POSTER ABSTRACTS COMPILATION

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1 Lead the way in blood safety BLOOD SAFETY POSTER ABSTRACTS COMPILATION 2017 THERAFLEX MB-Plasma THERAFLEX UV-Platelets SSP+ Additive Solution ISBT COPENHAGEN 2017

2 BLOOD SAFETY POSTER ABSTRACTS COMPILATION THERAFLEX MB-Plasma, THERAFLEX UV-Platelets & SSP+ THERAFLEX MB-Plasma YEAR CONGRESS CITATION TITLE AUTHORS 2017 ISBT P-258 ZIKA VIRUS INFECTIVITY IS REDUCED FOLLOWING TREATMENT WITH THE THERAFLEX UVC-PLATELET AND THERAFLEX MB-PLASMA SYSTEMS Denese C. Marks, Jesse J. Fryk, Jody Hobson-Peters, Daniel Watterson, Roy A. Hall, Paul R. Young, Stefan Reichenberg, Frank Tolksdorf, Chryslain Sumian, Helen M. Faddy 2017 ISBT P-257 INFLUENCE OF THE TEMPERATURE ON THE QUALITY AND VIRUS INACTIVATION CAPACITY OF METHYLENE-BLUE TREATED PLASMA USING THE THERAFLEX MB-PLASMA SYSTEM Ute Gravemann, Wiebke Handke, Chryslain Sumian, Ignacio Alvarez, Stefan Reichenberg, Axel Seltsam 2017 ISBT P-689 REVIEW OF NATIONAL HAEMOVIGILANCE REPORTS AS PART OF A PLASMA PATHOGEN INACTIVATION SYSTEM POST-MARKET SURVEILLANCE PROGRAM Alvarez Ignacio, Shchepetov Anton, Tolksdorf Frank, Reichenberg Stefan THERAFLEX UV-Platelets YEAR CONGRESS CITATION TITLE AUTHORS 2017 ISBT P-258 ZIKA VIRUS INFECTIVITY IS REDUCED FOLLOWING TREATMENT WITH THE THERAFLEX UVC-PLATELET AND THERAFLEX MB-PLASMA SYSTEMS Denese C. Marks, Jesse J. Fryk, Jody Hobson-Peters, Daniel Watterson, Roy A. Hall, Paul R. Young, Stefan Reichenberg, Frank Tolksdorf, Chryslain Sumian, Helen M. Faddy 2

3 YEAR CONGRESS CITATION TITLE AUTHORS 2017 ISBT P-251 EFFECTIVENESS OF THE THERAFLEX UV-PLATELETS TECHNOLOGY AGAINST CLINICALLY RELEVANT TRANSFUSION-TRANSMITTED BACTERIA STRAINS Gravemann, Ute; Tolksdorf, Frank; Handke, Wiebke; Müller, Thomas H.; Seltsam, Axel 2017 ISBT P-261 IN VITRO ASSESSMENT OF PLASMA-REDUCED SINGLE DONOR APHERESIS PLATELET CONCENTRATES: COMPARISON OF UVC-TREATED, GAMMA-IRRADIATED AND UNTREATED PLATELETS UNITS Doescher Andrea, Pohler Petra, Gravemann Ute, Petershofen Eduard K, Baume Hagen, Seltsam Axel 2017 ISBT P-253 IN VITRO ASSESSMENT OF UNTREATED, UVC-TREATED AND GAMMA-IRRADIATED PLASMA REDUCED PLATELET CONCENTRATES PREPARED FROM THROMBAPHERESIS UNDER ROUTINE CONDITIONS Brixner Veronika, Dombos, Sara, Weber Iuliia, Schäfer R, Schmidt Michael, Tolksdorf Frank, Pohler Petra, Seltsam Axel, Seifried Erhard 2017 ISBT P-167 DEVELOPMENT OF A MITOCHONDRIAL DNA MULTIPLEX REAL-TIME POLYMERASE CHAIN REACTION ASSAY FOR QUALITY CONTROL OF PATHOGEN INACTIVATION OF PLATELETS WITH UVC LIGHT Sinyoung Kim, Wiebke Handke, Ute Gravemann, Andrea Doescher, Veronika Brixner, Axel Seltsam SSP+ Platelet Additive Solution YEAR CONGRESS CITATION TITLE AUTHORS 2017 ISBT P-695 REVIEW OF NATIONAL HAEMOVIGILANCE REPORTS AS A PART OF THE POST-MARKET SURVEILLANCE PROGRAM FOR MACOPHARMA PLATELET ADDITIVE SOLUTIONS Alvarez Ignacio, Tolksdorf Frank, Shchepetov Anton 3

