Virus Inactivation of Fresh Frozen Plasma by a Solvent Detergent Procedure: Biological Results

Abstract

In order to increase the safety of blood products, we have developed a procedure for the virus inactivation of fresh frozen plasma. Several batches have been prepared and with the first 10 batches, each of them composed of 60 litres of plasma, we have determined a set of biological parameters. Virus inactivation was realised using TnBP (1%) and Octoxynol 9 (1%). After their elimination with castor oil using chromatography on insolubilized C18 resin, glycine was added and the pH of the plasma was adjusted to 7.4. Plastic bags were aseptically filled with a mean volume of 200 ml of plasma. The mean levels of coagulation factors were all over 0.7 U/ml and their recovery from initial plasma was nearly the same as total protein except for factor VIII:C. The net loss in factor VIII:C was 16%, when including the dilution of plasma. In vivo and in vitro tests demonstrated that in the final product there were no activated factors. As in fresh frozen plasma, the protein concentration was over 50 g/l and the potassium level lower than 5 mmol/l. According to these results, virus-inactivated plasma has the same qualities of fresh frozen plasma and could now replace it.

The Use of Solvent/Detergent Treatment in Pathogen Reduction of Plasma

“…SD treatment is preceded by filtration with a 1 μm filter to remove cells and debris, followed by sterile filtration into bags or vials using a 0.2 μm filter and aseptic filling [9]. Once manufacture of SD plasma at the Red Cross Center in Hagen was underway, Octapharma introduced the process to its factory in Vienna and licensed the process to the French Transfusion Service, which began the manufacture of SD plasma at the Centre régional de transfusion sanguine (CRTS) in Bordeaux in 1992 [11,12]. In the latter half of the 1990s, the National Bioproducts Institute (NBI) of Pinetown, South Africa, developed ABO-independent, universal plasma (Bioplasma FDP ® ) using the SD treatment manufacturing process licensed from Octapharma [13].…”

Pathogen reduction/inactivation of products for the treatment of bleeding disorders: what are the processes and what should we say to patients?

“…Process validation studies conducted in three European blood centres showed that PhC-treated plasma displayed a ~26% reduction in FVIII activity compared with that of FFP [94]. The activity level of other coagulation factors was also reduced, but to a lesser extent with clotting factor activity generally reduced by less than 20% [108]. Compared with FFP, SD-treated plasma displayed reduced activity levels for VWF and Protein S (67–76% and 35% reduction, respectively), while MB-L-treated plasma displayed lower fibrinogen activity levels (approximately 20% reduction) [94, 104, 109].…”

Solvent/detergent plasma: pharmaceutical characteristics and clinical experience

“…Neither anti-human leucocyte antigen (HLA) nor antihuman neutrophil antigen (HNA) antibodies are detectable in S/D plasma as they are diluted and neutralised by the presence of leukocytes or their fragments, which are then removed by the S/D treatment [24][25][26]. For this reason countries using S/D FFP have not reported any transfusionrelated acute lung injury (TRALI) case due to the transfusion of plasma [27,28].…”