Utilização de técnica de análise de risco numa unidade de produção de proteínas recombinantes: estudo de caso da ferramenta de análise de risco - HAZOP

Em novembro de 2005, com o guia de Gestão de Riscos à Qualidade (Q9) - a Conferência Internacional de Harmonização (ICH), em conjunto com as agências regulatórias dos Estados Unidos, Japão e Europa, passaram a recomendar que seja aplicado o gerenciamento de riscos para regulação da indústria farmacêutica. Em concordância, a Agência Nacional de Vigilância Sanitária (ANVISA) publicou a Resolução de Diretoria Colegiada - RDC 17/2010 que dispõe sobre as Boas Práticas de Fabricação de Medicamentos que possibilita a comercialização de produtos farmacêuticos. Esta resolução preconiza que a validação de um processo produtivo seja efetuada com base em uma análise de risco. Seguindo as orientações da RDC este trabalho se propôs a aplicar a ferramenta de análise de risco de Estudos de Perigos e Operabilidade HAZOP num sistema de biorreação bacteriana para produção de proteínas recombinantes instalado no Instituto de Tecnologia em Imunobiológicos Bio-Manguinhos/Fiocruz. Este sistema é formado por fermentadores de 100 (FE01) e 600 (FE02) litros, um tanque de colheita de 600 litros (HT01) e um tanque de preparo de meios de cultura de 600 litros (MT01). Através da aplicação desta ferramenta de análise de riscos foi possível classificar os riscos dos sistemas identificando os nós, palavras-guia primárias (parâmetros) e secundárias (desvios), assim como a severidade e frequência dos eventos. Foram identificados 82 riscos associados aos fermentadores FE01 e FE02, sendo 8,5% riscos insignificantes, 65,9% riscos aceitáveis e 25,6% riscos não desejáveis. No tanque de colheita HT01 foram identificados 55 riscos, dos quais 14,5% são insignificantes, 67,3% são aceitáveis e 18,2% não desejáveis. Para o tanque de preparo de meios MT01 foram identificados 66 riscos que estão divididos em 9% de riscos insignificantes, 69,7% de riscos aceitáveis e 21,3% de riscos não desejáveis. Foi percebido que não houve riscos catastróficos que pudessem comprometer os equipamentos fabricados, porém somente com utilização dos mesmos na rotina de produção e o ciclo de melhoria continua dos equipamentos será possível validar este estudo prospectivo

A Auditoria Interna como ferramenta de melhoria dos controles internos de uma organização: Estudo de caso em uma empresa do segmento industrial do Rio de Janeiro

A alteração no sistema de controles internos da empresa estudada teve como marco principal a mudança do foco no trabalho da auditoria interna, que começou a desempenhar suas atividades de forma estruturada e seguindo uma metodologia específica; além, de perseguir um objetivo estratégico da organização. A auditoria interna, antes do processo de certificação do sistema de controles internos exigido pela seção 404 da SOX, era apenas um instrumento de detecção de erros e compliance fiscal, que baseava seus trabalhos somente em fatos passados, com a constatação de deficiências de controles. Todavia, sem assessorar a alta a administração da empresa na resolução das deficiências, objetivando a implementação das melhorias dos controles internos. Com a necessidade de certificação da eficácia dos controles internos, a partir do ano de 2005, o foco dos trabalhos de auditoria interna foi direcionado para lograr melhorias nos métodos de controle, gestão de riscos, prevenção de fraudes e erros, nos processos operacionais, contábeis e financeiros da organização. O objetivo dessa pesquisa foi, por meio de estudo de caso único, mensurar os principais procedimentos realizados para a implantação do sistema de controles internos da empresa estudada, incluindo a metodologia adotada, o modelo escolhido, o processo de controle estabelecido, a identificação e avaliação dos principais riscos e controles, bem como a forma de seleção, avaliação e teste dos controles internos existentes. Buscou-se coletar dados preconizados pela literatura de autores renomados e analisar as diversas bibliografias, com o objetivo de comparar com a pesquisa que foi realizada nos documentos fornecidos pela empresa analisada. Este estudo levantou pontos importantes sobre o processo de gestão da empresa e da forma como se utilizou da auditoria interna como ferramenta para a melhoria de seus controles internos. Destacam-se a geração de valor empresarial que um bom ambiente de controle interno traz e os motivos que levam uma organização a implementar uma área de auditoria interna, com especial atenção ao foco de assessoramento e consultoria, alinhado as práticas internacionais de auditoria interna. Entretanto, apesar de observar melhorias na atuação da auditoria interna da organização, constata-se a necessidade de alinhamento de algumas práticas internacionais, ainda não implementadas. Descobriu-se, também, que a auditoria interna, com o devido emporwerment da alta administração, e utilizando-se das técnicas atuais e internacionais, aumentam a confiabilidade do sistema de controles internos e com isso geram valor às suas organizações. Nesta pesquisa pôde-se constatar a utilização da auditoria interna como ferramenta de gestão de recursos organizacionais, ocasionando melhorias no sistema de controles internos da empresa, e ficando constatada, por meio de auditoria executada por firma independente, a irrefutável melhoria dos controles internos da organização estudada.

