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Análise do comportamento estrutural de ligações parafusadas viga-pilar com chapa de topo estendida / Analysis of the structural behavior of bolted beam-column extended end plate connectionsMaggi, Yuri Ivan 26 May 2004 (has links)
Este trabalho apresenta uma análise numérica e experimental sobre o comportamento estrutural de ligações parafusadas viga-pilar com chapa de topo estendida. Discute-se, em particular, o comportamento da chapa de topo e dos parafusos na determinação da capacidade resistente dessas ligações. A análise de resultados numéricos é utilizada como base para as discussões neste trabalho e a modelagem numérica, realizada em elementos finitos com o software ANSYS, incluiu modelos tridimensionais de ligações com chapa de topo estendida e de ligações duplo T". Com os resultados numéricos e experimentais, os mecanismos de transferência dos esforços entre viga e pilar e os mecanismos de plastificação da chapa de topo e dos parafusos são observados, avaliando-se as linhas de plastificação na chapa de topo em confronto com a metodologia proposta pelo Eurocode 3 na determinação dos perfis T" equivalentes. Para esses fatores, observou-se que os modos de falha indicados pelo Eurocode 3 não representam satisfatoriamente o comportamento das ligações analisadas. A modelagem numérica, por sua vez, mostrou-se generalista e representativa como ferramenta para análises paramétricas e como complemento de análises experimentais / This work presents a numerical and experimental analysis on the structural behavior of bolted beam-column extended end plate connections. The behavior of the end plate and bolts used in the calculations of the end plate strength is specially discussed. Numerical results are used as basis to the discussions presented in this work and the modeling methodology, with FE models built with the ANSYS code, included 3D models of extended end plate and T-stub connections. The beam-to-column load transfer mechanisms and the yielding mechanisms at end plates and bolts are observed using numerical and experimental results. The yielding lines at the end plate are evaluated against the methodology proposed by Eurocode 3 for the calculations on the equivalent T-stub. Regarding the aforementioned factors, it is shown that the collapse modes indicated by Eurocode 3 do not represent satisfactorily the behavior of the analyzed connections. The numerical modeling was found to be general in application and reliable as a tool for parametric analyses and as a complement to experiments
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Estudo do moonpool como sistema de minimização de movimento em uma plataforma do tipo monocoluna. / Study of moonpool as a motion minimization device in a monocolumn type platform.Torres, Fernando Gomes da Silva 26 March 2007 (has links)
A maioria dos estudos realizados sobre moonpools existentes em embarcações sempre objetivou a redução das amplitudes de oscilação da água interna a estes, pois sua usual utilização é a passagem de linhas de produção, equipamentos e mergulhadores. Estes estudos mostram que com a mudança da geometria interna do moonpool é possível alterar o comportamento de oscilação da água interna ao mesmo. O presente trabalho tem como objetivo estudar o acoplamento entre o movimento vertical da água interna ao moonpool e a dinâmica em heave do corpo flutuante. Os adimensionais que regem o problema são apontados. Através das observações e conclusões em relação aos estudos numéricos e ensaios experimentais realizados, é proposto um modelo massa-mola-amortecedor representando o acoplamento entre o movimento vertical da água interna ao moonpool e a dinâmica em heave do corpo flutuante. / Most published studies related to moonpool existent in vessels always had as it main objective the reduction of vertical oscillation of the water inside the moonpool, as its usual function is the passage of production lines, equipments and divers. These studies show that, through the change of the moonpool\'s internal geometry, it is possible to modify the behavior of vertical oscillation of the water inside the moonpool. The present work has the objective of studying coupling between the vertical movement of the water inside the moonpool and the heave dynamics of the floating-body. The nondimensional numbers that guide the problem are indicated. Through the observations and conclusions in relation to the numerical studies and experimental analysis made, it is proposed a mass-spring-dumper model representing the coupling between the vertical movement of the water inside the moonpool and the heave dynamics of the floating-body.