4 BLOOD SAFETY POSTER ABSTRACTS 2017 THERAFLEX MB-Plasma ISBT COPENHAGEN

5 ZIKA VIRUS INFECTIVITY IS REDUCED FOLLOWING TREATMENT WITH THE THERAFLEX UVC-PLATELET AND MB-PLASMA SYSTEMS Denese C. Marks 1, Jesse J. Fryk 2, Jody Hobson-Peters 3, Daniel Watterson 3, Roy A. Hall 3, Paul R. Young 3, Stefan Reichenberg 4, Frank Tolksdorf 4, Chryslain Sumian 5, Helen M. Faddy 2 1 Research and Development, Australian Red Cross Blood Service, Sydney, Australia 2 Research and Development, Australian Red Cross Blood Service, Brisbane, Australia 3 Australian Infectious Disease Research Centre, School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Australia 4 MacoPharma International GmbH, Langen, Germany 5 MacoPharma, Tourcoing, France ISBT Congress 2017, Copenhagen, P-258. THERAFLEX MB-Plasma Background: Zika virus (ZIKV) has emerged as a pathogen of global significance with evidence of mosquito-borne transmission in 76 countries and territories since Given that asymptomatic infection can occur and that transfusion-transmission has been documented, this virus poses a potential threat to blood transfusion safety. In Australia there has been no local ZIKV transmission to date; however, vectorial capacity modelling suggests such a scenario is possible in areas with the mosquito vector. The Australian Red Cross Blood Service prevents individuals with a symptomatic illness or confirmed ZIKV infection from donating blood, and restricts fresh component donation from individuals returning from travel to countries with autochthonous ZIKV transmission. An alternative approach to manage the ZIKV transfusion-transmission risk is the use of pathogen inactivation (PI), such as the THERAFLEX UV-Platelet and THERAFLEX MB-Plasma systems. Aims: To investigate the efficacy of the THERAFLEX UV-Platelet and THERAFLEX MB-Plasma systems to inactivate ZIKV spiked into buffy coat-derived platelet concentrates (platelet concentrates) or pooled plasma. Methods: ZIKV was spiked into platelet concentrates or pooled plasma units (n=3 per blood component) to give a pre-treatment concentration of plaque forming units per ml. Spiked platelet concentrates were treated using the THERAFLEX UV-Platelet system at UVC doses of 0.05, 0.10, 0.15 and 0.20 (standard) J/ cm2. Spiked pooled plasma units were treated using the THERAFLEX MB-Plasma system at a dose of 20, 40, 60 and 120 (standard) J/cm 2 of visible light and approximately 0.8 µmol/l of methylene blue (MB). Samples were taken prior to the first and after each illumination dose and tested for residual virus using a modified plaque assay (normal and large-volume plating methods). The level of viral reduction was determined for each dose for each PI system. Results: At the standard UVC dose, ZIKV infectivity in platelet concentrates was reduced by 5.0 log, with dosedependency observed with increasing UVC dose. For pooled plasma treated with MB and visible light, ZIKV infectivity was reduced by at least 5.68 log, with residual viral infectivity detected at the detection limit of the assays used from 20 J/cm 2. Conclusions: This study has demonstrated the THERAFLEX UV-Platelet and THERAFLEX MB-Plasma systems can inactivate ZIKV spiked into platelet concentrates or pooled plasma. The level of reduction observed (5 log in platelet concentrates and at least 5.68 log in plasma) is similar to that for other viruses, including dengue, chikungunya and West Nile viruses, with these PI systems. To assess if the level of reduction in viral infectivity in these blood components is sufficient to prevent transfusion-transmission, studies examining the threshold concentration to elicit disease are needed. However, the reduction levels observed in this study demonstrate these PI systems may be an effective option for managing ZIKV transfusion-transmission risk in plasma and platelet concentrates. THERAFLEX UV-Platelets SSP+ Additive Solution 5

