Reducing the risk of infection from plasma products: specific preventative strategies

Ad hoc Working party on Biotechnology/Pharmacy. Note for guidance: CPMP Guideline: Validation of virus removal and inactivation procedures (III/8115/89). 1991, Feb, 11, 13 Commission of the European Communities, Ad hoc Working party on Biotechnology/Pharmacy. Contribution to Part II of the structure of the dossier for applications for marketing authorization – Control of starting materials for the production of blood derivatives. 1 July 1995 1998 Cuthbertson, 1991, Viral contamination of human plasma and procedures for preventing virus transmission by plasma products, 385 Burnouf, 1992, Safety aspects in the manufacturing of plasma-derived coagulation factor concentrates, Biologicals, 20, 91, 10.1016/S1045-1056(05)80056-9 Foster, 1994, Procedures for the prevention of virus transmission by blood products, 207 Horowitz, 1995, Strategies for viral inactivation, Curr Opin Hematol, 2, 484, 10.1097/00062752-199502060-00014 Willkommen, 1999, Serum and serum substitutes: virus safety by inactivation or removal, Dev Biol Stand, 99, 131 Burnouf, 2000, Prévention des risques infectieux des produits sanguins stables, 153 Schreiber, 1996, The risk of transfusion-transmitted viral infections, N Engl J Med, 334, 1685, 10.1056/NEJM199606273342601 Tabor, 1999, The epidemiology of virus transmission by plasma derivatives: clinical studies verifying the lack of transmission of hepatitis B and C viruses and HIV type 1, Transfusion, 39, 1160, 10.1046/j.1537-2995.1999.39111160.x Simmonds, 1998, Transfusion virology: progress and challenges, Blood Reviews, 12, 171, 10.1016/S0268-960X(98)90015-7 Vrielink, 1998, Transfusion-transmissible infections, Curr Opin Hematol, 5, 396, 10.1097/00062752-199811000-00008 Dodd, 1995, Transfusion – transmitted hepatitis virus infection, Hematol Oncol Clin North Am, 9, 137, 10.1016/S0889-8588(18)30113-8 Goto, 1999, Prevalence of GB virus C/hepatitis G virus ribonucleic acid and anti-hepatitis G virus-E2 antibodies among Japanese children with histories of transfusions or with liver diseases, Pediatr Res, 45, 128, 10.1203/00006450-199901000-00021 Simmonds, 1998, Detection of a novel DNA virus (TTV) in blood donors and blood products, Lancet, 352, 191, 10.1016/S0140-6736(98)03056-6 Mannucci, 1994, Low risk of transmission of hepatitis E virus by large-pool coagulation factor concentrates, Lancet, 343, 597, 10.1016/S0140-6736(94)91548-2 Inoue, 1999, Possible association between serum GB virus C RNA level and disease activity in fulminant hepatitis type G, J Hepatol, 30, 801, 10.1016/S0168-8278(99)80132-9 Jarvis, 1996, Infection with hepatitis G virus among recipients of plasma products, Lancet, 348, 1352, 10.1016/S0140-6736(96)04041-X Uhle, 1997, Virus inactivation and prevalence of GBV-C in haemophiliacs, Br J Haematol, 99, 837, 10.1046/j.1365-2141.1997.4883292.x Pisani, 1999, Prevalence of TT virus in plasma pools and blood products, Br J Haematol, 106, 431, 10.1046/j.1365-2141.1999.01568.x Chen, 1999, TT virus is present in a high frequency of italian hemophilic patients transfused with plasma-derived clotting factor concentrates, Blood, 94, 4333, 10.1182/blood.V94.12.4333 Dodd, 1998, Creutzfeld-Jakob disease and transfusion safety: tilting at icebergs?, Transfusion, 38, 221, 10.1046/j.1537-2995.1998.38398222863.x Yap, 1998, Prions: properties, occurrence, modes of transmission and relevance for blood transfusion and blood derivatives, Vox Sang, 74 (Suppl. 