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Análise numérica de ligações metálicas viga-coluna com coluna tubular circular / Numerical analysis of steel beam-to-column connection with circular hollow section columnFreitas, Pedro César de Barros 02 June 2009 (has links)
As estruturas tubulares, muitas vezes, têm sua aplicação restrita a construções onde a concepção arquitetônica determina o seu uso, no entanto há algumas vantagens do ponto de vista estrutural que podem justificar a sua aplicação. A reduzida área exposta ao fogo e aos ambientes agressivos, boa resistência a compressão axial com baixa tendência ao desenvolvimento de instabilidades localizadas, são algumas das vantagens da utilização destas estruturas. O objetivo principal deste trabalho é analisar numericamente o comportamento da ligação entre viga de seção I com coluna tubular circular, para tanto são consideradas configurações usuais de ligação com anéis externos transversais e chapa de alma. É ainda objetivo trazer um panorama das estruturas tubulares em geral, com o desenvolvimento histórico das pesquisas, e principalmente estabelecer uma compilação dos procedimentos analíticos de cálculo e classificação apresentados pelas normas Eurocode 3 e ANSI/AISC. A análise numérica foi realizada por meio dos pacotes comerciais TRUEGRID® e ANSYS®, os quais aplicam o método dos elementos finitos. Foram empregados modelos que consideram as características mecânicas do aço, como plastificação e encruamento, e ainda as não-linearidades geométricas e de contato. Os resultados numéricos apresentaram coerência razoável com os modelos analíticos normativos. Foi possível o conhecimento do comportamento M-\'fi\' (momento-rotação) das ligações, bem como a determinação dos parâmetros que caracterizam tal relação, como resistência, rigidez inicial e ductilidade. Os estudos comprovaram a eficácia dos anéis externos na distribuição dos esforços oriundos do engastamento parcial da viga, fazendo com que a coluna não seja comprometida. / The application of tubular structures is usually restricted to constructions on which the architectural conception demands them. However, there are also several structural advantages which justify their usage, such as a) reduced exposed area concerning fire and agressive environments; b) high axial compression resistance; c) high local buckling resistance. The aim of this work is the numerical analysis on the behavior of the I beam-circular hollow column connection, usually constituted by an external ring with single plate. It is presented a general view about the researchers development over the years on tubular structures focusing the compilation of the analytical design procedures and Eurocode 3 and ANSI/AISC classification as well. Finite element method softwares TRUEGRID and ANSYS are used for the numerical analysis in order to consider steel mechanical properties such as yielding, hardening and also geometric and contact nonlinearities. Numerical results present good agreement to codes\' analytical models. Analysis lead to understanding the connection\'s moment-rotation behavior and some of its parameters such as resistance, initial stiffness and ductility. It is shown external rings significantlly improve the semi-rigid connections stress distribution at the columns face.
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Optimisation-based retrofit of heat-integrated distillation systemsEnriquez Gutierrez, Victor Manuel January 2016 (has links)
Distillation systems consist of one or more distillation columns, in which a mixture is separated into higher-value products, and a heat exchanger network (HEN) that recovers and reuses heat within the system. For example, crude oil distillation systems comprise crude oil distillation units (CDU), in which crude oil is distilled into products for downstream processing, a HEN and a furnace. Heat-integrated distillation systems present complex interactions between the distillation columns and HEN. These interactions, together with the many degrees of freedom and process constraints, make it challenging to retrofit or modify the operating conditions of existing distillation processes to accommodate changes in process operating conditions. Retrofit designs aim to re-use existing equipment when process objectives change, for example to increase throughput, improve product quality, or reduce energy consumption or environmental impact. To achieve these retrofit objectives, operational, structural and/or flowsheet modifications to the overall system (distillation columns and HEN) may be considered, subject to specifications and system constraints. This work proposes an optimisation-based approach to retrofit design for the capacity expansion of heat-integrated distillation systems, with a particular focus on crude oil distillation systems. Existing retrofit approaches found in the open research literature consider operational optimisation, replacing column internals, adding preflash or prefractionation units and HEN retrofit to increase the capacity of existing systems. Constraints considered usually relate to the distillation column hydraulic limits, product quality specifications and heat exchanger performance (e.g. minimum temperature approach and, pressure drop). However, no existing methodologies consider these possible modifications simultaneously; thus, beneficial interactions between flowsheet modifications, operational changes, heat integration and equipment modifications may be missed. In this work, retrofit design solutions for crude oil distillation are developed using a stochastic optimisation framework implemented in MATLAB to optimise the system operating parameters and to propose flowsheet, column and HEN modifications. Within the framework, the optimiser can propose addition of a preflash unit, modifications to the CDU internals and changes to its operating conditions; the separation system is then simulated using Aspen HYSYS (via the MATLAB interface) and the hydraulic performance of the column is analysed using published hydraulic correlations. The optimiser also proposes modifications to the HEN (i.e. installed heat transfer area, HEN structure and operating conditions), which is then simulated to evaluate heating and cooling utility demand. Either simulated annealing and global search optimisation algorithms are applied to identify the optimal design and operating conditions that meet the production requirements and product specifications. Industrially relevant case studies demonstrate the effectiveness and benefits of using the proposed retrofit approach. The case studies illustrate that combined structural and operational modifications can be effectively and systematically identified to debottleneck an existing crude oil distillation system with a relatively short payback time, while simultaneously reducing energy consumption per barrel of crude oil processed.
