Two-Step Size-Exclusion Nanofiltration of Prothrombin Complex Concentrate Using Nanocellulose-Based Filter Paper

Manukyan, LevonUppsala universitet,Nanoteknologi och funktionella material (author)

Coagulation Factor IX-rich protrhombin complex concentrate (FIX-PCC) is a therapeutic biologic product that consists of a mixture of several human plasma-derived proteins, useful for treating hemophilia B. Due to its complex composition, FIX-PCC is very challenging to bioprocess through virus removing nanofilters in order to ensure its biosafety. This article describes a two-step filtration process of FIX-PCC using a nanocellulose-based filter paper with tailored porosity. The filters were characterized with scanning electron microscopy (SEM), cryoporometry with differential scanning calorimetry, and nitrogen gas sorption. Furthermore, in order to probe the filter's cut-off size rejection threshold, removal of small- and large-size model viruses, i.e., phi X174 (28 nm) and PR772 (70 nm), was evaluated. The feed, pre-filtrate, and permeate solutions were characterized with mass-spectrometric proteomic analysis, dynamic light scattering (DLS), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and analytical size-exclusion high-performance liquid chromatography (SEHPLC). By sequential filtration through 11 mu m pre-filter and 33 mu m virus removal filter paper, it was possible to achieve high product throughput and high virus removal capacity. The presented approach could potentially be applied for bioprocessing other protein-based drugs.

Mantas, AthanasiosUppsala universitet,Nanoteknologi och funktionella material(Swepub:uu)athma287 (author)
Razumikhin, MikhailNacimbio JC, 10,2nd Volkonsky Lane, Moscow 127473, Russia. (author)
Katalevsky, AndreyBiopharmgarant LLC, Stancionnaya 45, Vladimir 600901, Russia. (author)
Golubev, EugenNatl Res Ctr Hematol, Novyi Zykovskiy Proezd 4, Moscow 125167, Russia. (author)
Mihranyan, Albert,1978-Uppsala universitet,Nanoteknologi och funktionella material(Swepub:uu)almih677 (author)
Uppsala universitetNanoteknologi och funktionella material (creator_code:org_t)

By the author/editor: Manukyan, Levon; Mantas, Athanasi ...; Razumikhin, Mikh ...; Katalevsky, Andr ...; Golubev, Eugen; Mihranyan, Alber ...

About the subject

NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Microbiology

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