Blood Safety Is Pleased to Invite You to Its SYMPOSIUM

Macopharma Lead the way in blood safety is pleased to invite you to its SYMPOSIUM

BLOOD SAFETY Tuesday, June 5th 2018

www.bloodsafety.macopharma.com

ISBT Toronto 2018 BLOOD SAFETY

ISBT Toronto 2018 Tuesday, June 5th 2018 12.00 - 1.30 PM Room 718 B

Chairperson Prof. Dana Devine CBS, Vancouver

Presentations « THERAFLEX UV-Platelets: Mechanism of action, specifications and sterility studies » Prof. Axel Seltsam (DRK, Springe)

« The phase III CAPTURE Trial: routine use in the blood bank of Frankfurt » Dr. Veronika Brixner (DRK, Frankfurt)

« Review on the inactivation of arboviruses with THERAFLEX» Prof. Denese Marks (ARCBS, Sydney)

2 BLOOD SAFETY SYMPOSIUM BLOOD SAFETY SYMPOSIUM 3 PROF. DANA DEVINE Chairperson

Selected publications: Chief Scientist, Canadian Blood Services Devine DV. Pathogen Inactivation strategies to improve blood safety: let’s not throw pathogen-reduced platelets out with their bath water. JAMA Oncol, 2018; 1. DOI: 10.1001/jamaoncol.2017.4949 Professor of Pathology & Laboratory Medicine, Goldman M, W-Y Shih A, O’Brien SF, Devine D. Donor deferral policies for men who have sex with men: past, present and University of British Columbia, Vancouver, Canada future. Vox Sang 2018; 113(2):95-103.

Germain M, Delage G, O’Brien SF, Grégoire Y, Fearon M, Devine D. Mitigation of the threat posed to transfusion by donors traveling to Zika-affected areas: a Canadian risk-based approach. Transfusion 2017; 57(10):2463-2468.

EMPLOYMENT HISTORY Devine DV. Implementation of pathogen inactivation technology: how to make the best decisions? Transfusion 2017; 57(5):1109-1111. 2018 - present: Chief Scientist Klein-Bosgoed C, Schubert P, Devine DV. Riboflavin and ultraviolet illumination affects selected platelet mRNA transcript Canadian Blood Services amounts differently. Transfusion 2016; 56(9):2286-95.

2000 - present: Professor of Pathology & Laboratory Medicine Schubert P, Culibrk B, Karwal S, Serrano K, Levin E, Bu D, Bhakta V, Sheffield WP, Goodrich RP, Devine DV. Whole blood University of British Columbia, Vancouver, Canada treated with riboflavin and ultraviolet light: quality assessment of all blood components produced by the buffy coat method. Transfusion 2015; 55(4):815-23. 2006 – 2017: Chief Medical & Scientific Officer Canadian Blood Services Schubert P, Coupland D, Culibrk B, Goodrich RP, Devine DV. Riboflavin and ultraviolet light treatment of platelets triggers p38MAPK signaling: inhibition significantly improves in vitro platelet quality after pathogen reduction treatment.

Transfusion 2013; 53(12):3164-73. 1995 - 2000: Associate Professor of Pathology & Laboratory Medicine University of British Columbia, Vancouver, Canada Semple E, Bowes-Schmidt A, Yi QL, Shimla S, Devine DV. Transfusion reactions: a comparative observational study of blood

CURRICULUM VITAE CURRICULUM components produced before and after implementation of semiautomated production from whole blood. Transfusion 1999 – 2006: Director, Research & Development 2012; 52(12):2683-91. Canadian Blood Services Stein J, Besley J, Brook C, Hamill M, Klein E, Krewski D, Murphy G, Richardson M, Sirna J, Skinner M, Steiner R, van Aken P, Devine D. Risk-based decision-making for blood safety: preliminary report of a consensus conference. Vox Sang 2011;

101(4):277-81. EDUCATION Kleinman S, Cameron C, Custer B, Busch M, Katz L, Kralj B, Matheson I, Murphy K, Preiksaitis J, Devine D. Modeling the risk 1987 : PhD (Immunology) of an emerging pathogen entering the Canadian blood supply. Transfusion 2010; 50(12):2592-606. Duke University, Durham, North Carolina, USA

