Optimizing particle morphology during antibody precipitation for enhanced tangential flow filtration performance

Recent advances in cell culture have led to substantial increases in monoclonal antibody titer, leading to renewed interest in using precipitation for the initial capture and purification of high-value therapeutic proteins. One of the major challenges in developing continuous precipitation processes is ensuring stable operation of the tangential flow microfiltration membranes used for dewatering and washing. The objective of this study was to increase the filterability of the protein precipitate by addition of salts to control the particle morphology. Experiments were performed with human serum Immunoglobulin G (IgG) in different buffers and in the presence of different salts using zinc chloride and polyethylene glycol as precipitating agents. The addition of 300 mM CaCl2 caused more than a 2-fold increase in the critical flux. This behavior was not due simply to a shift in the particle size distribution, but it was instead related to an increase in the density of the precipitate. The precipitate density was readily measured by centrifugation, providing a rapid method for identifying precipitation conditions that lead to good filterability. Data obtained during a 24-hour filtration process showed minimal fouling with high degrees of purification, demonstrating the viability of this approach for optimizing precipitation conditions.

© This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/

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Work Title Optimizing particle morphology during antibody precipitation for enhanced tangential flow filtration performance
Access
Open Access
Creators
  1. Mirko Minervini
  2. Ali Behboudi
  3. Jovana R. Marzella
  4. Andrew L. Zydney
Keyword
  1. Protein precipitation
  2. Filterability
  3. Tangential flow filtration
  4. Monoclonal antibody
  5. Continuous processing
License CC BY-NC-ND 4.0 (Attribution-NonCommercial-NoDerivatives)
Work Type Article
Publisher
  1. Separation and Purification Technology
Publication Date June 19, 2024
Publisher Identifier (DOI)
  1. https://doi.org/10.1016/j.seppur.2024.126574
Deposited August 08, 2024

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Version 1
published

  • Created
  • Added Optimizing_TFF_performance-accepted.pdf
  • Added Creator Mirko Minervini
  • Added Creator Ali Behboudi
  • Added Creator Jovana R. Marzella
  • Added Creator Andrew L. Zydney
  • Published
  • Updated
  • Updated Keyword, Publisher Show Changes
    Keyword
    • Protein precipitation, Filterability , Tangential flow filtration, Monoclonal antibody, Continuous processing
    Publisher
    • Gas Separation and Purification
    • Separation and Purification Technology