O desempenho da Maternidade da Santa Casa de Angra dos Reis face aos critérios de qualidade do Programa Nacional de Avaliação dos Serviços de Saúde - PNASS.

A Santa Casa de Angra dos Reis é uma Instituição Filantrópica inaugurada em 06 de janeiro de 1839. A Unidade passa por Intervenção Municipal, recomendada pelo Ministério Público, no intuito de garantir o restabelecimento adequado de seus serviços, a eficiência desejável e para resgatar a credibilidade e sustentabilidade do Hospital. Da motivação pelos projetos da nova gestão emergiu a necessidade de conhecer a situação do desempenho desta unidade hospitalar, em especial a Maternidade, ponto de partida do projeto. Este estudo é relevante para a institucionalização da avaliação da qualidade nesta Unidade Hospitalar, bem como condição primária para construção de planos de trabalho. O Programa Nacional de Avaliação dos Serviços de Saúde PNASS é uma proposta do Ministério da Saúde, e é visto como uma ferramenta de gestão para monitoramento e avaliação. O programa pode apontar diversas oportunidades de melhorias e auxiliar a tomada de decisão tornando-se adequado seu emprego no levantamento das informações necessárias para o conhecimento do cenário da Maternidade, como base para um futuro plano de ação. Este estudo tem por objetivo aplicar o programa de avaliação normativa proposto pelo PNASS na Maternidade da Santa Casa, a fim de identificar seu desempenho, como primeiro passo para a construção do plano estratégico de ação em busca do aprimoramento da qualidade em saúde neste setor. Como metodologia, é uma pesquisa quantitativa onde foram utilizados padrões de conformidade, questionários fechados direcionados aos usuários e trabalhadores da Maternidade, e análise de indicadores. Resultados: foram entrevistadas 35 mulheres e 47 profissionais de saúde, num total de 85% da amostra desejada; ficou evidente a necessidade de intervenção e implementação de mudanças na área de Gerenciamento de Risco; e melhorias quanto às condições de trabalho relacionadas à infraestrutura e equipamentos. Os indicadores de internação apontam a necessidade de revisão do número de leitos disponíveis; a taxa de parto cesáreo, 59%, é extremamente alta e muito acima do preconizados pela Organização Mundial de Saúde. Este estudo mostrou um resultado positivo quanto à satisfação das parturientes com o serviço prestado, embora existam áreas carentes de melhorias. Melhorias também são necessárias para o dimensionamento efetivo do quadro de profissionais para atendimento à demanda. A interrupção do lançamento de relatórios sobre atuais avaliações feitas pelo PNASS e a pouca divulgação do mesmo são questões levantadas por este estudo. Considera-se que a aplicação do PNASS na Maternidade da Santa Casa de Angra dos Reis proporcionou embasamento para a elaboração de uma oportuna matriz de intervenção.

