Nanofiltration bei der Herstellung des PPSB-Konzentrates Beriplex® P/N

Zusammenfassung

Nanofiltration, bestehend aus der Kombination von Planova® 75 nm/35 nm Filtern, ist in den Produktionsprozeß des PPSB-Konzentrates Beriplex® P/N integriert. Abreicherungsfaktoren der mit umhüllten Viren versetzten Intermediärprodukte von mehr als 7,2 log₁₀ für HSV-1, mehr als 7,3 log₁₀ für HIV-1, von 3,8 log₁₀ für BVDV und von 4,3 log₁₀ für HBV wurden durch die Filtration erzielt. Durch das PPSB-Reinigungsverfahren, die Pasteurisierung und die Nanofiltration wird ein kumulierter Virusabreicherungsfaktor von mindestens 15 log₁₀ für in Zellkultur titrierbare Viren erzielt. Durch fünf konsekutive Aufarbeitungen im Produktionsmaßstab parallel mit/ohne Nanofiltration wurde die Reproduzierbarkeit und Beibehaltung der Produktqualität gezeigt. Die Einführung der Nanofiltration führte zu keinen nachteiligen Auswirkungen auf Beriplex® P/N; das Produktprofil blieb erhalten.

Schlüsselwörter

Nanofiltration - Virusreduktion - PPSB-Konzentrat - Beriplex® P/N - Produktqualität

