The viral safety of intravenous immune globulin

Abstract

The viral safety of intravenous immune globulin (IVIG) preparations has been investigated since 1983 when it was discovered that non‐A, non‐B hepatitis (NANBH) could be transmitted by an experimental IVIG preparation. Recently, it has been demonstrated that the virus causing NANBH is the hepatitis C virus (HCV). A number of subsequent episodes of HCV transmission by IVIG have been reported, but not all the factors that have led to this transmission arc clearly understood. However, based on two episodes of HCV transmission by anti‐D immune globulin (formulated for intravenous administration), it appears that cold ethanol fractionation is important in ensuring viral safety because both of the implicated anti‐D immune globulin preparations were manufactured without cold ethanol fractionation. Other HCV transmission episodes have been associated with chromatography (particularly DEAE‐Sephadcx chromatography) as a separation step carried out to further purify IgG, after cold ethanol fractionation, and it is possible that such a procedure has only a marginal partitioning capacity for infective HCV virions. The role of anti‐HCV screening in improving the viral safety of IVIG preparations remains unclear, but a recent transmission episode by a previously safe IVIG preparation suggests that the absence of anti‐HCV antibodies during plasma fractionation may affect the partitioning characteristics of HCV and may also cause a loss of neutralizing antibody against HCV. All of the IVIG preparations associated with HCV transmission have been formulated as freeze‐dried preparations and this may have been important in stabilizing HCV during the period prior to administration to patients. No other viruses appear to have been transmitted by IVIG preparations, but prior to seroconversion, HCV‐infected plasma donors may continue to contaminate plasma pools used for the manufacture of blood products, despite anti‐HCV screening, and additional viral inactivation steps such as incubation at pH4 or solvent‐detergent treatment should be incorporated into the production process of all IVIG preparations.

Psoriasis: response to high-dose intravenous immunoglobulin in three patients

“…28 However, hdIVIg is prepared from the pooled plasma of more than 10 000 healthy donors by cold ethanol fractionation 29 and, despite careful selection of donors, viral screening of individual donations and viral inactivation procedures, transmission of blood-borne pathogens remains a possibility. 30,31 Although there is no evidence to suggest that blood products are capable of transmitting new variant Creutzfeldt-Jakob disease, it is an area of potential concern. As a consequence, most hdIVIg is now prepared from non-European blood donations, with the U.S.A. providing most of the serum.…”

Pharmacy considerations for the use of IGIV therapy

“…In the mid-1990s, incidences of hepatitis C disease transmission with IGIV products occurred. 13,14 Since then, no new transmissions have occurred. However, manufacturers remain vigilant against emerging threats of infection such as Creutzfeldt-Jakob disease, severe acute respiratory syndrome (SARS), West Nile virus, and monkeypox virus (Table 3).…”

Assessment of the viral safety of antivenoms fractionated from equine plasma

“…Several human IgG preparations are subjected to an acid pH incubation that was historically introduced to reduce immediate adverse reactions subsequent to intravenous injections. In the late 1980s, acid pH treatment was also shown to contribute greatly to the Table 3 Comparison of conditions for caprylic acid treatment used for human IgG preparations (87) viral safety of human IgG preparations [90,91]. The treatment of human IgG generally consists of incubation at pH 4, with or without traces of pepsin, at temperatures from 30 to 37 C, using a protein content close to 50 g/l, and for more than 20 h. The treatment is intended to eliminate aggregates.…”