T. Burnouf - Academia.edu (original) (raw)

Papers by T. Burnouf

Africa Sanguine

Interest in Africa on therapeutic use of COVID-19 convalescent plasma (CCP) has increased with co... more Interest in Africa on therapeutic use of COVID-19 convalescent plasma (CCP) has increased with continental spread of the pandemic of SARS -CoV-2. Consequently, blood organisations in several countries have established governmentally approved investigational protocols for collection and use of CCP. However, other countries still seek advice in this area. Sources of guidance can be found in recent publications by the Working Party on Global Blood Safety of the International Society of Blood Transfusion (ISBT), the ISBT Convalescent Plasma Working Group, and the World Health Organization. Additionally, resources on CCP policies and protocols can be found at an ISBT open-access website: http://isbtweb.org/coronaoutbreak/convalescent-plasma-covid-19-resources/.The effectiveness and safety of CCP remain uncertain based on limitations of the available controlled studies and reported case series and fundamental questions regarding optimal use in patient management are unanswered. Neverthele...

Journal of Thrombosis and Haemostasis, 2016

To cite this article: Burnouf T, Strengers PFW. Risks of inhibitors from recombinant factor VIII:... more To cite this article: Burnouf T, Strengers PFW. Risks of inhibitors from recombinant factor VIII: a quarter of a century to reach the conclusion. J Thromb Haemost 2016; 14: 2073-4.

Revue Francaise de Transfusion et Immuno-hématologie, 1981

ABSTRACT

Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis, 2014

The world is regularly exposed to emerging infections with the potential to burst into a pandemic... more The world is regularly exposed to emerging infections with the potential to burst into a pandemic. One possible way to treat patients, when no other treatment is yet developed,is passive immunization performed by transfusing blood, plasma or plasma immunoglobul infractions obtained from convalescent donors who have recovered from the disease and have developed protective antibodies. The most recent on-going epidemic is caused by the Ebola virus, a filovirus responsible for Ebola virus disease, a severe, often lethal, hemorrhagic fever. Recently, the use of convalescent blood products was proposed by the WHO as one early option for treating patients with Ebola virus disease. This publication provides an overview of the various convalescent blood products and technological options that could theoretically be considered when there is a need to rely on this therapeutic approach.In countries without access to advanced blood-processing technologies, the choice may initially be restricted ...

World Health Organization technical report series, 2004

This report presents the recommendations of a WHO Expert Committee commissioned to coordinate act... more This report presents the recommendations of a WHO Expert Committee commissioned to coordinate activities leading to the adoption of international requirements for the production and control of vaccines and other biologicals and the establishment of international biological reference materials. The report starts with a discussion of general issues brought to the Committee's attention and provides information on the status and development of reference materials for various antibodies, antigens, blood products and related substances, cytokines, growth factors, and endocrinological substances. The second part of the report, of particular relevance to manufacturers and national regulatory authorities, contains recommendations for the production and quality control of meningococcal group C conjugate vaccines, guidelines for regulatory expectations for clinical evaluation of vaccines, guidelines for the production and quality control of inactivated oral cholera vaccines and guidelines ...

Journal of chromatography. B, Biomedical sciences and applications, Jan 11, 1998

This paper describes the increasingly unique and powerful role that affinity chromatography is oc... more This paper describes the increasingly unique and powerful role that affinity chromatography is occupying both as a tool for the treatment of extracorporeal plasma exchange (to discard biological compounds with noxious metabolic or immunologic effects in patients) and as a purification tool in the production of therapeutic plasma protein derivatives. Management of both applications requires careful monitoring of the parameters applied to the plasma material, to avoid immunological stimulation or activation of the coagulation cascade. Examples of direct current applications of affinity ligands in therapeutic removal and industrial production of plasma compounds are presented.

Journal of immunological methods, Jan 28, 1996

Inter-alpha-trypsin inhibitor (ITI) is a serine-proteinase inhibitor of human plasma enzymes. ITI... more Inter-alpha-trypsin inhibitor (ITI) is a serine-proteinase inhibitor of human plasma enzymes. ITI is composed of three polypeptide chains covalently linked: bikunin, responsible for the antiprotease activity and two heavy chains H1 and H2. Human plasma also contains other components immunologically related to ITI such as pre-alpha-trypsin inhibitor (paI), inter-alpha-like inhibitor (IalphaLI) and free bikunin. The ELISA procedure we propose exclusively measures native ITI within the range 12.5-200 microgram/l. The intra- and interassay coefficients of variation were less than 5.6% and 8.7%, respectively. When ITI was added to plasma samples, full recovery was obtained. EDTA-plasma from 30 healthy individuals revealed a mean level of 241.5 mg/l (range 145.5-506). The high specificity, sensitivity, reproducibility and accuracy of the present assay should facilitate the specific measurement of native ITI in blood and thus might represent a useful tool for further physiopathological stu...

