High-throughput techniques to evaluate the effect of ligand density for impurity separations with multimodal cation exchange resins

详细信息    查看全文

• 作者：John P. Welsh ; Haiying Bao ; Kenneth Barlow ; Jennifer M. Pollard ; Eggert Brekkan ; Karol M. Lacki ; Thomas O. Linden and David J. Roush
• 关键词：High-throughput screening ; Ligand density ; Monoclonal antibody ; Multimodal chromatography ; Resolution
• 刊名：Engineering in Life Sciences
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：16
• 期：2
• 页码：160-168
• 全文大小：782K
• ISSN：1618-2863

文摘

Scale-down, high-throughput screening techniques are well on their way to becoming a commodity in downstream bioprocess development, especially for the rapid development of chromatography process steps. This work used both resin slurry plate and miniature column high-throughput screening methodologies to identify the best resin properties for mAb separations utilizing a multimodal chromatography ligand interaction. A ligand with both cation exchange and hydrophobic interaction properties was studied at several ligand densities and compared to a commercially available multimodal resin with a larger particle size at high ligand density. The resins were screened with mAbs containing distinct process impurities (aggregates and a hydrophobic variant), and optimized conditions provided more than a log of clearance of both types of impurities for the different resins screened. These studies reveal that while a smaller particle size is generally preferable, optimal ligand densities can be different depending on the properties of both the mAb and impurity studied.