一种基于软件过程仿真的软件项目风险管理方法

软件开发是一项高度复杂的活动，涉及到人员、过程、产品、客户等多种因素，这些因素中存在着大量的不确定性，在软件项目中表现为风险。风险能够给软件项目带来严重的危害，造成工程延期、成本超支、软件产品质量低下等各种问题，因此软件项目管理者必须对软件项目风险进行有效的管理。 软件项目风险管理是软件项目管理中不可或缺的重要组成部分，但是在实际的软件项目中，软件项目风险管理却常常被忽略，很多项目管理者凭自己的经验和直觉来管理软件项目风险。造成这种现象的原因除了软件企业的文化因素外，主要是因为软件项目管理者缺少操作层面上有效的风险管理方法和工具。 软件过程仿真能够分析软件过程的动态行为特性，预测软件过程执行的性能，是一种很好的软件项目分析和管理工具。软件过程仿真已经广泛应用于包括风险管理在内的软件项目管理的多个方面。多项研究已经表明软件过程仿真作为一种有效的风险管理方法和工具，能够很好的支持软件项目风险管理过程。 为了指导软件项目管理者使用软件过程仿真进行风险管理，本文提出了一种基于软件过程仿真的软件项目风险管理方法（SPS-RM）。该方法是一种使用软件过程仿真进行软件项目风险管理的通用方法框架，实现了“风险监控风险影响分析风险解决”的风险管理过程，并且为每个风险管理活动都提供了相应的过程仿真模型。SPS-RM方法还包括使用软件过程仿真进行风险管理的通用步骤，以及建立和分析过程仿真模型的一般方法，并为模型、步骤和方法都提供了详细的指导说明。 本文的主要贡献包括： 对软件过程仿真在软件项目风险管理中的应用和研究现状进行了调研。调研的目的是为了获得当前的研究进展，找出目前存在的问题，并指出未来可能的研究方向。调研的结果为本文的研究方向提供了很好的指导，也为本文的具体研究内容提供了良好的理论和实际依据。 提出了一种基于软件过程仿真的软件项目风险管理方法（SPS-RM）。该方法是一个使用软件过程仿真进行软件项目风险管理的通用方法框架，其目的是指导广大的软件项目管理者使用软件过程仿真有效的管理软件项目风险。SPS-RM是本文的核心方法，后面对两个具体风险的研究都是基于该方法进行的。 提出了需求变更风险分析仿真方法（RVSim）。需求变更是一种在软件项目中常见的、对软件项目影响较大的风险。本文基于SPS-RM方法对需求变更风险进行研究，提出了需求变更风险分析仿真方法。该方法以需求的横向和纵向跟踪信息为基础，对需求变更的处理过程进行仿真，能够量化的给出单个需求变更或者一系列需求变更对软件项目的时间和工作量的影响，帮助项目管理者更好的理解和管理需求变更风险。 提出了人员离职风险解决仿真方法（LF-ETRS）。人员离职是软件项目中的另一个重要风险。本文基于SPS-RM方法对人员离职风险进行研究，提出了人员离职风险解决仿真方法。该方法的主要特点是首次在对软件项目中的人员进行建模时同时考虑了人的学习和遗忘行为，因此能够更加准确的预测人员替代所需的时间和成本。另外，该方法还考虑了除人员替代外的其他解决措施，通过对多种解决措施进行建模和仿真，项目管理者可以根据项目的实际情况和仿真结果选择最合适的措施来解决人员离职风险。