6 INFLUENCE OF THE TEMPERATURE ON THE QUALITY AND VIRUS INACTIVATION CAPACITY OF METHYLENE-BLUE TREATED PLASMA USING THE THERAFLEX MB-PLASMA SYSTEM Ute Gravemann, Wiebke Handke, Chryslain Sumian, Ignacio Alvarez, Stefan Reichenberg, Axel Seltsam ISBT Congress 2017, Copenhagen, P-257. Background: Photodynamic treatment using methylene blue (MB) and visible light is in routine use for pathogen reduction of human plasma in different countries. Temperature conditions of either environment or human plasma during production might vary between production sites. Aims: Aim of the study was to investigate the influence of different temperature conditions on the quality and virus inactivation capacity of the THERAFLEX MB-plasma procedure (MacoPharma). Methods: For quality investigations, plasma (n = 3) was pooled and split and either stored at room temperature (reference) or stored at 5 C and 30 C (test) for a minimum of 2h to ensure equilibration to the desired temperature. Plasma unit (n = 8 for each temperature) was connected to the MB bag system including a leukocyte depletion filter (Plasmaflex) and a filter for the removal of MB and its photoproducts (Blueflex). Treatment was done according to the manufacturer s instructions on the Macotronic B2 device (MacoPharma) with a light dose of 120 J/cm2. Samples were taken at different process steps to determine the activity of plasma factors and the concentrations of MB and photoproducts. For virus inactivation kinetics, plasma units (n = 3 for each temperature and virus species) were spiked with virus suspension (10%) of three different virus species and MB/light treated. Samples were taken after different dose steps and virus titers were determined by endpoint titration. Results: MB/light treatment affected the activity of most of the investigated coagulation proteins and inhibitors. The highest decrease in reference conditions were detected for Factor VIII (-17.7%, 22 C) and Fibrinogen (-14.4%, 22 C). There was a trend towards a higher loss of plasma factor activities with increasing plasma temperatures, albeit differences were statistically not significant, except for Factor VIII (p = 0.044). However, plasma temperature significantly influenced the solubility of the MB pill, the concentrations of MB and photoproducts after illumination and the virus inactivation capacity. Solubility of the MB pill was visibly reduced at 5 C. Degradation of MB during illumination increased with increasing temperature, resulting in augmented formation of photoproducts (mainly Azure B) at 30 C. However, the filtration efficacy of the Blueflex filter was sufficient to remove the photoactive compounds. Virus inactivation capacity increased with plasma temperature rising. Inactivation of Suid Herpes Virus (SHV-1), Bovine Viral Diarrhoea Virus (BVDV) and Vesicular Stomatitis Virus (VSV) was significantly lower for plasma units with a temperature of 5 C than for plasma with temperatures of 22 C and 30 C. Conclusion: The conditions for THERAFLEX MB-plasma treatment in routine production have to be chosen carefully to assure uniform quality of the pathogen-reduced plasma. Inactivation of cooled plasma is not recommended. 6

