Department of Chemical System Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
Airex Co., Ltd., Tsubaki-cho, Nakamura-ku, Nagoya-shi, Aichi 453-0015, Japan.
Int J Pharm. 2018 Sep 5;548(1):466-473. doi: 10.1016/j.ijpharm.2018.06.055. Epub 2018 Jun 30.
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.
我们开发了回归模型，用于设计无菌药物产品（如注射剂）制造过程中的快速有效的 HO 去污工艺。去污通常使用 HO 进行，是用于为产品灌装建立无菌环境的关键转换过程。在该过程中，需要在设计中考虑工艺持续时间和所需的无菌保证水平之间的权衡关系。我们的模型将这两个项目定义为目标函数，并将描述 HO 注射和初始湿度的参数定义为设计变量。我们的模型还将通风（即从环境中去除 HO）视为整个过程的一部分。这种考虑整个过程的面向设计的建模是这项工作的新颖之处。实验使用工业隔离器进行，以开发和验证一组回归模型，这些模型描述了设计变量与目标函数之间的关系。在模型的应用中，可以根据通风中的目标 HO 浓度指示帕累托最优条件，这对于药物制造商和/或隔离器制造商设计去污工艺非常有用。