2), 131, 10.1111/j.1423-0410.1998.tb05410.x Turner, 1998, New-variant Creutzfeldt-Jakob disease: the risk of transmission by blood transfusion, Blood Reviews, 12, 255, 10.1016/S0268-960X(98)90007-8 MacGregor, 1999, Normal prion protein is found in human plasma, but is removed by the SNBTS plasma fractionation process, Thromb Haemost, 82, 86 Foster, 2000, Removal of abnormal prion protein by plasma fractionation, Transf Sci, 22, 53, 10.1016/S0955-3886(00)00011-4 Foster, 2000, Studies on the removal of abnormal prion protein by processes used in the manufacture of human plasma proteins, Vox Sang, 78, 86, 10.1046/j.1423-0410.2000.7820086.x Brown, 1999, Further studies of blood infectivity in an experimental model of transmissible spongiform encephalopathy, with an explanation of why blood components do not transmit Creutzfeldt-Jakob disease in humans, Transfusion, 39, 1169, 10.1046/j.1537-2995.1999.39111169.x FDA Document: Revised precautionary measures to reduce the possible risk of transmission of Creutzfeldt-Jakob Disease (CJD) and New-Variant Creutzfeldt-Jakob Disease (nvCJD) by blood and blood products. US Department of Health and Human Services. Food and Drug Administration. Center for Biologics Evaluation and Research, August 1999 1999 Ludlam, 1997, Viral safety of plasma-derived factor VIII and IX concentrates, Blood Coagul Fibrinolysis, 8, 19 Chamberland, 1998, Emerging issues in blood safety, Infect Dis Clin North Am, 12, 217, 10.1016/S0891-5520(05)70419-0 Chamberland, 1999, Surveillance for bloodborne infections, Thromb Haemost, 82, 494, 10.1055/s-0037-1615870 Allain, 1998, Emerging viruses in blood transfusion, Vox Sang, 74 (Suppl. 2), 125, 10.1111/j.1423-0410.1998.tb05409.x Yee, 1996, Transmission of symptomatic parvovirus B19 infection by clotting factor concentrate, Br J Haematol, 93, 457, 10.1046/j.1365-2141.1996.5161062.x Soucie, 1998, Hepatitis A virus infections associated with clotting factor concentrate in the United States, Transfusion, 38, 573, 10.1046/j.1537-2995.1998.38698326337.x Prowse, 1997, Human parvovirus B19 and blood products, Vox Sang, 72(1), 1, 10.1046/j.1423-0410.1997.00001.x Barbara, 1998, Prevention of infections transmissible by blood derivatives, Transfus Sci, 19, 3, 10.1016/S0955-3886(98)00003-4 Alter, 1994, Transfusion transmitted hepatitis C and non-A, non-B, non-C, Vox Sang, 67, 19, 10.1111/j.1423-0410.1994.tb04539.x Committee for proprietary medicinal products (C. P. M. P). Plasma-derived medicinal products: position paper on ALT testing. 1999, July 29. Corrigendum September 1999 Kitayaporn, 1994, Potential deferral criteria predictive of human immunodeficiency virus positivity among blood donors in Thailand, Transfusion, 34, 152, 10.1046/j.1537-2995.1994.34294143945.x 1996, MMWR Morb Mortal Wkly Rep, 45, 1 Dodd, 1996, Infectious risk of plasma donations: relationship to safety of intravenous immune globulins, Clin Exp Immunol, 104, 31, 10.1111/cei.1996.104.s1.31 Takano, 1996, Prospective assessment of donor blood screening for antibody to hepatitis C virus by first and second-generation assays as a means of preventing post-transfusion hepatitis, Hepatology, 23, 708, 10.1002/hep.510230408 Gonzalez, 1995, Efficacy of screening donors for antibodies to the hepatitis C virus to prevent transfusion-associated hepatitis: final report of a prospective trial, Hepatology, 22, 4439 Bresee, 1996, Hepatitis C virus infection associated with administration of intravenous immune globulin. A cohort study, JAMA, 276, 1563, 10.1001/jama.1996.03540190035026 Yu, 1995, Hepatitis C transmission associated with intravenous immunoglobulins, Lancet, 345, 1173, 10.1016/S0140-6736(95)91002-6 Grandgeorge, 1996, Lessons from recent hepatitis C virus infections: Towards the ‘active’ safety of plasma derivatives, In: Quality and Safety of Plasma Products. Proceedings EPFA-EAPPI, 3rd Annual European Regulatory Affairs Symposium, Amsterdam., 81 Yap, 1997, Viral safety of IVIG, 67 Flanagan, 1999, PCR testing of plasma pools: from concept to reality, Transfus Med Rev, 13, 164, 10.1016/S0887-7963(99)80030-3 Rogers, 1997, Nucleic acid amplification tests (NAT) for the detection of blood-borne viruses, Vox Sang, 72, 199, 10.1046/j.1423-0410.1997.7240199.x Lee, 