4 BLOOD SAFETY SYMPOSIUM BLOOD SAFETY SYMPOSIUM 5 PROF. AXEL SELTSAM Prof. Axel Seltsam « THERAFLEX UV-Platelets: Mechanism of action, specifications Speaker and sterility studies »

« THERAFLEX UV-Platelets: Mechanism of action, specifications and sterility studies » THERAFLEX UV-PLATELETS: AN UPDATE ON THE CLINICAL DEVELOPMENT Associate Professor for Transfusion Medicine, Hanover Medical School, Germany In line with current microbial risk reduction efforts, pathogen inactivation (PI) technologies for Head of production and head of R&D, blood components promise to reduce the residual risk of known and emerging infectious German Red Cross Blood Service NSTOB, Springe agents. THERAFLEX UV-Platelets is a novel UVC-based PI technology for treatment of platelet concentrates (PCs) that works without photoactive substances. It is the product of a joint venture between Macopharma and the German Red Cross Blood Service NSTOB in EMPLOYMENT HISTORY Springe, Germany. Shortwave UVC light (254 nm) directly interacts with nucleic acids to form pyrimidine dimers that block the elongation of nucleic acid. UVC irradiation mainly 2008 - present: Head of production and head of R&D affects the nucleic acids of pathogens and leukocytes and does not impair plasma and German Red Cross Blood Service NSTOB, Springe platelet quality. The THERAFLEX UV-Platelets system effectively inactivates a broad range of 2003 - 2008: Associate Professor for Molecular Immunohaematology different disease-causing viruses, bacteria and protozoa. As no photoactive substances are Institute of Transfusion Medicine, Hannover Medical School, Germany involved, UVC treatment is just as simple but faster (takes less than 1 minute) than gamma irradiation, and can easily be integrated into the manufacturing processes at blood banks. 2001 - 2003: Resident physician and scientific assistant Institute of Transfusion Medicine, Hannover Medical School, Germany The THERAFLEX UV-Platelets system is currently under clinical investigation in a multicenter 1998 - 2001: Scientific assistant trial in Germany. This phase III, randomized, controlled, double blind study, called CAPTURE, Institute of Transfusion Medicine, University Hospital Charité investigates the clinically effectiveness and safety of UVC-treated PCs in comparison to Berlin, Germany

CURRICULUM VITAE CURRICULUM conventional (non-UVC-treated) PCs. Both, buffy-coat-derived pool PCs and apheresis PCs 1996 - 1998: Junior physician stored for up to 5 days in platelet additive solution (SSP+), are used in the study. Medical Clinic I of the Clinical Centre Fürth, teaching hospital Hematology-oncology patients with thrombocytopenia are randomly assigned to receive of the Friedrich-Alexander University Erlangen-Nuremberg prophylactic and therapeutic transfusions (either UVC-treated or control platelets). Primary endpoint of the study is 1-hour corrected count increment (CCI). Secondary endpoints EDUCATION include efficacy-related parameters (24-hour CCI, 1-hour and 24-hour CCIs, transfusion 2010: Master of Health Business Administration (MHBA) requirement of red cells and platelets, platelet transfusion interval) and safety parameters Friedrich-Alexander University Erlangen-Nuremberg, Germany (e.g., severe bleeding and platelet refractoriness). The ongoing study started in 2016. Patients will be enrolled up to a maximum of 166 patients. 2002: Specialist in Transfusion Medicine 1996: Doctor of Medicine Friedrich-Alexander University Erlangen-Nuremberg, Germany

6 BLOOD SAFETY SYMPOSIUM BLOOD SAFETY SYMPOSIUM 7 DR. VERONIKA BRIXNER Speaker

Selected publications: Kim S, Handke W, Gravemann U, Döscher A, Brixner V, Müller TH, Seltsam A. Mitochondrial DNA multiplex real-time «The phase III CAPTURE Trial: routine use in the blood bank of Frankfurt » polymerase chain reaction inhibition assay for quality control of pathogen inactivation by ultraviolet C light in platelet concentrates. Transfusion 2018; 58:758-65.

