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Updated: Jul 11, 2026

Three-Dimensionally Printed Microfluidic Cross-flow System for Ultrafiltration/Nanofiltration Membrane Performance Testing
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Prion removal by nanofiltration under different experimental conditions.

Mikihiro Yunoki1, Hiroyuki Tanaka, Takeru Urayama

  • 1Department of Virology, Research Institute for Microbial Diseases, Osaka University, Japan. yunoki.mikihiro@mk.m-pharma.co.jp

Biologicals : Journal of the International Association of Biological Standardization
|September 25, 2007
PubMed
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Filter efficacy against prion removal depends on the preparation of the spiked material. Optimized prion preparations require smaller filter pore sizes (15 nm) for effective removal, highlighting the importance of sample preparation in TSE agent clearance studies.

Area of Science:

  • Biopharmaceutical Manufacturing
  • Prion Disease Research
  • Filtration Technology

Background:

  • Transmissible spongiform encephalopathy (TSE) agents pose a risk in biopharmaceutical production.
  • Effective removal of prion protein (PrP Sc) is crucial for ensuring product safety.
  • Virus removal filters are commonly used, but their efficacy against prions needs thorough evaluation.

Purpose of the Study:

  • To assess the removal of scrapie prion protein (PrP Sc) using virus removal filters.
  • To investigate the impact of different starting material preparations on prion removal efficiency.
  • To determine the optimal filter pore size for PrP Sc clearance in bioprocessing.

Main Methods:

  • Evaluation of PrP Sc removal using virus filters with varying pore sizes (75 nm and 15 nm).

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  • Utilized hamster-adapted scrapie strain 263K (263K MF) as spike material, including untreated and 'super-sonicated' preparations.
  • Western blot (WB) analysis was employed to detect PrP Sc in filtrates.
  • Main Results:

    • PrP Sc was detected after 75 nm filtration with 'super-sonicated' 263K MF, but not with untreated 263K MF.
    • 15 nm filtration effectively removed PrP Sc below detection limits when spike materials had optimized particle size distribution.
    • Infectious PrP Sc was recovered in one instance following 15 nm filtration, indicating variability.

    Conclusions:

    • The preparation method of prion spike material significantly influences filter removal efficiency.
    • Minimizing prion particle size through sonication or detergent treatment is essential for accurate filter evaluation.
    • Careful consideration of spike preparation is necessary for validating prion clearance in biopharmaceutical manufacturing.