Data visualization in yield component analysis: an expert study

Even though data visualization is a common analytical tool in numerous disciplines, it has rarely been used in agricultural sciences, particularly in agronomy. In this paper, we discuss a study on employing data visualization to analyze a multiplicative model. This model is often used by agronomists, for example in the so-called yield component analysis. The multiplicative model in agronomy is normally analyzed by statistical or related methods. In practice, unfortunately, usefulness of these methods is limited since they help to answer only a few questions, not allowing for a complex view of the phenomena studied. We believe that data visualization could be used for such complex analysis and presentation of the multiplicative model. To that end, we conducted an expert survey. It showed that visualization methods could indeed be useful for analysis and presentation of the multiplicative model

Optimal Scheduling for Chemical Processes and its Integration with Design and Control

Optimal scheduling is an active area of research as the economics of many chemical processes is affected to a great extent with the optimality of schedules of their operations. Effective use of resources and their capacities is paramount in order to achieve optimal operations. Manual and heuristics-based approaches used for scheduling have their limitations which inhibit the chemical process industries to achieve economically attractive operations. One such sector is the analytical services industries and success of companies in this sector highly relies on the effective scheduling of operations as large numbers of samples from customers are received, analyzed and reports are generated for each sample. Therefore, it is extremely important to efficiently use all the various resources (labor and machine) for such facilities to remain competitive. This study focuses on the development of an algorithm to schedule operations in an actual large scale analytical services plant using models based on multi-commodity flow (MCF) and integer linear programming (IP) techniques. The proposed scheduling algorithm aims to minimize the total turnaround time of the operations subject to capacity, resource and flow constraints. The basic working principles of the optimization-based algorithm are illustrated with a small representative case study, while its relevance and significance is demonstrated through another case study of a real large scale plant. In the latter case study, the algorithm’s results are compared against historical data and results obtained by simulating the current policy implemented in the real plant, i.e., first-come first-served. Along with scheduling, many chemical processes require the optimization of other aspects that play major part in the process economics, e.g. design and control. An important section of the chemical process industry produces various grades of products (multi-product) and the scheduling of the production of these grades along with optimal design and control play important roles in the economy of the operations. As part of this research study, a new methodology that can address three aspects of the economy of the multiproduct processes together; i.e. simultaneous scheduling, design and control, has been developed. A mixed integer non linear programming (MINLP) optimization framework has been formulated, which aims to simultaneously evaluate optimal design, steady state operating conditions for each grade as a part of design, optimal tuning parameters for the controllers, optimal sequence of production of various grades of product and optimal smooth transitions between the grades. This is achieved via minimization of overall cost of the operation. The proposed methodology takes into account the influence of disturbances in the system by the identification of the critical frequency from the disturbances, which is used to quantify the worst-case variability in the controlled variables via frequency response analysis. The uncertainty in the demands of products has also been addressed by creating critical demand scenarios with different probabilities of occurrence, while the nominal stability of the system has been ensured. Two case studies have been developed as applications of the methodology. The first case study focuses on the comparison of classical semi-sequential approach against the simultaneous methodology developed in this work, while the second case study demonstrates the capability of the methodology in application to a large-scale nonlinear system

MODELING AND ASSESSMENT OF PROPYLENE/PROPANE SEPARATION BY PRESSURE SWING ADSORPTION ON SICHA

Ph.DDOCTOR OF PHILOSOPH

Cost Evaluation and Portfolio Management Optimization for Biopharmaceutical Product Development

