A potentially improved approach to methylene blue virus inactivation of plasma: the Maco Pharma Maco‐Tronic system

Abstract

Plasma was subjected to methylene blue (MB) photochemical virus inactivation using the Maco Pharma Maco-Tronic system which allows three units to be illuminated together, thus reducing processing time. The plasma bag system used incorporates an integral membrane plasma filter and a dry MB pill which dissolves in the plasma to give a 1-microM concentration. There is computer-controlled processing and datalogging. In an assessment of 10 pools of Group A plasma, the losses of coagulation factors, following MB/light treatment, were 23% fibrinogen, 10% FV, 26% FVIII, 11% FIX and 13% FXI. Group O, Group B and Group AB plasmas were not tested. Von Willebrand factor (vWf) multimers showed no substantial change when treated with MB, and no losses were seen for antithrombin III (ATIII), protein C and vWf:Ag. Measurements of C3a, C5a, prothrombin fragment 1+2 and FXIIa indicated that there was no activation as a result of filtration.

The effect of methylene blue photoinactivation and methylene blue removal on the quality of fresh‐frozen plasma

“…All units of plasma were frozen within 8 hours of collection in a freezer (Thermogenesis MP1101, Cheshire, UK) to −45°C within 45 minutes and stored frozen at −40°C for 4 days to 4 weeks. The units were then thawed at 37°C and immediately WBC reduced (PLAS 4, Maco Pharma, Middlesex, UK) and MB photoinactivated (Maco Pharma Maco‐Tronic system) as previously described 11 . For each pair of plasmas, MB was removed (either Pall MB1 or Maco Pharma Blueflex) according to the manufacturers’ instructions.…”

“…For MB photoinactivation of plasma to be centralized, but plasma from remote sites used as a start material, it is essential to be able to freeze and thaw plasma before treatment. Although we have previously evaluated the use of the two systems (Baxter and Maco Pharma) using fresh plasma, 10‐12 we have not evaluated freeze‐thawing of plasma before MB treatment using such systems. Although it is known that freeze‐thawing itself has minimal effect on the coagulation factor activity of plasma, 7 there are no comparative data available on whether the loss of coagulation factor activity due to the MB inactivation step is affected by prior freeze‐thawing.…”

Main Properties of the THERAFLEX MB-Plasma System for Pathogen Reduction

“…The effect of MB treatment on coagulation factors and anticoagulant proteins in plasma has been widely published and reviewed elsewhere [4,38,50,[58][59][60]. In brief, the loss of coagulation factors is mainly due to photo-oxidation of the proteins during the illumination process, and the loss caused by other steps, such as freeze-thawing, leucocyte filtration or MB removal, is negligible or limited [61], meeting phase 1 and 2 validation requirements.…”

“…non-treated FFP based on a limited number of samples tested [59] but remain within the specification set by the Council of Europe Guidelines, i.e. factor VIII ≥70% of the value of the freshly collected plasma unit [71].…”

Thrombin Generation Capacity of Methylene Blue-Treated Plasma Prepared by the Theraflex MB Plasma System

“…Mainly two different manufacturing procedures are applied, following either the original 'Springe Procedure' [1] or using the modified Theraflex ® MB Plasma System [5]. The methods differ in the way MB is added to the plasma.…”