An Optimization-Based Framework to Define the Probabilistic Design Space of Pharmaceutical Processes with Model Uncertainty [electronic resource]

• Ngôn ngữ: eng
• Ký hiệu phân loại: 664.9 Meats and allied foods
• Thông tin xuất bản: Washington, D.C. : Oak Ridge, Tenn. : United States. National Nuclear Security Administration ; Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy, 2019
• Mô tả vật lý: Size: Article No. 96 : , digital, PDF file.
• Bộ sưu tập: Metadata
• ID: 260067
• Chủ đề: 1. 60 applied life sciences; 2. Flexibility analysis; 3. Global optimization; 4. Pharmaceutical processes; 5. Probabilistic design space

Tóm tắt

To increase manufacturing flexibility and system understanding in pharmaceutical development, the FDA launched the quality by design (QbD) initiative. Within QbD, the design space is the multidimensional region (of the input variables and process parameters) where product quality is assured. Given the high cost of extensive experimentation, there is a need for computational methods to estimate the probabilistic design space that considers interactions between critical process parameters and critical quality attributes, as well as model uncertainty. In this paper we propose two algorithms that extend the flexibility test and flexibility index formulations to replace simulation-based analysis and identify the probabilistic design space more efficiently. The effectiveness and computational efficiency of these approaches is shown on a small example and an industrial case study.