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Prof. Jean-Pierre ALLAINChairperson

EDUCATION1967 MD University of Paris Medical School; Thesis: Platelet Factor 31986 PhD in Biochemistry; University of Paris1994 MSc in Clinical Psychology, University of Paris 5

POSTS HELD1967 Assistant Professor of Haematology, Hôpital St Louis, Paris1967 - 71 Assistant Professor of Haematology, Hôpital Bicêtre, University of Paris South 1971 - 77 Director, French Red Cross Haemophilia Centre,

La Queue Les Yvelines, France 1977 - 81 Senior Research Scientist (Haemostasis),

National Blood Transfusion Centre, Paris1981 - 86 Head of Dept of R & D for plasma derivatives, N B T Centre, Paris1986 - 89 Medical Research Laboratory Manager (Hepatitis & AIDS Diagnostics

Products), Abbott Laboratories, N. Chicago, IL, USA 1989 - 91 Medical Director, Diagnostic Division, Abbott Laboratories,

N. Chicago, IL, USA1991 - 92 Director of the RHA Cambridge Blood Centre, Cambridge, UK1991 - 2012 Professor of Transfusion Medicine, Dept of Haematology,

University of Cambridge,UK2012 Emeritus Professor of Transfusion Medicine, Dept of Haematology,

University of Cambridge, UK

FELLOWSHIPS- Department of Pathology, University of North Carolina, School of Medicine,

Chapel Hill, NC, USA 1973-74- Royal College of Pathologists, London, UK (FRCPath, 1991)- The Academy of Medical Sciences, London, UK (FMedSci, 2000).

WORK EXPERIENCE1970 - 77 French Red Cross Haemophilia Centre. Director with both Medical

and Administrative responsibilities. 1977 - 86 National Blood Transfusion Centre, Paris 1977 - 81 Head of the Blood Coagulation Research Laboratory (1977 – 1981)1981 - 86 Head of the Department of Research & Development for plasma derivatives1986 - 91 Abbott Laboratories, N. Chicago, IL, USA 1986 - 89 Manager of Medical Research Director of Medical Affairs

for 1989-1991 Hepatitis and Retroviruses from 1989 to 1991.1991 - 2009 Division of Transfusion Medicine, Department of Haematology,

University of Cambridge 2009 present Emeritus Professor of Transfusion Medicine,

University of Cambridge, Cambridge, UK

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Recent publications out of 352Stramer S, Wend U, Candotti D, Forster G, Hollinger B, Dodd R, Allain JP, Gerlich W. Occurrence and characterization of naturally acquired hepatitis B infection among vaccinated blood donors. N Engl J Med 2011: 364:236-47.Candotti D, Lin CK, Belkhiri D, Sakuldamrongpanich T, Biswas S, Lin S, Teo D, Ayob Y, Allain JP. Occult hepatitis B infection in blood donors from South East Asia: molecular characterisation and potential mechanisms of occurrence. Gut 2012; 61: 1744-53.Ala F, Allain JP, Bates I, et al. External financial aid to blood transfusion services in sub-Saharan Africa: a need for reflection. PLoS Med. 2012; 9: e1001309.Paraskevis D, Magiorkinis G, Magiorkinis E, Ho SY, Belshaw R, Allain JP, Hatzakis A. Dating the origin and dispersal of hepatitis B virus infection in humans and primates. Hepatology 2013; 57: 908-16. Biswas S, Candotti D, Allain JP. Specific amino acid substitutions in the S protein prevent its excretion in vitro and may contribute to occult hepatitis B virus infection. J Virol 2013; 87: 7882-92.Allain JP, Mihaljevic I, Gonzalez-Fraile MI, Gubbe K, Holm-Harritshøj L, Garcia JM, Brojer E, Erikstrup C, Saniewski M, Wernish L, Bianco L, Ullum H, Candotti D, Lelie N, Gerlich WH, Chudy M. Infectivity of blood products from donors with occult hepatitis B virus infection. Transfusion 2013; 53: 1405-1415.Li T, Zhu S, Shuai L, Xu Y, Yin S, Bian Y, Wang Y, Zuo B, Wang W, Zhao S, Zhang L, Zhang J, Gao GF, Allain JP, Li C.Infection of common marmosets with hepatitis C virus/GB virus-B chimeras. Hepatology 2014;59:789-802.

