A solvent/detergent‐treated and 15‐nm filtered factor VIII: a new safety standard for plasma‐derived coagulation factor concentrates

Abstract

Nanofiltration of FVIII at 15 nm is feasible despite the large molecular weight of FVIII and vWF. Nanofiltration has been proven to be highly effective at removing infectious agents while preserving the structural and functional integrity of FVIII.

Proteomic analysis for process development and control of therapeutic protein separation from human plasma

“…The development of new and safer methods for virus inactivation and removal has been for a long time the major focus in the plasma fractionation industry [9, 10]. Other aspects of clinical safety were covered by extensive and very expensive clinical trials, and, except for routine procedures like protein profiling by SDS-PAGE and some immunochemical investigations, these products have never been subjected to thorough protein-chemical analyses [10, 11]. Only few articles deal with both plasma fractionation and the proteomic characterization of the production process and the final product [12–16].…”

Cellulose-based virus-retentive filters: a review

“…Planova viral filters were used to pre-filtrate the spiked product solution. In the latter work, the association in series of 35N and 15N filters led to efficient removal of small viruses such as PPV (Chtourou et al 2007). 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).…”

“…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.…”

Factor VIII and methods of preparation of its concentrates

“…Поряд із проблемою вірусної безпеки існує інше клінічне ускладнення замісної терапії -це виникнення інгібіторних антитіл до FVIII [8,14,[17][18][19], що можуть роз-винутися при лікуванні кріопреципітатом або препаратами факторів як плазмово-го, так і рекомбінантного походження. Їх наявність може спричинити неефектив-ність замісної терапії.…”