title: TSE clearance during plasma products separation process by Gradiflow(TM).
abstract: OBJECTIVE
  Recent experimental evidence from rodent models suggests a potential risk for transmissible spongiform encephalopathy (TSE) transmission by blood. The emergence of a new variant Creutzfeldt-Jakob disease (vCJD) has raised increased concerns about the safety of blood components and plasma products derived from vCJD-infected donors. Recent risk-minimisation strategies have included a ban on the use of UK-sourced plasma for the preparation of licensed blood products and leukodepletion of blood donations for fear of possible transmission of the human TSE via blood or blood components. The aim of this study was to investigate the capability and efficacy of a preparative electrophoresis system (Gradiflow) in the removal of TSE contaminants during the separation of plasma products.
  
  
  METHODS
  Using hamster adapted scrapie 263 K as a model for TSE agent, albumin and IgG separation from human plasma by Gradiflow were performed separately by spiking a 263 K scrapie microsomal fraction to the feed material at each process step. Samples from pre- and post-Gradiflow separation process were titrated to the end-point for the detection of the disease-associated, proteinase K resistant form of the pathogenic prion protein (PrP(Sc)) by Western blot.
  
  
  RESULTS
  Under all conditions tested, a greater than 3 log(10) reduction was achieved with no PrP(Sc) detected in any of the pooled products for either of the IgG or albumin separations. These data show that Gradiflow processing has clear advantages for concurrent purification of plasma products and in-process TSE removal.
  
  
  CONCLUSIONS
  Our findings suggest that Gradiflow process is a viable alternative to remove causative TSE agents during plasma products separation, potentially eliminating the risk of TSE agents transmission.
authors.affiliation: Commercial Separations Division, Gradipore, NSW 2086, Australia. Kailing.wang@life-therapeutics.com
authors.forename: Kailing
authors.initials: K
authors.lastname: Wang
authors.forename: Annalese
authors.initials: A
authors.lastname: Johnson
authors.forename: Mina
authors.initials: M
authors.lastname: Obradovic
authors.forename: Graeme
authors.initials: G
authors.lastname: Anderson
authors.forename: Christine
authors.initials: C
authors.lastname: Maclean
authors.forename: Hari
authors.initials: H
authors.lastname: Nair
mesh_terms: D000818:Animals; D001769:Blood; D015153:Blotting, Western; D006224:Cricetinae; D006801:Humans; D018620:PrPSc Proteins / Q000097:blood*; D017096:Prion Diseases / Q000517:prevention & control* / Q000635:transmission; D014461:Ultracentrifugation
chemical_list: D018620:PrPSc Proteins