Current technologies to endotoxin detection and removal for biopharmaceutical purification.

Endotoxins are the major contributors to the pyrogenic response caused by contaminated pharmaceutical products, formulation ingredients, and medical devices. Recombinant biopharmaceutical products are manufactured using living organisms, including Gram-negative bacteria. Upon the death of a Gram-negative bacterium, endotoxins (also known as lipopolysaccharides) in the outer cell membrane are released into the lysate where they can interact with and form bonds with biomolecules, including target therapeutic compounds. Endotoxin contamination of biologic products may also occur through water, raw materials such as excipients, media, additives, sera, equipment, containers closure systems, and expression systems used in manufacturing. The manufacturing process is, therefore, in critical need of methods to reduce and remove endotoxins by monitoring raw materials and in-process intermediates at critical steps, in addition to final drug product release testing. This review paper highlights a discussion on three major topics about endotoxin detection techniques, upstream processes for the production of therapeutic molecules, and downstream processes to eliminate endotoxins during product purification. Finally, we have evaluated the effectiveness of endotoxin removal processes from a perspective of high purity and low cost.

The shape effect on the retention behaviors of ellipsoidal particles in field-flow fractionation: Theoretical model derivation considering the steric-entropic mode.

A theoretical model is proposed to analyze the shape effect on the retention behaviors of rod-like particles in field-flow fractionation. This model is improved from a previous model for slender-body rods by Park and Mittal [Chromatography (2015) 2: 472-487]: The model can predict the retention behaviors of the rods, of which shape is assumed as a prolate ellipsoid, with low and high aspect ratios in various flow conditions of the flow-field flow fractionation. The effects of rod aspect ratio on the retention behaviors of the rods with the same volume are investigated in each operation mode. In normal mode, the retention ratio decreases with increasing aspect ratio. In steric-entropic mode, where we substantially improved the model to evaluate the rod orientation and the cross-sectional concentration distribution more rigorously based on our recent studies [Nanomaterials (2018) 8:130; Chem. Eng. Sci. (2018) 189:396-400], the retention ratio increases with the increasing aspect ratio. In steric mode, the retention ratio decreases with increasing aspect ratio again. Those results are discussed based on how the cross-sectional concentration distributions are affected by the aspect ratio. The new criteria for the prediction of each mode are also discussed and suggested Comparison with the experimental data shows the qualitative agreement.