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.

Universal fresh‐frozen plasma (Uniplas): an exploratory study in adult patients undergoing elective liver resection

“…In agreement with previous reports [3–5,8], the current study demonstrated no viral transmission; however, passive immunization was evident for both anti‐HAV IgG and parvovirus B19 IgG.…”

“…It has been developed by Octapharma (Octapharma AG, Lachen, Switzerland) and is obtained by the proportional pooling of A, B and AB plasma in order to neutralize anti‐A and anti‐B immunoglobulins by A and B antigens (substances), and possible anti‐idiotypic antibodies, in plasma [2]. Virus inactivation is achieved by solvent/detergent (SD) treatment [3]. SD treatment is a well‐documented method used for virus inactivation and an extremely effective way to eliminate enveloped viruses from plasma and plasma products [4], while non‐enveloped viruses can be inhibited by immune antibodies in the plasma pool [5].…”

Expansion of adipose tissue mesenchymal stromal progenitors in serum‐free medium supplemented with virally inactivated allogeneic human platelet lysate

“…However, these technologies aim at altering pathogen nucleic acids and the conditions have been developed for preserving PLT integrity, 41 therefore limiting the release of the GF from the α‐granules. The reasons why we selected the S/D treatment are directly linked to the fact that it is a well‐established procedure to destroy lipid‐enveloped viruses that 1) preserves the functional activity of most proteins, 38,40,42 2) induces PLT lysis and massive release of GF, 31 and 3) can be readily applied to pooled PLT concentrates for small‐, medium‐, or large‐scale production as it has been for plasma products 43 . Removal of the S/D agents can be achieved by oil extraction and hydrophobic interaction chromatography, a mild process already used in the plasma industry 43 .…”

“…The reasons why we selected the S/D treatment are directly linked to the fact that it is a well‐established procedure to destroy lipid‐enveloped viruses that 1) preserves the functional activity of most proteins, 38,40,42 2) induces PLT lysis and massive release of GF, 31 and 3) can be readily applied to pooled PLT concentrates for small‐, medium‐, or large‐scale production as it has been for plasma products 43 . Removal of the S/D agents can be achieved by oil extraction and hydrophobic interaction chromatography, a mild process already used in the plasma industry 43 . The process includes centrifugation and a 0.2‐µm filtration step that remove blood cell membrane fragments, therefore reducing risks of alloimmunization in treated patients.…”

Immunologic analyses of bovine bone treated with a novel tissue sterilization process

“…The process provides for complete penetration of the inner matrices of tissue, removal of any contaminants as well as blood, bone marrow, and other unwanted endogenous materials through an extensive serial dilution process [26, 27]. As part of the BioCleanse ® process, two detergents, which have been proven to be inactivators of enveloped viruses, are used in combination [28, 29]. In accordance with the standardized BioCleanse ® protocol, bovine bone samples were submerged in a closed chamber and exposed to the previously mentioned cleansing solutions at varying pressures and alternated with vacuum cycles.…”