Virus safety of plasma products using 20 nm instead of 15 nm filtration as virus removing step

Cellulose-based virus-retentive filters: a review

“…This was also demonstrated by Roberts et al (2010) by filtrating poliovirus type 1 (a picorvanirus) through Planova filters manufactured with different pore sizes, ranging between 15 (LRV = 6.9) and 35 nm (LRV = 0.2). The two-filter combinations were globally more efficient than single filters at removing small viruses from spiked protein intermediates, though two 15N filters connected in parallel for tangential filtration (Koenderman et al 2012) yielded LRVs quite similar to those obtained using 15N alone (Terpstra et al 2006). Care should be taken when comparing vertically the data collected in Table 1, however.…”

“…Since filtration complements other viral clearance methods in the downstream processing of biotherapeutics (Brorson 2007;Klamroth et al 2014;Shukla et al 2007), several studies quoted in Table 1 also report LRVs for common virus reduction steps such as inactivation by pasteurization (Gröner 2014;Gröner et al 2012;Terpstra et al 2007) or solvent/detergent treatment (Dichtelmüller et al 2012;Terpstra et al 2006), and chromatographic capture (Gröner 2014;Gröner et al 2012). Virus removal during the plasma fractionation process (Bryant and Klein 2007) leading from the crude plasma pool to the product (immunoglobulin here) stream has also been quantified (Dichtelmüller et al 2012;Koenderman et al 2012;Terpstra et al 2006). Overall virus reduction factors obtained by addition of successive LRVs are given in these works, as illustrated by Table 3.…”

“…The presence of aggregated viruses may lead to overestimation of size exclusion effectiveness while contributing with protein aggregates to the fouling of viral filters, which reduces the membrane hydraulic permeability and may affect virus retention (Phillips et al 2007). Pre-filtration was performed on the spikevirus stock suspension (Caballero et al 2014;Gröner et al 2012;Roberts et al 2010) on the product intermediate before virus inoculation (Gröner et al 2012;Koenderman et al 2012), and/or on the virus Furuya et al (2006) and Terpstra et al (2006) CPV Canine parvovirus B19 V Gröner (2014), Gröner et al (2012), Koenderman et al (2012) and Terpstra et al (2006Terpstra et al ( , 2007 PPV and Terpstra et al (2006Terpstra et al ( , 2007 spiked material (Chtourou et al 2007;Dichtelmüller et al 2012;Koenderman et al 2012;Terpstra et al 2006Terpstra et al , 2007. For pre-filtration of the virus preparation, micro filters with a pore size adapted to the spike virus size, i.e., slightly lower than the virus size, were used to remove cell aggregates but not single viral particles-usual pore sizes ranging between 0.1 and 0.45 lm.…”

“…For pre-filtration of the virus preparation, micro filters with a pore size adapted to the spike virus size, i.e., slightly lower than the virus size, were used to remove cell aggregates but not single viral particles-usual pore sizes ranging between 0.1 and 0.45 lm. Micro filters with 0.1-0.2 lm pore size (Koenderman et al 2012;Terpstra et al 2007;, but also 75N (Dichtelmüller et al 2012) and 35N (Chtourou et al 2007). Planova viral filters were used to pre-filtrate the spiked product solution.…”

“…This was not the case when 35N was used as the main viral filter after pre-filtration with 75N (Dichtelmüller et al 2012), which confirms previous date showing that the 35 nm pore size was too large to retain the smallest viral particles (Furuya et al 2006;Hongo-Hirasaki et al 2006). Both 20N (Caballero et al 2014;Furuya et al 2006;Gröner 2014) and 15N (Caballero et al 2014;Roberts et al 2010;Terpstra et al 2007;) Planova filters and their combination (Gröner et al 2012;Koenderman et al 2012) showed effective virus removal over a wide range of viral particle sizes (Table 1). As a general rule, the removal efficiency of the filters increased with the ratio of pore size to virus size, as illustrated by Gröner (2014) and Terpstra et al (2007).…”