title: Hepatitis E virus and the safety of plasma products: investigations into the reduction capacity of manufacturing processes.
abstract: BACKGROUND
  Hepatitis E virus (HEV) has been transmitted by transfusion of labile blood products and the occasional detection of HEV RNA in plasma pools indicates that HEV viremic donations might enter the manufacturing process of plasma products. To verify the safety margins of plasma products with respect to HEV, virus reduction steps commonly used in their manufacturing processes were investigated for their effectiveness to reduce HEV.
  
  
  METHODS
  Detection methods for HEV removal (by reverse transcription quantitative polymerase chain reaction) and inactivation (using an infectivity assay) were established. Immunoaffinity chromatography and 20-nm virus filtration for Factor (F)VIII, cold ethanol fractionation, and low-pH treatment for immunoglobulin, heat treatment for human albumin, and 35-nm nanofiltration for FVIII inhibitor-bypassing activity (FEIBA) were investigated for their capacity to reduce HEV or the physicochemically similar viruses feline calicivirus (FCV) and hepatitis A virus (HAV).
  
  
  RESULTS
  For FVIII, HEV reduction of 3.9 and more than 3.9 log was demonstrated for immunoaffinity chromatography and 20-nm nanofiltration, respectively, and the cold ethanol fractionation for immunoglobulin removed more than 3.5 log of HEV, to below the limit of detection (LOD). Heat treatment of human albumin inactivated more than 3.1 log of HEV to below the LOD and 35-nm nanofiltration removed 4.0 log of HEV from the FEIBA intermediate. The results indicated HAV rather than FCV as the more relevant model virus for HEV.
  
  
  CONCLUSIONS
  Substantial HEV reduction during processes commonly used in the manufacturing of plasma products was demonstrated, similar to that previously demonstrated for HAV.
authors.affiliation: Global Pathogen Safety, Baxalta (previously Baxter BioScience), Vienna, Austria.
authors.forename: Maria R
authors.initials: MR
authors.lastname: Farcet
authors.affiliation: Global Pathogen Safety, Baxalta (previously Baxter BioScience), Vienna, Austria.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Lackner
authors.affiliation: Global Pathogen Safety, Baxalta (previously Baxter BioScience), Vienna, Austria.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Antoine
authors.affiliation: Global Pathogen Safety, Baxalta (previously Baxter BioScience), Vienna, Austria.
authors.forename: Philip O
authors.initials: PO
authors.lastname: Rabel
authors.affiliation: Global Pathogen Safety, Baxalta (previously Baxter BioScience), Vienna, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Wieser
authors.affiliation: Global Pathogen Safety, Baxalta (previously Baxter BioScience), Vienna, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Flicker
authors.affiliation: Global Pathogen Safety, Baxalta (previously Baxter BioScience), Vienna, Austria.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Unger
authors.affiliation: Global Pathogen Safety, Baxalta (previously Baxter BioScience), Vienna, Austria.
authors.forename: Jens
authors.initials: J
authors.lastname: Modrof
authors.affiliation: Global Pathogen Safety, Baxalta (previously Baxter BioScience), Vienna, Austria.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Kreil
mesh_terms: D058731:Blood Safety / Q000379:methods*; D005169:Factor VIII / Q000737:chemistry; D056945:Hep G2 Cells; D016752:Hepatitis E virus; D006801:Humans; D010949:Plasma / Q000737:chemistry* / Q000821:virology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D038301:Virus Inactivation
chemical_list: C078147:F8 protein, human; D005169:Factor VIII