Technology market transfer plan launch of DELIVES to E.U. Market©

Dissertação apresentada na Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa para obtenção do grau de Mestre em Biotecnologia

Enterococcus and biocides: mechanisms of tolerance and selection for vancomycin resistance

Dissertation presented to obtain a Doctoral degree in Biology, Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa.

Strategic account management: the path to gain customer loyalty

The account management field works closely with the sales team, serving as the customer’s primary point of contact. This project’s purpose was to understand if shifting the account management from brand centric to customer centric, would be the best fit for a Portuguese Pharmaceutical company. This customer centric approach - Strategic Account Management (SAM) - was studied, understanding the implicated trade-offs to the company. The workforce was probed about the project and their comments were analyzed. The conclusion points to an implementation of SAM and proposes the adaptations to follow in order to smooth the change.

The patent expiry as a major inflection point in a branded Rx drug's life and strategies to counter generic competition - exemplified at Pfizer's blockbuster drug Lipitor in the USA

A large number of expensive, but highly profitable branded prescription drugs will go off-patent in the USA between 2011 and 2015. Their revenues are crucial to fund the immense costs associated with the development of an innovative drug. The rising cost pressure on pharmaceutical stakeholders has increased the demand for more affordable medications, as provided by the branded drug's generic counterpart. Yet, research based incumbents are moving beyond the traditional late lifecycle strategies and deploy more aggressive tactics in order to protect their brands, as seen with Pfizer's Lipitor!. It is doubtful, whether these efforts will help the blockbuster business model to resist current market conditions.

Development of 3D in vitro models for prediction of hepatic metabolism and toxicity

The development of human cell models that recapitulate hepatic functionality allows the study of metabolic pathways involved in toxicity and disease. The increased biological relevance, cost-effectiveness and high-throughput of cell models can contribute to increase the efficiency of drug development in the pharmaceutical industry. Recapitulation of liver functionality in vitro requires the development of advanced culture strategies to mimic in vivo complexity, such as 3D culture, co-cultures or biomaterials. However, complex 3D models are typically associated with poor robustness, limited scalability and compatibility with screening methods. In this work, several strategies were used to develop highly functional and reproducible spheroid-based in vitro models of human hepatocytes and HepaRG cells using stirred culture systems. In chapter 2, the isolation of human hepatocytes from resected liver tissue was implemented and a liver tissue perfusion method was optimized towards the improvement of hepatocyte isolation and aggregation efficiency, resulting in an isolation protocol compatible with 3D culture. In chapter 3, human hepatocytes were co-cultivated with mesenchymal stem cells (MSC) and the phenotype of both cell types was characterized, showing that MSC acquire a supportive stromal function and hepatocytes retain differentiated hepatic functions, stability of drug metabolism enzymes and higher viability in co-cultures. In chapter 4, a 3D alginate microencapsulation strategy for the differentiation of HepaRG cells was evaluated and compared with the standard 2D DMSO-dependent differentiation, yielding higher differentiation efficiency, comparable levels of drug metabolism activity and significantly improved biosynthetic activity. The work developed in this thesis provides novel strategies for 3D culture of human hepatic cell models, which are reproducible, scalable and compatible with screening platforms. The phenotypic and functional characterization of the in vitro systems performed contributes to the state of the art of human hepatic cell models and can be applied to the improvement of pre-clinical drug development efficiency of the process, model disease and ultimately, development of cell-based therapeutic strategies for liver failure.

