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 comprehensive literature classification of simulation optimisation methods

Simulation Optimization (SO) provides a structured approach to the system design and configuration when analytical expressions for input/output relationships are unavailable. Several excellent surveys have been written on this topic. Each survey concentrates on only few classification criteria. This paper presents a literature survey with all classification criteria on techniques for SO according to the problem of characteristics such as shape of the response surface (global as compared to local optimization), objective functions (single or multiple objectives) and parameter spaces (discrete or continuous parameters). The survey focuses specifically on the SO problem that involves single per-formance measureSimulation Optimization, classification methods, literature survey

Energy efficiency in discrete-manufacturing systems: insights, trends, and control strategies

Since the depletion of fossil energy sources, rising energy prices, and governmental regulation restrictions, the current manufacturing industry is shifting towards more efficient and sustainable systems. This transformation has promoted the identification of energy saving opportunities and the development of new technologies and strategies oriented to improve the energy efficiency of such systems. This paper outlines and discusses most of the research reported during the last decade regarding energy efficiency in manufacturing systems, the current technologies and strategies to improve that efficiency, identifying and remarking those related to the design of management/control strategies. Based on this fact, this paper aims to provide a review of strategies for reducing energy consumption and optimizing the use of resources within a plant into the context of discrete manufacturing. The review performed concerning the current context of manufacturing systems, control systems implemented, and their transformation towards Industry 4.0 might be useful in both the academic and industrial dimension to identify trends and critical points and suggest further research lines.Peer ReviewedPreprin

The role of learning on industrial simulation design and analysis

The capability of modeling real-world system operations has turned simulation into an indispensable problemsolving methodology for business system design and analysis. Today, simulation supports decisions ranging from sourcing to operations to finance, starting at the strategic level and proceeding towards tactical and operational levels of decision-making. In such a dynamic setting, the practice of simulation goes beyond being a static problem-solving exercise and requires integration with learning. This article discusses the role of learning in simulation design and analysis motivated by the needs of industrial problems and describes how selected tools of statistical learning can be utilized for this purpose

Hybrid Meta-Heuristics for Robust Scheduling

The production and delivery of rapidly perishable goods in distributed supply networks involves a number of tightly coupled decision and optimization problems regarding the just-in-time production scheduling and the routing of the delivery vehicles in order to satisfy strict customer specified time-windows. Besides dealing with the typical combinatorial complexity related to activity assignment and synchronization, effective methods must also provide robust schedules, coping with the stochastic perturbations (typically transportation delays) affecting the distribution process. In this paper, we propose a novel metaheuristic approach for robust scheduling. Our approach integrates mathematical programming, multi-objective evolutionary computation, and problem-specific constructive heuristics. The optimization algorithm returns a set of solutions with different cost and risk tradeoffs, allowing the analyst to adapt the planning depending on the attitude to risk. The effectiveness of the approach is demonstrated by a real-world case concerning the production and distribution of ready-mixed concrete.Meta-Heuristics;Multi-Objective Genetic Optimization;Robust Scheduling;Supply Networks

Modelling Freight Allocation and Transportation Lead-Time

The authors have investigated sustainable environment delivery systems and identified transportation lead-time investigation cases. This research study aimed to increase freight delivery lead-time and minimize distance in transportation. To reach the goal, the paper\u27s authors, after analysis of the hierarchy of quantitative methods and models, proposed the framework for modeling freight allocation and transportation lead-time and delivered a study that includes discrete event simulation. During the simulation, various scenarios have been revised. Following the simulation mentioned above analysis, around 3.8 % of distance could be saved during freight delivery if lead-time for transportation were revised by choosing five days criteria for modeling freight allocation. The savings depend on the number of received orders from different geographic locations

Development of transportation and supply chain problems with the combination of agent-based simulation and network optimization