Journal of chromatography. B, Biomedical applications, Jan 3, 1995

Industrial-scale chromatographic fractionation and purification methods have been used increasing... more Industrial-scale chromatographic fractionation and purification methods have been used increasingly in the last few years for plasma fractionation. This has resulted in the development of a new generation of therapeutic plasma derivatives, especially coagulation factors, protease inhibitors and anticoagulants. Implementation and combination of ion-exchange, affinity and size-exclusion chromatography have allowed the development of new therapeutic products with improved purity and safety for treating congenital or acquired plasma protein deficiencies in patients. More recently, the benefit of chromatographic purification of plasma proteins in the removal of plasma-borne viruses has been revealed. Development of packing materials with improved characteristics for industrial applications, including higher capacity and rigidity, should further promote the use of chromatography as an essential plasma fractionation tool and confine more and more the traditional ethanol precipitation metho...

Revue Française de Transfusion et d'Hémobiologie, 1993

ABSTRACT

International Journal of Pharmaceutics, 1999

As foam appears during solution constitution and nebulisation of a 1 protease inhibitor (a 1 PI),... more As foam appears during solution constitution and nebulisation of a 1 protease inhibitor (a 1 PI), we selected in a previous work, antifoams likely to be associated with an a 1 PI solution to be nebulised: span 65 at a 0.025% concentration and cetyl alcohol at a 0.05% concentration associated with tyloxapol at 0.025% concentration. The purpose of this study was, on the one hand to study the influence of the formulation on nebulisation quality by relating physicochemical properties and nebulisation capacity, and on the other hand, to define the a 1 PI that will be retained for a clinical study. The properties of the different a 1 PI formulations are compared: surface tension, viscosity, time required to constitute the protein solution and pH. Nebulisation quality is evaluated under different operating conditions by measuring the droplet size, the quantity of a 1 PI nebulised, nebulisation time and the quantity of a 1 PI likely to reach the lungs which was subjected to statistical analysis. The statistical analysis of results indicates that the addition of the cetyl alcohol/tyloxapol mixture improves nebulisation effectiveness by significantly increasing the quantity of drug nebulised and therefore the quantity of a 1 PI likely to reach the lungs. It is this formulation that will be retained for clinical trials. We check that the nebuliser and operating conditions influence all the parameters, that is to say the respirable fraction, the quantity nebulised and the nebulisation time. Although there is no interaction between the nebuliser and the formulation, nebulisation quality is the combined result of the formulation, the nebuliser and the operating conditions.

International Journal of Pharmaceutics, 1997

ABSTRACT

Urologia Internationalis, 2000

The risk of transmission of bovine spongiform encephalopathy cannot be excluded from the use of b... more The risk of transmission of bovine spongiform encephalopathy cannot be excluded from the use of bovine-derived products. The present study was undertaken to evaluate the performance of a new fibrin glue free of bovine-derived components in vas anastomosis and to compare this product to conventional vas anastomosis with fibrin glue. Bilateral delayed vas anastomosis was performed in 40 Sprague-Dawley rats. All animals underwent a fibrin glue-assisted vas anastomosis with three transmural sutures tied prior to fibrin glue application. The composition and preparation of fibrin glue was similar for all vas anastomoses except the fibrinolysis inhibitor component which was aprotinin (3,000 KUI/ml) in group 1 and tranexamic acid (10 mg/ml) in group 2. The animals (20 rats in both groups) were sacrificed 7 weeks postoperatively and evaluated for gross patency, presence of sperm granuloma and tensile strength measurements at the anastomosis site. No difference was found between the 2 groups for all parameters evaluated whether a bovine-derived or a synthetic fibrinolysis inhibitor component was used. This study showed that tranexamic acid, a fibrinolysis inhibitor, can be substituted for conventional fibrin glue thereby avoiding the risks of bovine products.