References for malariaand pathogen inactivationAllain JP, Hsu J, Pranmeth M, Hanson D, Stassinopoulos A, Fischetti L, Corash L, Lin L. Quantification of viral inactivation by photochemical treatment with amotosalen and UV A light, using a novel polymerase chain reaction inhibition method with preamplification. J Infect Dis. 2006;194:1737-44.

Allain JP. Malaria and transfusion: a neglected subject coming back to the forefront. Clin Infect Dis 2010;51:1199-200.

Freimanis G, Sedegah M, Owusu-Ofori S, Kumar S, Allain JP. Investigating the prevalence of transfusion transmission of Plasmodium within a hyperendemic blood donation system. Transfusion 2013; 53: 1429-41.

Freimanis GL, Owusu-Ofori S, Allain JP. Hepatitis B virus infection does not signi-ficantly influence Plasmodium parasite density in asymptomatic infections in Ghanaian transfusion recipients. PLoS One. 2012;7.

El Chaar M, Atwal S, Freimanis GL, Dinko B, Sutherland CJ, Allain JP. Inactivation of Plasmodium falciparum in whole blood by riboflavin plus irradiation. Transfu-sion 2013 53: 3174-83.

Owusu-Ofori S, Kusi J, Owusu-Ofori A et al. Treatment of whole blood (WB) with riboflavin and UV light: impact on malaria parasite and WB storage. SHOCK 2014; in press.

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Prof. Olivier GARRAUD Chairperson

HIGHER EDUCATION1981 MSc in Human Biology – University of Paris 6 1981 MD – Faculty of Medicine of Limoges, FR – thesis defended with honors 1984 MSc in Human and Social Sciences (Ethnology) – Universities of Nouméa

and Bordeaux, FR1993 PhD (Immunology) – University of Paris 6 – thesis defended with honors 2002 University diploma in Transfusion Medicine (DUTS) – University of Paris 6

POSITIONS HELD (SENIOR POSITIONS)1987 - 99 Institut Pasteur (Paris – Cayenne – Dakar – Paris) 1999 - 2003 Associate and then, tenured Professor of Medicine (Immunology),

University Hospitals of Saint-Etienne, FR (University of Lyon/Saint-Etienne) – 2003… til’ present

2002 - 2003 Deputy Director of the EFS Auvergne-Loire, Saint-Etienne 2003 - 2014 General (Regional) Director of the EFS Auvergne-Loire, Saint-Etienne2010 - present Representative of the French Blood Establishment and Transfusion Systems

to the European Directorate for Quality of Medicine/European Pharmacopeia (Council of Europe)

2014 - present Senior Consultant, International Affairs, the Institut National de la Transfusion Sanguine (INTS), Paris

TEACHING ACTIVITIESChair of Fundamental Immunology, Faculty of Medicine of Saint-Etienne, University of Lyon/Saint-EtienneInvited Professor by French and Foreign Universities: Paris 5-6-7-12; Lyon I; Monastir (Tunisia)…Lecturer in many French and Foreign Universities Leader of a work-package of a Lifelong Education Program/Erasmus Mundus (European Universities): DoHeCa (Donor Health Care) – a specialized European Master, launched in 2014Author/coauthor of > 20 (education) book chapters in the field of immunology, hematology and transfusion

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Editorial activitiesReviewer of National and International Grants (ANR, European Programs, Sanquin, EFS, ABM…)Reviewer for numerous international, peer-reviewed, journals (such as Blood, Transfusion, Vox Sanguinis, British Journal of Haematology, Experimental Hematology, Journal of Thrombosis and Haemostasis, Thrombosis and Hemostasis, Thrombosis Research, PlosOne, J of Immunology, Cellular Immunology, Immunobiology, Scandinavian of Immunology, etc.)Section Editor, BMC ImmunologyEditor of a Book in Tropical Immunology (2005)Guest of Journal Series in Immunology (BMC Immunology, 2014; Frontiers in Immunology, 2014) and Transfusion (Presse Médicale, 2014; Quaterly Medical Journal: 2016)Author and co-author of near 215 peer-reviewed papers:http://www.ncbi.nlm.nih.gov/pubmed?term=garraud%20o

Dr. Hafiz R QURESHI Speaker

EDUCATION1997 – 99 Royal College of Pathologists, London - FRCPath.1986 Ayub Medical College MB;BS., Medicine1997 University of Peshawar, Pakistan. Royal College of Physicians of Ireland MRCPI

POSITIONS HELD (SENIOR POSITIONS)February 2005 - present Head of Service, Department of Transfusion Medicine