The pharmaceutical industry is suffering from declining R&D productivity and yet biopharmaceutical firms have been attracting increasing venture capital investment. Effective R&D portfolio management can deliver above average returns under increasing costs of drug development and the high risk of clinical trial failure. This points to the need for advanced decisional tools that facilitate decision-making in R&D portfolio management by efficiently identifying optimal solutions while accounting for resource constraints such as budgets and uncertainties such as attrition rates. This thesis presents the development of such tools and their application to typical industrial portfolio management scenarios. A drug development lifecycle cost model was designed to simulate the clinical and non-clinical activities in the drug development process from the pre-clinical stage through to market approval. The model was formulated using activity-based object-oriented programming that allows the activity-specific information to be collected and summarized. The model provides the decision-maker with the ability to forecast future cash flows and their distribution across clinical trial, manufacturing, and process development activities. The evaluation model was applied to case studies to analyse the non-clinical budgets needed at each phase of development for process development and manufacturing to ensure a market success each year. These cost benchmarking case studies focused on distinct product categories, namely pharmaceutical, biopharmaceutical, and cell therapy products, under different attrition rates. A stochastic optimization tool was built that extended the drug development lifecycle cost evaluation model and linked it to combinatorial optimization algorithms to support biopharmaceutical portfolio management decision-making. The tool made use of the Monte Carlo simulation technique to capture the impact of uncertainties inherent in the drug development process. Dynamic simulation mechanisms were designed to model the progression of activities and allocation of resources. A bespoke multi-objective evolutionary algorithm was developed to locate optimal portfolio management solutions from a large decision space of possible permutations. The functionality of the tool was demonstrated using case studies with various budget and capacity constraints. Analysis of the optimization results highlighted the cash flow breakdowns across both activity categories and development stages. This work contributed to the effort of providing quantitative support to portfolio management decision-making and illustrated the benefits of combining cost evaluation with portfolio optimization to enhance process understanding and achieve better performance

Optimisation du développement de nouveaux produits dans l'industrie pharmaceutique par algorithme génétique multicritère

