Vox Sanguinis (2015) 109, 129–137 © 2015 International Society of Blood Transfusion DOI: 10.1111/vox.12257
ORIGINAL PAPER
Challenge study of the pathogen reduction capacity of the THERAFLEX MB-Plasma technology S. Reichenberg,1 U. Gravemann,2 C. Sumian3 & A. Seltsam2 1
Maco Pharma International GmbH, Langen, Germany Red Cross Blood Service NSTOB, Institute Springe, Springe, Germany 3 Macopharma S.A., Tourcoing, France 2
Background and Objectives Although most pathogen reduction systems for plasma primarily target viruses, bacterial contamination may also occur. This study aimed to investigate the bacterial reduction capacity of a methylene blue (MB) treatment process and its virus inactivation capacity in lipaemic plasma. Materials and Methods Bacterial concentrations in plasma units spiked with different bacterial strains were measured before and after the following steps of the THERAFLEX MB-Plasma procedure: leucocyte filtration, MB/light treatment and MB filtration. Virus inactivation was investigated for three virus types in non-lipaemic, borderline lipaemic and highly lipaemic plasma. Results Leucocyte filtration alone efficiently eliminated most of the tested bacteria by more than 4 logs (Staphylococcus epidermidis and Staphylococcus aureus) or to the limit of detection (LOD) (≥ 48 logs; Escherichia coli, Bacillus cereus and Klebsiella pneumoniae). MB/light and MB filtration further reduced Staphylococcus epidermidis and Staphylococcus aureus to below the LOD. The small bacterium Brevundimonas diminuta was reduced by 17 logs by leucocyte filtration alone, and to below the LOD by additional MB/light treatment and MB filtration (≥ 37 logs). Suid herpesvirus 1, bovine viral diarrhoea virus and human immunodeficiency virus 1 were efficiently inactivated by THERAFLEX MB-Plasma, independent of the degree of lipaemia.
Received: 11 December 2014, revised 9 January 2015, accepted 13 January 2015, published online 20 April 2015
Conclusion THERAFLEX MB-Plasma efficiently reduces bacteria, mainly via the integrated filtration system. Its virus inactivation capacity is sufficient to compensate for reduced light transparency due to lipaemia. Key words: bacterial contamination, blood safety, lipaemic plasma, pathogen inactivation, methylene blue-treated plasma.
Introduction Pathogen reduction of blood components has been performed for decades. The first systems that were introduced were effective in treating plasma used for fractionation or therapeutic purposes. Previous pathogen reduction systems for plasma focus mainly on the inactivation and removal of viruses. However, bacteria can also survive freezing and thawing. The fact that the initial Correspondence: Stefan Reichenberg, Maco Pharma International GmbH, Robert-Bosch-Strasse 11, 63225 Langen, Germany E-mail: [email protected]
bacterial load is usually low limits the hazard potential for the recipient, but bacterial transmission is still a risk that can result in serious complications [1, 2]. Methylene blue (MB) plus visible light (MB/light), a photodynamic pathogen reduction procedure for single units of fresh frozen plasma (FFP), was primarily developed to increase the viral safety of plasma transfusions [3, 4]. More than 6 million units treated by this method have been transfused to patients since more than 10 years. THERAFLEX MB-Plasma (Macopharma, Tourcoing, France) is an advancement of the original method developed by the German Red Cross in Springe. The predecessor system used a freeze/thaw step that disrupts
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white blood cells to make intracellular viruses accessible to MB [5]. In contrast, the new THERAFLEX MB-Plasma system has a leucocyte depletion filter, called Plasmaflex, which eliminates intracellular viruses by removing residual cells present in plasma. In some models, a second specially designed Blueflex filter attached to the bag system removes 90% of the residual MB and its photoproducts after illumination (Fig. 1) [6]. Passage through filters with pores
ORIGINAL PAPER
Challenge study of the pathogen reduction capacity of the THERAFLEX MB-Plasma technology S. Reichenberg,1 U. Gravemann,2 C. Sumian3 & A. Seltsam2 1
Maco Pharma International GmbH, Langen, Germany Red Cross Blood Service NSTOB, Institute Springe, Springe, Germany 3 Macopharma S.A., Tourcoing, France 2
Background and Objectives Although most pathogen reduction systems for plasma primarily target viruses, bacterial contamination may also occur. This study aimed to investigate the bacterial reduction capacity of a methylene blue (MB) treatment process and its virus inactivation capacity in lipaemic plasma. Materials and Methods Bacterial concentrations in plasma units spiked with different bacterial strains were measured before and after the following steps of the THERAFLEX MB-Plasma procedure: leucocyte filtration, MB/light treatment and MB filtration. Virus inactivation was investigated for three virus types in non-lipaemic, borderline lipaemic and highly lipaemic plasma. Results Leucocyte filtration alone efficiently eliminated most of the tested bacteria by more than 4 logs (Staphylococcus epidermidis and Staphylococcus aureus) or to the limit of detection (LOD) (≥ 48 logs; Escherichia coli, Bacillus cereus and Klebsiella pneumoniae). MB/light and MB filtration further reduced Staphylococcus epidermidis and Staphylococcus aureus to below the LOD. The small bacterium Brevundimonas diminuta was reduced by 17 logs by leucocyte filtration alone, and to below the LOD by additional MB/light treatment and MB filtration (≥ 37 logs). Suid herpesvirus 1, bovine viral diarrhoea virus and human immunodeficiency virus 1 were efficiently inactivated by THERAFLEX MB-Plasma, independent of the degree of lipaemia.
Received: 11 December 2014, revised 9 January 2015, accepted 13 January 2015, published online 20 April 2015
Conclusion THERAFLEX MB-Plasma efficiently reduces bacteria, mainly via the integrated filtration system. Its virus inactivation capacity is sufficient to compensate for reduced light transparency due to lipaemia. Key words: bacterial contamination, blood safety, lipaemic plasma, pathogen inactivation, methylene blue-treated plasma.
Introduction Pathogen reduction of blood components has been performed for decades. The first systems that were introduced were effective in treating plasma used for fractionation or therapeutic purposes. Previous pathogen reduction systems for plasma focus mainly on the inactivation and removal of viruses. However, bacteria can also survive freezing and thawing. The fact that the initial Correspondence: Stefan Reichenberg, Maco Pharma International GmbH, Robert-Bosch-Strasse 11, 63225 Langen, Germany E-mail: [email protected]
bacterial load is usually low limits the hazard potential for the recipient, but bacterial transmission is still a risk that can result in serious complications [1, 2]. Methylene blue (MB) plus visible light (MB/light), a photodynamic pathogen reduction procedure for single units of fresh frozen plasma (FFP), was primarily developed to increase the viral safety of plasma transfusions [3, 4]. More than 6 million units treated by this method have been transfused to patients since more than 10 years. THERAFLEX MB-Plasma (Macopharma, Tourcoing, France) is an advancement of the original method developed by the German Red Cross in Springe. The predecessor system used a freeze/thaw step that disrupts
129
130 S. Reichenberg et al.
white blood cells to make intracellular viruses accessible to MB [5]. In contrast, the new THERAFLEX MB-Plasma system has a leucocyte depletion filter, called Plasmaflex, which eliminates intracellular viruses by removing residual cells present in plasma. In some models, a second specially designed Blueflex filter attached to the bag system removes 90% of the residual MB and its photoproducts after illumination (Fig. 1) [6]. Passage through filters with pores