University Hospitals of Leicester NHS Trust - Leicester, UKJanuary 2001 - present Consultant Haematologist (Haematology and Transfusion Medicine)

University Hospitals of Leicester - Leicester UK

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A prospective non-interventional study to evaluate the safety of Methylene Blue Plasma

Qureshi H,1 Noens N,2 Megalou A,3 Villamayor M,4

1University Hospitals of Leicester NHS Trust, United Kingdom, 2Universitair Ziekenhuis Gent, Belgium, 3Evaggelismos General Hospital of Athens, Greece, 4Complejo Universitario de Santiago de Compostela, Spain

Background and objectivesMethylene blue (MB) is a phenothiazine dye, which in combination with visible light has virucidal properties by interacting with nucleic acids and disrupting the replication of a broad range of enveloped viruses and some non-enveloped viruses. The objective of this non-interventional study was to gather data on adverse reactions occurring with MB plasma administered in a routine clinical practice environment; to know more about their characteristics and behaviour and the possible factors that may influence their presentation and evolution.

Materials and MethodsThis was an open label, multi-centre, non-controlled, non-randomized, non-interventional study to evaluate the safety of MB plasma. Patients who receive a MB plasma transfusion were observed for any signs and symptoms (adverse reactions) within 24 hours after the start of the transfusion, in different hospitals from 4 countries: Belgium, Greece, Spain and United Kingdom for, at least, one year.Inclusion criteria: a) Written informed consent; b) Patients, who have received a transfusion with MB plasma produced using the THERAFLEX MB-Plasma procedure from MacoPharma and experience an adverse reaction.Exclusion criteria: Patients receiving transfusion with other plasma types during the same transfusion episode.

Results9,315 MB-Plasma units were delivered. There were 8 patients with reactions recorded during the study, one of them serious. Two had more than one reaction (2 and 4, respectively). Three patients had previous transfusions with MB plasma. None of them had previous transfusions with other plasma types. For none of them any previous reactions were known. One of them had reported history of latex allergy..

ConclusionMB-Plasma has an excellent safety profile with a rate of Serious Adverse Reactions of 0.5/10,000 units, without any contamination reported.

EDUCATION2010 Master of Health Business Administration (MHBA)

Friedrich-Alexander University Erlangen-Nuremberg, Germany2002 Specialist in Transfusion Medicine 1996 Doctor of Medicine

Friedrich-Alexander University Erlangen-Nuremberg, Germany

EMPLOYMENT HISTORY2008 - present Head of production and head of R&D

German Red Cross Blood Service NSTOB, Springe2003 - 2008 Associate Professor for Molecular Immunohaematology

Institute of Transfusion Medicine, Hannover Medical School, Germany2001 - 2003 Resident physician and scientific assistant

Institute of Transfusion Medicine, Hannover Medical School, Germany1998 - 2001 Scientific assistant

Institute of Transfusion Medicine, University Hospital Charité Berlin, Germany1996 - 1998 Junior physician

Medical Clinic I of the Clinical Centre Fürth, teaching hospital of the Friedrich-Alexander University Erlangen-Nuremberg

ACADEMIC APPOINTMENTS2008 - present Associate Professor for Transfusion Medicine

Hannover Medical School, Germany

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Prof. Axel SELTSAM Speaker

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PEER-REVIEWED PUBLICATIONS (10 most relevant to blood safety)1. Thiele T, Pohler P, Kohlmann T, Sumnig A, Aurich K, Selleng K, Westphal A,

Bakchoul T, Petersmann A, Muller TH, Greinacher A, Seltsam A. Tolerance of platelet concentrates treated with UVC-light only for pathogen reduction - a phase I clinical trial. Vox Sang 2015. [Epub ahead of print]

2. Reichenberg S, Gravemann U, Sumian C, Seltsam A. Challenge study of the pathogen reduction capacity of the THERAFLEX MB-Plasma technology. Vox Sang 2015. [Epub ahead of print]

3 Pohler P, Müller M, Winkler C, Schaudien D, Sewald K, Müller TH, Seltsam A. Pathogen reduction by ultraviolet C light effectively inactivates human white blood cells in platelet products. Transfusion 2015;55:337-47.

4. Seltsam A, Muller TH. Update on the use of pathogen-reduced human plasma and platelet concentrates. Br J Haematol 2013;162: 442-54.

