title: Studies on the removal of abnormal prion protein by processes used in the manufacture of human plasma products.
abstract: OBJECTIVE
  To identify if any process steps used in plasma fractionation may have a capability of removing agents of human transmissible spongiform encephalopathy (TSE).
  
  
  METHODS
  Sixteen fractionation steps were investigated separately by adding a preparation of hamster adapted scrapie 263K to the starting material at each process step and determining the distribution into resultant fractions of protease-K-resistant (abnormal) prion protein by Western blot analysis.
  
  
  RESULTS
  A number of process operations were found to remove abnormal prion protein to the limit of detection of the assay. These were cold ethanol precipitation of fraction IV (log reduction, LR, >/=3.0) and a depth filtration (LR >/=4.9) in the albumin process; cold ethanol fraction I+III precipitation (LR >/=3.7) and a depth filtration (LR >/=2.8) in the immunoglobulin processes and adsorption with DEAE-Toyopearl 650M ion exchanger (LR >/=3.5) in the fibrinogen process. In addition, a substantial degree of removal of abnormal prion protein was observed across DEAE-Toyopearl 650M ion exchange (LR = 3.1) used in the preparation of factor-VIII concentrate; DEAE-cellulose ion exchange (LR = 3.0) and DEAE-sepharose ion exchange (LR = 3.0) used in the preparation of factor-IX concentrates and S-sepharose ion exchange (LR = 2.9) used in the preparation of thrombin.
  
  
  CONCLUSIONS
  Plasma fractionation processes used in the manufacture of albumin, immunoglobulins, factor-VIII concentrate, factor-IX concentrates, fibrinogen and thrombin all contain steps which may be capable of removing causative agents of human TSEs.
authors.affiliation: Scottish National Blood Transfusion Service Protein Fractionation Centre, Edinburgh, UK. peter.foster@snbts.csa.scot.nhs.uk
authors.forename: P R
authors.initials: PR
authors.lastname: Foster
authors.forename: A G
authors.initials: AG
authors.lastname: Welch
authors.forename: C
authors.initials: C
authors.lastname: McLean
authors.forename: B D
authors.initials: BD
authors.lastname: Griffin
authors.forename: J C
authors.initials: JC
authors.lastname: Hardy
authors.forename: A
authors.initials: A
authors.lastname: Bartley
authors.forename: S
authors.initials: S
authors.lastname: MacDonald
authors.forename: A C
authors.initials: AC
authors.lastname: Bailey
mesh_terms: D000818:Animals; D001921:Brain; D005591:Chemical Fractionation; D002852:Chromatography, Ion Exchange; D003257:Consumer Product Safety; D006224:Cricetinae; D005590:Fractional Precipitation; D006801:Humans; D008420:Manufactured Materials / Q000592:standards / Q000821:virology; D010949:Plasma / Q000737:chemistry*; D018620:PrPSc Proteins / Q000737:chemistry* / Q000302:isolation & purification; D017096:Prion Diseases / Q000209:etiology / Q000517:prevention & control; D012608:Scrapie
chemical_list: D018620:PrPSc Proteins