1998, Genomic screening for blood-borne viruses in transfusion settings, Vox Sang, 74, 119, 10.1111/j.1423-0410.1998.tb05408.x Roth, 1999, Feasibility and efficacy of routine PCR screening of blood donations for hepatitis C virus, hepatitis B virus, and HIV-1 in a blood-bank setting, Lancet, 353, 359, 10.1016/S0140-6736(98)06318-1 Tabor, 1999, Summary of a Food and Drug Administration workshop on nucleic acid testing to screen donations of blood and plasma for the hepatitis C virus, Transfusion, 39, 912, 10.1046/j.1537-2995.1999.39080912.x Lefrere, 1999, Screening for HBV, HCV, and HIV genomes in blood donations: shortcomings of pooling revealed by a multicenter study simulating real-time testing, J Virol Methods, 80, 33, 10.1016/S0166-0934(99)00028-2 The introduction of nucleic acid amplification technology (NAT) for the detection of hepatitis C virus RNA in plasma pools (CPMP/BWP/390/97). Addendum to note for guidance on plasma derived medicinal products (CPMP/BWP/269/95). 1998, March 24 Johannsen, 1999, Improving the safety of plasma derived factor concentrates, 14 Aubin, 2000, Large-scale screening for human parvovirus B19 DNA by PCR: application to the quality control of plasma for fractionation, Vox Sang, 78, 7, 10.1046/j.1423-0410.2000.7810007.x Saldanha, 1999, Sensitivity of PCR assays for the determination of hepatitis A virus RNA in plasma pools. A collaborative study, Vox Sang, 76, 163, 10.1046/j.1423-0410.1999.7630163.x Burnouf, 2000, Experience in implementing collection of plasma for fractionation in Taiwan, Transf Today, 9 More, 1991, Purification technologies for human plasma albumin, 261 Roussel, 1991, Antibody purification from plasma, 307 Feldman, 1991, Preparation of special plasma products, 341 Burnouf, 1995, Chromatography in plasma fractionation: benefits and future trends (review), J Chromatogr, Biomedical Applications, 664, 3, 10.1016/0378-4347(94)00532-A Burnouf, 1998, Application of bioaffinity technology in therapeutic extracorporeal plasmapheresis and large-scale fractionation of human plasma (Review), J Chromatogr, Biomedical Applications, 715, 65, 10.1016/S0378-4347(98)00052-8 Wells, 1986, Inactivation and partition of human T-cell lymphotropic virus, Type III, during ethanol fractionation of plasma, Transfusion, 26, 210, 10.1046/j.1537-2995.1986.26286152919.x Henin, 1988, Inactivation and partition of human immunodeficiency virus during Kistler and Nitschmann fractionation of human blood plasma, Vox Sang, 54, 78, 10.1111/j.1423-0410.1988.tb01621.x Morgenthaler, 1993, Partitioning and inactivation of viruses during isolation of albumin and immunoglobulins by cold ethanol fractionation, Dev Biol Stand, 81, 185 Murozuka, 1999, Removal and inactivation of hepatitis B virus from contaminated pooled plasma in a large-scale manufacturing process for factor VIII and human serum albumin, Vox Sang, 76, 181, 10.1046/j.1423-0410.1999.7630181.x Scheiblauer, 1996, Prevalence of hepatitis C virus in plasma pools and the effectiveness of cold ethanol fractionation, Clin Ther, 18, 59, 10.1016/S0149-2918(96)80196-2 Chandra, 1999, Virus reduction in the preparation of intravenous immune globulin: in vitro experiments, Transfusion, 39, 249, 10.1046/j.1537-2995.1999.39399219280.x Burnouf, 1993, Chromatographic removal of viruses from plasma derivatives, Dev Biol Stand,, 81, 199 Taylor, 2000, Inactivation of transmissible degenerative encephalopathy agents: a review, Vet J, 159, 10, 10.1053/tvjl.1999.0406 Morgenthaler, 1994, Methods for inactivation of viruses in plasma products, Biotechnology of blood proteins, Colloque INSERM, 227, 221 Horowitz, 1985, Inactivation of viruses in labile blood derivatives. I. Disruption of lipid-enveloped viruses by tri – (n-butyl) phosphate detergent combinations, Transfusion, 25, 516, 10.1046/j.1537-2995.1985.25686071422.x Horowitz, 1985, Inactivation of viruses in labile