7 REVIEW OF NATIONAL HAEMOVIGILANCE REPORTS AS PART OF A PLASMA PATHOGEN INACTIVATION SYSTEM POST-MARKET SURVEILLANCE PROGRAM Alvarez I. 1, Shchepetov A. 2, Tolksdorf F. 2, Reichenberg S. 2 1 Maco Spania, Madrid, Spain; 2 Maco Pharma International GmbH, Langen, Germany ISBT Congress 2017, Copenhagen, P-689. Background: National Haemovigilance (HV) Systems are an important tool for guaranteeing safety of patients, donors and transfusion service personnel, improving quality of blood products and promoting their optimal use in clinics. National HV reports are published on a regular basis by transfusion services, and provide data that can help medical device manufacturers complete their product-related safety data. In our organization, a review of multinational HV data is performed annually as a part of the post-market surveillance program. Here, we provide a summary of last results for Macopharma`s pathogen inactivation (PI) system designed to reduce viruses and bacteria in plasma. Aims: In order to establish a complete safety and performance profile for our THERAFLEX MB-Plasma system, we collected and analyzed data from peer reviewed journals as well as from sources which might report negative outcomes. Haemovigilance reports are supposed to focus mainly on adverse events and therefore meet this criteria perfectly. Moreover, they contain nationwide data from large patient populations and are a valuable tool for the identification of rare adverse events. Methods: For data collection, we identified countries, where the THERAFLEX MB-Plasma system or equivalent procedures using methylene blue (MB) in combination with visible light have been in use and national HV reports and/or publications with HV data are available. These reports were reviewed and relevant data were extracted for further analysis. In addition, we screened journal articles that might contain HV data, using PubMed and accessing transfusion journals directly. Some important numbers were taken from national transfusion service activity reports. This review was completed with results from a recent international, multicentric, prospective phase IV clinical study (NCT ) conducted by Macopharma in partnership with a globally recognised CRO from 2013 to THERAFLEX MB-Plasma THERAFLEX UV-Platelets Results: 41 HV reports and related documents (activity reports, official letters) and 21 publications containing HV data from clinical studies were identified and reviewed. The collected data related to the following countries: France, Belgium, Spain, Italy, the UK, Greece and Austria. The covered period was from 2007 and up to 2015, depending on the availability of HV reports and duration of use of the PI system. For equivalent methods, we reviewed HV and clinical data from 1992 onwards. During the analyzed period for THERAFLEX MB-Plasma and other PI systems, there was no indication from any country about an increased number of adverse reactions to MB-plasma compared to other types of plasma, with the only exception of France during There was no evidence for an increased plasma volume transfused with MB-treatment. Conclusion: This review of HV publications provided additional clinical data confirming the clinical efficacy and a good safety profile of THERAFLEX MB-Plasma system in terms of plasma transfusion-related adverse events and, particularly adverse reactions. SSP+ Additive Solution 7

8 BLOOD SAFETY POSTER ABSTRACTS 2017 THERAFLEX UV-Platelets ISBT COPENHAGEN

9 ZIKA VIRUS INFECTIVITY IS REDUCED FOLLOWING TREATMENT WITH THE THERAFLEX UVC-PLATELET AND MB-PLASMA SYSTEMS Denese C. Marks 1, Jesse J. Fryk 2, Jody Hobson-Peters 3, Daniel Watterson 3, Roy A. Hall 3, Paul R. Young 3, Stefan Reichenberg 4, Frank Tolksdorf 4, Chryslain Sumian 5, Helen M. Faddy 2 1 Research and Development, Australian Red Cross Blood Service, Sydney, Australia 2 Research and Development, Australian Red Cross Blood Service, Brisbane, Australia 3 Australian Infectious Disease Research Centre, School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Australia 4 MacoPharma International GmbH, Langen, Germany 5 MacoPharma, Tourcoing, France ISBT Congress 2017, Copenhagen, P-258. THERAFLEX MB-Plasma Background: Zika virus (ZIKV) has emerged as a pathogen of global significance with evidence of mosquito-borne transmission in 76 countries and territories since Given that asymptomatic infection can occur and that transfusion-transmission has been documented, this virus poses a potential threat to blood transfusion safety. In Australia there has been no local ZIKV transmission to date; however, vectorial capacity modelling suggests such a scenario is possible in areas with the mosquito vector. The Australian Red Cross Blood Service prevents individuals with a symptomatic illness or confirmed ZIKV infection from donating blood, and restricts fresh component donation from individuals returning from travel to countries with autochthonous ZIKV transmission. An alternative approach to manage the ZIKV transfusion-transmission risk is the use of pathogen inactivation (PI), such as the THERAFLEX UV-Platelet and THERAFLEX MB-Plasma systems. Aims: To investigate the efficacy of the THERAFLEX UV-Platelet and THERAFLEX MB-Plasma systems to inactivate ZIKV spiked into buffy coat-derived platelet concentrates (platelet concentrates) or pooled plasma. Methods: ZIKV was spiked into platelet concentrates or pooled plasma units (n=3 per blood component) to give a pre-treatment concentration of plaque forming units per ml. Spiked platelet concentrates were treated using the THERAFLEX UV-Platelet system at UVC doses of 0.05, 0.10, 0.15 and 0.20 (standard) J/ cm2. Spiked pooled plasma units were treated using the THERAFLEX MB-Plasma system at a dose of 20, 40, 60 and 120 (standard) J/cm 2 of visible light and approximately 0.8 µmol/l of methylene blue (MB). Samples were taken prior to the first and after each illumination dose and tested for residual virus using a modified plaque assay (normal and large-volume plating methods). The level of viral reduction was determined for each dose for each PI system. Results: At the standard UVC dose, ZIKV infectivity in platelet concentrates was reduced by 5.0 log, with dosedependency observed with increasing UVC dose. For pooled plasma treated with MB and visible light, ZIKV infectivity was reduced by at least 5.68 log, with residual viral infectivity detected at the detection limit of the assays used from 20 J/cm 2. Conclusions: This study has demonstrated the THERAFLEX UV-Platelet and THERAFLEX MB-Plasma systems can inactivate ZIKV spiked into platelet concentrates or pooled plasma. The level of reduction observed (5 log in platelet concentrates and at least 5.68 log in plasma) is similar to that for other viruses, including dengue, chikungunya and West Nile viruses, with these PI systems. To assess if the level of reduction in viral infectivity in these blood components is sufficient to prevent transfusion-transmission, studies examining the threshold concentration to elicit disease are needed. However, the reduction levels observed in this study demonstrate these PI systems may be an effective option for managing ZIKV transfusion-transmission risk in plasma and platelet concentrates. THERAFLEX UV-Platelets SSP+ Additive Solution 9