地震P-S波时差耦合作用的斜坡崩滑效应研究

China locates between the circum-Pacific and the Mediterranean-Himalayan seismic belt. The seismic activities in our country are very frequent and so are the collapses and slides of slope triggered by earthquakes. Many collapses and slides of slope take place mainly in the west of China with many earthquakes and mountains, especially in Sichuan and Yunnan Provinces. When a strong earthquake happening, the damage especially in mountains area caused by geological hazards it triggered such as rock collapses, landslides and debris flows is heavier than that it caused directly. A conclusion which the number of lives lost caused by geological hazards triggered by a strong earthquake in mountains area often accounts for a half even more of the total one induced by the strong earthquake can be made by consulting the statistical loss of several representative earthquakes. As a result, geological hazards such as collapses and slides of slope triggered by strong earthquakes attract wide attention for their great costs. Based on field geological investigation, engineering geological exploration and material data analysis, chief conclusions have been drawn after systematic research on formation mechanism, key inducing factors, dynamic characteristics of geological hazards such as collapses and slides of slope triggered by strong earthquakes by means of engineering geomechanics comprehensive analysis, finite difference numerical simulation test, in-lab dynamic triaxial shear test of rock, discrete element numerical simulation. Based on research on a great number of collapses and landslides triggered by Wenchuan and Xiaonanhai Earthquake, two-set methods, i.e. the method for original topography recovering based on factors such as lithology and elevation comparing and the method for reconstructing collapsing and sliding process of slope based on characteristics of seism tectonic zone, structural fissure, diameter spatial distribution of slope debris mass, propagation direction and mechanical property of seismic wave, have been gotten. What is more, types, formation mechanism and dynamic characteristics of collapses and slides of slope induced by strong earthquakes are discussed comprehensively. Firstly, collapsed and slided accumulative mass is in a state of heavily even more broken. Secondly, dynamic process of slope collapsing and sliding consists of almost four stages, i.e. broken, thrown, crushed and river blocked. Thirdly, classified according to failure forms, there are usually four types which are made up of collapsing, land sliding, land sliding-debris flowing and vibrating liquefaction. Finally, as for key inducing factors in slope collapsing and sliding, they often include characteristics of seism tectonic belts, structure and construction of rock mass, terrain and physiognomy, weathering degree of rock mass and mechanical functions of seismic waves. Based on microscopic study on initial fracturing of slope caused by seismic effect, combined with two change trends which include ratio of vertical vs. horizontal peak ground acceleration corresponding to epicentral distance and enlarging effect of peak ground acceleration along slope, key inducing factor of initial slope fracturing in various area with different epicentral distance is obtained. In near-field area, i.e. epicentral distance being less than 30 km, tensile strength of rock mass is a key intrinsic factor inducing initial fracturing of slope undergoing seismic effect whereas shear strength of rock mass is the one when epicentral distance is more than 30 km. In the latter circumstance, research by means of finite difference numerical simulation test and in-lab dynamic triaxial shear test of rock shows that initial fracture begins always in the place of slope shoulder. The fact that fracture strain and shear strength which are proportional to buried depth of rock mass in the place of slope shoulder are less than other place and peak ground acceleration is enlarged in the place causes prior failure at slope shoulder. Key extrinsic factors inducing dynamic fracture of slope at different distances to epicenter have been obtained through discrete element numerical simulation on the total process of collapsing and sliding of slope triggered by Wenchuan Earthquake. Research shows that combined action of P and S seismic waves is the key factor inducing collapsing and sliding of slope at a distance less than 64 km to initial epicenter along earthquake-triggering structure. What is more, vertical tensile action of P seismic wave plays a leading role near epicenter, whereas vertical shear action of S seismic wave plays a leading role gradually with epicentral distance increasing in this range. On the other hand, single action of P seismic wave becomes the key factor inducing collapsing and sliding of slope at a distance between 64 km and 216 km to initial epicenter. Horizontal tensile action of P seismic wave becomes the key factor gradually from combined action between vertical and horizontal tensile action of P seismic wave with epicentral distance increasing in this distance range. In addition, initial failure triggered by strong earthquakes begins almost in the place of slope shoulder. However, initial failure beginning from toe of slope relates probably with gradient and rock occurrence. Finally, starting time of initial failure in slope increases usually with epicentral distance. It is perhaps that the starting time increasing is a result of attenuating of seismic wave from epicenter along earthquake-triggering structure. It is of great theoretical and practical significance for us to construct towns and infrastructure in fragile geological environment along seism tectonic belts and conduct risk management on earthquake-triggered geological hazards by referring to above conclusions.

Knowledge based strategy: appraising knowledge creation capability in organisations.

This thesis sets out a journey which culminates in the development of an analytical framework, the "Organisational Creativity Appraisal" which is intended to assist organisations in evaluating their ability to support and develop creativity. This framework is derived from the common thread of the thesis, which is drawn from a range of research and consultancy projects, and the resulting published work, spanning an eight year period, centring on the role of knowledge and creativity in the strategy and performance of organisations. The literature of strategy, learning and creativity increasingly recognises that organisational context is critical to the formation of strategy, to the content of the strategy and to its successful implementation. The thesis explores the ways in which learning and creativity, the basis of knowledge-based strategy, are influenced by organisational context or social architecture. The research explores the ways in which managers can gain greater understanding of the social architectures of their organisations so as to assist in supporting their strategic development. The central core of the thesis is the nine published papers upon which it is based but it also derives from the broader perspective of my published work in the form of both articles and books. The thesis further draws upon my own experience as a leader and manager in the context of university business schools and as a consultant, researcher and developer in the context of a range of international private and public sector organisations. The work is based upon a premise that theory should inform practice and that practice should inform theory. The "Organisational Creativity Appraisal" framework is informed by both theory and practice and is intended to assist in management practice. There is no assumption that management research can arrive at prescriptions for managerial and organisational behaviour. On the other hand management research can usefully inform management and organisational behaviour, as long as it is employed in a critically reflective manner. The "Organisational Creativity Appraisal" presented in this work should be regarded as the framework in its present form which is likely to develop further as my research progresses in the future.

