Intravenous immunoglobulins: clinical experience and viral safety.

Abstract

To discuss the current procedures and processes by which viral safety is ensured for intravenous immunoglobulins (IVIGs), to place in context the current increase in clinical indications for IVIGs, and to describe the safety issues that have led to product shortages. Articles on viral safety retrieved from MEDLINE using the search terms gamma globulin, intravenous, adverse reaction, and infection and information from the manufacturers' literature and Food and Drug Administration package inserts. Studies that specifically addressed the areas of major concern or advancement in viral safety of IVIGs, including donor selection, plasma screening, and other quality control procedures to ensure safety of source plasma; detection of viruses that may have escaped antibody screening tests through the use of polymerase chain reaction-based assays, which are capable of detecting small amounts of viral genomic material (e.g., hepatitis C virus, hepatitis B virus, and human immunodeficiency virus [HIV]) in small plasma pools; and industrial-scale, validated viral inactivation methods, such as pasteurization and solvent/detergent treatment, that have been incorporated into the manufacturing processes of immunoglobulins to further minimize the risk of viral transmission. In addition to the treatment of primary immunodeficiency disorders, the clinical uses of IVIGs have expanded to include treatment of Kawasaki's syndrome, idiopathic thrombocytopenic purpura, infection following bone marrow transplantation, secondary immunologic disorders (e.g., pediatric HIV infection), hematologic disorders (e.g., chronic lymphocytic leukemia), and neurologic indications (e.g., Guillain-Barré syndrome). Although IVIG preparations are derived from human plasma, they have a long safety record and a low risk for transmitting viral infections. Viral validation studies demonstrated that the processes discussed herein differ in their capabilities to inactivate lipid-enveloped and nonlipid-enveloped viruses.