Inactivation of adenovirus type 5 by caustics

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.