Multiobjective strategies for New Product Development in the pharmaceutical industry

New Product Development (NPD) constitutes a challenging problem in the pharmaceutical industry, due to the characteristics of the development pipeline. Formally, the NPD problem can be stated as follows: select a set of R&D projects from a pool of candidate projects in order to satisfy several criteria (economic profitability, time to market) while coping 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 (NSGAII type, Non-Sorted Genetic Algorithm II) to optimize the highly combinatorial portfolio management 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. This work is illustrated with a study case involving nine interdependent new product candidates targeting three diseases. An analysis is performed for this test bench on the different pairs of criteria both for the bi- and tricriteria optimization: large portfolios cause resource queues and delays time to launch and are eliminated by the bi- and tricriteria optimization strategy. The optimization strategy is thus 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

Multiobjective strategies for New Product Development in the pharmaceutical industry

New Product Development (NPD) constitutes a challenging problem in the pharmaceutical industry, due to the characteristics of the development pipeline. Formally, the NPD problem can be stated as follows: select a set of R&D projects from a pool of candidate projects in order to satisfy several criteria (economic profitability, time to market) while coping 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 (NSGAII type, Non-Sorted Genetic Algorithm II) to optimize the highly combinatorial portfolio management 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. This work is illustrated with a study case involving nine interdependent new product candidates targeting three diseases. An analysis is performed for this test bench on the different pairs of criteria both for the bi- and tricriteria optimization: large portfolios cause resource queues and delays time to launch and are eliminated by the bi- and tricriteria optimization strategy. The optimization strategy is thus 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

A general framework integrating techniques for scheduling under uncertainty

Ces dernières années, de nombreux travaux de recherche ont porté sur la planification de tâches et l'ordonnancement sous incertitudes. Ce domaine de recherche comprend un large choix de modèles, techniques de résolution et systèmes, et il est difficile de les comparer car les terminologies existantes sont incomplètes. Nous avons cependant identifié des familles d'approches générales qui peuvent être utilisées pour structurer la littérature suivant trois axes perpendiculaires. Cette nouvelle structuration de l'état de l'art est basée sur la façon dont les décisions sont prises. De plus, nous proposons un modèle de génération et d'exécution pour ordonnancer sous incertitudes qui met en oeuvre ces trois familles d'approches. Ce modèle est un automate qui se développe lorsque l'ordonnancement courant n'est plus exécutable ou lorsque des conditions particulières sont vérifiées. Le troisième volet de cette thèse concerne l'étude expérimentale que nous avons menée. Au-dessus de ILOG Solver et Scheduler nous avons implémenté un prototype logiciel en C++, directement instancié de notre modèle de génération et d'exécution. Nous présentons de nouveaux problèmes d'ordonnancement probabilistes et une approche par satisfaction de contraintes combinée avec de la simulation pour les résoudre. ABSTRACT : For last years, a number of research investigations on task planning and scheduling under uncertainty have been conducted. This research domain comprises a large number of models, resolution techniques, and systems, and it is difficult to compare them since the existing terminologies are incomplete. However, we identified general families of approaches that can be used to structure the literature given three perpendicular axes. This new classification of the state of the art is based on the way decisions are taken. In addition, we propose a generation and execution model for scheduling under uncertainty that combines these three families of approaches. This model is an automaton that develops when the current schedule is no longer executable or when some particular conditions are met. The third part of this thesis concerns our experimental study. On top of ILOG Solver and Scheduler, we implemented a software prototype in C++ directly instantiated from our generation and execution model. We present new probabilistic scheduling problems and a constraintbased approach combined with simulation to solve some instances thereof

Project scheduling under uncertainty using fuzzy modelling and solving techniques

In the real world, projects are subject to numerous uncertainties at different levels of planning. Fuzzy project scheduling is one of the approaches that deal with uncertainties in project scheduling problem. In this paper, we provide a new technique that keeps uncertainty at all steps of the modelling and solving procedure by considering a fuzzy modelling of the workload inspired from the fuzzy/possibilistic approach. Based on this modelling, two project scheduling techniques, Resource Constrained Scheduling and Resource Leveling, are considered and generalized to handle fuzzy parameters. We refer to these problems as the Fuzzy Resource Constrained Project Scheduling Problem (FRCPSP) and the Fuzzy Resource Leveling Problem (FRLP). A Greedy Algorithm and a Genetic Algorithm are provided to solve FRCPSP and FRLP respectively, and are applied to civil helicopter maintenance within the framework of a French industrial project called Helimaintenance

Applications of fuzzy theories to multi-objective system optimization

Most of the computer aided design techniques developed so far deal with the optimization of a single objective function over the feasible design space. However, there often exist several engineering design problems which require a simultaneous consideration of several objective functions. This work presents several techniques of multiobjective optimization. In addition, a new formulation, based on fuzzy theories, is also introduced for the solution of multiobjective system optimization problems. The fuzzy formulation is useful in dealing with systems which are described imprecisely using fuzzy terms such as, 'sufficiently large', 'very strong', or 'satisfactory'. The proposed theory translates the imprecise linguistic statements and multiple objectives into equivalent crisp mathematical statements using fuzzy logic. The effectiveness of all the methodologies and theories presented is illustrated by formulating and solving two different engineering design problems. The first one involves the flight trajectory optimization and the main rotor design of helicopters. The second one is concerned with the integrated kinematic-dynamic synthesis of planar mechanisms. The use and effectiveness of nonlinear membership functions in fuzzy formulation is also demonstrated. The numerical results indicate that the fuzzy formulation could yield results which are qualitatively different from those provided by the crisp formulation. It is felt that the fuzzy formulation will handle real life design problems on a more rational basis

Effective retrieval and new indexing method for case based reasoning: Application in chemical process design

In this paper we try to improve the retrieval step for case based reasoning for preliminary design. This improvement deals with three major parts of our CBR system. First, in the preliminary design step, some uncertainties like imprecise or unknown values remain in the description of the problem, because they need a deeper analysis to be withdrawn. To deal with this issue, the faced problem description is soften with the fuzzy sets theory. Features are described with a central value, a percentage of imprecision and a relation with respect to the central value. These additional data allow us to build a domain of possible values for each attributes. With this representation, the calculation of the similarity function is impacted, thus the characteristic function is used to calculate the local similarity between two features. Second, we focus our attention on the main goal of the retrieve step in CBR to find relevant cases for adaptation. In this second part, we discuss the assumption of similarity to find the more appropriated case. We put in highlight that in some situations this classical similarity must be improved with further knowledge to facilitate case adaptation. To avoid failure during the adaptation step, we implement a method that couples similarity measurement with adaptability one, in order to approximate the cases utility more accurately. The latter gives deeper information for the reusing of cases. In a last part, we present a generic indexing technique for the base, and a new algorithm for the research of relevant cases in the memory. The sphere indexing algorithm is a domain independent index that has performances equivalent to the decision tree ones. But its main strength is that it puts the current problem in the center of the research area avoiding boundaries issues. All these points are discussed and exemplified through the preliminary design of a chemical engineering unit operation