Good Manufacturing Practice in Transfusion Medicine, 1994

Bulletin of the World Health Organization, 2014

Snakebite envenoming is a common but neglected public health problem, particularly in impoverishe... more Snakebite envenoming is a common but neglected public health problem, particularly in impoverished rural regions of sub-Saharan Africa, Asia and Latin America. The only validated treatment for this condition is passive immunotherapy with safe and effective animal-derived antivenoms. However, there is a long-lasting crisis in the availability of these life-saving medications, particularly in sub-Saharan Africa and parts of Asia. We herein advocate a multicomponent strategy to substantially improve the availability of safe and effective antivenoms at the global level. This strategy is based on: (i) preparing validated collections of representative venom pools from the most medically dangerous snakes in high-risk regions of the world; (ii) strengthening the capacity of national antivenom manufacturing and quality control laboratories and their regulatory authorities and establishing new facilities in developing countries through technology transfer, as an integral part of efforts to de...

BioMed research international, 2013

Polymorphism of human platelet antigens (HPAs) leads to alloimmunizations and immune-mediated pla... more Polymorphism of human platelet antigens (HPAs) leads to alloimmunizations and immune-mediated platelet disorders including fetal-neonatal alloimmune thrombocytopenia (FNAIT), posttransfusion purpura (PTP), and platelet transfusion refractoriness (PTR). HPA typing and knowledge of antigen frequency in a population are important in particular for the provision of HPA-matched blood components for patients with PTR. We have performed allele genotyping for HPA-1 through -6 and -15 among 998 platelet donors from 6 blood centers in Taiwan using sequence-specific primer polymerase chain reaction. The HPA allele frequency was 99.55, and 0.45% for HPA-1a and -1b; 96.49, and 3.51% for HPA-2a and -2b; 55.81, and 44.19% for HPA-3a and -3b; 99.75, and 0.25% for HPA-4a and -4b; 98.50, and 1.50% for HPA-5a and -5b; 97.75 and 2.25% for HPA-6a and -6b; 53.71 and 46.29% for HPA-15a and -15b. HPA-15b and HPA-3a, may be considered the most important, followed by HPA-2, -6, -1, -5, and -4 systems, as a c...

Vox Sanguinis, 1997

Fibrin sealant is a complex plasma-derived product which is increasingly used as a biodegradable ... more Fibrin sealant is a complex plasma-derived product which is increasingly used as a biodegradable tissue adhesive or sealant to stop or control bleeding or provide air and fluid tightness in many surgical situations. This review describes the historical development of current fibrin sealant preparations and the scientific rationale behind the alleged physiological benefits of its major plasma-derived components. A comparison in the extraction methods and viral reduction treatments applied to current commercial products and autologous preparations, and their respective advantages and limits, are discussed. Application devices used for surgical applications are described. A survey of the major clinical applications in various surgical areas is presented. Current issues in terms of viral safety, definition of optimal fibrin sealant composition, and regulatory concerns, especially to demonstrate clinical efficacy, are also included.

Vox Sanguinis, 2003

Major technical developments have been made in recent years to improve the quality and safety of ... more Major technical developments have been made in recent years to improve the quality and safety of human plasma for transfusion and fractionation. The present study was performed to assess, for the first time, the feasibility of applying a nanofiltration process, using 75-nm and 35-nm mean pore size membranes (Planova) 75N and Planova 35N), to human plasma. Ten apheresis plasma units were obtained from 10 plasma donors. Within 4 h of collection, plasma was subjected to leucoreduction and filtration (using 75-nm and 35-nm mean pore size membranes) at 35 degrees C, at less than 1 bar pressure. Aliquots of plasma were taken at all steps of the filtration procedure and numerous plasma quality parameters were measured. In addition, six hepatitis C virus (HCV)-positive plasma donations were experimentally subjected to the same filtration sequence and subsequently assessed by RNA polymerase chain reaction (PCR) and branched-chain DNA-quantification assays. Leucoreduced plasma can be reproducibly nanofiltered onto a sequence of 75-nm and 35-nm membranes, at a flow rate of 450 ml/h and a temperature of 35 +/- 0.5 degrees C. Some protein dilution, or loss, was found during filtration, but the plasma filtered through membranes with a mean pore size of 75 nm and 35 nm met in vitro specifications for use in transfusion or fractionation. There were no signs of activation of the coagulation system. HCV-positive plasma donations became negative, as judged by PCR and branched-chain DNA assay results, after filtration through the 35-nm membrane. It is possible to apply a 75 + 35-nm filtration process to leucoreduced human plasma. This technology may have important future benefits in improving the quality and safety of plasma, by removing blood cell debris and infectious agents.