Van der Meer PF, Gravemann U, de Korte D, Sumian C, Tolksdorf F, Müller TH, Seltsam A. Effect of increased agitation Head of production speed on pathogen inactivation efficacy and in vitro quality in UVC-treated platelet concentrates. Vox Sang 2016; German Red Cross Blood Service Baden-Württemberg - Hesse, Frankfurt 111:127-34.

Faddy HM, Fryk JJ, Prow NA, Watterson D, Young PR, Hall RA, Tolksdorf F, Sumian C, Gravemann U, Seltsam A, Marks DC. Inactivation of dengue, chikungunya, and Ross River viruses in platelet concentrates after treatment with ultraviolet C light. Transfusion 2016; 56:1548-55. EMPLOYMENT HISTORY 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 2017 - present: Head of production trial. Vox Sang 2015; 109:44-51. German Red Cross Blood Service Baden-Württemberg - Hesse, Frankfurt

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. 2002 – 2010: Resident physician and scientific assistant German Red Cross Blood Service Baden-Württemberg - Hesse, Frankfurt Seltsam A, Muller TH. Br J. Update on the use of pathogen-reduced human plasma and platelet concentrates. Haematol 2013; 162:442-54. 2000 – 2001: Junior physician Medical Clinic I of the St. Josefs Hospital Wiesbaden, teaching hospital Bashir S, Cookson P, Wiltshire M, Hawkins L, Sonoda L, Thomas S, Seltsam A, Tolksdorf F, Williamson LM, Cardigan R. of the Johann-Wolfgang Goethe University, Frankfurt, Germany Pathogen inactivation of platelets using ultraviolet C light: effect on in vitro function and recovery and survival of platelets. Transfusion 2013; 53:990-1000. EDUCATION

Steinmann E, Gravemann U, Friesland M, Doerrbecker J, Muller TH, Pietschmann T, Seltsam A. Two pathogen reduction VITAE CURRICULUM technologies-methylene blue plus light and shortwave ultraviolet light-effectively inactivate hepatitis C virus in blood 2016: Master of Science in Clinical Trial Management products. Transfusion 2013; 53:1010-8. Beuth University of Applied Science , Berlin, Germany

Pohler P, Lehmann J, Veneruso V, Tomm J, von Bergen M, Lambrecht B, Kohn B, Weingart C, Muller TH, Seltsam A. Evaluation 2010: Specialist in Transfusion Medicine of the tolerability and immunogenicity of ultraviolet C-irradiated autologous platelets in a dog model. Transfusion 2012; 52:2414-26. 2002: Doctor of Medicine Muller TH, Montag T, Seltsam A. Laboratory Evaluation of the Effectiveness of Pathogen Reduction Procedures for Bacteria. Johann-Wolfgang Goethe University, Frankfurt, Germany Transfus Med Hemother 2011; 38:242-50.

Seltsam A, Müller TH. UVC Irradiation for Pathogen Reduction of Platelet Concentrates and Plasma. Transfus Med Hemother 2011; 38:43-54.

8 BLOOD SAFETY SYMPOSIUM BLOOD SAFETY SYMPOSIUM 9 Dr. Veronika BRIXNER « The phase III CAPTURE Trial: routine use of THERAFLEX UV-Platelets in the blood bank of Frankfurt » Selected publications:

