Genibet : a biopharmaceutical contract manufacturing start-up

The thesis that is by this means present under the form of a case study intends to emphasize the challenges faced by a Portuguese start-up, Genibet, upon its initial years of operations and the need to grow internationally. The case study may also be used as a learning tool, once it enables instructors and students to apply strategic knowledge and frameworks on a real life situation of a company. Genibet is a biopharmaceutical contract manufacturing organization that provides cell, bacterial and viral production services to biopharmaceutical companies and clinical research institutes. Genibet’s services comprise the production of cell banks, virus banks, plasmid DNA, polysaccharides, vaccines and virus with therapeutic activity, recombinant proteins, cells for cell therapy and virus like particles. After analyzing the environment of the bio-CMOs industry, we were able to make some important keynotes: The biopharmaceutical CMO market amounted to over $3 billion in 2013 compared to approximately$ 2 billion in 2011. Regarding the two production segments within the whole market, the most relevant one is the animal cells segment (mammalian) since it is expected to have a CAGR of 14,2% (2011- 2018) against a CAGR in between 10%-15% of the whole market. To address start-ups and clinical/research groups needs, the more adequate providers are the small contract manufacturing organizations since they have just the right size and capacity. The regions in the world with emergent countries are where the industry will experience greater growth, meaning that the larger CMOs will tend to move to those places. For the small-medium CMOs will be left to cover the mature regions where the growth will not be as fast – Europe and US. The aim of the case study was to scrutinize Genibet’s current situation and strategy in order to find some possible improvement solutions for the coming years. Together with a mission to offer customers excellency and flexibility of services that will provide evolution of biological investigation, the company’s values rely on “Safety, Commitment, Excellence, Flexibility and Groupwork”. Thus, three segments were analyzed: Client segments, Production Segments and Geographic Segments. The hereby displayed case is based on a small company’s real life situation and its efforts to stay on the market through competitive advantage generated by its different Business Model structure.A tese que é por este meio apresentada sob a forma de Case de Estudo, tem como objective enfatizar os desafios enfrentados por um start-up Portuguesa, Genibet, durante os seus primeiros anos de operações e a necessidade da mesma de crescer a nível intrenacional. O Caso de Estudo pode para além do mais ser usado como ferramenta de aprendizagem, uma vez que permite ao professor e aos alunos aplicar conhecimento estratégico e quadros de aprendizafem na situação real de uma empresa. A Genibet é uma empresa que fabrica produtos biofarmacêuticos ara terceiros (Contract Manufacturing Organization – CMO) que oferece serviços de cultura de células e bactérias, bem como o desenvolvimento do processo viral. Os seus serviços incluem especificamente a produção de bancos de células, virus, DNA plasmídeo, polissacarídeos, vacinas e vírus com actividade terapêutica, proteínas recombinantes, células para terapia e vírus como partículas. Após uma análise do ambiente da indústria de CMOs biofarmacêuticas, for possível reter algumas ideias-chave: O mercado CMO biofarmacêutico foi avaliado em $3 biliões em 2013, em comparação com apenas$ 2 biliões em 2011. No que diz respeito aos segementos de produção existentes no mercado em geral, o mais relevante é o segmento de células animas (mammalian) uma vezt que este tem uma CAGR esperada de 14,2% entre 2011 e 2018, contra uma CAGR de 10%-15% do mercado em geral. Para responder às necessidades de start-ups e grupos clínicos e de investigação, os fornecedores mais adequados são as pequenas empresas de produção sub-contratada, já que estas apresentam a dimensão e capacidade certas. As regiões a nível mundias que incluem países em desenvolvimentos são aquelas que expericiarão maior crescimento. Isto significa que as empresas maiores terão tendência em mudar-se para estes sítios. Para as CMOs de pequena e média dimensão, ficarão disponíveis as regiões que já atingiram maturidade e que, como tal, não apresentam um crescimento tão acelerado. O propósito do Caso de Estudo for aprofundar a situação actual da Genibet bem como a sua estratégia por forma a descobrir potenciais melhoramentos para os próximos anos. A par com uma missão de oeferecer aos clientes excelência e flexibilidade de serviços que providenciarão evolução biológica, os valores da empresa assentam em “Segurança, Compromisso, Excelência, Flexibilidade e Trabalho de Equipa”. Desta forma, três segmenstos foram analisados: Segmentos ao nível de clientel, Segmentos de Produção e Segmentos Geográficos. O caso aqui proposto é então baseado na situação real de uma empresa e os seus esforços para se manter no mercado através de vantagem competitiva pela diferente estrutura que o seu Modelo de Negócio apresenta

