title: Evaluation of virus and prion reduction in a new intravenous immunoglobulin manufacturing process.
abstract: OBJECTIVE
  Minimizing the transmission risk of infectious diseases is of primary importance in the manufacture of products derived from human plasma. A novel chromatography-based intravenous immunoglobulin (IGIV) manufacturing process was developed and the reduction of virus and transmissible spongiform encephalopathies (TSE) during the manufacturing process was assessed. Mechanistically distinct steps that could affect virus reduction were identified, and the robustness of virus reduction over the range of process conditions was determined.
  
  
  METHODS
  Virus and TSE reduction by processing steps were assessed using a scaled-down version of the IGIV manufacturing process.
  
  
  RESULTS
  Virus and TSE reduction at manufacturing process set points were well within safety standards. Robustness studies verified that the reproducibility of virus reduction was maintained at or beyond operating parameter extremes. Virus reduction across two combined manufacturing steps was lower than the sum of virus-reduction values across the individual steps, indicating mechanistic similarity of the two steps with respect to virus reduction. Only reduction from mechanistically distinct steps was claimed.
  
  
  CONCLUSIONS
  This comprehensive approach to pathogen safety provides the new immunoglobulin manufacturing process with a detailed, yet realistic, assessment of the risk of transmission of infectious pathogens.
authors.affiliation: Pre-Clinical Research and Pathogen Safety, Bayer Healthcare, Biological Products Division, Research Triangle Park, North Carolina, USA.
authors.forename: S R
authors.initials: SR
authors.lastname: Trejo
authors.forename: J A
authors.initials: JA
authors.lastname: Hotta
authors.forename: W
authors.initials: W
authors.lastname: Lebing
authors.forename: C
authors.initials: C
authors.lastname: Stenland
authors.forename: R E
authors.initials: RE
authors.lastname: Storms
authors.forename: D C
authors.initials: DC
authors.lastname: Lee
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.forename: S
authors.initials: S
authors.lastname: Petteway
authors.forename: K M
authors.initials: KM
authors.lastname: Remington
mesh_terms: D002210:Caprylates / Q000494:pharmacology; D011232:Chemical Precipitation; D002845:Chromatography; D004203:Disinfection / Q000379:methods* / Q000592:standards; D004340:Drug Contamination / Q000517:prevention & control; D004345:Drug Industry / Q000379:methods* / Q000592:standards; D005374:Filtration; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000592:standards*; D008420:Manufactured Materials / Q000592:standards / Q000821:virology; D017096:Prion Diseases / Q000517:prevention & control / Q000635:transmission; D011328:Prions / Q000302:isolation & purification*; D014777:Virus Diseases / Q000517:prevention & control / Q000635:transmission; D014780:Viruses / Q000302:isolation & purification*
chemical_list: D002210:Caprylates; D016756:Immunoglobulins, Intravenous; D011328:Prions; C031492:octanoic acid