36 research outputs found
Robust Model Selection: Flatness-Based Optimal Experimental Design for a Biocatalytic Reaction
Considering the competitive and strongly regulated pharmaceutical industry, mathematical
modeling and process systems engineering might be useful tools for implementing quality by
design (QbD) and quality by control (QbC) strategies for low-cost but high-quality drugs. However,
a crucial task in modeling (bio)pharmaceutical manufacturing processes is the reliable identification
of model candidates from a set of various model hypotheses. To identify the best experimental
design suitable for a reliable model selection and system identification is challenging for nonlinear
(bio)pharmaceutical process models in general. This paper is the first to exploit differential flatness
for model selection problems under uncertainty, and thus translates the model selection problem
to advanced concepts of systems theory and controllability aspects, respectively. Here, the optimal
controls for improved model selection trajectories are expressed analytically with low computational
costs. We further demonstrate the impact of parameter uncertainties on the differential flatness-based
method and provide an effective robustification strategy with the point estimate method for
uncertainty quantification. In a simulation study, we consider a biocatalytic reaction step simulating
the carboligation of aldehydes, where we successfully derive optimal controls for improved model
selection trajectories under uncertainty
Global Sensitivity Methods for Design of Experiments in Lithium-ion Battery Context
Battery management systems may rely on mathematical models to provide higher
performance than standard charging protocols. Electrochemical models allow us
to capture the phenomena occurring inside a lithium-ion cell and therefore,
could be the best model choice. However, to be of practical value, they require
reliable model parameters. Uncertainty quantification and optimal experimental
design concepts are essential tools for identifying systems and estimating
parameters precisely. Approximation errors in uncertainty quantification result
in sub-optimal experimental designs and consequently, less-informative data,
and higher parameter unreliability. In this work, we propose a highly efficient
design of experiment method based on global parameter sensitivities. This novel
concept is applied to the single-particle model with electrolyte and thermal
dynamics (SPMeT), a well-known electrochemical model for lithium-ion cells. The
proposed method avoids the simplifying assumption of output-parameter
linearization (i.e., local parameter sensitivities) used in conventional Fisher
information matrix-based experimental design strategies. Thus, the optimized
current input profile results in experimental data of higher information
content and in turn, in more precise parameter estimates.Comment: Accepted for 21st IFAC World Congres
Robust Process Design in Pharmaceutical Manufacturing under Batch-to-Batch Variation
Model-based concepts have been proven to be beneficial in pharmaceutical manufacturing, thus contributing to low costs and high quality standards. However, model parameters are derived from imperfect, noisy measurement data, which result in uncertain parameter estimates and sub-optimal process design concepts. In the last two decades, various methods have been proposed for dealing with parameter uncertainties in model-based process design. Most concepts for robustification, however, ignore the batch-to-batch variations that are common in pharmaceutical manufacturing processes. In this work, a probability-box robust process design concept is proposed. Batch-to-batch variations were considered to be imprecise parameter uncertainties, and modeled as probability-boxes accordingly. The point estimate method was combined with the back-off approach for efficient uncertainty propagation and robust process design. The novel robustification concept was applied to a freeze-drying process. Optimal shelf temperature and chamber pressure profiles are presented for the robust process design under batch-to-batch variation
Hybrid Process Models in Electrochemical Syntheses under Deep Uncertainty
Chemical process engineering and machine learning are merging rapidly, and hybrid process models have shown promising results in process analysis and process design. However, uncertainties in first-principles process models have an adverse effect on extrapolations and inferences based on hybrid process models. Parameter sensitivities are an essential tool to understand better the underlying uncertainty propagation and hybrid system identification challenges. Still, standard parameter sensitivity concepts may fail to address comprehensive parameter uncertainty problems, i.e., deep uncertainty with aleatoric and epistemic contributions. This work shows a highly effective and reproducible sampling strategy to calculate simulation uncertainties and global parameter sensitivities for hybrid process models under deep uncertainty. We demonstrate the workflow with two electrochemical synthesis simulation studies, including the synthesis of furfuryl alcohol and 4-aminophenol. Compared with Monte Carlo reference simulations, the CPU-time was significantly reduced. The general findings of the hybrid model sensitivity studies under deep uncertainty are twofold. First, epistemic uncertainty has a significant effect on uncertainty analysis. Second, the predicted parameter sensitivities of the hybrid process models add value to the interpretation and analysis of the hybrid models themselves but are not suitable for predicting the real process/full first-principles process modelâs sensitivities
Model-Based Tools for Pharmaceutical Manufacturing Processes
The Special Issue on âModel-Based Tools for Pharmaceutical Manufacturing Processesâ will curate novel advances in the development and application of model-based tools to address ever-present challenges of the traditional pharmaceutical manufacturing practice as well as new trends. This book provides a collection of nine papers on original advances in the model-based process unit, system-level, quality-by-design under uncertainty, and decision-making applications of pharmaceutical manufacturing processes
Improved Railway Track Irregularities Classification by a Model Inversion Approach
Over time railway networks have become complex Systems characterized by manifold types of technical components with a broad range of age distribution. De facto, about 50 percent of the life cycle costs of railway infrastructures are made up by direct and indirect maintenance costs. A remedy can be provided by a condition based preventive maintenance strategy leading to an optimized scheduling of maintenance actions taking the actual aswell as the expected future infrastructure condition into account. A prerequisite is, however, that the thousands of Kilometers of railway tracks are almost continuously monitored. Thus, a promising approach is the usage of low-cost sensors, e.g. accelerometers and gyroscopes, which can be installed on common in-line freight and passenger trains. Due to ambiguous data records a credible classification of railway track irregularities directly from these data is challenging. Alternatively to this pure data-driven approach, in this paper a novel hybrid Approach is presented. To this end, a simplified vehicle Suspension model is applied for the purpose of railway track condition monitoring by analyzing the dynamic railway track - Train interactions. The inversion of the model can be used to recalculate the actual inputs (irregularities) of the monitored system (rail surface) which have caused recorded System Responses (dynamic vehicle reactions and acceleration data, respectively). These recalculated inputs are a sound Basis of subsequent data-driven condition monitoring analyses. In this preliminary study, a classification algorithm is implemented to identify a simulated railway track irregularity automatically