Demand drives a different range of supply chain and logistics location decisions, and agent-based modeling (ABM) introduces innovative solutions to address supply chain and logistics problems. This dissertation focuses on an agent-based and network optimization approach to resolve those problems and features three research projects that cover prevalent supply chain management and logistics problems. The first case study evaluates demographic densities in Norway, Finland, and Sweden, and covers how distribution center (DC) locations can be established using a minimizing trip distance approach. Furthermore, traveling time maps are developed for each scenario. In addition, the Nordic area consisting of those three countries is analyzed and five DC location optimization results are presented. The second case study introduces transportation cost modelling in the process of collecting tree logs from several districts and transporting them to the nearest collection point. This research project presents agent-based modelling (ABM) that incorporates comprehensively the key elements of the pick-up and delivery supply chain model and designs the components as autonomous agents communicating with each other. The modelling merges various components such as GIS routing, potential facility locations, random tree log pickup locations, fleet sizing, trip distance, and truck and train transportation. The entire pick-up and delivery operation are modeled by ABM and modeling outcomes are provided by time series charts such as the number of trucks in use, facilities inventory and travel distance. In addition, various scenarios of simulation based on potential facility locations and truck numbers are evaluated and the optimal facility location and fleet size are identified. In the third case study, an agent-based modeling strategy is used to address the problem of vehicle scheduling and fleet optimization. The solution method is employed to data from a real-world organization, and a set of key performance indicators are created to assess the resolution's effectiveness. The ABM method, contrary to other modeling approaches, is a fully customized method that can incorporate extensively various processes and elements. ABM applying the autonomous agent concept can integrate various components that exist in the complex supply chain and create a similar system to assess the supply chain efficiency.Tuotteiden kysyntä ohjaa erilaisia toimitusketju- ja logistiikkasijaintipäätöksiä, ja agenttipohjainen mallinnusmenetelmä (ABM) tuo innovatiivisia ratkaisuja toimitusketjun ja logistiikan ongelmien ratkaisemiseen. Tämä väitöskirja keskittyy agenttipohjaiseen mallinnusmenetelmään ja verkon optimointiin tällaisten ongelmien ratkaisemiseksi, ja sisältää kolme tapaustutkimusta, jotka voidaan luokitella kuuluvan yleisiin toimitusketjun hallinta- ja logistiikkaongelmiin. Ensimmäinen tapaustutkimus esittelee kuinka käyttämällä väestötiheyksiä Norjassa, Suomessa ja Ruotsissa voidaan määrittää strategioita jakelukeskusten (DC) sijaintiin käyttämällä matkan etäisyyden minimoimista. Kullekin skenaariolle kehitetään matka-aikakartat. Lisäksi analysoidaan näistä kolmesta maasta koostuvaa pohjoismaista aluetta ja esitetään viisi mahdollista sijaintia optimointituloksena. Toinen tapaustutkimus esittelee kuljetuskustannusmallintamisen prosessissa, jossa puutavaraa kerätään useilta alueilta ja kuljetetaan lähimpään keräyspisteeseen. Tämä tutkimusprojekti esittelee agenttipohjaista mallinnusta (ABM), joka yhdistää kattavasti noudon ja toimituksen toimitusketjumallin keskeiset elementit ja suunnittelee komponentit keskenään kommunikoiviksi autonomisiksi agenteiksi. Mallinnuksessa yhdistetään erilaisia komponentteja, kuten GIS-reititys, mahdolliset tilojen sijainnit, satunnaiset puunhakupaikat, kaluston mitoitus, matkan pituus sekä monimuotokuljetukset. ABM:n avulla mallinnetaan noutojen ja toimituksien koko ketju ja tuloksena saadaan aikasarjoja kuvaamaan käytössä olevat kuorma-autot, sekä varastomäärät ja ajetut matkat. Lisäksi arvioidaan erilaisia simuloinnin skenaarioita mahdollisten laitosten sijainnista ja kuorma-autojen lukumäärästä sekä tunnistetaan optimaalinen toimipisteen sijainti ja tarvittava autojen määrä. Kolmannessa tapaustutkimuksessa agenttipohjaista mallinnusstrategiaa käytetään ratkaisemaan ajoneuvojen aikataulujen ja kaluston optimoinnin ongelma. Ratkaisumenetelmää käytetään dataan, joka on peräisin todellisesta organisaatiosta, ja ratkaisun tehokkuuden arvioimiseksi luodaan lukuisia keskeisiä suorituskykyindikaattoreita. ABM-menetelmä, toisin kuin monet muut mallintamismenetelmät, on täysin räätälöitävissä oleva menetelmä, joka voi sisältää laajasti erilaisia prosesseja ja elementtejä. Autonomisia agentteja soveltava ABM voi integroida erilaisia komponentteja, jotka ovat olemassa monimutkaisessa toimitusketjussa ja luoda vastaavan järjestelmän toimitusketjun tehokkuuden arvioimiseksi yksityiskohtaisesti.fi=vertaisarvioitu|en=peerReviewed

Hybrid simulation-optimization methods: A taxonomy and discussion

The possibilities of combining simulation and optimization are vast and the appropriate design highly depends on the problem characteristics. Therefore, it is very important to have a good overview of the different approaches. The taxonomies and classifications proposed in the literature do not cover the complete range of methods and overlook some important criteria. We provide a taxonomy that aims at giving an overview of the full spectrum of current simulation-optimization approaches. Our study may guide researchers who want to use one of the existing methods, give insights into the cross-fertilization of the ideas applied in those methods and create a standard for a better communication in the scientific community. Future reviews can use the taxonomy here described to classify both general approaches and methods for specific application fields.The possibilities of combining simulation and optimization are vast and the appropriate design highly depends on the problem characteristics. Therefore, it is very important to have a good overview of the different approaches. The taxonomies and classifications proposed in the literature do not cover the complete range of methods and overlook some important criteria. We provide a taxonomy that aims at giving an overview of the full spectrum of current simulation-optimization approaches. Our study may guide researchers who want to use one of the existing methods, give insights into the cross-fertilization of the ideas applied in those methods and create a standard for a better communication in the scientific community. Future reviews can use the taxonomy here described to classify both general approaches and methods for specific application fields. (C) 2014 Elsevier B.V. All rights reserved