blood derivatives. II. Physical methods, Transfusion, 25, 523, 10.1046/j.1537-2995.1985.25686071423.x Heimburger, 1989, Strategies to produce virus-safe blood derivatives, 23 Mac Leod, 1984, Stabilisation of proteins to heat, Res Disclosures, 244, 380 Gellis, 1948, Chemical, clinical, and immunological studies on products of human plasma fractionation; inactivation of virus of homologous serum albumin by means of heat, J Clin Invest, 27, 239, 10.1172/JCI101939 Ng, 1985, Pasteurisation of antihemophilic factor and model virus inactivation studies, Thromb Res, 39, 439, 10.1016/0049-3848(85)90167-7 Hilfenhaus, 1986, Inactivation of the AIDS-causing retrovirus and other human viruses in antihemophilic plasma protein preparations by pasteurisation, Vox Sang, 50, 208, 10.1111/j.1423-0410.1986.tb04882.x Burnouf, 1989, Examples of virus inactivation treatment in plasma derivatives manufacturing, Colloque INSERM, Biotechnology of plasma proteins,, 175, 373 Burnouf, 1989, Purification of alpha-1 antitrypsin from human plasma, Colloque INSERM, Biotechnology of plasma proteins,, 175, 53 Nowak, 1993, Inactivation of HIV, HBV, HCV related viruses and other viruses in human plasma derivatives by pasteurisation, Dev Biol Stand, 81, 169 Burnouf-Radosevich, 1992, – A pasteurized therapeutic plasma, Infusionstherapie,, 19, 91 Pattison, 1976, An outbreak of type B hepatitis associated with transfusion of plasma protein fraction, Am J Epidemiol, 103, 398, 10.1093/oxfordjournals.aje.a112239 Brackmann, 1988, Acute hepatitis B infection after treatment with heat-inactivated factor VIII concentrate, Lancet, 967, 10.1016/S0140-6736(88)92638-4 Barrowcliffe, 1993, Viral inactivation vs biological activity, Dev Biol Stand, 81, 125 Winkelman, 1986, Pasteurisation induced changes in an antithrombin III concentrate, Thromb Res, 43, 219, 10.1016/0049-3848(86)90063-0 Chang, 1997, Commercial antithrombin concentrate contains inactive L-forms of antithrombin, Thromb Haemost, 77, 323, 10.1055/s-0038-1655962 Raut, 1998, Modification of factor VIII in therapeutic concentrates after virus inactivation by solvent-detergent and pasteurisation, Thromb Haemost, 80, 624 Peerlinck, 1997, Factor VIII inhibitors in previously treated haemophilia A patients with a double virus-inactivated plasma derived factor VIII concentrate, Thromb Haemost, 77, 80, 10.1055/s-0038-1655911 Josic, 1999, Degradation products of factor VIII which can lead to increased immunogenicity, Vox Sang, 77, 90, 10.1159/000056726 Biesert, 1996, Viral safety of a new highly purified factor VIII (OCTATE), J Med Virol, 48, 360, 10.1002/(SICI)1096-9071(199604)48:4<360::AID-JMV10>3.0.CO;2-F Rubinstein, 1989, Sequential dry heat treatments at sterilizing temperatures (100°C) to produce sterile factor VIII concentrates, Vox Sang, 57, 272, 10.1111/j.1423-0410.1989.tb00841.x McDougall, 1985, Thermal inactivation of the acquired immunodeficiency syndrome virus, human T cell lymphotropic virus-III/lymphadenopathy-associated virus, with special reference to antihemophilic factor, J Clin Invest, 76, 875, 10.1172/JCI112045 1988, MMWR, 37, 441 Dietrich, 1990, Transmission of human immunodeficiency virus type 1 by dry-heated clotting factor concentrates, Vox Sang, 59, 129, 10.1111/j.1423-0410.1990.tb00846.x Epstein, 1990, Current safety of clotting factor concentrates, Arch Pathol Lab Med, 114, 335 1988, Lancet, ii, 814 Lyon, 1989, Symptomatic parvovirus B19 infection and heat-treated factor IX concentrate, Lancet, i, 1085, 10.1016/S0140-6736(89)92488-4 Santagostino, 1997, Transmission of parvovirus B19 by coagulation factor concentrates exposed to 100°C heat after lyophilisation, Transfusion, 37, 517, 10.1046/j.1537-2995.1997.37597293884.x Barrett, 1997, Inactivation of hepatitis A virus in plasma products by vapor heating, Transfusion, 37, 215, 10.1046/j.1537-2995.1997.37297203527.x Mannucci, 1988, Prospective