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O problema de corte de estoque multiperíodo / The multiperiod cutting stock problemKelly Cristina Poldi 25 April 2007 (has links)
Problemas de corte de estoque consistem em arranjar peças menores, em tamanhos e quantidades especificados, dentro de peças maiores. Tais problemas têm sido investigados intensamente nas últimas décadas, acrescidos de novas características e novos métodos de solução. Nesta tese abordamos o problema de corte de estoque multiperíodo que surge imerso no planejamento e programação da produção em empresas que têm um estágio de produção caracterizado pelo corte de peças. As demandas dos itens ocorrem em períodos diversos de um horizonte de planejamento finito, sendo possível antecipar ou não a produção de itens. Os objetos disponíveis em estoque não utilizados em um período ficam disponíveis no próximo período, juntamente com novos objetos adquiridos ou produzidos pela própria empresa. Um modelo de otimização linear inteira de grande porte é proposto, cujo objetivo pondera o custo das perdas nos cortes, os custos de estocagem de objetos e itens. O método simplex com geração de colunas foi especializado para resolver a relaxação linear do modelo proposto. Foram realizados experimentos computacionais com problemas de corte de estoque unidimensional e bidimensional. Tais experimentos mostram que ganhos efetivos podem ser obtidos usando-se o modelo de corte de estoque multiperíodo, quando comparado com a solução lote-por-lote, tipicamente utilizada na prática. Porém, na prática, a solução relaxada é de pouca, ou nenhuma, utilidade. Assim, nesta tese, desenvolvemos dois procedimentos de arredondamento da solução do problema multiperíodo, baseado em horizonte rolante, ou seja, determinamos uma solução inteira factível apenas para o primeiro período, a qual será, de fato, implementada. Enfim, concluímos que o modelo para o problema de corte de estoque multiperíodo permite flexibilidade na análise de uma solução a ser implementada e, portanto, é uma ferramenta que permite ao gerente de produção uma visão global do problema para auxiliá-lo na tomada de decisões / Cutting stock problems consist of cutting a set of available stock objects in order to produce smaller ordered items. Such problems have been intensively researched over the last decades, together with additional characteristics and new methods for solving them. In this thesis, we address the multiperiod cutting stock problem, which arises in the production planning and programming in many industries that have a cutting process as an important stage. Ordered items have different due date over a finite planning horizon. An integer linear optimization model of large scale is proposed. The model makes possible to anticipate or not the production of items. Unused objects in inventory in a period become available to the next period, added to new inventory, which are acquired or produced by the own company. The mathematical model\'s objective is to minimize the cost of waste in the cutting process and costs for holding objects and fInal items. The simplex method with column generation was specialized to solve its linear relaxation. Computational experiments were carried out to solve one-dimensional and two-dimensional cutting stock problems. Such experiments showed that the multiperiod model could obtain effective gains when compared with the lot-for-lot solution, which is typically used in practice. However, in practical problems, the fractional solution is useless. So, in this thesis, two rounding procedures are developed to determine integer solutions for multiperiod cutting stock problems. Such procedures are based on a rolling horizon scheme, which roughly means, find an integer solution only for the first period, since this is the solution to be, in fact, carried out. Finally, we conclude that the proposed model for multiperiod cutting stock problems allows flexibility on analyzing a solution to be put in practice. The multiperiod cutting problem can be a tool that provides the decision maker a wide view of the problem and it may help him/her on making decisions