10 EFFECTIVENESS OF THE THERAFLEX UV-PLATELETS TECHNOLOGY AGAINST CLINICALLY RELEVANT TRANSFUSION-TRANSMITTED BACTERIAL STRAINS Gravemann, Ute; Tolksdorf, Frank; Handke, Wiebke; Müller, Thomas H.; Seltsam, Axel ISBT Congress 2017, Copenhagen, P-251. Background: The THERAFLEX UV-Platelets system (Macopharma) is a late generation pathogen inactivation system for platelet concentrates (PCs) that uses UVC light only (wavelength: 254 nm) without the need of any additional photoactive compound. UVC treatment has been shown to inactivate a broad range of viruses, bacteria, and protozoans. Previous studies with the first set of bacteria species of the WHO International Repository of Platelet-Transfusion Relevant Bacterial Reference Strains revealed a high inactivation capacity for clinically relevant bacteria. Aims: Aim of the current study was to validate the bacteria inactivation capacity using bacteria species that have recently been added to the WHO International Repository of Platelet-Transfusion Relevant Bacterial Reference Strains. Methods: PCs were produced from 5 buffy coats using the additive solution SSP+ (MacoPharma) with a residual plasma content of 35%. For inactivation kinetics, PCs (n=3) were spiked with bacteria to a final concentration of approx.106 colony forming units (CFU)/mL and irradiated with increasing doses until the full dose was UVC was achieved. Samples were taken for the bacterial titer determination after each irradiation step. Results: Treatment with the THERAFLEX UV-Platelets pathogen inactivation system caused dose-dependent inactivation of bacteria in plasma-reduced PCs. Mean log10 reduction factors ranged from 6 to 7 for Enterobacter cloacae (PEI-B-P-43), Morganella morganii (PEI-B-P-91), Proteus mirabilis (PEI-B-P-91), Pseudomonas fluorescens (PEI-B-P-77), Staphylococcus aureus (PEI-B-P-63), and Streptococcus bovis (PEI- B-P-61). Conclusion: The THERAFLEX UV-Platelets system efficiently inactivates a broad range of different bacteria species, including the WHO reference strains. 10

