title: Inactivation of adenovirus type 5 by caustics.
abstract: Adenovirus shows significant promise as a vehicle for transfer of therapeutic genes into humans. Based on the importance of this viral vector, it is critical that adequate decontamination procedures are implemented during its large-scale production in multiproduct manufacturing facilities to prevent cross-product contamination and to reduce the risk of personnel exposure. Liquid decontamination procedures based on caustics are easily implemented in a manufacturing setting and are not corrosive to stainless steel surfaces at the concentrations found to inactivate viral proteins and nucleic acids. In this study, we have conducted small-scale experiments to determine the effectiveness of caustic inactivation procedures on adenovirus type 5 and have evaluated the robustness of the process to different sample matrices and adenovirus constructs. We find that the pH of a sample post-addition of caustic solution is a more accurate indicator of the effectiveness of the caustic than its concentration. We have demonstrated that a greater than 6 log reduction in the potency of adenovirus type 5 may be obtained upon exposure of the sample to sodium hydroxide and CIP-100 at concentrations greater than 0.09 M and 0.9%, respectively, at times greater than 10 min.
authors.affiliation: Fermentation and Cell Culture, Bioprocess R&D, Merck Research Laboratories, West Point, Pennsylvania 19486, USA.
authors.forename: Risat
authors.initials: R
authors.lastname: Jannat
authors.forename: David
authors.initials: D
authors.lastname: Hsu
authors.forename: Gargi
authors.initials: G
authors.lastname: Maheshwari
mesh_terms: D000256:Adenoviridae / Q000187:drug effects* / Q000235:genetics; D006863:Hydrogen-Ion Concentration; D006878:Hydroxides / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D017680:Potassium Compounds / Q000494:pharmacology*; D012972:Sodium Hydroxide / Q000494:pharmacology*; D038301:Virus Inactivation / Q000187:drug effects*
chemical_list: D006878:Hydroxides; D017680:Potassium Compounds; D012972:Sodium Hydroxide; C029943:potassium hydroxide