Methodology and safety considerations in the production of an intravenous immunoglobulin preparation.
Intravenous immunoglobulins are biologic substances and differ in many respects from chemical pharmaceuticals. To produce a safe and efficacious preparation, special points must be considered. Careful screening procedures and excluding high-risk donor populations reduce the risk of transmitting viral disease from the starting material. With plasma fractionation the immunoglobulins are purified, and safety is further improved by eliminating potentially remaining viruses. Cold ethanol-fractionation methods have proved to be safe and economical. Anticomplementary aggregates, responsible for anaphylactoid reactions in agammaglobulinemic patients, are removed to achieve intravenous tolerance. Enzymatic digestion or chemical modifications impair the efficacy of the preparation. Ion-exchange adsorption removes immunoglobulin subpopulations. Mild acid treatment at pH 4 yields a safe product with intact potency. Optimal stability is ensured by freeze-drying. A fine net of quality controls virtually guarantees a safe preparation.