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Thermodynamic processes involved in wave energy extractionMedina-López, Encarnación January 2018 (has links)
Wave energy is one of the most promising renewable energy sources for future exploitation. This thesis focuses on thermodynamic effects within Oscillating Water Column (OWC) devices equipped withWells turbines, particularly humidity effects. Previous theoretical studies of the operation of OWCs have resulted in expressions for the oscillation of the water surface in the chamber of an OWC based on linear wave theory, and the air expansion{compression cycle inside the air chamber based on ideal gas theory. Although in practice high humidity levels occur in OWC devices open to the sea, the influence of atmospheric conditions such as temperature and moisture on the performance of Wells turbines has not yet been studied in the field of ocean energy. Researchers have reported substantial differences between predicted and measured power output, and performance rates of OWCs presently coming into operation. The effect of moisture in the air chamber of the OWC causes variations on the atmospheric conditions near the turbine, modifying its performance and efficiency. Discrepancies in available power to the turbine are believed to be due to the humid air conditions, which had not been modelled previously. This thesis presents a study of the influence of humid air on the performance of an idealised Wells turbine in the chamber of an OWC using a real gas model. A new formulation is presented, including a modified adiabatic index, and subsequent modified thermodynamic state variables such as enthalpy, entropy and specific heat. The formulation is validated against experimental data, and found to exhibit better agreement than the ideal approach. The analysis indicates that the real gas behaviour can be explained by a non{dimensional number which depends on the local pressure and temperature in the OWC chamber. A first approach to the OWC formulation through the calculation of real air flow in the OWC is given, which predicts a 6% decrease in efficiency with respect to the ideal case when it is tested with a hypothetical pulse of pressure. This is important because accurate prediction of efficiency is essential for the optimal design and management of OWC converters. A numerical model has also been developed using computational fluid dynamics (CFD) to simulate the OWC characteristics in open sea. The performance of an OWC turbine is studied through the implementation of an actuator disk model in Fluent®. A set of different regular wave tests is developed in a 2D numerical wave flume. The model is tested using information obtained from experimental tests on a Wells{type turbine located in a wind tunnel. Linear response is achieved in terms of pressure drop and air flow in all cases, proving effectively the applicability of the actuator disk model to OWC devices. The numerical model is applied first to an OWC chamber containing dry air, and then to an OWC chamber containing humid air. Results from both cases are compared, and it is found that the results are sensitive to the degree of humidity of the air. Power decreases when humidity increases. Finally, results from the analytical real gas and numerical ideal gas models are compared. Very satisfactory agreement is obtained between the analytical and the numerical models when humidity is inserted in the gaseous phase. Both analytical and numerical models with humid air show considerable differences with the numerical model when dry air is considered. However, at the resonance frequency, results are independent of the gas model used. At every other frequency analysed, the real gas model predicts reduced values of power that can fall to 50% of the ideal power value when coupled to the radiation-diffraction model for regular waves. It is recommended that real gas should be considered in future analyses of Wells turbines in order to calculate accurately the efficiency and expected power of OWC devices.
