In vitro and in vivo properties differ among liquid intravenous immunoglobulin preparations

Abstract

Objective To compare in vitro and in vivo biological and biochemical properties of five liquid intravenous immunoglobulin (IVIg) preparations licensed for therapeutic use in Europe.Methods ClairYg® was compared in a blinded manner to four other liquid IVIg preparations licensed in Europe (Octagam®, Kiovig®, Gamunex®, Privigen®). Three batches of each preparation were tested, except for the IgG repertoires and the animal model.Results Levels of anti-A and anti-B antibodies were lower in ClairYg® (0·11/0·11) relative to a positive EDQM standard and Octagam® (0·11/0·08) than in other preparations (0·33–0·69/0·42–0·46). IgG in ClairYg® recognized 365 and 416 protein spots in HEp-2 cell and Escherichia coli protein extracts vs. 230–330 and 402–842 protein spots, respectively, for IgG in other preparations. IgA content (301 vs. 165–820 ng/mg of IgG), Factor XI and Factor XII antigen (0·46 vs. 0·85–2·40 mU/mg of IgG and 7·8 vs. 20·0–46·2 lU/mg of IgG) C1q binding (0·42 vs. 0·67–1·89 arbitrary units) and C5a uptake (0·41 vs. 0·45–0·66% of activation) were lower in ClairYg® than in other preparations. Finally, intravenous infusion of ClairYg®, Gamunex® and Privigen® had no major effect on arterial blood pressure in spontaneously hypertensive rats.Conclusions Our results evidence some differences in the biological and biochemical properties among licensed liquid IVIg preparations.

Isoagglutinin reduction by a dedicated immunoaffinity chromatography step in the manufacturing process of human immunoglobulin products

“…With this IgG product, lower rates of hemolytic events were recorded: zero of 71 patients receiving Carimune/Sandoglobulin versus 13 of 154 patients on IVIG from chromatography‐based manufacturing processes (Gamunex, Gammagard Liquid, or Privigen) . Furthermore, the isoagglutinin levels in IAC‐purified Privigen and Hizentra lots are among the lowest reported for the IVIG products currently available, similar to those reported for another IgG preparation, ClairYg (LFB Biotechnologies, Courtaboeuf, France), that also relies on IAC for isoagglutinin reduction …”

Tolerability and safety of the intravenous immunoglobulin octagam®10% in patients with immune thrombocytopenia: a post-authorisation safety analysis of two non-interventional phase IV trials

“…Differences in the formulations, manufacturing processes, excipients, pH and other physicochemical properties of IVIG products may affect their safety [21][22][23]. For example, procoagulant substances in IVIG preparations, particularly FXIa, have been identified as a probable cause of IVIG-related TEEs [17,24,25].…”

Immunoglobulin Therapy

“…[71][72][73] Clinically significant hemolysis is very rare in licensing studies of IVIG for primary immune deficiency, using doses of 400-800 mg/kg. 75 mediated by an immunoregulatory tyrosine-based inhibition motif, e.g. 74 Despite this, current products meeting these regulations are still implicated in cases of hemolysis, and strategies to address this issue of hemolysis are being pursued by the FDA.…”