Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.
Virus validation of pH 4-treated human immunoglobulin products produced by the Cohn fractionation process.
Biologicals. 1998 Dec;26(4):267-76. Unique Identifier : AIDSLINE MED/99331462 Bos OJ; Sunye DG; Nieuweboer CE; van Engelenburg FA; Schuitemaker H; Over J; Department of Product and Process Development, CLB, Sanquin Blood; Supply Foundation, The Netherlands.
Abstract:
To assess the virus reducing capacity of Cohn's cold ethanol fractionation process for the production of intravenous (IVIg) and intramuscular (IMIg) immunoglobulin products, and treatment of these products at pH 4, a validation study of virus removal and/or inactivation was performed using both lipid-enveloped viruses [human immunodeficiency virus (HIV), bovine viral diarrhoea virus (BVDV) and pseudorabies virus (PSR)], and non-lipid-enveloped viruses [(simian virus 40 (SV40) and encephalomyocarditis virus (EMC)]. For the cold ethanol fractionation process, overall reduction factors of 3.0 logs, > or = 2.6 (< 5.5) logs, 4.6 logs, 5.8 logs and > or = 2.6 (< 6.2) logs were found for HIV, BVDV, PSR, SV40 and EMC, respectively. For all tested viruses the precipitation of fraction III from fraction II + III was the most effective step. From the overall reduction factors it appears that cold ethanol fractionation, although capable of reducing viral infectivity to a significant extent, is not sufficient to meet the requirements of regulatory bodies for viral safety of immunoglobulin products. However, pH 4 treatment contributes effectively to the viral safety of the final products. Treatment at pH 4.05 and 37 degrees C for 16 h, as is applied to IVIg, yields reduction factors of > or = 8.4 logs, > or = 4.0 logs, > or = 7.1 logs, 4.8 logs and 1.4 logs for HIV, BVDV, PSR, SV40 and EMC, respectively. The effectiveness of this process step could be enhanced by extending incubation to 40 h at pH 4.25 compared to 16 h at pH 4.05. The extended incubation, as applied in the production of IMIg, yields a reduction of infectivity of SV40 by > or = 5.5 (< 8.0) logs and of EMC by > or = 4.1 (< 7.1) logs. Storage of IMIg, which is formulated as a solution, at 2-8 degrees C also contributes to virus safety. For storage periods of 8 weeks or longer, reduction factors of 2 to 6 logs were found for all viruses, except for BVDV which remained unaffected. These data indicate that the production processes for IVIg and IMIg as described here have sufficient virus reducing capacity to achieve a high margin of virus safety.
Keywords: JOURNAL ARTICLE Animal Antibodies, Viral/IMMUNOLOGY/*ISOLATION & PURIF Cattle Cell Line Cercopithecus aethiops Cold Diarrhea Virus, Bovine Viral/IMMUNOLOGY Encephalomyocarditis Virus/IMMUNOLOGY Ethanol Fractionation Herpesvirus 1, Suid/IMMUNOLOGY Human Hydrogen-Ion Concentration HIV Antibodies/IMMUNOLOGY/*ISOLATION & PURIF HIV-1/IMMUNOLOGY HIV-2/IMMUNOLOGY Immunoglobulins/IMMUNOLOGY/*ISOLATION & PURIF Injections, Intramuscular Injections, Intravenous Polyomavirus macacae/IMMUNOLOGY Vero Cells 991130
A99B1091
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Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.
