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

Multiobjective optimization as a decision aid for managing build-to-order supply chains

This paper provides an overview of multiobjective optimization (MOO) as a decision aid in build-to-order supply chains (BTO-SC). The main features of BTO-SCs are discussed along with capabilities of MOO to enhance decision making at different points along the chain. Key decision points across a typical BTO-SC are identified and potential applications of MOO are discussed. A sample application is presented and future avenues for further research highlighted

The Multiobjective Average Network Flow Problem: Formulations, Algorithms, Heuristics, and Complexity

Integrating value focused thinking with the shortest path problem results in a unique formulation called the multiobjective average shortest path problem. We prove this is NP-complete for general graphs. For directed acyclic graphs, an efficient algorithm and even faster heuristic are proposed. While the worst case error of the heuristic is proven unbounded, its average performance on random graphs is within 3% of the optimal solution. Additionally, a special case of the more general biobjective average shortest path problem is given, allowing tradeoffs between decreases in arc set cardinality and increases in multiobjective value; the algorithm to solve the average shortest path problem provides all the information needed to solve this more difficult biobjective problem. These concepts are then extended to the minimum cost flow problem creating a new formulation we name the multiobjective average minimum cost flow. This problem is proven NP-complete as well. For directed acyclic graphs, two efficient heuristics are developed, and although we prove the error of any successive average shortest path heuristic is in theory unbounded, they both perform very well on random graphs. Furthermore, we define a general biobjective average minimum cost flow problem. The information from the heuristics can be used to estimate the efficient frontier in a special case of this problem trading off total flow and multiobjective value. Finally, several variants of these two problems are discussed. Proofs are conjectured showing the conditions under which the problems are solvable in polynomial time and when they remain NP-complete

Un modelo bi-objetivo de programación entera para localizar puntos de acumulación de residuos: un estudio de caso

Aumentar la eficiencia en la gestión de los Residuos Sólidos Urbanos (RSU) es crucial para los gobiernos municipales, que son los que generalmente se encargan de la recolección, ya que esta actividad consume un porcentaje importante de sus recursos presupuestarios. La incorporación de herramientas de apoyo a la toma de decisiones puede contribuir a mejorar el sistema de gestión de RSU, especialmente reduciendo los costos de inversión requeridos. Este artículo propone una formulación metemática, basada en programación entera, para determinar la localización de puntos de acumulación de residuos minimizando los costos del sistema, incluyendo tanto el costo de instalación de los contenedores como la cantidad de visitas necesarias del vehículo de recolección, lo cual está relacionado con los costos de la logística de recolección. El modelo se aplicó en un conjunto de escenarios reales de una importante ciudad argentina que todavía utiliza un sistema de puerta a puerta, incluyendo tanto intancias que donde los residuos son recolectados sin clasficar, como actualmente se realiza en esta ciudad, como instancias que incorporan la clasificación en origen de los mismos. A pesar de que los escenarios con clasificación en origen resultaron más desafiantes para el algoritmo de resolución propuesto, se obtuvieron un conjunto de soluciones factibles para todos los escenarios planteados. Estas soluciones pueden ser utilizadas como un punto inicial para migrar desde un sistema de puerta a puerta a uno de contenedores comunitarios.Enhancing efficiency in Municipal Solid Waste (MSW) management is crucial for local governments, which are generally in charge of collection, since this activity explains a large proportion of their budgetary expenses. The incorporation of decision support tools can contribute to improve the MSW system, specially by reducing the required investment of funds. This article proposes a mathematical formulation, based on integer programming, to determine the location of garbage accumulation points while minimizing the expenses of the system, i.e., the installment cost of bins and the required number of visits the collection vehicle which is related with the routing cost of the collection. The model was tested in some scenarios of an important Argentinian city that stills has a door-to-door system, including instances with unsorted waste, which is the current situation of the city, and also instances with source classified waste. Although the scenarios with classified waste evidenced to be more challenging for the proposed resolution approach, a set of solutions was provided in all scenarios. These solutions can be used as a starting point for migrating from the current door-to-door system to a community bins system.Fil: Rossit, Diego Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Económicas y Sociales del Sur. Universidad Nacional del Sur. Departamento de Economía. Instituto de Investigaciones Económicas y Sociales del Sur; ArgentinaFil: Nesmachnow, Sergio. Universidad de la República; UruguayFil: Toutouh, Jamal. Massachusetts Institute of Technology; Estados Unido

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

Multiobjective optimization of 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, 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