O setor de distribuição farmacêutica em Portugal estrutura e estratégias

A presente investigação desenvolveu uma análise profunda do setor da distribuição farmacêutica, no período compreendido entre 2000 e 2009, procurando identificar as possíveis relações de interdependência entre o meio envolvente e as opções de estratégia das empresas que constituíram a amostra de estudo e entre as referidas opções de estratégia e as estruturas e o desempenho dessas empresas. A dinâmica do mercado do medicamento na economia nacional, com um valor de 3,2 mil milhões de euros anuais (Infarmed, 2010), apresenta um impacto significativo na esperança de vida e na qualidade de vida dos cidadãos. Segundo a OCDE, os produtos farmacêuticos são responsáveis por quase um quinto de todos os gastos com saúde, em média, nos países da OCDE. Neste contexto, a distribuição farmacêutica representa uma componente crítica. A disponibilização de medicamentos em ambulatório num curto espaço de tempo só é possível devido a uma estrutura logística com características muito específicas. A qualidade do armazenamento e do transporte dos medicamentos desde a saída dos laboratórios até à chegada às farmácias é rigorosamente monitorizada e controlada. O setor da distribuição farmacêutica assume assim uma postura elementar na cadeia do medicamento, contribuindo para a melhoria da qualidade do sistema de saúde que se tem vindo a verificar nas últimas décadas e prestando um serviço com valor para a comunidade, uma vez que se compromete a assegurar um adequado e contínuo fornecimento de medicamentos para que as necessidades dos doentes e das populações em geral sejam satisfeitas. As alterações verificadas ao longo dos últimos anos estimularam a dinâmica concorrencial entre os diferentes agentes neste mercado, bastante regulamentado e com elevado entrosamento financeiro com o Estado, o que obrigou a rápidas mudanças. Neste contexto, a sobrevivência das empresas, o seu crescimento e a sua perenidade futura têm constituído um desafio abordado de forma diversa por cada empresa.

Patente farmacêutica: especificidades e tutela

Dissertação de mestrado em Direito dos Contratos e da Empresa

Síntese de péptidos contendo resíduos de aminoácidos não proteinogénicos

Dissertação de mestrado em Química Medicinal

Implementation of the I.S. EN 16001:2009 energy management standard into GlaxoSmithKline (GSK) Ltd, Cork

As manufacturers face an increasingly competitive environment, they seek out opportunities to reduce production costs without negatively affecting the yield or the quality of their finished products. The challenge of maintaining high product quality while simultaneously reducing production costs can often be met through investments in energy efficient technologies and energy efficiency practices. Energy management systems can offer both technological and best practice efficiencies in order to achieve substantial savings. A strong energy management system provides a solid foundation for an organisation to reduce production costs and improve site efficiency. The I.S EN16001 energy management standard specifies the requirements for establishing, implementing, maintaining and improving an energy management system and represents the latest best practice for energy management in Ireland. The objective of the energy management system is to establish a systematic approach for improving energy performance continuously. The I.S EN16001 standard specifies the requirements for continuous improvement through using energy more efficiently. The author analysed how GlaxoSmithKline’s (GSK) pharmaceutical manufacturing facility in Cork implemented the I.S. EN16001 energy management system model, and defined how energy saving opportunities where identified and introduced to improve efficiency performance. The author performed an extensive literature research in order to determine the current status of the pharmaceutical industry in Ireland, the processes involved in pharmaceutical manufacturing, the energy users required for pharmaceutical manufacturing and the efficiency measures that can be applied to these energy users in order to reduce energy consumption. The author then analysed how energy management standards are introduced to industry and critically analysed the driving factors for energy management performance in Ireland through case studies. Following an investigation as to how the I.S. EN16001 energy management standard is operated in GSK, a critical analysis of the performance achieved by the GSK energy management system is undertaken in order to determine if implementing the I.S EN16001 standard accelerates achieving energy savings. Since its introduction, the I.S. EN16001 model for energy management has enabled GSK to monitor, target and identify energy efficiency opportunities throughout the site. The model has put in place an energy management system that is continuously reviewed for improvement and to date has reduced GSK’s site operations cost by over 30% through technical improvements and generating energy awareness for smarter energy consumption within the GSK Cork site. Investment in I.S. EN16001 has proved to be a sound business strategy for GSK especially in today's manufacturing environment.

Short Guide to Hepatitis C

Hepatitis C is a rapidly developing area of medicine – diagnostic tools are ever more refined, and entirely new treatments and treatment strategies are arriving, with more on the horizon. And because the virus affects such a large and varying population – up to 170 million at last count – we think it is important to have a pocket reference especially devoted to hepatitis C. We look forward to your comments on the usefulness of our 2014 Short Guide to Hepatitis C, which is an expansion and update of the HCV chapters in Hepatology – A Clinical Textbook (2014), also published by Flying Publisher. As always, we invite qualified people everywhere to translate this book into other languages, and make them available widely. This web-based free-of- harge concept is made possible by unrestricted educational grants from the pharmaceutical industry and has allowed the material to reach countries usually not covered by print media. We are convinced that this new pocket guide concept, focusing here on hepatitis C, will become a valuable source of information for our readers.

