title: Development of a candidate reference material for adventitious virus detection in vaccine and biologicals manufacturing by deep sequencing.
abstract: BACKGROUND
  Unbiased deep sequencing offers the potential for improved adventitious virus screening in vaccines and biotherapeutics. Successful implementation of such assays will require appropriate control materials to confirm assay performance and sensitivity.
  
  
  METHODS
  A common reference material containing 25 target viruses was produced and 16 laboratories were invited to process it using their preferred adventitious virus detection assay.
  
  
  RESULTS
  Fifteen laboratories returned results, obtained using a wide range of wet-lab and informatics methods. Six of 25 target viruses were detected by all laboratories, with the remaining viruses detected by 4-14 laboratories. Six non-target viruses were detected by three or more laboratories.
  
  
  CONCLUSIONS
  The study demonstrated that a wide range of methods are currently used for adventitious virus detection screening in biological products by deep sequencing and that they can yield significantly different results. This underscores the need for common reference materials to ensure satisfactory assay performance and enable comparisons between laboratories.
authors.affiliation: Division of Virology, National Institute for Biological Standards and Control, Medicines and Healthcare Products Regulatory Agency, South Mimms, Hertfordshire EN6 3QG, United Kingdom. Electronic address: edward.mee@nibsc.org.
authors.forename: Edward T
authors.initials: ET
authors.lastname: Mee
authors.affiliation: Division of Technology, Development and Infrastructure, National Institute for Biological Standards and Control, Medicines and Healthcare Products Regulatory Agency, South Mimms, Hertfordshire EN6 3QG, United Kingdom.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Preston
authors.affiliation: Division of Virology, National Institute for Biological Standards and Control, Medicines and Healthcare Products Regulatory Agency, South Mimms, Hertfordshire EN6 3QG, United Kingdom.
authors.forename: Philip D
authors.initials: PD
authors.lastname: Minor
authors.affiliation: Division of Virology, National Institute for Biological Standards and Control, Medicines and Healthcare Products Regulatory Agency, South Mimms, Hertfordshire EN6 3QG, United Kingdom.
authors.forename: Silke
authors.initials: S
authors.lastname: Schepelmann
mesh_terms: D001688:Biological Products / Q000592:standards*; D004340:Drug Contamination / Q000517:prevention & control*; D059014:High-Throughput Nucleotide Sequencing; D007753:Laboratories; D012015:Reference Standards; D014612:Vaccines / Q000592:standards*; D014780:Viruses / Q000302:isolation & purification*
chemical_list: D001688:Biological Products; D014612:Vaccines
keywords: Adventitious virus; Collaborative study; Deep sequencing; Reference material; Vaccine