study of hepatitis after factor VIII concentrate exposed to hot vapour, Br J Haematol, 68, 427, 10.1111/j.1365-2141.1988.tb04230.x Mannucci, 1990, Antibody to hepatitis C virus after a vapour-heated factor VIII concentrate, Thromb Haemostas, 64, 232, 10.1055/s-0038-1647291 De Filippi, 1998, Transmission of hepatitis G virus in patients with angioedema treated with steam-heated plasma concentrates of C1 inhibitor, Transfusion, 38, 307, 10.1046/j.1537-2995.1998.38398222877.x Kernoff, 1987, Reduced risk of non-A, non-B hepatitis after a first exposure to ‘wet heated’ factor VIII concentrate, Br J Haematol, 67, 207, 10.1111/j.1365-2141.1987.tb02328.x Horowitz, 1993, Viral safety of solvant-detergent treated blood products. Virological Safety Aspects of Plasma derivatives (Brown, F, ed), IABS Congress, Cannes, Nov 1992, Dev Biol Stand, 81, 147 Horowitz, 1998, Virus inactivation by solvent/detergent treatment and the manufacture of SD-plasma, Vox Sang, 74, 203, 10.1111/j.1423-0410.1998.tb05473.x Chudy, 1999, A new cluster of hepatitis A infection in hemophiliacs traced to a contaminated plasma pool, J Med Virol, 57, 91, 10.1002/(SICI)1096-9071(199902)57:2<91::AID-JMV1>3.0.CO;2-L Laurian, 1994, Transmission of human parvovirus B19 by plasma derived factor VIII concentrates, Nouv Rev Fr Hematol, 36, 449 Bos, 1998, Virus validation of pH4-treated human immunoglobulin products produced by the Cohn fractionation process, Biologicals, 26, 267, 10.1006/biol.1998.0148 Hämäläinen, 1992, Virus inactivation during intravenous immunoglobulin production, Vox Sang, 63, 6, 10.1111/j.1423-0410.1992.tb01211.x Prince, 1983, β-propiolactone/ultraviolet irradiation: a review of its effectiveness for inactivation of viruses in blood derivatives, Rev Infect Dis, 5, 92, 10.1093/clinids/5.1.92 Stephan, 1989, Virus inactivation in human plasma and plasma fractions by means of β-propiolactone (β-PL) and β-PL/UV. Biotechnology of plasma proteins (Stoltz JF, Rivat C, eds), Colloque INSERM, Nancy, 17–19 mai 1988, Colloque INSERM, 175, 391 Scheidler, A. Rokos, K. Reuter, T. Ebermann, R. Pauli, G. Inactivation of viruses by beta-propiolactone in human cryo poor plasma and IgG concentrates. Biologicals, 1998, 26, 135, 44 Kleim, 1990, Acute HIV-1 infection in patients with hemophilia B treated with β-propiolactone-UV-inactivated clotting factor, Thromb Haemostas, 64, 336, 10.1055/s-0038-1647314 Dichtelmuller, 1993, Validation of virus inactivation and removal for the manufacturing procedure of two immunoglobulins and a 5% serum protein solution treated with beta-propiolactone, Biologicals, 21, 259, 10.1006/biol.1993.1083 Kallenbach, 1989, Inactivation of viruses by ultraviolet light. Virus inactivation in plasma products (Morgenthaler JJ, ed), Curr Stud Hematol Blood Transfus., 56, 23 Chin, 1995, Virucidal short wavelength ultraviolet light treatment of plasma and factor VIII concentrate: protection of proteins by antioxydants, Blood, 86, 4431, 10.1182/blood.V86.11.4331.bloodjournal86114331 Chin, 1997, Virucidal treatment of blood protein products with UVC irradiation, Photochem Photobiol, 65, 432, 10.1111/j.1751-1097.1997.tb08584.x McLean, 1999, Validation of virus inactivation by UV-C irradiation of 4.5% human albumin, Transf Med, 9, 47 Hamamoto, 1989, A novel method for removal of human immunodeficiency virus: filtration with porous polymeric membranes, Vox Sang, 56, 230, 10.1111/j.1423-0410.1989.tb02034.x Yamaguchi, 1989, Microparticle removability of regenerated cellulose hollow fibers (BMM), J Electron Microsc, 38, 259 Ikeda, 1990, Complete removal of HIV from intermediate concentrate of factor VIII preparation using BMM membrane filtration, Artificial Organs, 14, 259 Burnouf, 1994, Strategy of virus removal/inactivation of plasma-derived products: Interest of nanofiltration as a new virus elimination method Burnouf, 1996, Value of virus