Africa Sanguine

Interest in Africa on therapeutic use of COVID-19 convalescent plasma (CCP) has increased with co... more Interest in Africa on therapeutic use of COVID-19 convalescent plasma (CCP) has increased with continental spread of the pandemic of SARS -CoV-2. Consequently, blood organisations in several countries have established governmentally approved investigational protocols for collection and use of CCP. However, other countries still seek advice in this area. Sources of guidance can be found in recent publications by the Working Party on Global Blood Safety of the International Society of Blood Transfusion (ISBT), the ISBT Convalescent Plasma Working Group, and the World Health Organization. Additionally, resources on CCP policies and protocols can be found at an ISBT open-access website: http://isbtweb.org/coronaoutbreak/convalescent-plasma-covid-19-resources/.The effectiveness and safety of CCP remain uncertain based on limitations of the available controlled studies and reported case series and fundamental questions regarding optimal use in patient management are unanswered. Neverthele...

Journal of Thrombosis and Haemostasis, 2016

To cite this article: Burnouf T, Strengers PFW. Risks of inhibitors from recombinant factor VIII:... more To cite this article: Burnouf T, Strengers PFW. Risks of inhibitors from recombinant factor VIII: a quarter of a century to reach the conclusion. J Thromb Haemost 2016; 14: 2073-4.

Revue Francaise de Transfusion et Immuno-hématologie, 1981

ABSTRACT

Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis, 2014

The world is regularly exposed to emerging infections with the potential to burst into a pandemic... more The world is regularly exposed to emerging infections with the potential to burst into a pandemic. One possible way to treat patients, when no other treatment is yet developed,is passive immunization performed by transfusing blood, plasma or plasma immunoglobul infractions obtained from convalescent donors who have recovered from the disease and have developed protective antibodies. The most recent on-going epidemic is caused by the Ebola virus, a filovirus responsible for Ebola virus disease, a severe, often lethal, hemorrhagic fever. Recently, the use of convalescent blood products was proposed by the WHO as one early option for treating patients with Ebola virus disease. This publication provides an overview of the various convalescent blood products and technological options that could theoretically be considered when there is a need to rely on this therapeutic approach.In countries without access to advanced blood-processing technologies, the choice may initially be restricted ...

World Health Organization technical report series, 2004

This report presents the recommendations of a WHO Expert Committee commissioned to coordinate act... more This report presents the recommendations of a WHO Expert Committee commissioned to coordinate activities leading to the adoption of international requirements for the production and control of vaccines and other biologicals and the establishment of international biological reference materials. The report starts with a discussion of general issues brought to the Committee's attention and provides information on the status and development of reference materials for various antibodies, antigens, blood products and related substances, cytokines, growth factors, and endocrinological substances. The second part of the report, of particular relevance to manufacturers and national regulatory authorities, contains recommendations for the production and quality control of meningococcal group C conjugate vaccines, guidelines for regulatory expectations for clinical evaluation of vaccines, guidelines for the production and quality control of inactivated oral cholera vaccines and guidelines ...

Journal of chromatography. B, Biomedical sciences and applications, Jan 11, 1998

This paper describes the increasingly unique and powerful role that affinity chromatography is oc... more This paper describes the increasingly unique and powerful role that affinity chromatography is occupying both as a tool for the treatment of extracorporeal plasma exchange (to discard biological compounds with noxious metabolic or immunologic effects in patients) and as a purification tool in the production of therapeutic plasma protein derivatives. Management of both applications requires careful monitoring of the parameters applied to the plasma material, to avoid immunological stimulation or activation of the coagulation cascade. Examples of direct current applications of affinity ligands in therapeutic removal and industrial production of plasma compounds are presented.

Journal of immunological methods, Jan 28, 1996

Inter-alpha-trypsin inhibitor (ITI) is a serine-proteinase inhibitor of human plasma enzymes. ITI... more Inter-alpha-trypsin inhibitor (ITI) is a serine-proteinase inhibitor of human plasma enzymes. ITI is composed of three polypeptide chains covalently linked: bikunin, responsible for the antiprotease activity and two heavy chains H1 and H2. Human plasma also contains other components immunologically related to ITI such as pre-alpha-trypsin inhibitor (paI), inter-alpha-like inhibitor (IalphaLI) and free bikunin. The ELISA procedure we propose exclusively measures native ITI within the range 12.5-200 microgram/l. The intra- and interassay coefficients of variation were less than 5.6% and 8.7%, respectively. When ITI was added to plasma samples, full recovery was obtained. EDTA-plasma from 30 healthy individuals revealed a mean level of 241.5 mg/l (range 145.5-506). The high specificity, sensitivity, reproducibility and accuracy of the present assay should facilitate the specific measurement of native ITI in blood and thus might represent a useful tool for further physiopathological stu...

