Biological Safety of a Highly Purified 10% Liquid Intravenous Immunoglobulin Preparation from Human Plasma

Goussen, Caroline; Simoneau, Steve; Bérend, Soline; Jehan-Kimmel, Christine; Bellon, Alfredo; Ducloux, Céline; You, Bruno; Paolantonacci, Philippe; Ollivier, Monique; Burlot, Ludovic; Chtourou, Sami; Flan, Benoît

doi:10.1007/s40259-017-0222-9

Cited by 8 publications

(6 citation statements)

References 25 publications

(27 reference statements)

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“…The PRFs claimed by one manufacturer ranged from 4.8 log to >11 log for a range of PDMPs; another reported 12.9 log reduction for an immunoglobulin preparation, and manufacturer responses quoted in the MHRA risk assessment for immunoglobulin range from 4.8 log to 10.5 log and from 7.3 to 9.4 for hyperimmune immunoglobulin [2,40,45]. Comprehensive reviews of processes and PRFs have been published [39,46].…”

Section: Rising Patient Demand For Pdmpsmentioning

confidence: 99%

Safety profile of plasma for fractionation donated in the United Kingdom, with respect to variant Creutzfeldt–Jakob disease

Thomas

Roberts

Domanović³

et al. 2023

Vox Sanguinis

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Plasma‐derived medicinal products (PDMPs) are life‐saving and life‐improving therapies, but the raw material is in short supply: Europe depends on importation from countries including the United States. Plasma from donors resident in the United Kingdom has not been fractionated since 1999 when a precautionary measure was introduced in response to the outbreak of variant Creutzfeldt–Jakob disease (vCJD). Cases of vCJD have been far fewer than originally predicted in the 1990s. Since the introduction of leucodepletion in 1999, and accounting for the incubation period, more than 40 million UK‐derived blood components have been issued with no reports of TT vCJD. In February 2021, the UK Government authorized manufacture of immunoglobulin from UK plasma. Following separate reviews concluding no significant difference in the risk posed, the United States, Australia, Ireland and Hong Kong also lifted their deferrals of blood donors with a history of living in the United Kingdom. Other countries are actively reviewing their position. Demand is rising for PDMPs, and Europe faces a threat of supply shortages. Industry and patient groups are clear that using UK plasma would bring significant immediate benefits to patients and to the resilience of the European supply chain. From this scientific review, we conclude that UK plasma is safe for fractionation and urge blood regulators and operators to take account of this safety profile when considering fractionation of UK plasma, and to revise their guidelines on the deferral of donors who have lived in, or received a transfusion in, the United Kingdom.

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Section: Rising Patient Demand For Pdmpsmentioning

confidence: 99%

Safety profile of plasma for fractionation donated in the United Kingdom, with respect to variant Creutzfeldt–Jakob disease

Thomas

Roberts

Domanović³

et al. 2023

Vox Sanguinis

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“…The efficacy of the virus filtration step, validated at laboratory scale with small filter devices based on a validated down scale of the manufacturing process, was shown to be relevant also for the large scale filter devices up to 4 m 2 used in manufacturing 40 . Besides the removal of viruses, virus retentive filters remove also prions, the causative agent for TSEs (transmissible spongiform encephalopathies) as (variant) Creutzfeldt–Jakob disease ((v)CJD) to a high degree 41–46 …”

Section: Discussionmentioning

confidence: 99%

“…Creutzfeldt-Jakob disease ((v)CJD) to a high degree. [41][42][43][44][45][46] Taking together, virus filtration is an excellent virus reduction step when introduced into the manufacturing process of biologicals due to the orthogonal mechanism compared to other manufacturing steps; a high margin of virus safety for the respective finished products is achieved by removing viruses based on size and not on resistance to physicochemical treatment relevant for manufacturing steps inactivating viruses. [5][6][7]13 Conditions of the feed stream as type and concentration of desired protein (and lead contaminants), pH, conductivity, and temperature as well as volume and protein load/filter area, transmembrane pressure, and flux and flux decay have to be defined during development and the manufacture operating within these robust ranges/specifications is very important to ensure effective removal of viruses, especially adventitious viruses as parvoviruses as demonstrated for these parameters in virus validation studies.…”

Section: Filtration Of Large Viruses Throughmentioning

confidence: 99%

Integration of Planova filters in manufacturing processes of biologicals improve the virus safety effectively: A review of publicly available data

