Solvent/detergent-treated plasma: a virus-inactivated substitute for fresh frozen plasma

Abstract

Fresh frozen plasma (FFP) is prepared in blood banks world-wide as a by- product of red blood cell concentrate preparation. Appropriate clinical use is for coagulation factor disorders where appropriate concentrates are unavailable and when multiple coagulation factor deficits occur such as in surgery. Viral safety depends on donor selection and screening; thus, there continues to be a small but defined risk of viral transmission comparable with that exhibited by whole blood. We have prepared a virus sterilized FFP (S/D-FFP) by treatment of FFP with 1% tri(n-butyl)phosphate (TNBP) and 1% Triton X-100 at 30 degrees C for 4 hours. Added reagents are removed by extraction with soybean oil and chromatography on insolubilized C18 resin. Treatment results in the rapid and complete inactivation of greater than or equal to 10(7.5) infectious doses (ID50) of vesicular stomatitis virus (VSV) and greater than or equal to 10(6.9) ID50 of sindbis virus (used as marker viruses), greater than or equal to 10(6.2) ID50 of human immunodeficiency virus (HIV), greater than or equal to 10(6) chimp infectious doses (CID50) of hepatitis B virus (HBV), and greater than or equal to 10(5) CID50 of hepatitis C virus (HCV). Immunization of rabbits with S/D-FFP and subsequent adsorption of elicited antibodies with untreated FFP confirmed the absence of neoimmungen formation. Coagulation factor content was comparable with that found in FFP. Based on these laboratory and animal studies, together with the extensive history of the successful use of S/D-treated coagulation factor concentrates, we conclude that replacement of FFP with S/D-FFP, prepared in a manufacturing facility, will result in improved virus safety and product uniformity with no loss of efficacy.

SARS-coronavirus (SARS-CoV) and the safety of a solvent/detergent (S/D) treated immunoglobulin preparation

“…The SD method irreversibly disrupts the lipid coat of enveloped viruses and its associated binding sites under mild process conditions. The efficacy of the SD method has been extensively validated with human and model viruses, as weIl as by animal studies under both standard and robustness conditions of the product-specific manufacturing processes [1,9,17]. Due to the nonselective mode of action, the SD method is capable of inactivating not only the viruses of most concern, e.g.…”

Preparation, quality criteria, and properties of human blood platelet lysate supplements for ex vivo stem cell expansion

“…However, pooling increases the need for implementation of dedicated viral-inactivation treatment(s) when PLs are used for clinical-grade SC expansion. A solvent/detergent (S/D) treatment developed for inactivating lipid-enveloped viruses (e.g., HIV, HBV, and HCV) in plasma [85] was adapted for pooled PL supplements for ex vivo SC expansion and other uses in regenerative medicine [86]. The treatment contributes to an extensive release of platelet growth factors [86].…”

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

“…Working with the German Red Cross Center in Hagen, Germany, Octapharma matured the laboratory process to a form suitable for industrial-scale manufacturing. Characterization of the manufactured product was published in 1992 [4], at which time also Horowitz and his collaborators published their results [5]. Biesert and Shartono [6] subsequently validated the robustness of SD plasma treatment in their study of the virus safety of Octaplas ® (Octapharma AG, Lachen, Switzerland).…”

“…The concentration of tri-(N-butyl)-phosphate (TNBP) was increased from 0.3 to 1% to accommodate the lipid content of plasma, and temperature was raised to 30 °C for 4 h to ensure efficient virus kill [4,5]. Sodium cholate, the usual detergent used in the SD treatment of coagulation factors, was substituted by 1% polyoxyethylene-p-t-octylphenol (Triton X-100), because it can easily be removed together with TNBP by a simple and effective hydrophobic chromatographic step [7].…”