Hazard and early warning analysis based on domain specific modeling technologies

An aim of proactive risk management strategies is the timely identification of safety related risks. One way to achieve this is by deploying early warning systems. Early warning systems aim to provide useful information on the presence of potential threats to the system, the level of vulnerability of a system, or both of these, in a timely manner. This information can then be used to take proactive safety measures. The United Nation’s has recommended that any early warning system need to have four essential elements, which are the risk knowledge element, a monitoring and warning service, dissemination and communication and a response capability. This research deals with the risk knowledge element of an early warning system. The risk knowledge element of an early warning system contains models of possible accident scenarios. These accident scenarios are created by using hazard analysis techniques, which are categorised as traditional and contemporary. The assumption in traditional hazard analysis techniques is that accidents are occurred due to a sequence of events, whereas, the assumption of contemporary hazard analysis techniques is that safety is an emergent property of complex systems. The problem is that there is no availability of a software editor which can be used by analysts to create models of accident scenarios based on contemporary hazard analysis techniques and generate computer code that represent the models at the same time. This research aims to enhance the process of generating computer code based on graphical models that associate early warning signs and causal factors to a hazard, based on contemporary hazard analyses techniques. For this purpose, the thesis investigates the use of Domain Specific Modeling (DSM) technologies. The contributions of this thesis is the design and development of a set of three graphical Domain Specific Modeling languages (DSML)s, that when combined together, provide all of the necessary constructs that will enable safety experts and practitioners to conduct hazard and early warning analysis based on a contemporary hazard analysis approach. The languages represent those elements and relations necessary to define accident scenarios and their associated early warning signs. The three DSMLs were incorporated in to a prototype software editor that enables safety scientists and practitioners to create and edit hazard and early warning analysis models in a usable manner and as a result to generate executable code automatically. This research proves that the DSM technologies can be used to develop a set of three DSMLs which can allow user to conduct hazard and early warning analysis in more usable manner. Furthermore, the three DSMLs and their dedicated editor, which are presented in this thesis, may provide a significant enhancement to the process of creating the risk knowledge element of computer based early warning systems.

Early warning sign attributes for the safety of drinking water treatment works

A proactive risk management strategy seeks to prevent accidents from taking place and maintain the safety of a system. In this context, the task of identifying and disseminating early warning signs and signals is among the most important. The problem is that warning signs that are present before an accident takes place are often being overlooked and not picked up or identified as warning signs. If these warning signs were responded to, then an accident may be averted. Accidents occuring in the critical domain of a drinking water treatments works can have serious implications for the public health of consumers of the water supplied. Realising and comprehending early warning signs is a major challenge for the domain of systems safety and especially in the domain of a water treatment works. The approaches that are typically used to enhance the realisation, comprehension and dissemination of early warning signs in the water treatment domain in Ireland mainly involves the creation of accident scenarios, the use of monitoring data and procedures for the dissemination of warnings. While all of these approaches are all useful to inform the mental or process models of possible accident scenarios, nevertheless, accidents are still occurring in this domain. Therefore, a new approach to enhance the comprehension of and effective dissemination of early warning signs is required in order to improve safety and proactive risk management strategies. The contributions of this thesis is the provision of a set of attributes associated with the early warning sign concept that provides meaningful data on the early warning signs and allows recipients to better comprehend them. The values of these attributes were customised for application in the water treatment domain. This research proves that early warning signs at a water treatment works received with information on their attributes are comprehended and communicated more effectively and efficiently than the usual pragmatic approach and thereby improves the safety and proactive risk management strategies.