5. Seltsam A, Mueller TH. Updated hemovigilance data do not show an increased risk of allergic reactions to methylene blue-treated plasma. J Allergy Clin Immunol 2013;131: 1253-4.

6. Bashir S, Cookson P, Wiltshire M, Hawkins L, Sonoda L, Thomas S, Seltsam A, Tolksdorf F, Williamson LM, Cardigan R. Pathogen inactivation of platelets using ultraviolet C light: effect on in vitro function and recovery and survival of platelets. Transfusion 2013;53:990-1000.

7. Steinmann E, Gravemann U, Friesland M, Doerrbecker J, Muller TH, Pietschmann T, Seltsam A. Two pathogen reduction technologies-methylene blue plus light and shortwave ultraviolet light-effectively inactivate hepatitis C virus in blood products. Transfusion 2013;53:1010-8.

8. Pohler P, Lehmann J, Veneruso V, Tomm J, von Bergen M, Lambrecht B, Kohn B, Weingart C, Muller TH, Seltsam A. Evaluation of the tolerability and immunogenicity of ultraviolet C-irradiated autologous platelets in a dog model. Transfusion 2012;52: 2414-26.

9. Muller TH, Montag T, Seltsam AW. Laboratory Evaluation of the Effectiveness of Pathogen Reduction Procedures for Bacteria. Transfus Med Hemother 2011;38: 242-50.

10. Seltsam A, Müller TH. UVC Irradiation for Pathogen Reduction of Platelet Concentrates and Plasma. Transfusion Medicine and Hemotherapy 2011;38: 43-54.

Challenge studies of the pathogen inactivation capacity of THERAFLEX MB-Plasma

Although most pathogen reduction systems for plasma primarily target viruses, bacterial contamination may also occur. Moreover, light penetration is crucial for efficient pathogen reduction using the THERAFLEX MB-Plasma system. This study aimed to investigate the bacterial reduction capacity of this process and its virus inactivation capacity in lipaemic plasma.THERAFLEX MB-Plasma efficiently reduced a variety of transfusion-relevant bacteria including Escherichia coli, Bacillus cereus and Klebsiella pneumoniae, mainly via the integrated filtration system.Suid herpesvirus 1, bovine viral diarrhoea virus and human immunodeficiency virus 1 were efficiently inactivated by MB/light treatment, independent of the degree of lipaemia. Thus, the virus inactivation capacity of the THERAFLEX MB-Plasma system is sufficient to compensate for reduced light transparency due to lipaemia.

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EDUCATION1995 Doctor of Philosophy,

University of Technology, Sydney, Australia; Bachelor of Applied Science (Honours Class 1)

1991 University Medal for Science; University of Technology, Sydney, Australia

EMPLOYMENT HISTORYAugust 2008 - present National R&D Leader – Product Development and Storage

The Australian Red Cross Blood ServiceJanuary 2015 - present Associate Editor, ISBT Science Series2003 - 2005 Head of Cell Biology and Project Leader: Preclinical Studies

Apollo Life Sciences, Sydney, Australia 2001 - 2003 Senior Postdoctoral Research Fellow

Molecular Haematology and Cancer Biology Institute of Child Health, London, England

1999 - 2001 Risk Analyst and Procurement Analyst Global Markets Dresdner Kleinwort Wasserstein, London, England

1996 - 1999 Senior Postdoctoral Fellow Department of Medicine, University of Melbourne, Australia

1994 - 1996 Liese Meitner Research Fellow Department of Molecular Genetics Vienna University Biocenter, Vienna, Austria

ACADEMIC APPOINTMENTS2008 - present Senior Lecturer, Sydney Medical School, The University of Sydney

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Dr. Denese C MARKS Speaker

PEER-REVIEWED PUBLICATIONS (10 most relevant to blood safety)1. Loh YS, Dean MM, Johnson L, Marks DC. Treatment of platelets with riboflavin

and ultraviolet light mediates complement activation and suppresses monocyte interleukin-12 production in whole blood. Accepted in Vox Sanguinis 2015. DOI: 10.1111/vox.12283

2. Johnson L and Marks DC. Treatment of platelet concentrates with the Mirasol pathogen inactivation system modulates platelet oxidative stress and NF-KB activation. Accepted in Transfusion Medicine and Hemotherapy 2015 Published online May 7

