Predicting pharmaceutical particle size distributions using kernel mean embedding

In the pharmaceutical industry, the transition to continuous manufacturing of solid dosage forms is adopted by more and more companies. For these continuous processes, high-quality process models are needed. In pharmaceutical wet granulation, a unit operation in the ConsiGmaTM-25 continuous powder-to-tablet system (GEA Pharma systems, Collette, Wommelgem, Belgium), the product under study presents itself as a collection of particles that differ in shape and size. The measurement of this collection results in a particle size distribution. However, the theoretical basis to describe the physical phenomena leading to changes in this particle size distribution is lacking. It is essential to understand how the particle size distribution changes as a function of the unit operation's process settings, as it has a profound effect on the behavior of the fluid bed dryer. Therefore, we suggest a data-driven modeling framework that links the machine settings of the wet granulation unit operation and the output distribution of granules. We do this without making any assumptions on the nature of the distributions under study. A simulation of the granule size distribution could act as a soft sensor when in-line measurements are challenging to perform. The method of this work is a two-step procedure: first, the measured distributions are transformed into a high-dimensional feature space, where the relation between the machine settings and the distributions can be learnt. Second, the inverse transformation is performed, allowing an interpretation of the results in the original measurement space. Further, a comparison is made with previous work, which employs a more mechanistic framework for describing the granules. A reliable prediction of the granule size is vital in the assurance of quality in the production line, and is needed in the assessment of upstream (feeding) and downstream (drying, milling, and tableting) issues. Now that a validated data-driven framework for predicting pharmaceutical particle size distributions is available, it can be applied in settings such as model-based experimental design and, due to its fast computation, there is potential in real-time model predictive control

Stable Feature Selection for Biomarker Discovery

Feature selection techniques have been used as the workhorse in biomarker discovery applications for a long time. Surprisingly, the stability of feature selection with respect to sampling variations has long been under-considered. It is only until recently that this issue has received more and more attention. In this article, we review existing stable feature selection methods for biomarker discovery using a generic hierarchal framework. We have two objectives: (1) providing an overview on this new yet fast growing topic for a convenient reference; (2) categorizing existing methods under an expandable framework for future research and development

Failure Diagnosis and Prognosis of Safety Critical Systems: Applications in Aerospace Industries

Many safety-critical systems such as aircraft, space crafts, and large power plants are required to operate in a reliable and efficient working condition without any performance degradation. As a result, fault diagnosis and prognosis (FDP) is a research topic of great interest in these systems. FDP systems attempt to use historical and current data of a system, which are collected from various measurements to detect faults, diagnose the types of possible failures, predict and manage failures in advance. This thesis deals with FDP of safety-critical systems. For this purpose, two critical systems including a multifunctional spoiler (MFS) and hydro-control value system are considered, and some challenging issues from the FDP are investigated. This research work consists of three general directions, i.e., monitoring, failure diagnosis, and prognosis. The proposed FDP methods are based on data-driven and model-based approaches. The main aim of the data-driven methods is to utilize measurement data from the system and forecast the remaining useful life (RUL) of the faulty components accurately and efficiently. In this regard, two dierent methods are developed. A modular FDP method based on a divide and conquer strategy is presented for the MFS system. The modular structure contains three components:1) fault diagnosis unit, 2) failure parameter estimation unit and 3) RUL unit. The fault diagnosis unit identifies types of faults based on an integration of neural network (NN) method and discrete wavelet transform (DWT) technique. Failure parameter estimation unit observes the failure parameter via a distributed neural network. Afterward, the RUL of the system is predicted by an adaptive Bayesian method. In another work, an innovative data-driven FDP method is developed for hydro-control valve systems. The idea is to use redundancy in multi-sensor data information and enhance the performance of the FDP system. Therefore, a combination of a feature selection method and support vector machine (SVM) method is applied to select proper sensors for monitoring of the hydro-valve system and isolate types of fault. Then, adaptive neuro-fuzzy inference systems (ANFIS) method is used to estimate the failure path. Similarly, an online Bayesian algorithm is implemented for forecasting RUL. Model-based methods employ high-delity physics-based model of a system for prognosis task. In this thesis, a novel model-based approach based on an integrated extended Kalman lter (EKF) and Bayesian method is introduced for the MFS system. To monitor the MFS system, a residual estimation method using EKF is performed to capture the progress of the failure. Later, a transformation is utilized to obtain a new measure to estimate the degradation path (DP). Moreover, the recursive Bayesian algorithm is invoked to predict the RUL. Finally, relative accuracy (RA) measure is utilized to assess the performance of the proposed methods