Data-driven model predictive control for continuous pharmaceutical manufacturing

IF 5.2 2区 医学 Q1 PHARMACOLOGY & PHARMACY International Journal of Pharmaceutics Pub Date : 2025-02-05 DOI:10.1016/j.ijpharm.2025.125322
Consuelo Vega-Zambrano , Nikolaos A. Diangelakis , Vassilis M. Charitopoulos
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Abstract

This study demonstrates that the development of interpretable, data-driven models for pharmaceutical continuous manufacturing is feasible using a machine learning method called Dynamic Mode Decomposition with Control (DMDc). This approach facilitates adoption within Good Manufacturing Practice (GMP)-regulated areas in the pharmaceutical industry. Furthermore, since the pharmaceutical industry needs to be more operationally efficient to be profitable and sustainable, we present a real-time monitoring strategy framework using an interpretable DMDc dynamic model for the design and tuning of a model predictive control (MPC) system for granule size control in a twin-screw granulation process. This model exhibits low computational complexity without requiring first principles knowledge, while effectively capturing nonlinear dynamics of this multiple input multiple output (MIMO) system, with enhanced performance (e.g., R2 > 0.93 for D50 predictions) in the reconstruction of unseen test data in comparison with benchmark data-driven methods for system identification. The DMDc-MPC was implemented and tested on setpoint tracking and disturbance rejection and the proposed advanced process control framework guaranteed both.

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医药连续生产的数据驱动模型预测控制。
该研究表明,使用一种称为动态模式分解与控制(DMDc)的机器学习方法,为制药连续生产开发可解释的数据驱动模型是可行的。这种方法有助于在制药行业的GMP监管领域内采用。此外,由于制药行业需要提高运营效率以实现盈利和可持续发展,我们提出了一个实时监测策略框架,该框架使用可解释的DMDc动态模型来设计和调整模型预测控制(MPC)系统,用于双螺杆造粒过程中的粒度控制。该模型具有较低的计算复杂度,不需要第一流原理知识,同时有效地捕获了该多输入多输出(MIMO)系统的非线性动力学,与用于系统识别的基准数据驱动方法相比,在重建未见测试数据方面具有更好的性能(例如,r2 > 0.93 vs.0用于D50预测)。对DMDc-MPC进行了设定值跟踪和干扰抑制的实现和测试,提出的先进过程控制框架保证了这两个目标。
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来源期刊
CiteScore
10.70
自引率
8.60%
发文量
951
审稿时长
72 days
期刊介绍: The International Journal of Pharmaceutics is the third most cited journal in the "Pharmacy & Pharmacology" category out of 366 journals, being the true home for pharmaceutical scientists concerned with the physical, chemical and biological properties of devices and delivery systems for drugs, vaccines and biologicals, including their design, manufacture and evaluation. This includes evaluation of the properties of drugs, excipients such as surfactants and polymers and novel materials. The journal has special sections on pharmaceutical nanotechnology and personalized medicines, and publishes research papers, reviews, commentaries and letters to the editor as well as special issues.
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