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Modelagem do problema de escalonamento de veículos com múltiplas garagens usando rede tempo-espaço : grandes instâncias e frota heterogêneaGuedes, Pablo Cristini January 2014 (has links)
O problema de escalonamento de veículos com múltiplas garagens (MDVSP, do inglês Multi-Depot Vehicle Scheduling Problem) é um problema clássico de logística e transportes. O MDVSP também é a base para a solução de vários problemas correlatos, tais como o problema de escalonamento de veículos em tempo-real e soluções integradas com o escalonamento de veículos, tais como o escalonamento da tripulação e otimização da tabela de horários. Desta forma, aprimorar a solução deste problema pode ser considerado de grande relevância, a qual permitirá resolver grandes instâncias reais de forma eficiente, bem como permitir a solução de problemas correlatos. O objetivo desta dissertação é verificar a aplicabilidade da utilização da rede tempo-espaço e do método de geração de colunas modificado proposto, para a solução deste problema, e de sua variante com frota heterogênea, considerando grandes instâncias. Diversos testes foram realizados utilizando o gerador de instâncias aleatórias com base na distribuição de demandas proposto. Grandes instâncias, envolvendo milhares de viagens (entre 500-10.000) e dezenas de garagens (4-128) são resolvidas em tempos razoáveis. / The multiple-depot vehicle-scheduling problem (MDVSP) is a classic logistic and transportation problem. The MDVSP is also a subproblem for solving various related problems, such as the real time vehicle scheduling problem, disruption management; and integrated problems such as the vehicle and crew scheduling problems. Although several mathematical and solution method have been developed in the literature, large instances (involving thousands of trips and several depots) are still difficult to solve in a reasonable time. The objective of this research work is to verify the applicability of the use of the space-time network towards obtaining good solutions for large instances in short time. Time-space network was suggested by Kliewer et al (2006), and it is positioned with respect to two-dimensional axes, one representing time and the other one space or stations. The arcs represent deadheading movements; and waiting periods in the same station. Solution methods for the MDVS combining time space with integer linear programming solvers and column generation were developed. Extensive testing was carried out using random generated instances, based on demands distribution. Large instances, involving thousands of trips (between 1,000-10,000) and dozen (4-64) depots, are solved in reasonable times.
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Desenvolvimento de colunas capilares e aplicação de programação de temperatura em cromatografia líquida capilar / Development of capillary columns and application of temperature programming in capillary liquid chromatographyVivane Lopes Leal 23 November 2018 (has links)
O presente estudo visa o desenvolvimento de pesquisas em uma área altamente promissora da cromatografia líquida moderna, denominada genericamente de cromatografia líquida capilar (cLC). Sua principal característica é o uso de instrumentação miniaturizada, cujos benefícios em relação à HPLC são fartamente documentados. O Grupo de Cromatografia do IQSC-USP vem desenvolvendo, há vários anos, instrumentação e colunas para esta área, havendo construído um sistema, para micro e nano LC, completo. O objetivo deste trabalho foi ampliar o emprego do mesmo, através do uso de programação de temperatura em cromatografia líquida capilar, fazendo uso de colunas empacotadas e tubulares abertas (OT), desenvolvidas no laboratório. Uma metodologia relativamente simples foi desenvolvida para preparar as colunas capilares com fases estacionárias C18 com boa repetitividade. Para tal, a influência de várias características da coluna, tais como, tamanho da partícula, comprimento, diâmetro interno, tipos de hardwares empregados como corpo da coluna e sistema de bombeamento, foram avaliadas, sendo estabelecida uma relação entre as mesmas e o desempenho da coluna. As microcolunas empacotadas obtidas apresentaram excelente desempenho. Colunas tubulares abertas, OT do tipo WCOT e PLOT (com diferentes tipos de fases, comprimentos e diâmetros internos) foram produzidas e avaliadas, utilizando uma mistura de alquilbenzenos. Os resultados sugerem um desempenho ainda insatisfatório das colunas OTLC, embora os compostos avaliados tenham sido separados indicando, de forma promissora, que uma otimização nas características das colunas poderá contribuir para se alcançar maiores eficiências. Foi aplicada programação de temperatura na separação de diferentes classes de compostos resultando na redução de, pelo menos, metade do tempo de análise com aumento da eficiência de, no mínimo 2 vezes, quando comparado à separação realizada em condição isotérmica. Isto ilustra a importância da utilização da programação de temperatura em cromatografia líquida capilar. Por último, foi avaliado o desempenho de uma coluna capilar empacotada em um sistema cLC comercial e no cLC desenvolvido no