title: Prion removal capacity of plasma protein manufacturing processes: a data collection from PPTA member companies.
abstract: BACKGROUND
  The variant Creutzfeldt-Jakob disease incidence peaked a decade ago and has since declined. Based on epidemiologic evidence, the causative agent, pathogenic prion, has not constituted a tangible contamination threat to large-scale manufacturing of human plasma-derived proteins. Nonetheless, manufacturers have studied the prion removal capabilities of various manufacturing steps to better understand product safety. Collectively analyzing the results could reveal experimental reproducibility and detect trends and mechanisms driving prion removal.
  
  
  METHODS
  Plasma Protein Therapeutics Association member companies collected more than 200 prion removal studies on plasma protein manufacturing steps, including precipitation, adsorption, chromatography, and filtration, as well as combined steps. The studies used a range of model spiking agents and bench-scale process replicas. The results were grouped based on key manufacturing variables to identify factors impacting removal. The log reduction values of a group are presented for comparison.
  
  
  RESULTS
  Overall prion removal capacities evaluated by independent groups were in good agreement. The removal capacity evaluated using biochemical assays was consistent with prion infectivity removal measured by animal bioassays. Similar reduction values were observed for a given step using various spiking agents, except highly purified prion protein in some circumstances. Comparison between combined and single-step studies revealed complementary or overlapping removal mechanisms. Steps with high removal capacities represent the conditions where the physiochemical differences between prions and therapeutic proteins are most significant.
  
  
  CONCLUSIONS
  The results support the intrinsic ability of certain plasma protein manufacturing steps to remove prions in case of an unlikely contamination, providing a safeguard to products.
authors.affiliation: Baxter BioScience, Vienna, Austria; Biotest AG, Dreieich, Germany; CSL Behring, Marburg, Germany; CSL Behring, Berne, Switzerland; Grifols, Research Triangle Park, North Carolina; Grifols, Parets del Vallès, Spain; Kedrion, Castelvecchio Pascoli, Italy; PPTA, Brussels, Belgium.
authors.forename: Kang
authors.initials: K
authors.lastname: Cai
authors.forename: Albrecht
authors.initials: A
authors.lastname: Gröner
authors.forename: Herbert O
authors.initials: HO
authors.lastname: Dichtelmüller
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Fabbrizzi
authors.forename: Eckhard
authors.initials: E
authors.lastname: Flechsig
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Gajardo
authors.forename: Ilka
authors.initials: I
authors.lastname: von Hoegen
authors.forename: Juan I
authors.initials: JI
authors.lastname: Jorquera
authors.forename: Christoph
authors.initials: C
authors.lastname: Kempf
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Kreil
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Lee
authors.forename: Mila
authors.initials: M
authors.lastname: Moscardini
authors.forename: Gerhard
authors.initials: G
authors.lastname: Pölsler
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Roth
mesh_terms: D001798:Blood Proteins / Q000737:chemistry*; D011232:Chemical Precipitation; D002846:Chromatography, Affinity; D002852:Chromatography, Ion Exchange; D007562:Creutzfeldt-Jakob Syndrome / Q000517:prevention & control; D004340:Drug Contamination / Q000517:prevention & control; D005374:Filtration; D006801:Humans; D011328:Prions / Q000302:isolation & purification*
chemical_list: D001798:Blood Proteins; D011328:Prions