3. Faddy HM, Prow NA, Fryk JJ, Hall RA, Keil SD, Goodrich RP, Marks DC. The effect of riboflavin and ultraviolet light on the infectivity of arboviruses. Accepted in Transfusion 2014; DOI: 10.1111/trf.12899

4. Marks DC, Faddy H, Johnson L. Pathogen Reduction Technologies. Invited review, ISBT Science Series 2014; 9: 44-50

5. Winter KM, Johnson L, Kwok M, Vidovic D, Hyland RA, Mufti N, Erickson E, Marks DC. Red cell in vitro quality and function is maintained following S-303 pathogen inactivation. Transfusion 2014; 54: 1798-1807

6. Loh YS, Johnson L, Kwok M, Marks DC. Pathogen reduction treatment alters the immunomodulatory capacity of buffy-coat derived platelet concentrates. Transfusion 2014; 54: 577-584

7. Marks DC, Faddy H, Johnson L. Pathogen Reduction Technologies. Invited review, ISBT Science Series 2014; 9: 44-50

8. Johnson L, Loh YS, Kwok M, Marks DC. In vitro assessment of buffy-coat derived platelet components suspended in SSP+ treated with the INTERCEPT Blood System. Transfusion Medicine 2013; 23:121-129

9. Reid S, Johnson L, Woodland N and Marks DC. Pathogen reduction treatment of buffy coat platelet concentrates in additive solution induces proapoptotic signalling. Transfusion 2012; 52: 2094-2103

10. Johnson L, Winter K, Reid S, Hartkopf-Theis T, Marschner S, Goodrich R, Marks D. The effect of pathogen reduction technology (Mirasol) on platelet quality when treated in additive solution with low plasma carryover Vox Sanguinis 2011; 101: 208-214

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The effect of THERAFLEX MB-Plasma on the infectivity of arboviruses

The dengue viruses (DENV 1-4) are emerging or re-emerging pathogens, with outbreaks increasing in size and frequency in many regions, including Australia. These viruses pose a risk for transfusion safety. One approach to manage the risk of transfusion-transmissible DENV could be the use of pathogen inactivation technologies (PI), such as the THERAFLEX MB-Plasma system. In this study, DENV 1-4 was spiked into DENV-antibody negative pooled plasma, which was treated with the THERAFLEX MB-Plasma system at increasing doses of visible light (20, 40, 60, and 120 J/cm2). The level of DENV infectivity was determined using a modified version of a conventional plaque assay and the reduction in viral infectivity was calculated for each dose. Viral inactivation of up to 3.97 log10 or more at the highest light doses (60 and 120 J/cm2) was observed. The highest amount of inactivation was seen for DENV-3 (up to >5.78 log10). As expected, a dose-dependency in viral inactivation was observed with increasing light doses.

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MECHANISM OF ACTIONMethylene blue is a phenothiazine-based photosensitizer with particular affinityfor guanosine-cytosine pairs.

Methylene Blue molecule

FOCUS ON METHYLENE BLUE

• Methylene Blue has a monograph in the European Pharmacopeia (8th edition, 2013) and the US

Pharmacopeia (USP 38-NF 33, 2015) • Methylene Blue is in clinical use

for organ staining, as disinfectant drug and for reversal of methemoglobinemia

in very high concentrations (1.000 to 10.000 times higher than used in the

THERAFLEX MB-Plasma)

It intercalates into viral nucleic acid and subsequent illumination generates singlet oxygen leading to guanosine oxidation and destruction of the viral nucleic acid preventing viral replication.3,4

Destruction of the viral nucleic acid

Intercalation of Methylene Blue into nucleic acid

Methylene Blue pill MacoPharma (85µg / unit of plasma)

Visible light Formation of singlet oxygen1 2 3

4

Since 1992, over 6.5 million units of MB-FFP have been transfused in various clinical settings. Currently there is clinical experience with MB-treated plasma produced with the THERAFLEX MB-Plasma system26 for more than 15 years in more than 19 countries.

CLINICAL EXPERIENCE AND WORLDWIDE PRESENCE

Clinical experience of THERAFLEX MB-Plasma: Routine use in Europe, South America and Asia Pacific.

Countries:GermanySpainGreeceItalyUnited Kingdom Belgium

Malaysia ArgentinaRussiaBelarusAustriaBrazil

SingaporeArmenia Kazakhstan Turkmenistan Hong KongSaudi Arabia

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MACOPHARMARue LorthioisF-59420 Mouvaux (France)www.bloodsafety.macopharma.com

Lead the wayin blood safety

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