Virus Safety of Intravenous Immunoglobulin: Future Challenges

Abstract

Patients with immunodeficiencies or some types of autoimmune diseases are dependent on safe therapy with intravenous immunoglobulins. State-of-the-art manufacturing processes provide a high safety standard by incorporating virus elimination procedures into the manufacturing process. Based on their mechanism, these procedures are grouped into three classes: partitioning, inactivation, and removal based on size. Because of current socioeconomic and ecological changes, emerging pathogens continue to be expected. Such pathogens may spread very quickly because of increased intercontinental traffic. Severe acute respiratory syndrome-coronavirus and the West Nile virus are recent examples. Currently, it is not possible to predict the impact such a pathogen will have on blood safety because the capacity for a globally coordinated reaction to such a threat is also evolving. The worst-case scenario would be the emergence of a transmissible, small, nonenveloped virus in the blood donor population. Examples of small nonenveloped viruses, which change host and tissue tropism, are discussed, with focus on parvoviridae. Although today's immunoglobulins are safer than ever, in preparation for future challenges it is a high priority for the plasma industry to proactively investigate such viruses on a molecular and cellular level to identify their vulnerabilities.

Contribution to safety of immunoglobulin and albumin from virus partitioning and inactivation by cold ethanol fractionation: a data collection from Plasma Protein Therapeutics Association member companies

“…10 log) in a 1000‐L plasma pool, when NAT tested and the load is not higher than 10 4 /mL. Consequently, production processes of immunoglobulins and albumin must essentially include additional dedicated virus inactivation and/or removal procedures, such as pasteurization, 20 low pH treatment, 11,21 S/D treatment, 12,22‐24 caprylate treatment, 13,25,26 virus filtration, 14,15 or other procedures to further improve on the safety margins.…”

High-Level Human Herpesvirus-6 Viremia Associated With Onset of Stevens-Johnson Syndrome: Report of Two Cases

“…In Case #1, it is unclear if this represented primary or reactivated infection. The patient was younger, had no clear medication precipitant, and her HHV-6 viral load remained high for several weeks which may favor primary infection (serologies were confounded by the administration of IVIG; the IVIG administered to the patient was not tested for the presence of HHV-6 viral particles by PCR or culture, however standard manufacturing processes for IVIG incorporate rigorous viral elimination procedures [23]). However, reactivation still remains more likely based on sero-epidemiologic data supporting greater than 90% sero-prevalence of HHV-6 by the age of 2 (24).…”

Multiple sclerosis treatment and infectious issues: update 2013

“…Despite extensive and modern safety measures in the manufacturing process and in the choice of blood donors, IVIg, as biological products, have a small residual risk for the transfer of infectious agents such as uncoated viruses or prions [125].…”