Gröner

2023

Biotechnology Progress

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The capacity to remove viruses by Planova filters produced by Asahi Kasei, primarily by small virus‐retentive filters, were compiled from data in peer‐reviewed publications and, partly, publicly available data from presentations at conferences (Planova workshops). Data from more than 100 publications and presentations at conferences covering Planova filters were assessed. The data were grouped according to the different virus filters regarding mean pore sizes and viruses of different sizes for plasma and cell culture derived products. Planova 15N and 20N filters removed parvoviruses below the limit of detection of viruses in the filtrate in approx. 50% of all studies and mean LRFs (log reduction factors) for viruses detected in the filtrate were above 4, demonstrating effective parvovirus reduction. Parvovirus removal capacity increased for Planova BioEX filters as well as for 2 Planova 20N in series. Large viruses as retroviruses (e.g., HIV and MuLV), herpesviruses, flaviviruses and togaviruses were removed effectively by Planova 15N, 20N and BioEX filters and also by Planova 35N filters. Flow interruption, transmembrane pressure, volume and protein concentration per filter area had had no substantial impact on virus removal capacity at manufacturing specification. In conclusion, the incorporation of Planova filters in manufacturing processes of biologicals remove, depending on the filter pore size, small and large viruses from the feed stream reliably. This virus reduction step with an orthogonal mechanism integrated in the manufacturing processes of biologicals, based primarily on size exclusion of viruses, improves the virus safety of these biopharmaceutical products considerably.

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“…3,6,13,14,20 Isoagglutinins can be efficiently reduced during IVIG manufacturing by an IAC step, as used for IgPro10 and some other products. 14,15,21 A donor screening and exclusion program is a less efficient measure to reduce isoagglutinins in chromatographically purified IVIG. CSL Behring implemented a donor screening and exclusion program for IgPro10 from 2014 to 2016.…”

Section: Discussionmentioning

confidence: 99%

Isoagglutinin reduction in intravenous immunoglobulin (IgPro10, Privigen) by specific immunoaffinity chromatography reduces its reporting rates of hemolytic reactions: an analysis of spontaneous adverse event reports

et al. 2020

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BACKGROUND Hemolysis is an infrequent but recognized and potentially serious adverse effect of intravenous immunoglobulin (IVIG). Relatively elevated hemolysis reporting rates were seen with some IVIG products with high anti‐A/B isoagglutinin content, among which IgPro10 (Privigen, CSL Behring). For IgPro10, two isoagglutinin reduction measures were successively implemented: 1) anti‐A donor screening and 2) immunoaffinity chromatography (IAC; Ig IsoLo)–based isoagglutinin reduction step included in the production process. The aim of this analysis was to investigate the effects of these isoagglutinin reduction measures on the reporting rates of IgPro10 hemolysis worldwide. STUDY DESIGN AND METHODS Between February 2008 and December 2018, hemolysis reports from the CSL Behring Global Safety Database were analyzed in relationship to changes in IVIG IgPro10 production methods. Further analysis classified hemolysis reports by indication and blood group. RESULTS Median (minimum‐maximum) anti‐A/anti‐B titers were 32 (8‐64)/16 (8‐32) at baseline, 32 (8‐64)/16 (8‐32) after donor screening, and 8 (8‐32)/4 (2‐8) after implementation of IAC. The reporting rate of hemolytic reactions per 1000 kg IgPro10 sold was 4.05 cases at baseline, 2.00 after donor screening, and 0.50 after implementation of IAC. In 2018, there were seven reports of hemolytic reactions; representing 0.18 cases per 1000 kg IgPro10 sold, with a reduction of 95.6% versus baseline. CONCLUSION Following implementation of the IAC isoagglutinin reduction step, spontaneous reports of hemolytic events with IgPro10 were significantly and consistently reduced versus IgPro10 without isoagglutinin reduction, offering patients a more favorable benefit‐risk profile.

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Biological Safety of a Highly Purified 10% Liquid Intravenous Immunoglobulin Preparation from Human Plasma

Cited by 8 publications

References 25 publications

Safety profile of plasma for fractionation donated in the United Kingdom, with respect to variant Creutzfeldt–Jakob disease

Safety profile of plasma for fractionation donated in the United Kingdom, with respect to variant Creutzfeldt–Jakob disease

Integration of Planova filters in manufacturing processes of biologicals improve the virus safety effectively: A review of publicly available data

Isoagglutinin reduction in intravenous immunoglobulin (IgPro10, Privigen) by specific immunoaffinity chromatography reduces its reporting rates of hemolytic reactions: an analysis of spontaneous adverse event reports

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