Properties of a new intravenous immunoglobulin (IGIV-C, 10%) produced by virus inactivation with caprylate and column chromatography.
OBJECTIVE
Current manufacture of intravenous immunoglobulin (Gamimune N) uses four cold-ethanol precipitation steps and solvent-detergent treatment. Our objective was to design a new manufacturing process to maximize immunoglobulin G (IgG) purity, achieve robust viral safety, preserve all the biological activities of antibody and avoid unnecessary protein loss.


METHODS
The new process combines multiple functions in single steps. Caprylate is added to precipitate non-IgG proteins and to inactivate enveloped viruses. Two successive anion-exchange columns are used to purify IgG and remove caprylate. The new product, IGIV-C (Gamunex, 10%) is formulated with glycine at 100 mg/ml IgG, pH 4.25. Vials are incubated for 21 days at 23-27 degrees C in a final virus-inactivation step.


RESULTS
Compared with the process for production of Gamimune N, that for IGIV-C requires a shorter production time, achieves more robust virus inactivation, increases IGIV yield from plasma, improves physiological IgG subclass distribution (resulting in higher levels of IgG4), and improves purity, with lower levels of IgA (40 microg/ml), IgM (< 2 microg/ml) and albumin (< 20 microg/ml). Antibody binding, opsonization and protective activities are similar.


CONCLUSIONS
Compared with the current commercial process, the new IGIV-C manufacturing process produces a more highly purified preparation that contains slightly higher levels of IgG4 and retains antibody activities required for clinical efficacy.
Lebing
W
W
Technology Department, Bayer Health Care, Biological Products Division, Clayton, North Carolina 27520, USA. wytold.lebing.b@bayer.com
Remington
K M
KM
Schreiner
C
C
Paul
H-I
HI
D000818:Animals; D001424:Bacterial Infections / Q000188:drug therapy; D002210:Caprylates / Q000494:pharmacology; D011232:Chemical Precipitation; D002845:Chromatography; D004203:Disinfection / Q000379:methods* / Q000592:standards; D004340:Drug Contamination / Q000517:prevention & control; D004345:Drug Industry / Q000379:methods / Q000592:standards; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000032:analysis / Q000494:pharmacology / Q000592:standards*; D051379:Mice; D015996:Survival Rate; D014777:Virus Diseases / Q000517:prevention & control / Q000635:transmission; D014780:Viruses / Q000302:isolation & purification*
D002210:Caprylates; D016756:Immunoglobulins, Intravenous; C031492:octanoic acid