Reduction of Isoagglutinin in Intravenous Immunoglobulin (IVIG) Using Blood Group A- and B-Specific Immunoaffinity Chromatography: Industry-Scale Assessment.
BioDrugs
; 30(5): 441-451, 2016 Oct.
Article
em En
| MEDLINE
| ID: mdl-27646589
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 18 and 14, respectively, when measured by the Ph. Eur. direct method, and 12 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Cromatografia de Afinidade
/
Imunoglobulinas Intravenosas
/
Hemaglutininas
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article