Le développement de nouveaux produits constitue une priorité stratégique de l'industrie pharmaceutique, en raison de la présence d'incertitudes, de la lourdeur des investissements mis en jeu, de l'interdépendance entre projets, de la disponibilité limitée des ressources, du nombre très élevé de décisions impliquées dû à la longueur des processus (de l'ordre d'une dizaine d'années) et de la nature combinatoire du problème. Formellement, le problème se pose ainsi : sélectionner des projets de Ret D parmi des projets candidats pour satisfaire plusieurs critères (rentabilité économique, temps de mise sur le marché) tout en considérant leur nature incertaine. Plus précisément, les points clés récurrents sont relatifs à la détermination des projets à développer une fois que les molécules cibles sont identifiées, leur ordre de traitement et le niveau de ressources à affecter. Dans ce contexte, une approche basée sur le couplage entre un simulateur à événements discrets stochastique (approche Monte Carlo) pour représenter la dynamique du système et un algorithme d'optimisation multicritère (de type NSGA II) pour choisir les produits est proposée. Un modèle par objets développé précédemment pour la conception et l'ordonnancement d'ateliers discontinus, de réutilisation aisée tant par les aspects de structure que de logique de fonctionnement, a été étendu pour intégrer le cas de la gestion de nouveaux produits. Deux cas d'étude illustrent et valident l'approche. Les résultats de simulation ont mis en évidence l'intérêt de trois critères d'évaluation de performance pour l'aide à la décision : le bénéfice actualisé d'une séquence, le risque associé et le temps de mise sur le marché. Ils ont été utilisés dans la formulation multiobjectif du problème d'optimisation. Dans ce contexte, des algorithmes génétiques sont particulièrement intéressants en raison de leur capacité à conduire directement au front de Pareto et à traiter l'aspect combinatoire. La variante NSGA II a été adaptée au problème pour prendre en compte à la fois le nombre et l'ordre de lancement des produits dans une séquence. A partir d'une analyse bicritère réalisée pour un cas d'étude représentatif sur différentes paires de critères pour l'optimisation bi- et tri-critère, la stratégie d'optimisation s'avère efficace et particulièrement élitiste pour détecter les séquences à considérer par le décideur. Seules quelques séquences sont détectées. Parmi elles, les portefeuilles à nombre élevé de produits provoquent des attentes et des retards au lancement ; ils sont éliminés par la stratégie d'optimistaion bicritère. Les petits portefeuilles qui réduisent les files d'attente et le temps de lancement sont ainsi préférés. Le temps se révèle un critère important à optimiser simultanément, mettant en évidence tout l'intérêt d'une optimisation tricritère. Enfin, l'ordre de lancement des produits est une variable majeure comme pour les problèmes d'ordonnancement d'atelier. ABSTRACT : New Product Development (NPD) constitutes a challenging problem in the pharmaceutical industry, due to the characteristics of the development pipeline, namely, the presence of uncertainty, the high level of the involved capital costs, the interdependency between projects, the limited availability of resources, the overwhelming number of decisions due to the length of the time horizon (about 10 years) and the combinatorial nature of a portfolio. Formally, the NPD problem can be stated as follows: select a set of R and D projects from a pool of candidate projects in order to satisfy several criteria (economic profitability, time to market) while copying with the uncertain nature of the projects. More precisely, the recurrent key issues are to determine the projects to develop once target molecules have been identified, their order and the level of resources to assign. In this context, the proposed approach combines discrete event stochastic simulation (Monte Carlo approach) with multiobjective genetic algorithms (NSGA II type, Non-Sorted Genetic Algorithm II) to optimize the highly combinatorial portfolio management problem. An object-oriented model previously developed for batch plant scheduling and design is then extended to embed the case of new product management, which is particularly adequate for reuse of both structure and logic. Two case studies illustrate and validate the approach. From this simulation study, three performance evaluation criteria must be considered for decision making: the Net Present Value (NPV) of a sequence, its associated risk defined as the number of positive occurrences of NPV among the samples and the time to market. Theyv have been used in the multiobjective optimization formulation of the problem. In that context, Genetic Algorithms (GAs) are particularly attractive for treating this kind of problem, due to their ability to directly lead to the so-called Pareto front and to account for the combinatorial aspect. NSGA II has been adapted to the treated case for taking into account both the number of products in a sequence and the drug release order. From an analysis performed for a representative case study on the different pairs of criteria both for the bi- and tricriteria optimization, the optimization strategy turns out to be efficient and particularly elitist to detect the sequences which can be considered by the decision makers. Only a few sequences are detected. Among theses sequences, large portfolios cause resource queues and delays time to launch and are eliminated by the bicriteria optimization strategy. Small portfolio reduces queuing and time to launch appear as good candidates. The optimization strategy is interesting to detect the sequence candidates. Time is an important criterion to consider simultaneously with NPV and risk criteria. The order in which drugs are released in the pipeline is of great importance as with scheduling problems

Use of genetic algorithms in multi-objective multi-project resource constrained project scheduling

Resource Constrained Project Scheduling Problem (RCPSP) has been studied extensively by researchers by considering limited renewable and non-renewable resources. Several exact and heuristic methods have been proposed. Some important extensions of RCPSP such as multi-mode RCPSP, multi-objective RCPSP and multi-project RCPSP have also been focused. In this study, we consider multi-project and multi-objective resource constrained project scheduling problem. As a solution method, non-dominated sorting genetic algorithm is adopted. By experimenting with different crossover and parent selection mechanisms, a detailed fine-tuning process is conducted, in which response surface optimization method is employed. In order to improve the solution quality, backward-forward pass procedure is proposed as both post-processing as well as for new population generation. Additionally, different divergence applications are proposed and one of them, which is based on entropy measure is studied in depth. The performance of the algorithm and CPU times are reported. In addition, a new method for generating multi-project test instances is proposed and the performance of the algorithm is evaluated through test instances generated through this method of data generation. The results show that backward-forward pass procedure is successful to improve the solution quality

Planning and scheduling in pharmaceutical supply chains

Ph.DDOCTOR OF PHILOSOPH