Modelling and optimization of a full-scale enhanced biological phosphorus removal System

This work in this thesis was conducted in partnership with the company ÁGUAS DO ALGARVE, and had as main objective to characterise the performance of the enhanced biological phosphorus removal wastewater treatment in Boa vista, through the utilisation of an activated sludge model and aim to test various operating factors to optimize the process. Characterization of the sewage influent and effluent was performed in order to evaluate the content of organic matter (i.e., chemical oxygen demand - COD) and its biodegradability (Biological Oxygen Demand - BOD) as well as nutrients (such as nitrogen (N) and phosphorus (P)). The influent COD was also characterized in terms of particulate, biodegradable and inert fractions. This information was used as input in the GPS-X program, where the ASM2d model was tested. The biological treatment system of the Boavista plant consists of an extended aeration activated sludge system with nitrification/denitrification and biological phosphorus removal. For model calibration purposes, a through, 6-day sampling campaign was conducted in June 2015, where all relevant flow rates and CDO, N and P fractions were measured in the influent, effluent and recycles. The calibrated model was able to describe very well the performance during this period. This calibration model was then applied to describe the performance data during the year 2014. A substantial deviation was found between the model predicts and the measured process data. This derivation is likely at least partially attributable to the different aeration regimes employed in 2014 vs 2015, as well as the cessation of iron coagulant addition in 2015, which could necessitate recalibration of the ASM2d model. A simulation study carried out with and without iron sulfate addition suggested that the Boavista plant could eliminated iron sulfate addition without an appreciable increase in effluent phosphorus concentration. This hypothesis was indeed supported by the effluent phosphorus data achieved at Boavista, which actually experienced a decrease in effluent p levels after ceasing iron sulfate addition in 2015 as compared to 2014, thereby lowering operational costs at theWWTP

Púrpura Fulminante numa Jovem de 20 Anos

A previously healthy 20-year-old female presented with extensive retiform purpura located at the face, upper and lower limbs, one week after an episode of acute tonsillitis. Despite the exuberance of the cutaneous findings and progression to skin necrosis she had no accompanying symptoms. Laboratory investigation revealed a heterozygous protein C mutation (exon 9, c.1332G> C, p.Trp444Cys), accounting for a partial deficiency of this anticoagulant protein. The patient was started on broad spectrum antibiotics, anticoagulation and systemic corticosteroids, with no lesional progression and complete resolution of cutaneous ulceration within 6 months. This is a singular case of purpura fulminans, since two different causative factors precipitated the events. The previous tonsillitis reported by the patient is significant, because the serum concentration of protein S may also decrease after an infectious event - post-infectious purpura fulminans. This case illustrates that purpura fulminans due to autoantibodies against protein S, although rare, should be considered, especially in the absence of a severe acute infection. It also illustrates how in a given patient different independent factors can act simultaneously, triggering potentially devastating clinical scenarios.Apresentamos o caso de uma jovem do sexo feminino, de 20 anos de idade, previamente saudável, que se apresentou com lesões muito extensas de púrpura retiforme localizadas na face, membros superiores e inferiores, uma semana após um episódio de amigdalite aguda. Apesar das lesões cutâneas exuberantes que evoluiram para necrose cutânea, a doente não apresentava qualquer sintomatologia associada. A investigação laboratorial revelou uma mutação em heterozigotia da proteína C (exon 9, c.1332G> C, p.Trp444Cys), condicionando um deficit parcial desta proteína anticoagulante. Iniciou antibioticoterapia de largo espectro, anticoagulação e corticoterapia sistémica, sem progressão das lesões no imediato, e resolução completa das ulcerações em 6 meses. Este é um caso singular de púrpura fulminante, visto que que dois fatores etiológicos diferentes precipitaram os eventos. A amigdalite prévia rela- tada pela doente é significativa, pois a concentração sérica da proteína S também pode diminuir após um evento infeccioso - purpura fulminans pós-infecciosa. Este caso ilustra que a púrpura fulminante decorrente de auto-anticorpos contra a proteína S, embora rara, deve ser considerada, principalmente na ausência de infecção aguda grave. Também evidencia como, em um determinado doente, diferentes fatores independentes podem atuar simultaneamente, desencadeando cenários clínicos potencialmente devastadores

