Enhanced Virus Removal by Flocculation and Microfiltration

  • Han Binbing (Department of Chemical and Bioresource Engineering, Colorado State University) ;
  • Carlson Jonathan O. (Department of Chemical and Bioresource Engineering, Colorado State University) ;
  • Powers Scott M. (Department of Chemical and Bioresource Engineering, Colorado State University) ;
  • Wickramasinghe S. Ranil (Department of Chemical and Bioresource Engineering, Colorado State University)
  • Published : 2002.01.01

Abstract

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.

Keywords

References

  1. U. S. Department of health and Human Services Points to consider in the manufacture and Testing of Monoclonal Antibody Products for Human Use Food and Drug Administration
  2. Virus validation Sartorius AG(Germany)
  3. Bioseparations Belter, P. A.;E. L. Cussler;W. S. Hu
  4. Virus Taxonomy.(sixth Report of the international Committee on Taxonomy of Viruses Murphy, F. A.;C. M. Fauquet;D. H. Bishop;S. A. Ghabrial;A. W. Jarvis;G. P. Martelli;M. A. Mayo;M. D. Summers
  5. Physical Chemistry of Macromolecules Tanford, C.
  6. J. AWWA v.73 Virus remaval by coagulation and flocculation Malek, B.;D. B. George;D. S. Filip
  7. J. AWWA v.61 Virus removla by polyelectrolyte-aided filtration Amirhor, P.;R. S. Engelbrecht
  8. J. Membr. Sci. v.182 Flocculation to enhance microfiltration Kim, J. S.;S. Akeprathumchai;S. R. Wickramasinghe https://doi.org/10.1016/S0376-7388(00)00564-0
  9. Wirology Methods Manual Mahy, B. W. J.;H. O. Kangro
  10. J. Membr. Sci. v.96 The behavior of suspensions and macromolecular solutions on crossflow microfiltration Belfort, G.;R. H. Davis;A. L. Zydney https://doi.org/10.1016/0376-7388(94)00119-7