This work presents an uncertainty-conscious methodology for the assessment of process performance—for example, run time—in the manufacturing of biopharmaceutical drug products. The methodology is presented as an activity model using the type 0 integrated definition (IDEF0) functional modeling method, which systematically interconnects information, tools, and activities. In executing the methodology, a hybrid stochastic–deterministic model that can reflect operational uncertainty in the assessment result is developed using Monte Carlo simulation. This model is used in a stochastic global sensitivity analysis to identify tasks that had large impacts on process performance under the existing operational uncertainty. Other factors are considered, such as the feasibility of process modification based on Good Manufacturing Practice, and tasks to be improved is identified as the overall output. In a case study on cleaning and sterilization processes, suggestions were produced that could reduce the mean total run time of the processes by up to 40%. © 2017 American Institute of Chemical Engineers AIChE J, 2017

中文翻译：

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用于生物制药产品制造过程性能评估的不确定性意识方法

这项工作提出了一种不确定性意识的方法，用于评估生物制药产品的过程性能（例如运行时间）。该方法作为活动模型使用类型0集成定义（IDEF0）功能建模方法来表示，该模型系统地互连信息，工具和活动。在执行该方法时，使用蒙特卡洛模拟方法开发了一种可在评估结果中反映操作不确定性的混合随机确定性模型。该模型用于随机全局敏感性分析中，以识别在现有操作不确定性下对过程性能有重大影响的任务。还应考虑其他因素，例如根据《良好生产规范》进行流程修改的可行性，待改进的任务被确定为总体产出。在有关清洁和灭菌过程的案例研究中，提出了一些建议，这些建议可以将这些过程的平均总运行时间减少多达40％。©2017美国化学工程师学会AIChE的Ĵ，2017年