Calibration transfer in pharmaceutical process engineering

我的研究项目侧重于开发监控和优化工业过程的方法。具体来说，我从事过程分析技术（PAT），如近红外探头（NIR），以提供有关产品的实时信息。这些探头对于适当的监测、理解和控制至关重要。为此，它们需要多变量数学模型将原始数据转换为感兴趣的变量（例如，将NIR光谱转换为成分）。然而，PAT的实施受到大规模校准模型的时间和成本的限制。在小型系统上校准模型并将其应用于工业系统要简单得多，成本效益也高得多。然而，这种转移并不容易完成。即使采集条件（例如照明强度）和材料属性（例如样品密度）的微小差异也足以阻止直接模型转移（CT：校准转移）。因此，多功能CT的发展是至关重要的工业规模和建模。我建议开发更好的方法，从小规模的应用到更大的CT。这对于改进制造以提高工艺理解、安全性和效率至关重要。它对开发新的生产方法也至关重要，例如用连续方法取代间歇方法。 我专门从事过程工程和通过使用多变量数据分析进行在线监测。我的短期目标是开发PAT来监控制药过程。 我的项目包含2个相互关联的主题：-主题1集中在用于生产药品片剂的压片机单位的校准转移。新奇在于使用存在于压制粉末中的流动中的空间信息（例如分离）来改善校准转移-主题2集中于用于药物产品中的味道掩蔽的流化床包衣单元的校准转移。新颖之处在于使用的时间信息的批处理（其动态），以改善校准转移虽然定制的制药环境，该项目涉及到任何制造业。除此之外，改进的过程监测方法，特别是那些低成本的方法，可能会影响任何工业生产。 该项目旨在使学生能够掌握质量控制，过程监控和应用统计的先进概念。这些关键概念对我们行业的福祉至关重要，下一代工程师必须接受培训以掌握它们。

My research program focuses on the development of methods to monitor and optimize industrial processes. Specifically, I work on Process Analytical Technologies (PAT), such as near infrared probes (NIR), to provide real-time information on the products. These probes are critical to proper monitoring, understanding and control. To do so, they require multivariate mathematical models to convert the raw data into a variable of interest (e.g. a NIR spectrum into composition). However, PAT implementation is limited by the time and cost to calibrate the models at large scales. It is much simpler and cost efficient to calibrate models on small systems and apply them to industrial ones. However, this transfer is not easily done. Even minor differences in acquisition conditions (e.g. lighting intensity) and material properties (e.g. sample density) may be enough to prevent direct model transfer (CT: calibration transfer). The development of versatile CT is therefore critical to industrial scale up and modeling. I propose to develop better methods for CT from small scale applications to larger ones. This is critical to the improvement of manufacturing to improve process understanding, safety and efficiency. It is also critical to the development of new production methods, such as the replacing batch processes by continuous ones. I specialize in process engineering and on-line monitoring through the use of multivariate data analysis. My short-term objectives seek to develop PAT to monitor pharmaceutical processes. My project contains 2 inter-related themes: - Theme 1 centers on calibration transfer for tablet press units used to produce pharmaceutical tablets. The novelty lies in the use of the spatial information present in the flowing in the press powder (such as segregation) to improve calibration transfer - Theme 2 centers on calibration transfer for fluid bed coating units used for taste masking in the pharmaceutical products. The novelty lies in the use of the temporal information of the batch process (its dynamics) to improve calibration transfer While tailored to a pharmaceutical context, this project pertains to any manufacturing sector. Beyond this, improved process monitoring methods, especially those available at low cost, are liable to impact any industrial production. This project seeks to put students in a position to grasp advanced concepts of quality control, process monitoring and applied statistics. These key notions are critical to the well-being of our industries and the next generation of engineers must be trained to master them.