11 IN VITRO ASSESSMENT OF PLASMA-REDUCED SINGLE DONOR APHERESIS PLATELET CONCENTRATES: COMPARISON OF UVC-TREATED, Y-IRRADIATED AND UNTREATED PLATELET UNITS Doescher Andrea 1, Pohler Petra 2, Gravemann Ute 2, Petershofen Eduard K. 1, Baume Hagen 1, Seltsam Axel 2 1 German Red Cross Blood Service NSTOB, Institute Bremen-Oldenburg, Germany. 2 German Red Cross Blood Service NSTOB, Institute Springe, Germany. ISBT Congress 2017, Copenhagen, P-261. Introduction: Treatment of apheresis platelet concentrates (PCs) with UVC may enhance transfusion safety of platelets with respect to contamination with pathogens. In vitro quality of UVC-irradiated PCs (UVC-PCs) was compared with that of y-irradiated PCs (y-pcs) and untreated PCs (AP-PCs) under routine production conditions. Methods: 18 PCs were prepared from single donors with standard operation procedures (Amicus) using SSP+ (Macopharma, Mouvaux; France) as additive solution and divided into three groups (n=6 each): UVC- PCs were treated with UVC within six hours after preparation using the THERAFLEX UV-Platelets system (Macopharma); y-pcs were y-irradiated with a minimum of 25 Gy; and AP-PCs were left untreated. Sampling for quality control parameters was done on day of preparation (day 0) and after six days of storage (day 6). The following parameters were examined on day 0: PC volume, platelet concentrations before and after UVC treatment, plasma content, residual erythrocyte and leucocyte counts, ph, swirling and scd62 (with and without thrombin-receptor activating peptide [TRAP]/collagen activation); measurements on day 6 were: platelet concentration, ph, swirling, scd62 and sterility testing. Results: Mean volumes were 333 ± 5.4mL in AP-PCs, 341 ±7.1mL in y-pcs and 329 ±6.0mL in UVC-PCs with platelet counts of 3.6 ± 0.5/unit, 3.8 ± 0.3/unit and 3.9 ± 0,3/unit, respectively. Residual plasma concentration ranged between 31% and 38%. Residual erythrocytes and leucocytes met the standard specifications for PC products in Germany. At the end of shelf life, the ph value of UVC-PCs was significantly lower (7.01 ±0.05) compared to y-pcs (7.18 ±0.04) and AP-PCs (7.17 ±0.05). No differences were detected for scd62 expression between the three PC types with and without TRAP/collagen activation. Tests for bacterial contamination were negative for all tested PCs. Conclusion: Study results demonstrate that plasma-reduced UVC-treated apheresis PCs meet the standard specifications for PC products in Germany. The significantly lower ph value at end of storage may be attributable to a higher metabolic activity in UVC-PCs. The safety and efficacy of UVC-treated PCs is being evaluated in a clinical study. THERAFLEX UV-Platelets THERAFLEX MB-Plasma SSP+ Additive Solution 11

