Design and optimization of Single Pass Tangential Flow Filtration for inline concentration of monoclonal antibodies

A number of Single Pass Tangential Flow Filtration (SPTFF) systems have recently been commercialized for inline concentration of monoclonal antibodies and other biotherapeutics, both to resolve bottlenecks in existing processes and as part of the development of integrated continuous downstream processes. The objective of this study was to examine the design and optimization of SPTFF modules using a previously developed mathematical model for the filtrate flux and pressure drop that specifically accounts for the concentration dependence of the antibody viscosity and osmotic pressure as well as the variation of the flow rate and antibody concentration with position in the long pathlength SPTFF device. Model simulations were performed to examine the effects of channel width, length, and cassette staging (number of parallel cassettes in each stage) on SPTFF performance. The concentration factor (conversion) was greatest for a long thin channel configuration, but this also caused very large feed-side pressure drops. The use of cascade configurations, with greater number of parallel channels near the feed inlet, significantly reduced the pressure drop but with a corresponding increase in total membrane area. A key factor governing the SPTFF performance was the increase in viscosity of the antibody solution at high conversion. These results provide important insights into the design and optimization of SPTFF systems for monoclonal antibody processing.

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Work Title Design and optimization of Single Pass Tangential Flow Filtration for inline concentration of monoclonal antibodies
Access
Open Access
Creators
  1. Mario G. Jabra
  2. Andrew Zydney
Keyword
  1. SPTFF
  2. Ultrafiltration
  3. Diafiltration
  4. Antibody
  5. Continuous processing
License CC BY-NC-ND 4.0 (Attribution-NonCommercial-NoDerivatives)
Work Type Article
Publisher
  1. Journal of Membrane Science
Publication Date November 11, 2021
Publisher Identifier (DOI)
  1. https://doi.org/10.1016/j.memsci.2021.120047
Deposited July 21, 2022

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Version 1
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  • Created
  • Added SPTFF_optimization_-_unmarked.docx
  • Added Creator Mario G. Jabra
  • Added Creator Andrew Zydney
  • Published
  • Updated Keyword Show Changes
    Keyword
    • SPTFF, Ultrafiltration, Diafiltration, Antibody, Continuous processing
  • Updated Publication Date Show Changes
    Publication Date
    • 2022-03-01
    • 2021-11-11
  • Updated