laboratório, onde se observou que o desempenho da coluna foi melhor quando utilizada no cromatógrafo líquido capilar desenvolvido pelo grupo (\"homemade\"). / The present study aims to develop research in a highly promising field of general report generation, generally referred to as capillary liquid chromatography (cLC). Its main feature is the use of miniaturized instrumentation, whose benefits in relation to HPLC are well documented. O Grupo de Cromatografia do IQSC-USP vem desenvolvendo, há vários anos, instrumentação e colunas para esta área, havendo construído um sistema, para micro e nano LC, completo. The objective of this work was to extend the use of the same, by using temperature programming in capillary liquid chromatography, making use of packed and open tubular columns (OT), developed in the laboratory. A relatively simple methodology was developed to prepare capillary columns with C18 stationary phases with good repeatability. To do this, the influence of various column characteristics, such as particle size, length, internal diameter, types of hardware used as column body and pumping system, were evaluated, establishing a relationship between them and the performance of the column. The packaged microcolumns obtained showed excellent performance. Open tubular columns, OT WCOT and PLOT (with different types of phases, lengths and internal diameters) were produced and evaluated using a mixture of alkylbenzenes. The results suggest a still unsatisfactory performance of the OTLC columns, although the compounds evaluated were promising, indicating that an optimization of the characteristics of the columns could contribute to higher efficiencies. Temperature programming was applied in the separation of different classes of compounds resulting in the reduction of at least half of the analysis time with increase of the efficiency of at least 2 times when compared to the separation realized in isothermal condition. This illustrates the importance of using temperature programming in capillary liquid chromatography. Finally, the performance of a capillary column packed in a commercial cLC system and in the cLC developed in the laboratory was evaluated, where it was observed that the performance of the column was better when used in the liquid capillary chromatograph developed by the group (\"homemade\").
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Scheduling of Electric Buses with Column GenerationSundin, Daniel January 2018 (has links)
Column generation has during the last years been popular in vehicle scheduling as it for larger problems can find an optimum faster than using an ordinary mixed-integer programming (MIP) model. We study the problem of finding optimal schedules for electric buses by means of column generation. The motive for this approach is that when the size of the problem becomes very large in terms of variables and different solutions, solving it with a mixed- integer programming model can take a lot time. The purpose of this work is to investigate how the best found integral solution and the solution time vary between different column generation methods and how these methods perform compared to a MIP. This has been done by implementing these methods on a test problem for scheduling of electric buses. The results indicate that column generation methods can be very efficient in terms of time and best found integral solution for larger problems. A modified column generation method has been created in order to accelerate the generation of columns, which is better than standard column generation in terms of solution time and best found integral solution.
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Évaluation des procédés de chromatographie multi-colonne pour la production industrielle d’anticorps monoclonaux / Evaluation of multi-column chromatography processes for the industrial manufacturing of monoclonal antibodiesHilbold, Nicolas-Julian 10 December 2018 (has links)
L'industrie biopharmaceutique voit la plupart des thérapies basées sur les anticorps monoclonaux passer du statut de blockbuster à un marché de niche et personnalisé, dans un monde globalisé. Pour poursuivre le développement de nouveaux médicaments, les installations de production existantes et futures doivent accroître leur flexibilité et leur productivité. La chromatographie multi-colonne est l'un des outils potentiels pour y parvenir, comme elle l’a été au cours des dernières décennies pour la pétrochimie et l'industrie alimentaire. En parallèle, l'étape de capture protéine A reste incontournable pour toutes les lignes industrielles de purification grâce à sa spécificité et sa capacité à atteindre facilement un haut niveau de pureté en une seule étape. Ce travail de recherche est une évaluation des procédés de chromatographie multi-colonnes combinés à l'étape de capture protéine A pour augmenter la productivité et l'applicabilité des plateformes de purification actuelles aux activités de production clinique et commerciale. Dans chaque partie du travail, la technologie des colonnes de chromatographie pré-packées a été évalué en tant que facilitateur de procédé multi-colonnes, libérant les équipes opérationnelles des activités