title: Single-use technology for solvent/detergent virus inactivation of industrial plasma products.
abstract: Virus inactivation of plasma products is conducted using stainless-steel vessels. Single-use technology can offer significant benefits over stainless such as operational flexibility, reduced capital infrastructure costs, and increased efficiency by minimizing the time and validation requirements associated with hardware cleaning. This study qualifies a single-use bag system for solvent/detergent (S/D) virus inactivation.
  
  
  
  Human plasma and immunoglobulin test materials were S/D-treated in Mobius single-use bags using 1% tri-n-butyl phosphate (TnBP) with 1% Triton X-100 or 1% Tween 80 at 31°C for 4 to 6 hours to evaluate the impact on protein quality. Volatile and nonvolatile organic leachables from low-density polyethylene film (Pureflex film) used in 1-L-scale studies after exposure to S/D in phosphate-buffered saline were identified compared to controls in glass containers. Virus inactivation studies were performed with xenotropic murine leukemia virus (XMuLV) and bovine viral diarrhea virus (BVDV) to determine the kinetics of virus inactivation, measured using infectivity assays.
  
  
  
  S/D treatment in Mobius bags did not impact the protein content and profile of plasma and immunoglobulin, including proteolytic enzymes and thrombin generation. Cumulative leachable levels after exposure to S/D were 1.5 and 1.85 ppm when using 0.3% TnBP combined with 1% Tween 80 or 1% Triton X-100, respectively. Efficient inactivation of both XMuLV and BVDV was observed, with differences in the rate of inactivation dependent on both virus and S/D mixture.
  
  
  
  Effective S/D virus inactivation in single-use container technology is achievable. It does not alter plasma proteins and induces minimal release of leachables.
authors.affiliation: Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan;
authors.forename: Yao-Ting
authors.initials: YT
authors.lastname: Hsieh
authors.affiliation: Virology and Microbiological Sciences, EMD Millipore Corporation, Bedford, Massachusetts;
authors.forename: Lori
authors.initials: L
authors.lastname: Mullin
authors.affiliation: Virology and Microbiological Sciences, EMD Millipore Corporation, Bedford, Massachusetts;
authors.forename: Patricia
authors.initials: P
authors.lastname: Greenhalgh
authors.affiliation: Biomanufacturing Sciences Network, Application Engineering Group, and, EMD Millipore Corporation, Billerica, Massachusetts.
authors.forename: Michael
authors.initials: M
authors.lastname: Cunningham
authors.affiliation: Biomanufacturing Sciences Network, Application Engineering Group, and, EMD Millipore Corporation, Billerica, Massachusetts.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Goodrich
authors.affiliation: Provantage Lab Services, EMD Millipore Corporation, Billerica, Massachusetts.
authors.forename: Jessica
authors.initials: J
authors.lastname: Shea
authors.affiliation: Merck KGaA Life Sciences, Molsheim, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Youssef
authors.affiliation: Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan;
authors.forename: Thierry
authors.initials: T
authors.lastname: Burnouf
mesh_terms: D000818:Animals; D002417:Cattle; D003902:Detergents / Q000494:pharmacology*; D001908:Diarrhea Viruses, Bovine Viral; D006801:Humans; D007221:Industry; D007700:Kinetics; D009052:Leukemia Virus, Murine; D051379:Mice; D010949:Plasma / Q000382:microbiology; D012997:Solvents / Q000494:pharmacology; D038301:Virus Inactivation / Q000187:drug effects*
chemical_list: D003902:Detergents; D012997:Solvents