Properties of a new intravenous immunoglobulin (IGIV‐C, 10%) produced by virus inactivation with caprylate and column chromatography

Vox Sanguinis - Tập 84 Số 3 - Trang 193-201 - 2003
Wytold Lebing1, Kathryn Martin Remington2, Ceinwen A. Schreiner1, H.‐I. Paul3
1Technology Department, Bayer Health Care, Biological Products Division, Clayton, North Carolina, USA
2Pre-Clinical Research and Pathogen Safety, Bayer Health Care, Biological Products Division, Research Triangle Park, North Carolina, USA
3Bayer AG, Leverkusen, Germany

Tóm tắt

Background and Objectives 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.Materials and 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 °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 µg/ml), IgM (< 2 µg/ml) and albumin (< 20 µg/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.

Từ khóa


Tài liệu tham khảo

10.1021/ja01207a034

10.1021/ja01170a048

Finlayson JS, 1980, Immunoglobulins: Characteristics and Uses of Intravenous Preparations, 173

10.1542/peds.9.6.722

Janeway CA, 1953, Agammaglobulinemia, Trans Assoc Am Physicians, 66, 200

10.1111/j.1423-0410.1962.tb03240.x

10.1055/s-0028-1113997

Sgouris JT, 1967, The preparation of plasmin treated immune serum globulin for intravenous use, Vox Sang, 13, 71

10.1111/j.1423-0410.1975.tb02791.x

10.1111/j.1423-0410.1977.tb00622.x

Barandun S, 1980, Immunoglobulins: Characteristics and Uses of Intravenous Preparations, 31

10.1111/j.1423-0410.1981.tb00725.x

10.1111/j.1423-0410.1981.tb00726.x

10.1093/infdis/147.6.1090

10.1093/infdis/153.6.1092

10.1007/BF00915058

10.1111/j.1423-0410.1987.tb04921.x

Zaia JA, 1986, Clinical Use of Intravenous Immunoglobulin, 299

10.1056/NEJM196804252781701

10.1007/BF00918366

10.1093/infdis/155.5.897

HooperJA MankariousS Liu‐RashCR: Stabilized gamma globulin concentrate. US Patent No. 4 439 421 1984

10.1093/clinids/8.Supplement_4.S374

10.1046/j.1537-2995.1986.26486262753.x

10.1006/biol.1994.1003

Center for Disease Control and Prevention, 1993, Outbreak of hepatitis C associated with intravenous immunoglobulin administration‐ United States, October 1993–June 1994, Morb Mortal Wkly Rep, 43, 505

10.1111/j.1423-0410.1991.tb00878.x

10.1016/S0021-9673(01)94720-X

Alving BM, 1980, Contact‐activated factors: contaminants of immunoglobulins preparations with coagulant and vasoactive properties, J Lab Clin Med, 96, 334

Mayer MM, 1961, Experimental Immunochemistry, 227

Section H, 1986, Manual of Clinical Laboratory Immunology, 488

10.1006/biol.1994.1009

Widman F, 1985, Technical Manual of the American Association of Blood Banks

10.1046/j.1423-0410.2003.00279.x

10.1006/biol.2002.0334

Cavalli‐Sforza L, 1974, Biometrie Grundzuge Biologischmedizinischer Statistik [Biometry, the Basics of Biological and Medical Statistics].

10.1016/S0166-0934(99)00135-4

10.1046/j.1537-2995.2001.41040449.x

10.1126/science.168.3938.1462

10.1046/j.1537-2995.1992.32993110753.x

10.1080/10826068408070610

Stecher PG, 1968, The Merck Index

10.1172/JCI101939

10.1111/j.1423-0410.1984.tb01558.x

Hollinger FB, 1996, Fields Virology, 2739

Ballow M, 2001, Pharmacokinetics of a novel, intravenous immunoglobulin preparation, J Allergy Clin Immunol, 107, a685

10.1046/j.1423-0410.2003.00286.x

Thông tin
Thông tin xuất bản

Vox Sanguinis

Tập 84 Số 3

193-201

Thông tin tác giả