UVC Irradiation for Pathogen Reduction of Platelet Concentrates and Plasma

Abstract

Besides the current efforts devoted to microbial risk reduction, pathogen inactivation technologies promise reduction of the residual risk of known and emerging infectious agents. A novel pathogen reduction process for platelets, the THERAFLEX UV-Platelets system, has been developed and is under clinical evaluation for its efficacy and safety. In addition, proof of principle has been shown for UVC treatment of plasma units. The pathogen reduction process is based on application of UVC light of a specific wavelength (254 nm) combined with intense agitation of the blood units to ensure a uniform treatment of all blood compartments. Due to the different absorption characteristics of nucleic acids and proteins, UVC irradiation mainly affects the nucleic acid of pathogens and leukocytes while proteins are largely preserved. UVC treatment significantly reduces the infectivity of platelet units contaminated by disease-causing viruses and bacteria. In addition, it inactivates residual white blood cells in the blood components while preserving platelet function and coagulation factors. Since no photoactive compound needs to be added to the blood units, photoreagent-related adverse events are excluded. Because of its simple and rapid procedure without the need to change the established blood component preparation procedures, UVC-based pathogen inactivation could easily be implemented in existing blood banking procedures.

Pathogen-Inaktivierungssysteme für Thrombozytenkonzentrate

“…Dabei zeigte sich mit steigender UVC-Dosis eine Zunahme der Inaktivierungseffizienz [123]. Das THERAFLEX Verfahren ist gegenwärtig für TK in Additivlösung mit einer UV-Dosis von 0,2 J/cm² ausgelegt [121]. Diese Spezifikation wurde auch in der präklinischen Entwicklung des THERAFLEX UV-Platelets Verfahrens verwendet [124,125].…”

“…Enterobacter cloacae 6,3 ± 0,6 [134] Escherichia coli 7,3 ± 0,4 [127] Klebsiella pneumoniae 5,9 ± 0,7 [127] Morganella morganii 7,5 ± 0,3 [134] Proteus mirabilis 7,0 ± 0,6 [134] Pseudomonas aeruginosa ≥ 4,92 [121] Pseudomonas fluorescens 7,1 ± 0,4 [134] Serratia marcescens 5,8 ± 0,2 [134] Bakterien, gram-positiv…”

“…4,3 ± 0,81 [121] Clostridium perfringens ≥ 4,73 [121] Propionibacterium acnes 4,53 ± 1,13 [121] Staphylococcus aureus 6,6 ± 0,4 [134] Staphylococcus epidermidis 4,6 ± 0,5 [127] Streptococcus bovis 7,0 ± 0,3 [134] Streptococcus dysgalactiae 3,5 ± 0,3 [134] Streptococcus pyogenes 4,4 ± 0,8 [134] Streptococcus pyogenes 4,1 ± 0,9 [127] a LRF: ≥ bedeutet, dass im Experiment eine vollständige Inaktivierung erreicht wurde. Die Zahl gibt die Nachweisgrenze an.…”

Pathogen reduction through additive-free short-wave uv light irradiation retains the optimal efficacy of human platelet lysate for the expansion of human bone marrow mesenchymal stem cells

“…Indeed, it has been estimated that residual quantities of S-59 (1 μg/kg) and its photoproducts (115 μg/kg) have been infused to the platelet recipient after pathogen reduction using Intercept technology [52]. Even though toxicological studies in animals [52,66] and clinical trials [67][68][69][70] have demonstrated the safety of photochemical-based pathogen reduction technologies, long-term studies may be needed for the evaluation of the risk of adverse effects, especially of carcinogenesis [23].…”

“…On the other hand, it has been difficult to assess the safety margin of psoralen or its photoproducts bound to or incorporated by platelets when transfused into a patient [23] and quantities infused into the recipient may be increased in the case of BM-hMSCs cultured for several passages in hPL prepared from pathogen-reduced PCs. Considering this and the fact that pathogen-reduced PCs using S-59 and UV-A are contraindicated in patients displaying allergy to psoralens, the use of hPL prepared from pathogen-reduced PCs using Intercept technology [36,71,72] for BM-hMSCs intended for clinical use may lead to a regulatory issue.…”