Viral inactivation of intramuscular immune serum globulins.

A new process for the production of intramuscular immunoglobulin products is described which includes viral inactivation through solvent-detergent treatment. Removal of solvent-detergent was accomplished by precipitation, filtration and diafiltration. Process-scale preparations had appropriate antibody potency levels, and improved IgG integrity relative to traditional IGIM products. Moreover, acceptable results were obtained in all in vitro and in vivo pre-clinical toxicology testing, as well as clinical evaluation. Scaled-down experiments demonstrated that the new process provides effective viral inactivation. Taken together, these results indicate that the new products should have the same efficacy of the previous IGIM products albeit with safety and processing improvements.

Infection potential of nondisposable pressure transducers prepared prior to use.

This study was designed to examine whether pressure transducer systems prepared hours or days before actual use represent an infection potential. Twenty-one nondisposable transducers assembled with sterile plastic disposable domes and extension tubing were utilized. The systems were prefilled with heparinized flush solution (2 U sodium heparin per ml normal saline). Flush solution samples were cultured from the distal end of the equipment immediately after set-up (time 0) and 24, 48, and 72 h after set-up in all 21 transducers. In 11 of 21 transducers, cultures were also taken at 168 h (1 wk) and 336 h (2 wk) after set-up. Out of the total 106 cultures, only two showed growth, both of which proved to be external skin or mouth contaminants. Binomial distribution testing indicated that if a .05 probability level was used, the chance was 1.3% that one or more transducers in 100 could become contaminated by 72 h. Using the same statistical analyses for the 66 cultures involving the 11 transducers cultured for 2 wk, the chance of contamination in 100 cultures is 2.7% at 2 wk. We conclude from these data that nondisposable transducer systems, when preassembled using standard aseptic precautions and sterile disposable plastics, show no evidence of significant contamination when allowed to stand in readiness after assembly but not connected to a patient. We feel it is safe to preassemble transducers for at least a 72-h period before use. Longer intervals from set-up to use may also be justified.

Three generations of immunoglobulin G preparations for clinical use.

The first purified human immunoglobulin G (IgG) preparation used clinically was immune serum globulin (ISG), which was prepared in the 1940s by E. J. Cohn's group. It was originally formulated in water with 0.3 M glycine at pH 6.8 and was 70%-80% monomeric. ISG was safe when given intramuscularly and efficacious for measles and hepatitis prophylaxis. The next generation of purified IgG began in the 1960s with chemically modified preparations suitable for intravenous administration. The first such IgG intravenous preparation (IGIV) in the United States was IGIV pH 6.8 (Gamimune, Cutter Biological), in which the anticomplement activity found in ISG was removed by reduction and alkylation of disulfide bridges. This product was originally formulated as a 5% IgG solution in water (pH 6.8) with 0.2 M glycine in 10% maltose for stabilization. It remained stable for at least 2.5 years at 5 degrees C, was 80%-90% monomeric, had virtually no anticomplement activity, was safe given intravenously, and was efficacious for prophylaxis in agammaglobulinemic patients. A third generation of purified IgG has since been developed; IGIV pH 4.25, (Gamimune N, Cutter Biological), which was isolated by the Cohn method from human plasma and is safe for intravenous use, is a 5% solution of IgG in water (pH 4.25) with 10% maltose. The product is greater than 99% IgG, greater than 95% monomeric, and has greater than 90% less anticomplement activity than ISG.