12 IN VITRO ASSESSMENT OF UNTREATED, UVC-TREATED AND GAMMA-IRRADIATED PLASMA REDUCED PLATELET CONCENTRATES PREPARED FROM THROMBAPHERESIS UNDER ROUTINE CONDITIONS Brixner Veronika 1, Dombos, Sara 1, Weber Iuliia 1, Schäfer R 1, Schmidt Michael 1, Tolksdorf Frank 2, Pohler Petra 3, Seltsam Axel 3, Seifried Erhard 1 1 German Red Cross Blood Donor Service Baden-Württemberg-Hessen GmbH 2 MacoPharma International GmbH, Langen, German 3 German Red Cross Blood Service NSTOB, Springe, Germany ISBT Congress 2017, Copenhagen, P-253. Background: Pathogen reduction technology may enhance microbial safety of platelet transfusion by reducing bacterial and viral contamination. We established the manufacturing of UVC-treated apheresis platelet concentrates (PCs) under routine conditions. Aims: The objective of this study was to evaluate potential in vitro effects of the THERAFLEX UV-Platelets treatment on platelets collected by thrombapheresis in comparison to untreated and gamma irradiated platelets. Methods: Twenty-four leukocyte reduced and plasma reduced platelet concentrates (PCs) were prepared by apheresis using SSP+ as additive solution (Macopharma, Mouvaux, France). We established the preparation of three different platelet products: PCs treated with the THERAFLEX UV-Platelets system (Macopharma) within 6h after PC preparation, untreated PCs and gamma-irradiated (30 Gy) PCs. Platelet products were all stored for 7 days in the storage bag of the THERAFLEX UV-Platelets kit. To evaluate the quality of these products, we analyzed product volume, residual erythrocytes, residual leukocytes, platelet content, total protein concentration, ph, sterility and CD62P expression. CD62P surface expression, a marker of platelet activation, was analyzed by flow cytometry with and without activation by thrombin-receptor activating peptide (TRAP) after production and at the end of shelf life. For statistical analysis the Kruskal-Wallis-test was applied, and p-values <0.05 were considered as statistically significant. Results: UVC-treated PCs showed no significant differences compared to untreated or gamma-irradiated PCs with respect to volume (untreated PCs 330±11 ml, gamma irradiated PCs 328±5 ml, UVC-treated PCs 328±13 ml), platelet content (untreated PCs 2.9±0.3 x1011 per unit, gamma irradiated PCs 2.9±0.2 x1011 per unit, UVC-treated PCs 2.9±0.1 x1011 per unit), residual leukocytes, residual erythrocytes, total protein concentration (untreated PCs 23±1,5 g/l, gamma irradiated PCs 23±1,8 g/l, UVC-treated PCs 23±1,9 g/l) and ph at the end of shelf life. CD62P expression was variable between the PC groups with and without activation by TRAP but did not reach statistical significance. Tests for bacterial contamination were negative for all tested PCs. Conclusions: This data indicate that plasma reduced, UVC treated PCs meet the quality standards for PC products according to the German Guidelines. Safety, tolerance and efficacy of PCs manufactured by the THERAFLEX-UV Platelets system are currently evaluated in a clinical study. 12

13 DEVELOPMENT OF A MITOCHONDRIAL DNA MULTIPLEX REAL-TIME POLYMERASE CHAIN REACTION ASSAY FOR QUALITY CONTROL OF PATHOGEN INACTIVATION OF PLATELETS WITH UVC LIGHT Sinyoung Kim 1,2, Wiebke Handke 1, Ute Gravemann 1, Andrea Doescher 3, Veronika Brixner 4, Axel Seltsam 1 1 German Red Cross Blood Service NSTOB, Institute Springe, Springe, Germany; 2 Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Korea; 3 German Red Cross Blood Service NSTOB, Institute Oldenburg-Bremen, Oldenburg, Germany; 4 German Red Cross Blood Service Baden-Württemberg-Hessen, Frankfurt, Germany ISBT Congress 2017, Copenhagen, P-167. Background: Several ultraviolet (UV) light-based pathogen inactivation (PI) technologies for platelet products have been developed or are under development. Upon implementation of PI technologies, quality control measures are required to ensure consistent efficacy of UV illumination process. Previous reports showed that amotosalen/uva and riboflavin/uv-based PI technologies induce modifications of the platelet-derived mitochondrial DNA (mtdna) that can be detected by polymerase chain reaction (PCR) inhibition assays. Aims: To develop multiplex real-time PCR for detection of UVC-induced mtdna modifications as a quality control for PI of platelets by the THERAFLEX UV-Platelets system. Methods: Based on a binucleotide frequency analysis of the mtdna genome, a multiplex real-time PCR assay was developed to simultaneously amplify short (143 bp)- and long (794 bp)-amplicons from a template DNA prepared using a platelet count adjusted DNA extraction method. Multiplex real-time PCR assay performance was evaluated on apheresis and buffy coat-derived UVC-treated and untreated plasmareduced platelet concentrates (PCs) and challenged by using PCs with volumes, platelet counts and plasma contents at the upper and lower limits of the specifications defined for the THERAFLEX UV-Platelets system. Results: PI of platelets using UVC light resulted in significant inhibition of PCR amplification of long-amplicon mtdna targets relative to untreated products. Amplification of short-amplicon mtdna targets was not affected by treatment. Evaluation of blinded platelet samples from routine-like production resulted in prediction of UVC treatment status with 100% accuracy. Conclusion: A differential sized amplicon real-time PCR assay of mtdna effectively documents nucleic acid damage induced by UVC illumination of platelets and could be used as an informative quality indicator of PI by the THERAFLEX UV-Platelets system. THERAFLEX UV-Platelets THERAFLEX MB-Plasma SSP+ Additive Solution 13

