Advances in Membrane Chromatography

Dear Colleagues,

Chromatography is commonly an integral part of the downstream processing of biologicals, with a preference for the use of conventional bead-based resins. However, since 1990, the development of convective chromatographic matrices has greatly progressed. Regardless of the target compounds to be purified, their main advantage, compared with conventional resins, is the flow-independent performance over a wide range of flow regimes. Consequently, the applied flow rates clearly exceed the limits of conventional resin columns, allowing for reduced processing times and, thus, an improved process productivity. Moreover, the purification performance for macromolecules or larger biological nanoplexes, such as viruses, virus-like particles (VLPs), phages, exo- and endosomes, lipid nanoparticles, and polynucleotides, is commonly limited in the case of classical bead-based resins by pore-diffusion or pore-exclusion effects. Consequently, convective chromatography matrices are generally used if larger target compounds are to be purified via a direct interaction with the stationary chromatographic phase. The backbones of these chromatographic matrices generally consists of membranes or monoliths. The focus of this Special Issue, however, will be on membrane adsorbers, as these permit a more economical and ecological single-use application, which is of particular importance for the production of pharmaceutically relevant products. In recent years, several developments have emerged to align the performance of membrane adsorbers to the current challenges. Examples of these comprise the physicochemical membrane properties, the applied membrane capsules to improve the scalability, the resolution, the product concentration factor, and the dynamic binding capacity, as well as to reduce the buffer consumption during the process. Another example embraces membrane adsorbers with newly applied ligands, for instance, sulfated cellulose and primary amines. The latter overcomes the reduced binding capacity for host cell depletions and can be used in high-salt conditions. The sulfated cellulose ligands represent a platform technology by mimicking heparin ligands, suitable for the purification of various heparin-binding components, such as influenza viruses. In this context, membrane-based steric exclusion chromatography, which has been described numerous times in recent years, should be mentioned. This method stands out due to its high recovery of viral products and its wide applicability for different biological nanoplexes.

This is a small selection of the achievements in the field of membrane chromatography in recent years. The aim of this Special Issue is to summarize the current developments in the field for the purification of biotechnological products, including but not limited to recombinant proteins and biological nanoplexes, and to illustrate how these developments can address current challenges in biotechnological production processes.

Dr. Michael Wolff
Guest Editor

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