Chromatographic supports with short-fiber geometry have been evaluated for process-scale applications. Using a prototype silica-based ion-exchange fiber and bovine serum albumin as the model biomolecule, a comparison of the throughput characteristics of fiber columns with those of conventional columns (spherical packing) has been made. The comparison accounts for the influences of pressure drop, adsorption thermodynamics, and mass transfer. It has been shown that retention characteristics, mass dispersion, and intraparticle mass-transfer resistance are critical in determining which column has a higher throughput. In general, if the capacity factor of the desired product is high, it is predicted that the fiber column will give higher throughputs, except for separations that involve closely eluting impurities. Based on these results, guidelines detailing desired properties of short-fiber chromatographic supports are provided.