14 BLOOD SAFETY POSTER ABSTRACTS 2017 SSP+ Additive Solution ISBT COPENHAGEN

15 REVIEW OF NATIONAL HAEMOVIGILANCE REPORTS AS A PART OF A PLATELET ADDITIVE SOLUTIONS POST-MARKET SURVEILLANCE PROGRAM Alvarez I. 1, Tolksdorf F. 2, Shchepetov A. 2 1 Maco Spania, Madrid, Spain; 2 Maco Pharma International GmbH, Langen, Germany ISBT Congress 2017, Copenhagen, P-695. Background: National Haemovigilance (HV) Systems play an important role for guaranteeing safety of patients, donors and transfusion service personnel, while improving quality of blood products and technologies and optimizing their clinical use. National HV reports are published on a regular basis and provide data that can help medical device manufacturers to complete their product safety- data base and to meet regulatory requirements for post-market surveillance (PMS). A review of multinational HV data can be also interesting for transfusion specialists. This review deals with HV data on platelets suspended in platelet additive solutions (PAS). Macopharma is the manufacturer of SSP (PAS II, PAS-B) and SSP+ (PAS IIIM, PAS-E) platelet additive solution. Aims: In order to establish a complete safety and performance profile for our platelet additive solutions, we collected and analyzed data not only from peer reviewed journals, but also from sources which might report negative results. Haemovigilance reports are supposed to focus mainly on problematic issues and therefore meet these criteria perfectly. Moreover, they contain nationwide data from large patient population and are a valuable tool for identification of rare adverse events. Methods: For data collection, we identified countries, where Macopharma SSP and/or SSP+ solution is marketed and national HV reports and/or publications with HV data are available. Those reports were reviewed and relevant data were extracted for further qualitative and quantitative analysis. In addition, we screened peer reviewed journal articles that might contain HV data, using PubMed and accessing transfusion journals directly. We compared results with data from two randomized clinical studies with PAS from the past. Some important numbers were taken from national transfusion service activity reports. Results: 82 HV and related reports and 3 publications containing HV data from clinical studies were identified and reviewed. The collected data related to the following countries: Australia, Austria, Belgium, Denmark, France, Germany, Ireland, Italy, New Zealand, Russia, Spain, Sweden, UK, and Switzerland. The covered period was from 2007 until 2015, depending on the availability of HV reports and the beginning of PAS usage. In New Zealand, Switzerland and the UK, the introduction of PAS significantly reduced the rate of adverse (primarily allergic) reactions related to platelet transfusions. Furthermore, a prospective clinical study in a pediatric haematology hospital in Moscow demonstrated a significant reduction of nonhaemolitic febrile transfusion reactions for platelets prepared in SSP+ compared to those suspended in plasma. No adverse reaction related to PAS was reported in any report or publication. One bacterial transmission through a platelet concentrate in SSP+ was recorded in Austria in However, further investigations excluded the PAS as a cause of bacterial contamination. Conclusions: National HV reports are a valuable source of safety data not only for transfusion services, but also for manufacturers for the PMS program. This review of HV publications provided additional clinical data confirming a good safety profile of platelets in additive solutions. The replacement of plasma with PAS, including Macopharma SSP and SSP+, results in fewer adverse transfusion reactions. SSP+ Additive Solution THERAFLEX UV-Platelets THERAFLEX MB-Plasma 15

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17 BLOOD SAFETY POSTER ABSTRACTS 2017 ISBT COPENHAGEN

18 BLOOD SAFETY POSTER ABSTRACTS 2017 ISBT COPENHAGEN

19 BLOOD SAFETY POSTER ABSTRACTS 2017 ISBT COPENHAGEN

20 Lead the way in blood safety RCS : Lille Métropole MACOPHARMA Rue Lorthiois F Mouvaux (France)