Journal of chromatography. B, Biomedical applications, Jan 3, 1995

Industrial-scale chromatographic fractionation and purification methods have been used increasing... more Industrial-scale chromatographic fractionation and purification methods have been used increasingly in the last few years for plasma fractionation. This has resulted in the development of a new generation of therapeutic plasma derivatives, especially coagulation factors, protease inhibitors and anticoagulants. Implementation and combination of ion-exchange, affinity and size-exclusion chromatography have allowed the development of new therapeutic products with improved purity and safety for treating congenital or acquired plasma protein deficiencies in patients. More recently, the benefit of chromatographic purification of plasma proteins in the removal of plasma-borne viruses has been revealed. Development of packing materials with improved characteristics for industrial applications, including higher capacity and rigidity, should further promote the use of chromatography as an essential plasma fractionation tool and confine more and more the traditional ethanol precipitation metho...

Revue Française de Transfusion et d'Hémobiologie, 1993

ABSTRACT

International Journal of Pharmaceutics, 1999

As foam appears during solution constitution and nebulisation of a 1 protease inhibitor (a 1 PI),... more As foam appears during solution constitution and nebulisation of a 1 protease inhibitor (a 1 PI), we selected in a previous work, antifoams likely to be associated with an a 1 PI solution to be nebulised: span 65 at a 0.025% concentration and cetyl alcohol at a 0.05% concentration associated with tyloxapol at 0.025% concentration. The purpose of this study was, on the one hand to study the influence of the formulation on nebulisation quality by relating physicochemical properties and nebulisation capacity, and on the other hand, to define the a 1 PI that will be retained for a clinical study. The properties of the different a 1 PI formulations are compared: surface tension, viscosity, time required to constitute the protein solution and pH. Nebulisation quality is evaluated under different operating conditions by measuring the droplet size, the quantity of a 1 PI nebulised, nebulisation time and the quantity of a 1 PI likely to reach the lungs which was subjected to statistical analysis. The statistical analysis of results indicates that the addition of the cetyl alcohol/tyloxapol mixture improves nebulisation effectiveness by significantly increasing the quantity of drug nebulised and therefore the quantity of a 1 PI likely to reach the lungs. It is this formulation that will be retained for clinical trials. We check that the nebuliser and operating conditions influence all the parameters, that is to say the respirable fraction, the quantity nebulised and the nebulisation time. Although there is no interaction between the nebuliser and the formulation, nebulisation quality is the combined result of the formulation, the nebuliser and the operating conditions.

International Journal of Pharmaceutics, 1997

ABSTRACT

Urologia Internationalis, 2000

The risk of transmission of bovine spongiform encephalopathy cannot be excluded from the use of b... more The risk of transmission of bovine spongiform encephalopathy cannot be excluded from the use of bovine-derived products. The present study was undertaken to evaluate the performance of a new fibrin glue free of bovine-derived components in vas anastomosis and to compare this product to conventional vas anastomosis with fibrin glue. Bilateral delayed vas anastomosis was performed in 40 Sprague-Dawley rats. All animals underwent a fibrin glue-assisted vas anastomosis with three transmural sutures tied prior to fibrin glue application. The composition and preparation of fibrin glue was similar for all vas anastomoses except the fibrinolysis inhibitor component which was aprotinin (3,000 KUI/ml) in group 1 and tranexamic acid (10 mg/ml) in group 2. The animals (20 rats in both groups) were sacrificed 7 weeks postoperatively and evaluated for gross patency, presence of sperm granuloma and tensile strength measurements at the anastomosis site. No difference was found between the 2 groups for all parameters evaluated whether a bovine-derived or a synthetic fibrinolysis inhibitor component was used. This study showed that tranexamic acid, a fibrinolysis inhibitor, can be substituted for conventional fibrin glue thereby avoiding the risks of bovine products.