• LITERATUR

• 1 Aronson DL, Ménaché D. Thrombogenicity of factor IX complex: in-vivo investigations. Dev Biol Standard 1987; 67: 149-55.
• 2 Barrowcliffe TW. Standardization of factors II, VII, IX and X in plasma and concentrates. Thromb Haemost 1988; 59: 334.
• 3 Bernhardt D, Beschle HG, Niedrig M, Nowak T. Kreuzreaktive Antikörper bei Parvoviren. Tierärztl Umschau 1994; 49: 481-3.
• 4 Burnouf T. Safety aspects in the manufacturing of plasma-derived coagulation factor concentrates. Biologicals 1992; 20: 91-100.
• 5 Burnouf-Radosevich M, Appourchaux P, Huart JJ, Burnouf T. Nanofiltration, a new specific virus elimination method applied to high-purity factor IX and factor XI concentrates. Vox Sang 1994; 67: 132-8.
• 6 Chandra S, Wickershauser M. Contact factors are responsible for the thrombogenicity of prothrombin complex. Thromb Res 1979; 14: 189-98.
• 7 Chandra S, Brummelhuis HGJ. Prothrombin complex concentrates for clinical use. Vox Sang 1981; 41: 257-73.
• 8 Clark DB, Drohan WN, Miekka SI, Katz AJ. Strategy for purification of coagulation factor concentrates. Ann Clin Lab Sei 1989; 19: 196-207.
• 9 CPMP Guidelines. Ad hoc working party biotechnology/pharmacy. Note for guidance “Validation of virus removal and inactivation procedures” (III/8115/89). Biologicals 1991; 19: 247-51.
• 10 Eibl J, Kaeser A. Ways to reduce the risk of transmission of viral infections by plasma and plasma products. Vox Sang 1988; 54: 228-30.
• 11 Fuhge P, Gratz P, Geiger H. Modern methods for the manufacture of coagulation factor concentrates. Transfus Sei 1990; 11: 23S-33S.
• 12 Hamamoto Y, Harada S, Kobayashi S. et al. A novel method for removal of human immunodeficiency virus: filtration with porous polymeric membranes. Vox Sang 1989; 56: 230-6.
• 13 Heimburger N, Karges HE, Kumpe G. Highly purified and heat sterilized concentrates of factor IX and PPSB. Thromb Haemost 1983; 50: 109.
• 14 Heimburger N, Karges HE. Ways to reduce the risk of transmission of viral infections by plasma and plasma products. Vox Sang 1988; 54: 231-5.
• 15 Heimburger N, Karges HE. Strategies to produce virus-safe blood derivatives. Curr Stud Hematol Blood Transfers 1989; 56: 23-33.
• 16 Hilfenhaus J, Geiger H, Lemp J, Hung CL. A strategy for testing established human plasma protein manufacturing procedures for their ability to inactivate or eliminate human immunodeficiency virus. J Biol Standard 1987; 15: 251-63.
• 17 Hilfenhaus J, Gregersen JP. Inactivation of AIDS-causing retroviruses by the manufacturing procedures for human plasma proteins. Behring Inst Res Commun 1988; 82: 82-93.
• 18 Hilfenhaus J. Virus safety of plasma proteins: elimination of the viruses of risk by the manufacturing procedure. Transf Sei 1990; 11: 35S-41S.
• 19 Horowitz B. Ways to reduce the risk of transmission of viral infections by plasma and plasma products. Vox Sang 1988; 54: 235-7.
• 20 Ikeda H, Tomono T, Hanamoto Y. et al. Complete removal of HIV from intermediate concentrate of factor VIII preparations using BMM membrane filtration. Organs 1990; 14: 259-60.
• 21 Ishizawa M, Kubayashi Y, Miyamura T, Matsuura A. Simple procedure of DNA isolation from human serum. Nucleic Acid Res 1991; 19: 5792.
• 22 Johnson AJ, Matthews RW, Fulton AJ. Fractionation of factor VIII and IX -an overview. Scand J Haematol 1984; 40: 513-24.
• 23 Köhler M, Heiden M, Harbauer G. et al. Comparison of different prothrombin complex concentrates - in vitro and in vivo studies. Thromb Res 1990; 60: 63-70.
• 24 Kolde HJ, Deubel R. Development of a rapid kinetic assay for the function of the classical pathway of the complement system and for C2 and C4. J Clin Lab Immunol 1986; 21: 201-7.
• 25 Lundblad JL, Mozen MM. Ways to reduce the risk of transmission of viral infections by plasma and plasma products. Vox Sang 1988; 54: 237-8.
• 26 Lusher JM. Thrombogenicity associated with factor IX complex concentrates. Semin Hematol 1991; 28: 3-5.
• 27 Makino M, Ishikawa G, Yamaguchi K. et al. Concentration of live retrovirus with a regenerated cellulose hollow fiber, BMM. Arch Viral 1994; 139: 87-96.
• 28 Mannucci PM, Morfini PM. Ways to reduce the risk of transmission of viral infections by plasma and plasma products. Vox Sang 1988; 54: 238-40.
• 29 Maurin N. Therapie lebensbedrohlicher Cumarin-Blutungen. Intensiv- und Notfallbehandlung 1994; 01: 42-4.
• 30 Morgenthaler JJ. Ways to reduce the risk of transmission of viral infections by plasma and plasma products. Vox Sang 1988; 54: 240-2.
• 31 Müller HG, Bonik K. Qualitätskriterien von Prothrombinkomplex-Konzentraten (PPSB). Krankenhauspharm 1992; 11: 528-31.
• 32 Péjaudier L, Kichenin-Martin V, Boffa MC, Steinbuch M. Appraisal of the Protein C composition of prothrombin complex concentrates of different origins. Vox Sang 1987; 52: 1-9.
• 33 Piszkiewicz D. Ways to reduce the risk of transmission of viral infections by plasma and plasma products. Vox Sang 1988; 54: 242-3.
• 34 Riess H, Binsack T, Hiller E. Protein C antigen in prothrombin complex concentrates: content, recovery and half life. Blut 1985; 50: 303-6.
• 35 Römisch J, Diehl KH, Hoffmann D. et al. Comparison of in vitro and in vivo properties of r-hirudin (HBW 023) and a synthetic analogous peptide. Haemostas 1993; 23: 249-58.
• 36 Scherer R, Gille A, Erhard J. et al. Substitutionseffekt von AT III- und PPSB-Konzentraten bei Patienten mit terminaler Leberinsuffizienz. Anaesth 1994; 43: 178-82.
• 37 Soulier JP. The history of PPB S. Vox Sang 1984; 46: 55-61.
• 38 Steinbuch M, Péjaudier L, Kichenin V, Boffa MC. Studies on prothrombin complex concentrates, contact factors, complement components and proteine inhibitors. Thromb Haemost 1984; 52: 256-62.
• 39 Stephan W. Ways to reduce the risk of transmission of viral infections by plasma and plasma products. Vox Sang 1988; 54: 244-5.
• 40 Tegtmeier GE. Infectious diseases transmitted by transfusion: a miscellanea. Vox Sang 1994; 67: 179-81.
• 41 Tsurumi T, Osawa N, Hirasaki T. et al. Mechanism of removing monodisperse gold particles from a suspension using cuprammonium-regenerated cellulose hollow fiber (BMM hollow fiber). Polym J 1990; 22: 304-11.
• 42 Wessler S, Ward K, Ho C. Studies in intravascular coagulation III. The pathogenesis of serum-induced venous thrombosis. J Clin Invest 1995; 34: 647-51.
• 43 Wüst T, Beeser H, Lang HR. Diagnostik und Therapie der Verbrauchskoagulopathie. Intensivmed 1990; 27: 177-82.
• 44 Yamaguchi K, Hamamoto Y, Takamatsu K. et al. Microparticle removability of regenerated cellulose hollow fibres (BMM). J Electron Microsc 1989; 38: 259.
• 45 Yuasa T, Ishikawa G, Manabe S. et al. The particle size of hepatitis C virus estimated by filtration through microporous regenerated cellulose fibre. J Gen Virol 1991; 72: 2021-4.