A PROTEÇÃO AO EMPREGO COMO DIREITO FUNDAMENTAL

Pretende o presente artigo, diante do grande problema social brasileiro: o desemprego, analisar a proteção constitucional ao emprego no Brasil. Dentro desse contexto, será feita uma análise do artigo 7º, inciso I, da Constituição Federal Brasileira, o qual protege a relação de emprego contra a despedida arbitrária ou sem justa causa, observando-se a necessidade de lei complementar, ainda não promulgada, para regulamentar a proteção ao emprego. Dando continuidade, analisa-se a flexibilização do mercado de trabalho através de óticas distintas: dos empresários e trabalhadores por meio dos seus sindicatos. Confrontando dados estatísticos apresentados por ambos, busca-se definir se existe um engessamento por parte das leis referente às relações trabalhistas ou se a proteção existente, mesmo que em grande número no ordenamento pátrio, é suficiente para proteger o trabalhador contra a despedida arbitrária

A dependência da Internet : efeitos na saúde

Hoje em dia a grande maioria das pessoas tem acesso à Internet, sendo atualmente utilizada em diferentes contextos. Contudo, certos utilizadores fazem uso excessivo da mesma perdendo a noção do tempo, chegando a passar demasiadas horas online, trocando os dias pelas noites, chegando mesmo a esquecer-se de comer e dormir. Quando o seu uso interfere na vida normal de uma pessoa, pode causar sérios problemas de saúde, tornando-se praticamente a única coisa que a pessoa faz na vida, ficando esta dependente da Internet. As aplicações Web são cada vez mais habituais, surgindo como sistemas projetados para utilização através de um browser. O aparecimento e desenvolvimento de aplicações Web estão relacionados com a necessidade de simplificar a atualização e manutenção mantendo o código-fonte no mesmo local, de onde ele é acedido pelos diferentes utilizadores. Dada a importância deste tema e a possibilidade de trazer consequências negativas para a vida do ser humano, resolvi desenvolver como Projeto Final uma aplicação web (CiberDependencia Online) sobre a Dependência da Internet. Inicialmente foi necessário pesquisar informação existente sobre o tema, por forma a tentar ir ao encontro das necessidades das pessoas. Numa fase posterior, foi feita uma análise de requisitos para o desenvolvimento da aplicação. Esta, além de permitir aos utilizadores consultar informação sobre o tema, permite ainda calcular o Nível de Dependência através do preenchimento de questionários. Consoante o resultado do questionário poderão efetuar o pedido de uma consulta com um Especialista para futuro acompanhamento. O Especialista faz a gestão de consultas através da aplicação desenvolvida. Foi necessário optar por utilizar uma tecnologia entre as várias existentes. Após analisar previamente as diversas possibilidades, optei por implementar a aplicação em ASP.NET MVC 4, sendo também necessário a utilização de diversas linguagens de programação e componentes que nunca antes tinha utilizado, nomeadamente jQuery e Ajax. Este relatório descreve informação sobre o tema abordado, bem como toda a constituição e linguagens de programação utilizadas no desenvolvimento da aplicação

Dye assessment in nanostructured TiO2 sensitized films by microprobe techniques

Dye sensitized solar cells (DSCs) have received considerable attention once this technology offers economic and environmental advantages over conventional photovoltaic (PV) devices. The PV performance of a DSC relies on the characteristics of its photoanode, which typically consists of a nanocrystalline porous TiO2 film, enabled with a large adsorptive surface area. Dye molecules that capture photons from light during device operation are attached to the film nanoparticles. The effective loading of the dye in the TiO2 electrode is of utmost importance for controlling and optimizing solar cell parameters. Relatively few methods are known today for quantitative evaluation of the total dye adsorbed on the film. In this work, a new approach combining microprobe techniques namely, Ion Beam Analytical (IBA) techniques using a micro-ion beam (Rutherford Backscattering Spectrometry (RBS) and Particle Induced X-ray Emission (PIXE)) and Electron Probe Micro-Analysis (EPMA) was carried out to assess dye distribution and depth profile in TiO2 films and the dye load based on Ru/Ti mass ratio. Different 1D nanostructured TiO2 films were prepared, morphologically characterised by SEM, sensitized and analysed by the referred techniques. Dye load evaluation in different TiO2 films by three different techniques (PIXE, RBS and EPMA/ wavelength dispersive spectrometry (WDS)) provided similar results of Ru/Ti mass fraction ratio. Moreover, it was possible to assess dye surface distribution and its depth profile, by means of Ru signal, and to visualise the dye distribution in sample cross-section through X-ray mapping by EPMA/ energy dispersive spectrometry (EDS). PIXE maps of Ru and Ti indicated an homogeneous surface distribution. The assessment of ruthenium depth profile by RBS showed that some films have homogeneous Ru depth distribution while others present different Ru concentration in the top layer (2 ìm thickness). These results are consistent with the EPMA/EDS maps obtained. EPMA (WDS and EDS) together with IBA techniques proved to be powerful tools for functional materials characterisation and provided very promising results in the study of nanostructured TiO2 sensitized films

