[Evaluation criteria for intravenous immunoglobulin G preparations]

The need for quantitative or qualitative immunoglobulin replacement therapy in patients with hypogammaglobulinaemia or in immuno-compromised subjects has greatly encouraged the development of preparations suitable for intravenous use. A major requirement in plasma fractionation is that ready-to-use preparations must be free from contamination by immunoglobulin aggregates likely to produce harmful reactions. To avoid this, three methods are available:--splitting-up with enzymes (pepsin or plasmin) which separate the Fc and Fab fragments, thereby damaging the molecule and definitely preventing the formation of IgG aggregates;--treatment of the preparation with chemical compounds altering the primary structure of the molecule that mediates spontaneous aggregation;--adjunction of special agents (e.g. polyethyleneglycol) or treatment at low pH, which eliminates IgG aggregates and prevents them from forming anew. The properties of immunoglobulins prepared by these three methods are discussed on the basis of two criteria: clinical tolerability and therapeutic effectiveness, including antigen neutralization, sustained normal half-life and full ability to interact with humoral and cellular receptors.