Brixner V, Kiessling AH, Madlener K, Müller MM, Leibacher J, Dombos S, Weber I, Pfeiffer HU, Geisen C, Schmidt M, Henschler R, North A, Huang N, Mufti N, Erickson A, Ernst C, Rico S, Benjamin RJ, Corash LM, Seifried E. Red blood cells treated with the amustaline (S-303) pathogen reduction system: a transfusion study in cardiac surgery. Transfusion 2018; Improvements in donor selection, infectious disease testing, and donor deferral policies 1. DOI: 10.1111/trf.14528. have effectively reduced but not eliminated the risk of transfusion-transmitted infectious Kim S, Handke W, Gravemann U, Döscher A, Brixner V, Müller TH, Seltsam A. Mitochondrial DNA multiplex real-time diseases. polymerase chain reaction inhibition assay for quality control of pathogen inactivation by ultraviolet C light in platelet Prevention of transfusion transmitted infection and, at the same time, preservation of cell concentrates. Transfusion 2018; 58(3):758-765. vitality are core objectives for pathogen inactivation methods for blood products. Leibacher J, Dauber K, Ehser S, Brixner V, Kollar K, Vogel A, Spohn G, Schäfer R, Seifried E, Henschler R. Human Pathogen reduction technology may enhance microbial safety of platelet transfusion by mesenchymal stromal cells undergo apoptosis and fragmentation after intravenous application in immune-competent mice. Cytotherapy 2017; 19(1):61-74. reducing bacterial and viral contamination. Skrablin PS, Richter R, Brixner V, Seifried E, Seidl C. The novel allele HLA-DQB1*0636 of Caucasian origin has a unique amino acid exchange at position 186 of the beta 2 region. Tissue Antigens 2010; 76(1):72-4. We established the manufacturing of UVC-treated pooled platelet concentrates (PPCs) and UVC-treated apheresis platelet concentrates (APCs) under routine conditions using the Hourfar MK, Jork C, Schottstedt V, Weber-Schehl M, Brixner V, Busch MP, Geusendam G, Gubbe K, Mahnhardt C, Mayr-Wohlfart U, Pichl L, Roth WK, Schmidt M, Seifried E, Wright DJ. German Red Cross NAT Study Group. Experience THERAFLEX UV-Platelets method. Both UVC-treated and non UVC treated PPCs and APCs, of German Red Cross blood donor services with nucleic acid testing: results of screening more than 30 million blood have been used as clinical investigational products for the CAPTURE (Clinical Assessment of donations for human immunodeficiency virus-1, hepatitis C virus, and hepatitis B virus. Transfusion 2008; 48(8):1558-66. Platelets Treated with UVC in Relation to Established Preparations) clinical trial. Brixner V, Richter R, Bader P, Seifried E, Seidl C. A new HLA-B*08 allele, HLA-B*0828, found in two voluntary stem cell donors. Tissue Antigens 2008; 71(5):482-3. UVC treated PPCs were produced within the routine production area using 5 buffy coats and Rehbinder B, Wullstein Ch, Bechstein WO, Probst M, Engels K, Kriener S, Döbert N, Schwarz W, Brixner V, Steffan D, Gauer 280 ml SSP+ additive solution. There was no need to adapt the separation conditions for the S, Geiger H, Hauser IA. Epstein-Barr virus-associated posttransplant lymphoproliferative disorder of donor origin after manufacturing of the UVC treated PPCs. simultaneous pancreas-kidney transplantation limited to pancreas allograft: A case report. Am J Transplant 2006; Total protein concentration and platelet concentration were analyzed prior UVC treatment 6(10):2506-11. for all UVC treated PPCs. Preiser W, Rabenau HF, Vogel JU, Brixner V, Doerr HW. Performance characteristics of an automated PCR assay for the Every process step was documented using our standard Blood Bank software. quantification of cytomegalovirus DNA in plasma, J Virol Methods 2002; 101(1-2):149-57. We produced more than 650 UVC treated PPCs. Batch size was 2-10 PPCs per run. Drosten C, Nippraschk T, Manegold C, Meisel H, Brixner V, Roth WK, Apedjinou, A, Günther S. Prevalence of hepatitis B virus Tests for bacterial contamination were negative for all tested PPCs (n = 120). DNA in anti-HBc-positive/HBsAg-negative sera correlates with HCV but not HIV serostatus. J Clin Virol 2004; 29(1):59-68. Schmidt M, Brixner V, Ruster B, Hourfar MK, Drosten C, Preiser W, Seifried E, Roth WK. NAT screening of blood donors for Due to the modest hands-on time and the lack of an incubation time integration of UVC severe acute respiratory syndrome coronavirus can potentially prevent transfusion associated transmissions. Transfusion treatment for platelets into routine production was easily possible. 2004; 44(4):470-5.

