title: A survey of quality attributes of virus spike preparations used in clearance studies.
abstract: Demonstration of effective and consistent viral clearance by small scale models of downstream processing, typically cited as logarithmic reduction value (LRV), is an important safety requirement for biotech products. LRVs have anecdotally been reported to be inconsistent in these small-scale studies, even under controlled conditions when all process parameters are held constant. It was postulated that the quality of virus spike preparations used can in some cases adversely affect performance of these studies, which, from a regulatory standpoint, would be undesirable. This, along with topics discussed in PDA's Technical Report 47 (TR47), "Virus Preparations Used in Viral Clearance Studies," suggests that improving the quality and consistency of virus spike quality and utilizing testing procedures as described within should make these studies more reliable. However, an extensive survey to assess overall quality attributes to date has not been performed. To scout the landscape of spike preparation quality, we systematically characterized 18 commercially available virus preparations, focusing on key attributes identified in TR47: (1) infectious/total- and infectious/particle-associated copy numbers, (2) exogenous DNA/protein content and banding patterns, and (3) presence of aggregates. We found substantial variation across many of the preparations tested, often in more than one category. By modeling small-virus retentive filtration and low-pH inactivation unit operations, we show that virus preparation quality can potentially affect unit operation performance and viral clearance outcome. Our data supports the notion that during early-phase development, characterization of virus stock quality may provide an added level of control.
  Demonstration of effective and consistent viral clearance is an important safety requirement for biotech products. However, accumulating evidence suggests that the quality of virus preparations used in clearance studies often vary, and thus potentially affect their performance. To scout the landscape of virus preparation quality, we systematically characterized 18 commercially available virus preparations, focusing on key attributes identified in PDA's Technical Report 47 (TR47). Virus Preparations Used in Viral Clearance Studies. We found substantial variation across many of the preparations tested, often in more than one attribute category. By performing small-virus retentive filtration and low-pH inactivation unit operations on a small scale, we also show that virus preparation quality can affect unit operation performance and viral clearance outcome. Our data supports the notion that during early-phase development, characterization of virus stock quality may provide an added level of control.
authors.affiliation: Office of Biotechnology Products, CDER/FDA, 10903 New Hampshire Ave. Silver Spring, MD 20903.
authors.forename: George
authors.initials: G
authors.lastname: Miesegaes
authors.forename: Scott
authors.initials: S
authors.lastname: Lute
authors.forename: Jessica
authors.initials: J
authors.lastname: Dement-Brown
authors.forename: Simran
authors.initials: S
authors.lastname: Kaushal
authors.forename: Daniel
authors.initials: D
authors.lastname: Strauss
authors.forename: Dayue
authors.initials: D
authors.lastname: Chen
authors.forename: Kurt
authors.initials: K
authors.lastname: Brorson
mesh_terms: D005374:Filtration; D007700:Kinetics; D004364:Pharmaceutical Preparations; D011786:Quality Control; D011795:Surveys and Questionnaires; D038301:Virus Inactivation; D014780:Viruses
chemical_list: D004364:Pharmaceutical Preparations