Task force IV: Clinical use of ambulatory blood pressure monitoring. Participants of the 1999 Consensus Conference on Ambulatory Blood Pressure Monitoring

OBJECTIVE: To reach a consensus on the clinical use of ambulatory blood pressure monitoring (ABPM). METHODS: A task force on the clinical use of ABPM wrote this overview in preparation for the Seventh International Consensus Conference (23-25 September 1999, Leuven, Belgium). This article was amended to account for opinions aired at the conference and to reflect the common ground reached in the discussions. POINTS OF CONSENSUS: The Riva Rocci/Korotkoff technique, although it is prone to error, is easy and cheap to perform and remains worldwide the standard procedure for measuring blood pressure. ABPM should be performed only with properly validated devices as an accessory to conventional measurement of blood pressure. Ambulatory recording of blood pressure requires considerable investment in equipment and training and its use for screening purposes cannot be recommended. ABPM is most useful for identifying patients with white-coat hypertension (WCH), also known as isolated clinic hypertension, which is arbitrarily defined as a clinic blood pressure of more than 140 mmHg systolic or 90 mmHg diastolic in a patient with daytime ambulatory blood pressure below 135 mmHg systolic and 85 mmHg diastolic. Some experts consider a daytime blood pressure below 130 mmHg systolic and 80 mmHg diastolic optimal. Whether WCH predisposes subjects to sustained hypertension remains debated. However, outcome is better correlated to the ambulatory blood pressure than it is to the conventional blood pressure. Antihypertensive drugs lower the clinic blood pressure in patients with WCH but not the ambulatory blood pressure, and also do not improve prognosis. Nevertheless, WCH should not be left unattended. If no previous cardiovascular complications are present, treatment could be limited to follow-up and hygienic measures, which should also account for risk factors other than hypertension. ABPM is superior to conventional measurement of blood pressure not only for selecting patients for antihypertensive drug treatment but also for assessing the effects both of non-pharmacological and of pharmacological therapy. The ambulatory blood pressure should be reduced by treatment to below the thresholds applied for diagnosing sustained hypertension. ABPM makes the diagnosis and treatment of nocturnal hypertension possible and is especially indicated for patients with borderline hypertension, the elderly, pregnant women, patients with treatment-resistant hypertension and patients with symptoms suggestive of hypotension. In centres with sufficient financial resources, ABPM could become part of the routine assessment of patients with clinic hypertension. For patients with WCH, it should be repeated at annual or 6-monthly intervals. Variation of blood pressure throughout the day can be monitored only by ABPM, but several advantages of the latter technique can also be obtained by self-measurement of blood pressure, a less expensive method that is probably better suited to primary practice and use in developing countries. CONCLUSIONS: ABPM or equivalent methods for tracing the white-coat effect should become part of the routine diagnostic and therapeutic procedures applied to treated and untreated patients with elevated clinic blood pressures. Results of long-term outcome trials should better establish the advantage of further integrating ABPM as an accessory to conventional sphygmomanometry into the routine care of hypertensive patients and should provide more definite information on the long-term cost-effectiveness. Because such trials are not likely to be funded by the pharmaceutical industry, governments and health insurance companies should take responsibility in this regard.

The de facto independence of regulatory agencies and its consequences for policy making and regulatory outcomes

