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BioDrugs
Published in: BioDrugs 5/2016

Open Access 01-10-2016 | Original Research Article

Reduction of Isoagglutinin in Intravenous Immunoglobulin (IVIG) Using Blood Group A- and B-Specific Immunoaffinity Chromatography: Industry-Scale Assessment

Authors: Simon Gerber, Annette Gaida, Nicole Spiegl, Sandra Wymann, Adriano Marques Antunes, Ibrahim El Menyawi, Brigitte Zurbriggen, Alphonse Hubsch, Martin Imboden

Published in: BioDrugs | Issue 5/2016

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Abstract

Background

Hemolysis, a rare but potentially serious complication of intravenous immunoglobulin (IVIG) therapy, is associated with the presence of antibodies to blood groups A and B (isoagglutinins) in the IVIG product. An immunoaffinity chromatography (IAC) step in the production process could decrease isoagglutinin levels in IVIG.

Objectives

Our objectives were to compare isoagglutinin levels in a large number of IVIG (Privigen®) batches produced with or without IAC and to assess the feasibility of the production process with an IAC step on an industrial scale.

Methods

The IAC column comprised a blend of anti-A and anti-B resins formed by coupling synthetic blood group antigens (A/B-trisaccharides) to a base bead matrix, and was introduced towards the end of the industrial-scale IVIG manufacturing process. Isoagglutinin levels in IVIG were determined by anti-A and anti-B hemagglutinin direct and indirect methods according to the European Pharmacopoeia (Ph. Eur.) and an isoagglutinin flow cytometry assay. IVIG product quality was assessed with respect to the retention of immunoglobulin G (IgG) subclasses, specific antibodies, and removal of IgM using standardized procedures.

Results

The IAC step reduced isoagglutinins in IVIG by two to three titer steps compared with lots produced without IAC. The median anti-A and anti-B titers with IAC were 1:8 and 1:4, respectively, when measured by the Ph. Eur. direct method, and 1:2 and <1, respectively, when measured by the Ph. Eur. indirect method. The isoagglutinin flow cytometry assay showed an 87–90 % reduction in isoagglutinins in post-IAC versus pre-IAC fractions. IAC alone reduced anti-A and anti-B of the IgMs isotype by 92.5–97.8 % and 95.4–99.2 %, respectively. Other product quality characteristics were similar with and without IAC.

Conclusions

IAC is an effective method for reducing isoagglutinin levels in IVIG, and it is feasible on an industrial scale.
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Metadata
Title
Reduction of Isoagglutinin in Intravenous Immunoglobulin (IVIG) Using Blood Group A- and B-Specific Immunoaffinity Chromatography: Industry-Scale Assessment
Authors
Simon Gerber
Annette Gaida
Nicole Spiegl
Sandra Wymann
Adriano Marques Antunes
Ibrahim El Menyawi
Brigitte Zurbriggen
Alphonse Hubsch
Martin Imboden
Publication date
01-10-2016
Publisher
Springer International Publishing
Published in
BioDrugs / Issue 5/2016
Print ISSN: 1173-8804
Electronic ISSN: 1179-190X
DOI
https://doi.org/10.1007/s40259-016-0192-3

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