10 BLOOD SAFETY SYMPOSIUM BLOOD SAFETY SYMPOSIUM 11 PROF. DENESE MARKS Prof. Denese Marks Speaker « Review on the inactivation of arboviruses with THERAFLEX » « Review on the inactivation of arboviruses with THERAFLEX »

Product Development and Storage The Australian Red Cross Blood Service Associate Professor Sydney Medical School, The University of Sydney

EMPLOYMENT HISTORY

August 2008 - present: National R&D Leader – Product Development and Storage VIRAL INACTIVATION WITH THERAFLEX MB-PLASMA AND THERAFLEX UV-PLATELETS The Australian Red Cross Blood Service SYSTEMS January 2015 - present: Associate Editor, ISBT Science Series 2005 - 2008: Head of Cell Biology and Project Leader: Preclinical Studies Many arthropod-borne viruses have emerged as threats to the safe supply of blood. Apollo Life Sciences, Sydney, Australia 2003 - 2005: Post-doctoral Fellow These include dengue virus (DENV), chikungunya (CHIKV), Ross River virus (RRV), which Faculty of Pharmacy, The University of Sydney, Australia has been reported across Australia and the Pacific, and more recently, Zika virus (Zika) and yellow fever virus (YFV). One approach to manage the risk of transfusion-transmis- 2001 - 2003: Senior Postdoctoral Research Fellow Molecular Haematology and Cancer Biology sion of these viruses could be the use of pathogen inactivation technologies (PI), such Institute of Child Health, London, England as the THERAFLEX MB-Plasma system and THERAFLEX UV-Platelets system.

CURRICULUM VITAE CURRICULUM 1999 - 2001: Risk Analyst and Procurement Analyst We have examined the ability of these systems to inactivate DENV strains, CHIKV, RRV, Global Markets Dresdner Kleinwort Wasserstein, London, England 1996 - 1999: Senior Postdoctoral Fellow Zika and YFV in platelets and plasma. The level of viral infectivity was determined using a modified version of a conventional plaque assay and the reduction in viral infectivity Department of Medicine, University of Melbourne, Australia 1994 - 1996: Liese Meitner Research Fellow was calculated. Findings from our studies will be reported. Department of Molecular Genetics Vienna University Biocenter, Vienna, Austria

EDUCATION 1995: Doctor of Philosophy, 1991: University of Technology, Sydney, Australia; Bachelor of Applied Science (Honours Class 1) University Medal for Science; University of Technology, Sydney, Australia

ACADEMIC APPOINTMENTS 2008 - present: Associate Professor, Sydney Medical School, The University of Sydney,

12 BLOOD SAFETY SYMPOSIUM BLOOD SAFETY SYMPOSIUM 13 BLOOD SAFETY SYMPOSIUM

Selected publications:

Fryk JJ, Marks DC, Hobson-Peters J, Prow NA, Watterson D, Hall RA, Young PR, Reichenberg S, Sumian C, Faddy HM. Dengue and chikungunya viruses in plasma are effectively inactivated after treatment with methylene blue and visible light. Transfusion 2016; 56: 2278-2285.

Faddy HM, Fryk JJ, Watterson D, Young PR, Modhiran N, Muller D, Keil SD, Goodrich RP, Marks DC. Riboflavin and ultraviolet light: impact on dengue virus infectivity. Vox Sang 2016; 111: 235-241.

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. Vox Sang 2015; 109: 327-335.

Johnson L & Marks DC. Treatment of platelet concentrates with the Mirasol pathogen inactivation system modulates platelet oxidative stress and NF-κB activation. Transfusion Medicine and Hemotherapy 2015; 42: 167-173.

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. Transfusion 2014; DOI: 10.1111/trf.12899

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

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

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

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

14 BLOOD SAFETY SYMPOSIUM BLOOD SAFETY SYMPOSIUM 15 Lead the way in blood safety RCS : 391 600 905 Lille Métropole MACOPHARMA Rue Lorthiois F-59420 Mouvaux (France) www.bloodsafety.macopharma.com