(198p) Model-Based Design of the Next-Generation Decontamination Technology for Sterile Manufacturing

In the biopharmaceutical industry, maintaining sterile conditions is of utmost importance. Isolator chambers, which are closed systems, are used to ensure aseptic production and prevent contamination of the products [1]. Isolators need to be decontaminated regularly, and the most encountered technology of decontamination in the pharmaceutical industry is vapor-phase hydrogen peroxide (VHP). This decontamination method is very effective in eliminating pathogens. However, the usage of VHP brings several challenges: (i) an excessive amount of hydrogen peroxide is needed, (ii) an important energy input is required for vaporization (iii) longer aeration time is needed, which reduces the process productivity. An alternative approach using aerosol hydrogen peroxide has been proposed to address these challenges. However, the problem with aerosol hydrogen peroxide is that it tends to be unevenly distributed inside the isolator, which reduces its efficacy in achieving complete decontamination [2]. This research work studies a new decontamination technology to improve the limited reach of aerosolized hydrogen peroxide inside the isolator by implementing ultrasound waves.

Given the complex nature of the phenomena at play, a model-based approach is required to design the new technology. The primary goal of this work is to build a model to evaluate the impact of different operation parameters, i.e., temperature, humidity, and ultrasound intensity, and geometric design parameters, i.e., ultrasound source placement inside the isolator chamber. Simulation results showed a strong dependence of the generated acoustic streaming on the parameters mentioned above. Furthermore, particle tracing simulations showed that aerosol particle size strongly impacts aerosol distribution. These results pave the way for building a comprehensive design space for ultrasound-assisted decontamination technology to guide its experimental characterization and industrial implementation.

[1] K. Yabuta, H. Futamura, M. Hirao and H. Sugiyama, "Design-oriented regression models for H₂O₂ decontamination processes in sterile drug product manufacturing considering rapidity and sterility," International Journal of Pharmaceutics, pp. 466-473, 2018.

[2] Fu TY, Gent P, Kumar V. "Efficacy, efficiency and safety aspects of hydrogen peroxide vapour and aerosolized hydrogen peroxide room disinfection systems." The Journal of hospital infection, pp. 199–205, 2012.