This dissertation focuses on the practice of regulatory governance, throughout the study of the functioning of formally independent regulatory agencies (IRAs), with special attention to their de facto independence. The research goals are grounded on a "neo-positivist" (or "reconstructed positivist") position (Hawkesworth 1992; Radaelli 2000b; Sabatier 2000). This perspective starts from the ontological assumption that even if subjective perceptions are constitutive elements of political phenomena, a real world exists beyond any social construction and can, however imperfectly, become the object of scientific inquiry. Epistemologically, it follows that hypothetical-deductive theories with explanatory aims can be tested by employing a proper methodology and set of analytical techniques. It is thus possible to make scientific inferences and general conclusions to a certain extent, according to a Bayesian conception of knowledge, in order to update the prior scientific beliefs in the truth of the related hypotheses (Howson 1998), while acknowledging the fact that the conditions of truth are at least partially subjective and historically determined (Foucault 1988; Kuhn 1970). At the same time, a sceptical position is adopted towards the supposed disjunction between facts and values and the possibility of discovering abstract universal laws in social science. It has been observed that the current version of capitalism corresponds to the golden age of regulation, and that since the 1980s no government activity in OECD countries has grown faster than regulatory functions (Jacobs 1999). Following an apparent paradox, the ongoing dynamics of liberalisation, privatisation, decartelisation, internationalisation, and regional integration hardly led to the crumbling of the state, but instead promoted a wave of regulatory growth in the face of new risks and new opportunities (Vogel 1996). Accordingly, a new order of regulatory capitalism is rising, implying a new division of labour between state and society and entailing the expansion and intensification of regulation (Levi-Faur 2005). The previous order, relying on public ownership and public intervention and/or on sectoral self-regulation by private actors, is being replaced by a more formalised, expert-based, open, and independently regulated model of governance. Independent regulation agencies (IRAs), that is, formally independent administrative agencies with regulatory powers that benefit from public authority delegated from political decision makers, represent the main institutional feature of regulatory governance (Gilardi 2008). IRAs constitute a relatively new technology of regulation in western Europe, at least for certain domains, but they are increasingly widespread across countries and sectors. For instance, independent regulators have been set up for regulating very diverse issues, such as general competition, banking and finance, telecommunications, civil aviation, railway services, food safety, the pharmaceutical industry, electricity, environmental protection, and personal data privacy. Two attributes of IRAs deserve a special mention. On the one hand, they are formally separated from democratic institutions and elected politicians, thus raising normative and empirical concerns about their accountability and legitimacy. On the other hand, some hard questions about their role as political actors are still unaddressed, though, together with regulatory competencies, IRAs often accumulate executive, (quasi-)legislative, and adjudicatory functions, as well as about their performance.

Immunisation Guidelines for Ireland

This revised report on immunisation guidelines for Ireland has been prepared with the assistance of an active committee from associated disciplines in Paediatrics, Infectious Diseases, General Practice and Public Health. The report itself is designed to be simple and concise and of course does not claim to contain all information on any pharmacological material. It does, however, give the current information and guidelines concerning immunisation. Vaccines are continually evolving and guidelines will obviously change given the nature of these developments. This is a tribute to the pharmaceutical industry who invest so much money in research and development in this particular field. Download document here

Sixth Annual Report of the Independent Monitoring Group for A Vision for Change - the Report of the Expert Group on Mental Health Policy - July 2012

Sixth Annual Report of the Independent Monitoring Group for A Vision for Change – the Report of the Expert Group on Mental Health Policy – July 2012 This is the 6th Annual Report of the Independent Monitoring Group for A Vision for Change (IMG) and the final report of the Second Group. It is clear to the IMG that the implementation of A Vision for Change (AVFC) to date including 2011 has been slow and inconsistent. There is a continued absence of a National Mental Health Service Directorate with authority and control of resources. Such a body has the potential to give strong corporate leadership and act as a catalyst for change. Click here to download HSE National and Regional Progress ReportsHSE – 6th Annual Report HSE – National and Regional Progress Report Progress Reports from Government DepartmentsDepartment of Children and Youth AffairsDepartment of Education and SkillsDepartment of Health Department of Justice and Equality Department of Social ProtectionDepartment of Environment, Community & Local Government National Mental Health Programme Plan Consultation Document What We Heard Submissions Received by the IMGAmnesty International Ireland submission Association of Occupational Therapists submission College of Psychiatry of Ireland submissionCollege of Psychiatry of Ireland – Press Release regarding Social Psychiatry and Recovery Conference College of Psychiatry of Ireland – regarding Psychotherapy Training for Psychiatric TraineesCollege of Psychiatry of Ireland – regarding relationship with Pharmaceutical Industry College of Psychiatry of Ireland – Mental Health in Primary CareDisability Federation of IrelandHealth Research Board submission Irish Association of Social Workers – Adult Mental Health Irish Association of Social Workers – Child and Adolescent Mental Health Irish College of General PractitionersMental Health CommissionMental Health ReformPharmaceutical Society of IrelandIrish Advocacy Network Childrens Mental Health CoalitionNational Disability AuthorityNational Service Users ExecutiveNational Service Users Executive – Second Opinions ReportNational Federation of Voluntary BodiesHeadstrong  

Control de la producció d'una empresa farmacèutica

Estudi de la implantació del control automàtic en la producció d'una indústria farmacèutica, concretament en sis línies de màquines. A part de portar un control es pretén millorar la producció i a la vegada detectar qualsevol error o anomalia que es produeixi en aquestes màquines