Purification of monoclonal antibody using cation exchange z2 laterally-fed membrane chromatography – A potential alternative to protein A affinity chromatography

Ultrahigh‐speed, ultrahigh‐resolution preparative separation of protein biopharmaceuticals using membrane chromatography

“…Some of the attractive features of membrane chromatography that were initially highlighted are speed, scalability, and amenability to single-use applications [6]. Some more recent studies have shown that membrane chromatography is superior to resin-based chromatography in terms of resolution in preparative protein separations [10][11][12][13]. In other words, a membrane chromatography-based purification process would give high recovery of a highly pure product at a very high speed.…”

“…The second term on the right-hand side of Equation ( 1), that is, B/u, signifies the effect of molecular diffusion in the axial direction on solute dispersion within the column. For macromolecules such as proteins that have low diffusion coefficients, this term is significant only at very low flow rates [10,12]. Also, membrane chromatography is usually carried out at extremely high flow rates and hence the effect of axial diffusion on dispersion is expected to be very small.…”

“…It is possible that this may have shaped the view that membrane chromatography is only suitable for fast, lowresolution applications. Of course, as evident from recent publications, it is now possible to use membrane chromatography for high-resolution purification of biopharmaceutical proteins [10,12,13] and therapeutic viruses [30]. Indeed, in many of these studies, membrane chromatography significantly out-performed equivalent resin-based chromatography in terms of separation attributes such as resolution, recovery, and purity [10,12,13].…”

“…Of course, as evident from recent publications, it is now possible to use membrane chromatography for high-resolution purification of biopharmaceutical proteins [10,12,13] and therapeutic viruses [30]. Indeed, in many of these studies, membrane chromatography significantly out-performed equivalent resin-based chromatography in terms of separation attributes such as resolution, recovery, and purity [10,12,13]. However, as bemoaned earlier, these high-resolution membrane chromatography devices continue to remain in the realm of academia.…”

“…Here, we discuss the fast and ultrahigh-resolution purification of proteins using an in-house designed and fabricated cation exchange membrane chromatography device. The design of the device is designated z 2 laterally-fed membrane chromatography (or z 2 LFMC) [10], and the use of such membrane chromatography devices for highresolution protein purification has been described in earlier studies [10,12]. In this study, the separation performance of such a device is further challenged and explored by carrying out preparative separation of a hard to separate binary protein mixture.…”