de package et des infrastructures associées. Un premier chapitre décrit la traditionnelle revue de la littérature et l'état actuel des connaissances dans le domaine concerné, ainsi qu'une description théorique de la chromatographie en général, et des processus multi-colonnes en particulier. Dans un deuxième chapitre, plusieurs résines protéine A récentes, disponibles sur le marché, ont été comparées dans le cadre de deux procédés multi-colonnes –la chromatographie séquentielle sur plusieurs colonnes (SMCC) et le procédé par Batch Parallèle– et comparées à un procédé traditionnel mono-colonne. Sur la base d'un logiciel de simulation et d'optimisation, les deux processus proposés ont été comparés en termes de gains et de performances. Des recommandations sur la résine et le type de procédé à choisir ont été proposées. Dans un troisième chapitre, l'impact des procédés multi-colonnes sur la qualité et la pureté résultante a été abordé par plusieurs séries d'expériences. L'impact de l'organisation séquentielle d'un processus SMCC a été évalué. L'impact du temps de séjour sur les étapes de lavage et d'élution a également été évalué, afin d'accélérer potentiellement l'étape de capture. Troisièmement, l'impact de la saturation de la résine sur la conception de l'étape de lavage a été évalué. Finalement, des études de cycling ont été réalisées pour détecter si les différents processus multi-colonnes avaient un impact différent sur la durée de vie et les performances de la résine. Dans un quatrième chapitre, un outil de calcul simplifié a été conçu pour proposer un dimensionnement simple des procédés multi-colonnes, tenant mieux compte des contraintes de production de Merck. Cet outil a été utilisé pour évaluer la performance des procédés Batch Parallèle pour deux études de cas. Enfin, dans un chapitre plus exploratoire, l'outil simplifié développé précédemment a été adapté pour évaluer la faisabilité et les contraintes principales des étapes de capture en continu, caractérisées soit par une étape de chargement continu, soit par une étape d'élution continue / The biopharma industry sees most of the therapeutics based on monoclonal antibodies shifting from the blockbuster status to a niche and personalized market, in a globalized world. To continue the development of new drugs, existing and future production facilities have to increase in flexibility and productivity. Multi-column chromatography is one of the potential tools to make that happen, as the technology did in the last decades for the petro and for the food industries. In parallel, the protein A capture step remains a must for all purification trains of the industrial manufacturing capacities due to its specificity and capability to easily reach a high level of purity in a single step. This research work is an evaluation of the multi-column chromatography processes combined with the protein A capture step to increase the productivity and the applicability of current purification platforms for clinical and commercial manufacturing activities. In every part of the work, prepacked chromatography columns have been evaluated as an enabler of multi-column processes, freeing the operational teams from the packing activities burden and associated infrastructures. A first chapter describes the traditional literature review and current state-of-the-art in the relevant field, together with a theoretical description of chromatography in general, and multi-column processes in particular. In a second chapter, several recent, commercially-available protein A resins have been compared when involved in 2 multi-column processes: the Sequential Multi-Column Chromatography (SMCC) process and the Parallel Batch process, and compared to a traditional mono-column process. Based on a simulation and optimization software, both processes proposed have been compared in terms of gains and performance. Recommendations on the resin and the type of process to be selected have been proposed. In a third chapter, the impact of multi-column processes on the resulting quality and purity has been addressed through several sets of experiments. The impact of the sequential organization of an SMCC process has been evaluated. The impact of the residence time on the washing and the elution steps has also been evaluated, in order to potentially speed-up the capture step. Third, the impact of the resin saturation on the design of the washing step has been assessed. Eventually, cycling studies have been performed to detect if the different multi-column processes were impacting differently the resin’s lifetime and performance. In a fourth chapter, a simplified calculation tool has been designed to propose simple sizing of multi-column processes, accounting more accurately for Merck’s production constraints. This tool has been used to evaluate the performance of Parallel Batch processes for 2 case-studies. Eventually, in a more exploratory chapter, the simplified tool previously developed has been adapted to evaluate the feasibility and the primary constraints of continuous capture steps, characterized by either a continuous loading step or a continuous elution step
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