Virus Retentive Filters - Effective Virus Removal in the Manufacturing Process of Biologicals
Main Article Content
Abstract
inactivation or removal – have to be implemented to assure a high margin of virus safety of these products. Orthogonal mechanisms of virus clearance should be integrated in the manufacturing process in order to inactivate / remove viruses/virus aggregates having been able to escape to a certain degree the reduction capacity of the previous virus clearance step. Virus retentive filters as an orthogonal virus clearance step are frequently implemented in the manufacturing process of biologicals as the virus removal capacity of virus retentive filters is based on size exclusion. Only the size of a virus impacts the removal capacity and not virus properties as enveloped/ non-enveloped or RNA / DNA viruses and their resistance to physiochemical treatment. Viruses larger than the mean pore size of a virus retentive filter are removed from the feed stream and the desired protein – if smaller than the pore size of the filter membrane – will pass the filter and can be collected in the filtrate without / with very low virus contamination. Depending on the filter pore size, virus retentive filters are grouped in large and small virus retentive filters i.e., filters removing large viruses as retroviruses and small viruses as picornaviruses and, especially, parvoviruses. Data of virus reduction factors from 89 publications, resulting in a total of close to 500 virus clearance studies for different viruses, product intermediates and large and small virus retentive filters are assessed. The virus clearance capacity of these filters can depend on the membrane layout and chemistry, the volumetric throughput of product intermediate as well as of buffer flush and transmembrane pressure including pressure/flow interruption and flow decay. These parameters, when disclosed in published data, show filter brand specific differences but, having the above-mentioned parameters for each filter optimised, effective virus removal could mostly be demonstrated in virus validation studies for each filter brand.
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How to Cite
GRONER, Albrecht.
Virus Retentive Filters - Effective Virus Removal in the Manufacturing Process of Biologicals.
Medical Research Archives, [S.l.], v. 12, n. 12, dec. 2024.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/6084>. Date accessed: 06 jan. 2025.
doi: https://doi.org/10.18103/mra.v12i12.6084.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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12. Lute S, Riordan W, Pease LF 3rd, et al. A consensus rating method for small virus-retentive filters. I. Method development. PDA J Pharm Sci Technol 2008;62(5):318-333. PMID: 19055228.
13. Brorson K, Lute S, Haque M, et al. A consensus rating method for small virus-retentive filters. II. Method evaluation. PDA J Pharm Sci Technol 2008;62(5):334-343. PMID: 19055229
14. Brorson K, Sofer G, Aranha H. Nomenclature standardization for ‘large pore size’ virus-retentive filters. PDA J Pharm Sci Technol 2005;59(6):341-345. PMID: 16471421
15. Bao R-M, Shibuya A, Uehira T, et al. Successful removal of porcine circovirus-1 from immunoglobulin G formulated in glycine solution using nanofiltration. Biologicals 2018;51:32-36. doi:10.1016/j.biologicals.2017.10.006
16. Hilfenhaus J, Gröner A, Nowak T, Weimer T. Analysis of human plasma products: polymerase chain reaction does not discriminate between live and inactivated viruses. Transfusion 1997;37(9):935-940. doi: 10.1046/j.1537-2995.1997.37997454021.x.
17. Brorson K, Krejci S, Lee K, Hamilton E, Steil K, Xu Y. Bracketed generic inactivation of rodent retroviruses by low pH treatment for monoclonal antibodies and recombinant proteins. Biotechnol Bioeng 2003;82(3):321-329. doi:10.1002/bit.10574
18. Anwaruzzaman M, Wang W, Wang E, Erfe L, Lee J, Lui S. Evaluation of infectivity and reverse transcriptase real-time polymerase chain reaction assays for detection of xenotropic murine leukemia virus used in virus clearance validation. Biologicals 2015;43(4):256-265. doi:10.1016/j.biologicals.2015.04.001
19. Tsujikawa M, Ohkubo Y, Masuda M, et al. Caution in evaluation of removal of virus by filtration: Misinterpretation due to detection of viral genome fragments by PCR. J Virol Methods 2011;178(1-2):39-43. doi:10.1016/j.jviromet.2011.08.009
20. Zhao X, Bailey MR, Emery WR, Lambooy PK, Chen D. Evaluation of viral removal by nanofiltration using real-time quantitative polymerase chain reaction. Biotechnol Appl Biochem 2007;47(Pt 2):97-104. doi:10.1042/BA20060195
21. Blümel J, Musso D, Teitz S, et al. Inactivation and removal of Zika virus during manufacturing of plasma-derived medicinal products. Transfusion 2017;57(3pt2):790-796. doi:10.1111/trf.13873
22. Yue C, Teitz S, Miyabashi T, et al. Inactivation and removal of Chikungunya virus and Mayaro virus from plasma-derived medicinal products. Viruses. 2019;11(3):234. doi:10.3390/v11030234
23. Preparation of virus spike used for virus clearance studies. Technical Report No. 47. Parenteral Drug Association. 2010
24. Slocum A, Burnham M, Genest P, Venkiteshwaran A, Chen D, Hughes J. Impact of virus preparation quality on parvovirus filter performance. Biotechnol Bioeng. 2013;110(1):229-239. doi:10.1002/bit.
25. Roush DJ, Myrold A, Burnham MS, And JV, Hughes JV. Limits in virus filtration capacity? Impact of virus quality and spike level on virus removal with xenotropic murine leukemia virus. Biotechnol Prog. 2015;31(1):135-144. doi:10.1002/btpr.2020
26. Hongo-Hirasaki T, Yamaguchi K, Yanagida K, Hayashida H, Ide S. Effects of varying virus-spike conditions on a virus-removal filter Planova 20N in a virus validation study of antibody solutions. Biotechnol Prog. 2011;27(1):162-169. doi:10.1002/btpr.533
27. Bolton G. Spector S, LaCasse D. Increasing the capacity of parvovirus retentive membranes: Performance of the Viresolve prefilter. Biotechnol Appl Biochem. 2006;43(Pt 1):55-63. doi:10.1042/BA20050108
28. Brown A, Bechtel C, Bill J, et al. Increasing parvovirus filter throughput of monoclonal antibodies using ion exchange membrane adsorptive pre-filtration. Biotechnol Bioeng. 2010;106(4):627-637. doi:10.1002/bit.22729
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