Corporate Bond Market in the Transition Economy of Vietnam, 1990-2010

Corporate bond appeared early in 1992-1994 in Vietnamese capital markets. However, it is still not popular to both business sector and academic circle. This paper explores different dimensions of Vietnamese corporate bond market using a unique, and perhaps, most complete dataset. State not only intervenes in the bond markets with its powerful budget and policies but also competes directly with enterprises. The dominance of SOEs and large corporations also prevents SMEs from this debt financing vehicle. Whenever a convertible term is available, bondholders are more willing to accept lower fixed income payoff. But they would not likely stick to it. On one hand, prospective bondholders could value the holdings of equity when realized favorably ex ante. On the other hand, the applicable coupon rate for such bond could turn out negative inflationadjusted payoff when tight monetary policy is exercised and the corresponding equity holding turns out valueless, ex post. Given the weak primary market and virtually nonexistent secondary market, the corporate bond market in Vietnam reflects our perception of the relationship-based and rent-seeking behavior in the financial markets. For the corporate bonds to really work, they critically need a higher level of liquidity to become truly tradable financial assets.

Operational scales, sources of finance, and firms’ performance: evidence from Vietnamese longitudinal data

This study investigates a longitudinal dataset consisting of financial and operational data from 37 listed companies listed on Vietnamese stock market, covering the period 2004-13. By performing three main types of regression analysis - pooled OLS, fixed-effect and random-effect regressions - the investigation finds mixed results on the relationships between operational scales, sources of finance and firms' performance, depending on the choice of analytical model and use of independent/dependent variables. In most situation, fixed-effect models appear to be preferable, providing for reasonably consistent results. Toward the end, the paper offers some further explanation about the obtained insights, which reflect the nature of a business environment of a transition economy and an emerging market.

Extreme weather events and business continuity planning

There is now a broad scientific consensus that the global climate is changing in ways that are likely to have a profound impact on human society and the natural environment over the coming decades. The challenge for Facilities Mangers is to ensure that business continuity plans acknowledge the potential for such events and have contingencies in place to ensure that their organisation can recover from an extreme weather event in a timely fashion. This paper will review current literature/theories pertinent to extreme weather events and business continuity planning; will consider issues of risk; identify the key drivers that need to be considered by Facilities Managers in preparing contingency/disaster recover plans; and identify gaps in knowledge (understanding and toolkits) that need to be addressed. The paper will also briefly outline a 3 year research project underway in the UK to address the issues

Treatment of effluents contaminated with prions. Chemical reactor design

The control and elimination of prionic infective agents that may be present in the effluents, turns out to be a complicated mechanism inside a High Containment bological Facility. There are two ways to carry out this neutralization: Installation of thermal systems to ensure achieve a minimum temperature of 134 ° C sterilization plateau for a residence time of 18 minutes, and the use of chemical reactors based on the addition of sodium hypochlorite so the mixture maintained 2% of free chlorine during the reaction period. This study presents the design phases, elements and benefits, of a chemical reactor that allows the treatment of prion effluents in order to serve as a model to biocontainment facilities with areas of animal experimentation, who want to develop their work with prions.

Kinetics of the oxidation of methyl tert-butyl ether (MTBE) by potassium permanganate

The occurrence of the fuel oxygenate methyl tert-butyl ether (MTBE) in the environment has received considerable scientific attention. The pollutant is frequently found in the groundwater due to leaking of underground storage tanks or pipelines. Concentrations of more than several mg/L MTBE were detected in groundwater at several places in the US and Germany in the last few years. In situ chemical oxidation is a promising treatment method for MTBE-contaminated plumes. This research investigated the reaction kinetics for the oxidation of MTBE by permanganate. Batch tests demonstrated that the oxidation of MTBE by permanganate is second order overall and first order individually with respect to permanganate and MTBE. The second-order rate constant was 1.426 x 10(-6) L/mg/h. The influence of pH on the reaction rate was demonstrated to have no significant effect. However, the rate of MTBE oxidation by potassium permanganate is 2-3 orders of magnitude lower than of other advanced oxidation processes. The slower rates of MTBE oxidation by permanganate limit the applicability of this process for rapid MTBE cleanup strategies. However, permanganate oxidation of MTBE has potential for passive oxidation risk management strategies. (C) 2002 Elsevier Science Ltd. All rights reserved.