title: Generic/matrix evaluation of SV40 clearance by anion exchange chromatography in flow-through mode.
abstract: The potential of viral contamination is a regulatory concern for continuous cell line-derived pharmaceutical proteins. Complementary and redundant safety steps, including an evaluation of the viral clearance capacity of unit operations in the purification process, are performed prior to registration and marketing of biotechnology pharmaceuticals. Because process refinement is frequently beneficial, CBER/FDA has published guidance facilitating process improvement by delineating specific instances where the bracketing and generic approaches are appropriate for virus removal validation. In this study, a generic/matrix study was performed using Q-Sepharose Fast Flow (QSFF) chromatography to determine if bracketing and generic validation can be applied to anion exchange chromatography. Key operational parameters were varied to upper and lower extreme values and the impact on viral clearance was assessed using simian virus 40 (SV40) as the model virus. Operational ranges for key chromatography parameters were identified where an SV40 log(10) reduction value (LRV) of >or=4.7 log(10) is consistently achieved. On the basis of the apparent robustness of SV40 removal by Q-anion exchange chromatography, we propose that the concept of "bracketed generic" validation can be applied to this and potentially other chromatography unit operations.
authors.affiliation: Process Sciences, Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: Sherrie
authors.initials: S
authors.lastname: Curtis
authors.forename: Kitty
authors.initials: K
authors.lastname: Lee
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Blank
authors.forename: Kurt
authors.initials: K
authors.lastname: Brorson
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000818:Animals; D000838:Anions / Q000737:chemistry; D001688:Biological Products / Q000302:isolation & purification; D001709:Biotechnology / Q000379:methods*; D002460:Cell Line; D002847:Chromatography, Agarose; D002852:Chromatography, Ion Exchange / Q000379:methods; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics / Q000302:isolation & purification; D004340:Drug Contamination / Q000517:prevention & control*; D004553:Electric Conductivity; D006863:Hydrogen-Ion Concentration; D016133:Polymerase Chain Reaction; D013539:Simian virus 40 / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000838:Anions; D001688:Biological Products; D004279:DNA, Viral