Microscopy techniques for dye distribution in DSCs nanocrystalline TiO2 films

Capture of sunlight has attracted an increasing interest in the scientific community and triggered the development of efficient and cheap photovoltaic devices. Amongst recent generation technologies for solar energy conversion, dye-sensitized solar cells (DSCs) show an optimal trade-off between high-conversion efficiency and low-cost manufacturing. For the last two decades, significant progress has been made and best energy conversion efficiency of the DSC at the laboratory scale has surpassed 12% [1]. A lot of work has focused on the enlargement of surface areas to enhance the amount of adsorbed dyes by reduction of nanoparticle sizes or utilization of novel structures. Nevertheless there remain some crucial details of DSC operation for which limited information is available, namely dye diffusion and adsorption, surface coverage and dye distribution throughout the nc-TiO2 film. Microprobe techniques can be powerful tools to evaluate the dye load, the dye distribution and dye depth profile in sensitized films. Electron Probe Microanalysis (EPMA) and Ion Beam Analytical (IBA) techniques using a micro-ion beam, namely micro-Particle Induced X-ray Emission ( PIXE) and Rutherford Backscattering Spectrometry (RBS), were used to quantify and to study the distribution of the ruthenium organometallic (N719) dye in TiO2 films, profiting from the different penetration depth and beam sizes of each technique. Two different types of films were prepared and sensitized, mesoporous nanoparticles and 1D nanostructured TiO2 films (figure 1). Despite the low concentration of Ru, the high sensitive analytical techniques used allowed to assess the Ru surface distribution and depth profile. Fig. 2 shows the PIXE maps of Ru and Ti indicating an homogeneous surface distribution. The same figure presents the RBS spectra obtained with a 2 MeV proton beam of the same sample showing that a good spectra fit is obtained considering only two sample layers: the first one with a 1.7 ìm thickness; the second one being the SiO2 substrate. The Ru RBS signal also shows that the dye has an homogeneous depth distribution. Due to the fine spatial resolution of the EPMA/WDS (Wavelength Dispersive Spectroscopy) technique it was possible to visualise the dye distribution in sample cross-section (with micrometer or submicrometer dimensions) as presented in Fig. 3 for the elemental mapping of a mesoporous nanoparticle TiO2 film. Dye load evaluation by two different techniques (ìPIXE and EPMA/WDS) provided similar results (Ru/Ti values around 0.5 %). The distribution analysis of the organometallic dye (N719) was done through ruthenium distribution via X-ray mapping. RBS was used to assess the ruthenium depth profile. This assessment can lead to a better understanding of the device performance

Assessment of dye distribution in sensitized solar cells by microprobe techniques

Dye sensitized solar cells (DSCs) have received considerable attention once this technology offers economic and environmental advantages over conventional photovoltaic (PV) devices. The PV performance of a DSC relies on the characteristics of its photoanode, which typically consists of a nanocrystalline porous TiO2 film, enabled with a large adsorptive surface area. Dye molecules that capture photons from light during device operation are attached to the film nanoparticles. The effective loading of the dye in the TiO2 electrode is of paramount relevance for controlling and optimizing solar cell parameters. Relatively few methods are known today for quantitative evaluation of the total dye adsorbed on the film. In this context, microprobe techniques come out as suitable tools to evaluate the dye surface distribution and depth profile in sensitized films. Electron Probe Microanalysis (EPMA) and Ion Beam Analytical (IBA) techniques using a micro-ion beam were used to quantify and to study the distribution of the Ru organometallic dye in TiO2 films, making use of the different penetration depth and beam sizes of each technique. Different 1D nanostructured TiO2 films were prepared, morphologically characterized by SEM, sensitized and analyzed by the referred techniques. Dye load evaluation in different TiO2 films by three different techniques (PIXE, RBS and EPMA/WDS) provided similar results of Ru/Ti mass fraction ratio. Moreover, it was possible to assess dye surface distribution and its depth profile, by means of Ru signal, and to visualize the dye distribution in sample cross-section through X-ray mapping by EPMA/EDS. PIXE maps of Ru and Ti indicated an homogeneous surface distribution. The assessment of Ru depth profile by RBS showed that some films have homogeneous Ru depth distribution while others present different Ru concentration in the top layer (2 lm thickness). These results are consistent with the EPMA/EDS maps obtained