Good Manufacturing Practice in Transfusion Medicine, 1994

Bulletin of the World Health Organization, 2014

Snakebite envenoming is a common but neglected public health problem, particularly in impoverishe... more Snakebite envenoming is a common but neglected public health problem, particularly in impoverished rural regions of sub-Saharan Africa, Asia and Latin America. The only validated treatment for this condition is passive immunotherapy with safe and effective animal-derived antivenoms. However, there is a long-lasting crisis in the availability of these life-saving medications, particularly in sub-Saharan Africa and parts of Asia. We herein advocate a multicomponent strategy to substantially improve the availability of safe and effective antivenoms at the global level. This strategy is based on: (i) preparing validated collections of representative venom pools from the most medically dangerous snakes in high-risk regions of the world; (ii) strengthening the capacity of national antivenom manufacturing and quality control laboratories and their regulatory authorities and establishing new facilities in developing countries through technology transfer, as an integral part of efforts to de...

BioMed research international, 2013

Polymorphism of human platelet antigens (HPAs) leads to alloimmunizations and immune-mediated pla... more Polymorphism of human platelet antigens (HPAs) leads to alloimmunizations and immune-mediated platelet disorders including fetal-neonatal alloimmune thrombocytopenia (FNAIT), posttransfusion purpura (PTP), and platelet transfusion refractoriness (PTR). HPA typing and knowledge of antigen frequency in a population are important in particular for the provision of HPA-matched blood components for patients with PTR. We have performed allele genotyping for HPA-1 through -6 and -15 among 998 platelet donors from 6 blood centers in Taiwan using sequence-specific primer polymerase chain reaction. The HPA allele frequency was 99.55, and 0.45% for HPA-1a and -1b; 96.49, and 3.51% for HPA-2a and -2b; 55.81, and 44.19% for HPA-3a and -3b; 99.75, and 0.25% for HPA-4a and -4b; 98.50, and 1.50% for HPA-5a and -5b; 97.75 and 2.25% for HPA-6a and -6b; 53.71 and 46.29% for HPA-15a and -15b. HPA-15b and HPA-3a, may be considered the most important, followed by HPA-2, -6, -1, -5, and -4 systems, as a c...

Vox Sanguinis, 1997

Fibrin sealant is a complex plasma-derived product which is increasingly used as a biodegradable ... more Fibrin sealant is a complex plasma-derived product which is increasingly used as a biodegradable tissue adhesive or sealant to stop or control bleeding or provide air and fluid tightness in many surgical situations. This review describes the historical development of current fibrin sealant preparations and the scientific rationale behind the alleged physiological benefits of its major plasma-derived components. A comparison in the extraction methods and viral reduction treatments applied to current commercial products and autologous preparations, and their respective advantages and limits, are discussed. Application devices used for surgical applications are described. A survey of the major clinical applications in various surgical areas is presented. Current issues in terms of viral safety, definition of optimal fibrin sealant composition, and regulatory concerns, especially to demonstrate clinical efficacy, are also included.

Vox Sanguinis, 2003

Major technical developments have been made in recent years to improve the quality and safety of ... more Major technical developments have been made in recent years to improve the quality and safety of human plasma for transfusion and fractionation. The present study was performed to assess, for the first time, the feasibility of applying a nanofiltration process, using 75-nm and 35-nm mean pore size membranes (Planova) 75N and Planova 35N), to human plasma. Ten apheresis plasma units were obtained from 10 plasma donors. Within 4 h of collection, plasma was subjected to leucoreduction and filtration (using 75-nm and 35-nm mean pore size membranes) at 35 degrees C, at less than 1 bar pressure. Aliquots of plasma were taken at all steps of the filtration procedure and numerous plasma quality parameters were measured. In addition, six hepatitis C virus (HCV)-positive plasma donations were experimentally subjected to the same filtration sequence and subsequently assessed by RNA polymerase chain reaction (PCR) and branched-chain DNA-quantification assays. Leucoreduced plasma can be reproducibly nanofiltered onto a sequence of 75-nm and 35-nm membranes, at a flow rate of 450 ml/h and a temperature of 35 +/- 0.5 degrees C. Some protein dilution, or loss, was found during filtration, but the plasma filtered through membranes with a mean pore size of 75 nm and 35 nm met in vitro specifications for use in transfusion or fractionation. There were no signs of activation of the coagulation system. HCV-positive plasma donations became negative, as judged by PCR and branched-chain DNA assay results, after filtration through the 35-nm membrane. It is possible to apply a 75 + 35-nm filtration process to leucoreduced human plasma. This technology may have important future benefits in improving the quality and safety of plasma, by removing blood cell debris and infectious agents.