Safety and availability of immunoglobulin replacement therapy in relation to potentially transmissable agents

Polyclonal immunoglobulin, used for replacement therapy in immune deficiencies, must contain the full range of protective antibodies in order to provide prophylaxis against infections. Unlike Factor VIII, there is no possibility that this therapy could be provided solely by recombinant technology. Immunoglobulin for immunodeficient patients will continue to be produced from large pools of human plasma which maximizes protection but increases the chance that a unit of plasma contaminated with an infectious agent will be included. For clinicians to ensure that benefit to an individual immunodeficient patient is maximal, this life-long therapy must be as safe as possible. Recently, immunoglobulin products have been withdrawn and plasma donors restricted in attempts to prevent transmission of blood-borne agents. Such measures have resulted in alarming shortages of therapeutic immunoglobulin worldwide. 1 This balance must be redressed by a critical look at the evidence regarding transmission of the wide range of blood-borne diseases potentially contaminating immunoglobulin for replacement therapy. The safety of replacement and high-dose therapies in relation to infusion-related reactions is not included here. There are several methods by which immunoglobulin preparations are produced from human plasma and each product is generically different. Although efficacy is equivalent between these products, there are important differences which impinge on their long-term safety. Worldwide, there are currently over 25 preparations of immunoglobulin for use intravenously and more than six preparations used subcutaneously or intramuscularly. Almost all are produced by initial processing of pooled human plasma (from 1000 to 10 000 donors) by cold ethanol precipitation (Cohn–Oncley procedure),2 resulting in five plasma fractions. Cohn fraction II provides a preparation appropriate for intramuscular and subcutaneous use and is the starting material for purification of immunoglobulin for intravenous use by a variety of methods. Blood-borne agents have the potential to contaminate immunoglobulin, and therefore additional antiviral steps are used, before or after the Cohn–Oncley procedure, to reduce these risks. As the evidence for viral transmission by immunoglobulin is fragmentary, recommendations for a more systemic method of data collection are made so that real risk–benefit assessments for immunodeficient patients can be ascertained.