooling fractions from repetitive analytical HPLC runs (potentially hundreds). However, this process can be time-consuming and challenging. N-Rich is a twin-column cyclical enrichment process run by the Contichrom CUBE that can automate the process of impurity enrichment and purification.

The N-Rich Concept

N-Rich employs a cyclical process where a target molecule or chromatographic region is selectively enriched while the undesired products are simultaneously depleted (see process animation). After the multi-cycle enrichment phase, the enriched region is then finely separated and fractionated by applying a shallow gradient, using a low flow rate and doubling the bed height. By following the lower resolution enrichment phase with a single much less productive, but very high resolution gradient for final fractionation, great productivity and resolution can be achieved in one process.

N-Rich Applications

• Isolation of product-related impurities for active pharmaceutical ingredients

• Biosimilar CMC characterization

• Characterization of antibody-drug conjugate isoforms

• Identification of biomarkers and compounds in proteomics and metabolomics research

• Purification of ultra-pure compounds as reference materials

• Isolation of impurities after stability and formulation studies

N Rich Resources:

N-Rich Webinars

Introduction to N-Rich and the Contichrom CUBE

N-Rich Selected Publications

• Enrichment and purification of peptide impurities using twin-column continuous chromatography
  Richard Weldon, Thomas Müller-Späth, Journal of Chromatography A, Volume 1667, 2022, 462894 (Open Access, Tutorial Article)

• Enrichment and recovery of oligonucleotide impurities by N-Rich twin-column continuous chromatography, Giulio Lievore, Richard Weldon, Martina Catani, Alberto Cavazzini, Thomas Müller-Späth, Journal of Chromatography B, Volume 1209, 2022, 123439 (Open Access  )

• Using continuous chromatography methodology to achieve high-productivity and high-purity enrichment of batch variants for analytical characterization. Elizabeth Bigelow, Yuanli Song, Jie Chen, Melissa Holstein, Yunping Huang, Lauren Duhamel, Kelly Stone, Ran Furman, Zheng Jian Li, Sanchayita Ghose. Journal of Chromatography A, Volume 1643, 2021, 462008

• A novel twin-column continuous chromatography approach for separation and enrichment of monoclonal antibody charge variants
  Jing, Shu-Ying, Shi, Ce, Leong, Hui Yi, Yuan, Jun-Jie, Gao, Dong, Wang, Hai-Bin, Yao, Shan-Jing, Lin, Dong-Qiang. Engineering in Life Sciences, 2021, 6, 1618-0240 (Open Access)

N-Rich Application Note (.pdf)

N-Rich - Automated enrichment and purification of mAb charge variants and peptide impurities