Scale-down prediction of industrial scale pleated membrane cartridge performance

Flat‐sheet membrane discs represent the current standard format used for experimental prediction of the scale‐up of normal flow filtration processes. Use of this format is problematic, however, since the scale‐down results typically show a 40–55% difference in performance compared to large‐scale cartridges depending upon the feedstock used. In this work, novel pleated scale‐down devices (A_m = 1.51–15.1 × 10⁻³ m²) have been designed and fabricated. It is shown that these can more accurately predict the performance of industrial scale single‐use pleated membrane cartridges (A_m = 1.06 m²) commonly used within biopharmaceutical manufacture. The single‐use scale‐down cartridges retain the same pleat characteristics of the larger cartridges, but require a reduced feed volume by virtue of a substantially diminished number of active membrane pleats. In this study, a 1,000‐fold reduction in feed volume requirement for the scale‐down cartridge with the smallest membrane area was achieved. The scale‐down cartridges were tested both with clean water and a pepsin protein solution, showing flux‐time relationships within 10% of the large‐scale cartridge in both cases. Protein transmission levels were also in close agreement between the different scale cartridges. The similarity in performance of the scale‐down and the large‐scale cartridges, coupled with the low feed requirement, make such devices an excellent method by which rapid scale‐up can be achieved during early stage process development for biopharmaceutical products. This new approach is a significant improvement over using flat‐sheet discs as the quantitative similarity in performance with the large‐scale leads to reliable scale‐up predictions while requiring especially small volumes of feed material. Biotechnol. Bioeng. 2011; 108:830–838. © 2010 Wiley Periodicals, Inc.