Single-use technology for solvent/detergent virus inactivation of industrial plasma products.

BACKGROUND: Virus inactivation of plasma products is conducted using stainless-steel vessels. Single-use technology can offer significant benefits over stainless such as operational flexibility, reduced capital infrastructure costs, and increased efficiency by minimizing the time and validation requirements associated with hardware cleaning. This study qualifies a single-use bag system for solvent/detergent (S/D) virus inactivation. STUDY DESIGN AND METHODS: Human plasma and immunoglobulin test materials were S/D-treated in Mobius single-use bags using 1% tri-n-butyl phosphate (TnBP) with 1% Triton X-100 or 1% Tween 80 at 31°C for 4 to 6 hours to evaluate the impact on protein quality. Volatile and nonvolatile organic leachables from low-density polyethylene film (Pureflex film) used in 1-L-scale studies after exposure to S/D in phosphate-buffered saline were identified compared to controls in glass containers. Virus inactivation studies were performed with xenotropic murine leukemia virus (XMuLV) and bovine viral diarrhea virus (BVDV) to determine the kinetics of virus inactivation, measured using infectivity assays. RESULTS: S/D treatment in Mobius bags did not impact the protein content and profile of plasma and immunoglobulin, including proteolytic enzymes and thrombin generation. Cumulative leachable levels after exposure to S/D were 1.5 and 1.85 ppm when using 0.3% TnBP combined with 1% Tween 80 or 1% Triton X-100, respectively. Efficient inactivation of both XMuLV and BVDV was observed, with differences in the rate of inactivation dependent on both virus and S/D mixture. CONCLUSION: Effective S/D virus inactivation in single-use container technology is achievable. It does not alter plasma proteins and induces minimal release of leachables.

Continuous In-Line Virus Inactivation for Next Generation Bioprocessing.

Viral inactivation plays a critical role in assuring the safety of monoclonal antibody (mAb) therapeutics. Traditional viral inactivation involves large holding tanks in which product is maintained at a target low pH for a defined hold time, typically 30-60 min. The drive toward continuous processing and improved facility utilization has provided motivation for development of a continuous viral inactivation process. To this end, a lab-scale prototype viral inactivation system was designed, built, and characterized. Multiple incubation chamber designs are evaluated to identify the optimal design that enables narrow residence time distributions in continuous flow systems. Extensive analysis is conducted supporting rapid low pH viral inactivation and included evaluations with multiple viruses, a range of pH levels, buffer compositions, mAb concentrations, and temperatures. Multiple test conditions are evaluated using the in-line system and results compared to traditional batch-mode viral inactivation. Comparability in kinetics of virus inactivation suggests equivalency between the two approaches.