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Enhanced virus removal by flocculation and microfiltration


In this work we have investigated the feasibility of virus clearance by flocculation and tangential flow microfiltration. Chinese hamster ovary cell feed streams were spiked with minute virus of mice and then flocculated using cationic polyelectrolytes prior to tangential flow microfiltration. Our results indicate that flocculation prior to microfiltration leads to more than 100 fold clearance of minute virus of mice particles in the permeate. Today, validation of virus clearance is a major concern in the manufacture of biopharmaceutical products. Frequently new unit operations are added simply to validate virus clearance thus increasing the manufacturing cost. The results obtained here suggest that virus clearance can be obtained during tangential flow microfiltration. Since tangential flow microfiltration is frequently used for bioreactor harvesting this could be a low cost method to validate virus clearance.

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  1. Food and Drug Administration (1997)Points to Consider in the Manufacture and Testing of Monoclonal Antibody Products for Human Use. U. S. Department of Health and Human Services, Rockville, MD, USA

    Google Scholar 

  2. Sartorius AG (Germany) (1997) Virus validation.Focal Points 7: 1–3.

    Google Scholar 

  3. Belter, P. A., E. L. Cussler, and W. S. Hu (1988)Bioseparations. John Wiley & Sons, New York, NY, USA.

    Google Scholar 

  4. Murphy, F. A., C. M. Fauquet, D. H. L. Bishop, S. A. Ghabrial, A. W. Jarvis, G. P. Martelli, M. A. Mayo, and M. D. Summers (1995)Virus Taxonomy. Sixth Report of the International Committee on Taxonomy of Viruses. Springer-Verlag, New York, NY, USA

    Google Scholar 

  5. Tanford, C. (1961)Physical Chemistry of Macromolecules. John Wiley & Sons, New York, NY, USA.

    Google Scholar 

  6. Malek, B., D. B. George, and D. S. Filip (1981) Virus removal by coagulation and flocculation.J. AWWA 73: 164–168.

    CAS  Google Scholar 

  7. Amirhor, P., and R. S. Engelbrecht (1975) Virus removal by polyelectrolyte-aided filtration.J. AWWA 67: 187–192.

    Google Scholar 

  8. Kim, J. S., S. Akeprathumchai, and S. R. Wickramasinghe (2001) Flocculation to enhance microfiltration.J. Membr. Sci. 182: 161–172.

    Article  CAS  Google Scholar 

  9. Mahy, B. W. J., and H. O. Kangro (1996)Virology Methods Manual. Academic Press, London, UK.

    Google Scholar 

  10. Belfort, G., R. H. Davis, and A. L. Zydney (1994) The behavior of suspensions and macromolecular solutions in crossflow microfiltration.J. Membr. Sci. 96: 1–58.

    Article  CAS  Google Scholar 

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Correspondence to S. Ranil Wickramasinghe.

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Han, B., Carlson, J.O., Powers, S.M. et al. Enhanced virus removal by flocculation and microfiltration. Biotechnol. Bioprocess Eng. 7, 6–9 (2002).

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  • flocculation
  • hollow fibres
  • membranes
  • microfiltration
  • virus clearance