Design-oriented regression models for HO decontamination processes in sterile drug product manufacturing considering rapidity and sterility.

We developed regression models for designing rapid and effective HO decontamination processes in the manufacturing of sterile drug products such as injectables. Decontamination, which is typically performed by using HO, is a critical changeover process used to establish a sterile environment for filling products. In the process, there is a trade-off relationship between the duration of the process and the level of sterility assurance that needs to be considered in the design. Our model defines these two items as objective functions and the parameters describing the profile of HO injection and the initial humidity as design variables. Our model also considers aeration, i.e., removal of HO from the environment, as a part of the entire process. This design-oriented modeling considering the entire process is the novelty of the work. Experiments were performed using an industrial isolator to develop and validate a set of regression models that describe the relationship between the design variables and the objective functions. In the application of the model, Pareto-optimal conditions could be indicated given the target HO concentration in aeration, which is useful for the makers of drugs and/or isolators for designing decontamination processes.