filtration as a method for improving the safety of plasma products. (Letter to the Editor), Vox Sang, 70, 235, 10.1111/j.1423-0410.1996.tb01334.x Burnouf-Radosevich, 1994, Nanofiltration, a New Specific Virus Elimination Method applied to High-Purity Factor IX and Factor XI concentrates, Vox Sang, 67, 132, 10.1111/j.1423-0410.1994.tb01647.x Hoffer, 1995, Improved virus safety and purity of a chromatographically produced factor IX concentrate by nanofiltration, J Chromatogr B Biomed Appl, 669, 187, 10.1016/0378-4347(95)00107-T Feldman, 1998, Virus-filtration of Factor IX – An approach to process validation, PLANOVA workshop (Asahi Chemical Industry Co. Ltd, ed.), Oslo, June 27: Schulman, 1999, Efficacy of a high purity, chemically treated and nanofiltered factor IX concentrate for continuous infusion in haemophilia patients undergoing surgery, Haemophilia, 5, 96, 10.1046/j.1365-2516.1999.00284.x Romisch, 1996, Nanofiltration in production of Beriplex P/N: increasing the capacity of virus elimination while maintaining product quality, Beitr Infusionther Transfusionsmed, 33, 220 Over, 1998, Nanofiltration, the EPFA experience, PLANOVA workshop (Asahi Chemical Industry Co.Ltd), Oslo, June 27, O’Grady, 1996, Virus removal studies using nanofiltration membranes, Dev Biol Stand, 88, 319 Stucki, 1997, Characterisation of a chromatographically produced anti-D immunoglobulin product, J Chromatogr B Biomed Sci Appl, 700, 141, 10.1016/S0378-4347(97)00319-8 Troccoli, 1998, Removal of viruses from human intravenous immune globulin by 35 nm nanofiltration, Biologicals, 26, 321, 10.1006/biol.1998.0164 Suomela, 1998, Virus removal filtration of Factor IX concentrate and IV immunoglobulin by Planova 15, PLANOVA workshop (Asahi Chemical Industry Co.Ltd.), Oslo Poulle, 1994, Large-scale preparation of highly purified human C1-inhibitor for therapeutic use, Blood Coagul Fibrinolysis, 5(4), 543 Goudemand, J. Personal communication Tateishi, 1993, Removal of causative agent of Creutzfeld-Jacob disease (CJD) through membrane filtration method, Membrane, 18, 101, 10.5360/membrane.18.357 Tateishi, 1997, Scrapie removal study using Planova filtration system Goudemand, 1998, A cross-over pharmacokinetic study of a double viral inactivated factor IX concentrate (15 nm filtration and SD) compared to a SD factor IX concentrate, Thromb Haemost, 80, 919, 10.1055/s-0037-1615389 Ways, 1999, Good manufacturing practices (GMP) compliance in the biologics sector: plasma fractionation, Biotechnol Appl Biochem, 30, 257 Radosevich, 2000, Safety of recombinant and plasma-derived medicinals for the treatment of coagulopathies, Hematol Oncol Clin North Am, 14, 459, 10.1016/S0889-8588(05)70145-3 Larzul, 1999, Viral validation desing of a manufacturing process, Dev Biol Stand, 99, 139 Hilfenhaus, 1997, Analysis of human plasma products: polymerase chain reaction does not discriminate between live and inactivated viruses, Transfusion, 37, 935, 10.1046/j.1537-2995.1997.37997454021.x Lawlor, 1999, Transmission rates of hepatitis C virus by different batches of a contaminated anti-D immunoglobulin preparation, Vox Sang, 76, 138, 10.1046/j.1423-0410.1999.7630138.x Hsu, 1997, Surface gene mutants of hepatitis B virus in infants who develop acute or chronic infections despite immunoprophylaxis, Hepatology, 26, 786, 10.1002/hep.510260336 Jongerius, 1998, New hepatitis B virus mutant form in a blood donor that is undetectable in several hepatitis B surface antigen-screening assays, Transfusion, 38, 56, 10.1046/j.1537-2995.1998.38198141499.x Radosevich, 1998, Research and development commitments in an integrated plasma collection and plasma fractionation environment, Semin Thromb Haemost, 24, 157, 10.1055/s-2007-995835 Goubran, H. A. Burnouf, T. Radosevich, M. Virucidal heat-treatment of single plasma units: A potential approach for developing countries. Hemophilia