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Linear scale ultrafiltration
Author(s) -
van Reis Robert,
Goodrich Elizabeth M.,
Yson Christine L.,
Frautschy Leah N.,
Dzengeleski Stephen,
Lutz Herb
Publication year - 1997
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/(sici)1097-0290(19970905)55:5<737::aid-bit4>3.0.co;2-c
Subject(s) - ultrafiltration (renal) , filtration (mathematics) , turbulence , scale up , volumetric flow rate , scale (ratio) , flow (mathematics) , membrane , cross flow filtration , chemistry , volume (thermodynamics) , mechanics , materials science , mechanical engineering , mathematics , chromatography , engineering , physics , thermodynamics , statistics , biochemistry , classical mechanics , quantum mechanics
Tangential flow filtration has traditionally been scaled up by maintaining constant the filtrate volume to membrane surface area ratio, membrane material and pore size, channel height, flow path geometry and retentate and filtrate pressures. Channel width and the number of channels have been increased to provide increased membrane area. Several other parameters, however, have not been maintained constant. A new comprehensive methodology for implementation of linear scale up and scale down of tangential flow filtration processes has been developed. Predictable scale up can only be achieved by maintaining fluid dynamic parameters which are independent of scale. Fluid dynamics are controlled by operating parameters (feed flow rate, retentate pressure, fed batch ratio and temperature), geometry (channel length, height, turbulence promoter and entrance/exit design), materials (membrane, turbulence promoter, and encapsulant compression), and system geometry (flow distribution). Cassette manufacturing procedures and tolerances also play a significant role in achieving scale independent performance. Extensive development work in the aforementioned areas has resulted in the successful implementation of linear scale up of ultrafiltration processes for recovery of human recombinant DNA derived pharmaceuticals. A 400‐fold linear scale up has been achieved without intermediate pilot scale tests. Scale independent performance has a direct impact on process yield, protein quality and product economics and is therefore particularly important in the biotechnology industry. © 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 55 : 737–746, 1997.