(233f) Developing Process Models of Hydrogen Peroxide Decontamination in Pharmaceutical Manufacturing

Authors: 
Sugiyama, H., The University of Tokyo
Futamura, H., Airex Co., Ltd.
Hirao, M., The University of Tokyo
Kawasaki, K., Airex Co., Ltd.
Decontamination is a critical technology for providing sterile environment in the production of sterile drug products such as injectables, intravenous bags and eye-drops. In the modern production facilities, these drug products are filled in the equipment such as isolators, which are decontaminated before the operation using vapor hydrogen peroxide. This industry-standard decontamination agent is diffused in the equipment as vapor and mist, kills the microorganisms on the surface, and removed by aeration before the filling can start. The success of this decontamination process is a prerequisite for assuring the quality of the above mentioned sterile drug products. Furthermore, decontamination is a relevant process regarding productivity, because the entire process including conditioning and aeration dominates the production time. Despite of such relevance in quality and productivity, scientific elucidation of decontamination is still in infancy, which is the obstacle to more rational design of decontamination processes.

The objective of our research is to develop a model of decontamination using hydrogen peroxide, which can serve as the basis for process design in pharmaceutical manufacturing. We aim to create a model with linking the design parameters to so-called â??D-valueâ?, and further to the objective functions such as time required for decontamination or energy consumption. D-value is the representative parameter of decontamination efficacy, and is defined as the time required to kill 90% of surviving microorganisms. As the design parameters, concentration of hydrogen peroxide as well as humidity are considered, and the influence of condensation is also taken into account in the model. The relationship between the design parameters and D-value is to be investigated by experiments using biological indicators with following the standard application procedure in the pharmaceutical industry. In addition to decontamination efficacy, our investigation will cover time and energy consumption required for the decontamination process including conditioning and aeration.

So far we set up experimental apparatus for the decontamination process in the steady-state condition, and measured D-values with varying humidity and hydrogen peroxide concentration. The preliminary results of the experiments suggested that the influence of humidity and concentration on decontamination efficacy is strong as known in the previous studies. A mathematical expression has been firstly created considering the relationship between the varied parameters and the observed D-values. This initial mathematical model will incorporate the influence of condensation on decontamination efficacy by using vapor-liquid equilibrium, diffusion, and mass transfer. Additionally, the model will cover the effect of the concentration of residual hydrogen peroxide on the product. After consideration of the condensation and the residual concentration, the time required for decontamination process will be evaluated, and the time will be linked to the objective functions. In future, we intend to create a design method for the decontamination processes using the process model to be developed in this work.