Projeto de mestrado para implementação de um sistema de gestão da qualidade em farmácia comunitária

Nos últimos anos, a Qualidade em Instituições de saúde tem sido um tema relevante. O conceito de qualidade tem várias definições, sendo um conceito difícil de medir e definir. A Qualidade é uma ferramenta cada vez mais almejada pelas instituições que prestam cuidados de saúde e neste caso particular pela Farmácia Comunitária. Essa procura advém da necessidade de garantir um atendimento aos utentes cada vez mais eficaz e eficiente, capaz de satisfazer as suas reais necessidades e expectativas, por meio da otimização de processos e economização de recursos, tornando-se, por isso, uma prioridade nas áreas onde os farmacêuticos operam. O objetivo deste projeto é clarificar e explicar as etapas para a implementação de um Sistema de Gestão da Qualidade, com base na Norma ISO 9001:2008, numa Farmácia Comunitária, encorajando toda a equipa e promovendo o empenho e envolvência de todos nas práticas de gestão integrada da qualidade e nas estratégias de melhoria contínua. A Implementação de um Sistema de Gestão da Qualidade com base na norma ISO 9001:2008 poderá ter um impacto muito positivo, contribuindo não apenas para a melhoria da qualidade interna da organização, nas suas diversas vertentes, como também para a focalização nos seus clientes, melhorando ainda mais a qualidade dos serviços prestados, demonstrando ser relevante para a saúde, para a forma como os recursos humanos se organizam em torno do trabalho e para racionalização dos recursos. Desta forma se demonstra o valor desta ferramenta na gestão, eficácia e segurança no sistema de utilização do medicamento em Farmácia Comunitária.

The evolving profile, role and relevance of the medical director in a pharmaceutical company

Over the last years, operations in Pharmaceutical Companies have become more complex, trying to adapt to new demands of the market environment. Overall, the observed change of paradigm requires adapting, mainly by the setting of new priorities, diversification of investments, cost containment strategies, exploring new markets and developping new sets of skills. In this context, new functions have been created, the relevance of some has diminished, and the importance of others has arisen. Amongst these, the medical structure within a Pharmaceutical Company, increased to meet demands, with companies adopting different models to respond to these needs, and becoming a pillar to the business. Assuming the leading role within a medical department, the medical director function often lies in the shadow. It is a key function within Pharma Industry, either on a country or on a Global basis. It has evolved and changed in the past years to meet the constant demands of a changing environment. The Medical Director is a highly skilled and differeniated professional who provides medical and scientific governance within a Pharmaceutical company, since early stages of drug development and up to loss of exclusivity, not only but also by leading a team of other physicians, pharmacists or life scientists whose functions comprise specificities that the medical director needs to understand, provide input to, oversee and lead. As the organization of Pharmaceutical Companies tends to be different, in accordance to values, culture, markets and strategies, the scope of activities of a Medical Director can be broader or may be limited, depending on size of the organization and governance model, but they must fulfil a large set of requirements in order to leverage impact on internal and internal customers. Key technical competencies for medical directors such as an MD degree, a strong clinical foundation, knowledge of drug development, project and team management experience and written and verbal skills are relatively easy to define, but underlying behavioural competencies are more difficult to ascertain, and these are more often the true predictors of success in the role. Beyond seamless proficiency in technical skills, at this level interpersonal skills become far more important, as they are the driver and the distinctive factor between a good and an excelent medical director. And this has impact in the business and in the people doing it.

Isolation and structural characterization of fucoidans from the brown algae Fucus vesiculosus

agricultural, pharmaceutical, cosmetic or bioenergy applications. They contain bioactive compounds, namely, polysaccharides Fucoidan. These polysaccharides are mainly constituted by fucose residues and sulfate esters, and have been reported to possess a broad variety of bioactivities, such as anticoagulant, anti-thrombotic, anti-inflammatory, anti-tumor, antiviral and antioxidant. In this work, the fucoidans from brown seaweed Fucus vesiculosus from “Ria de Aveiro” were isolated and characterized in order to add value to this natural resource of the region. The polysaccharides from the algae were extracted with hot water and fractioned by ethanol precipitation and calcium chloride salts. They were further purified by using anion-exchange chromatography, allowing to separate the neutral polysaccharides (laminaranas) from those negatively charged (sulfated fucoidans and alginate). The purified polysaccharides showed high content of fucose (41 mol%) and sulfates (50 mol%), having also galactose residues (6 mol%), which confirm the presence of only sulfated fucoidans. Glycosidic linkages analysis show the presence of high amounts of terminal fucose (25%) and (1→3,4)-Fuc (26%), allowing to infer that the fucoidans were highly branched. These fucoidans are composed also by (1→2)-Fuc (14%) and (1→3)-Fuc linkages (10-16%). In this work it was also tested an alternative extraction technology, the microwave hydrodiffusion and gravity system, where it was possible to extract sugars, although in low yields. However, this methodology allowed to extract polysaccharides, constituted mainly by fucose and uronic acids, as well as mannitol, without the need to add any solvent, obtaining at the end the dry alga. The current work allowed to characterize the structure of the fucoidans isolated from “Ria de Aveiro” F. vesiculosus. The presence of high content of sulfate residues and the high branch degree of the purified fucoidans allow to infer that these polysaccharides could have potential to be studied for biomedical applications, according to their biological activities.

Product quality and compliance in the pharmaceutical industry

This thesis aims to highlight the importance of a Product Quality & Compliance department in a Pharmaceutical Industry, on the good performance of company's activities and the achievement of their goals and mission. Despite the wide activities performed by this Department, the purpose of this work will be completed by describing only some of their reponsibilities. The tasks described are specifically the ones I have been performing throughout my professional experience at Bluepharma - Pharmaceutical Industry, SA, initiated in June 2012 in the Quality Assurance Department until today in the currently named Product Quality & Compliance department. This thesis is structured into 4 parts. The first chapter is an introduction to this thesis, and includes its context and objectives, followed by a brief overview of the state-of-the art in the pharmaceutical industry, including the market environment, the regulatory environment and quality requirements. A small presentation of the company and the department where were and still are developed my professional activity is also made in this chapter. In the following chapter are described the main tasks performed, the complementary activities and key skills acquired throughout this professional experience. A discussion and conclusion is presented at the end, including an analysis of the reported activities, main difficulties encountered its role and importance in the company performance as well as the skills acquired during this work experience.

Fingolimod real world experience

Fingolimod is a Multiple Sclerosis treatment licensed in Europe since 2011. Its efficacy has been demonstrated in three large phase III trials, used in the regulatory submissions throughout the world. As usual, in these trials the inclusion and exclusion criteria were designed to obtain a homogeneous population, with interchangeable characteristics in the different treatment arms. Although this is the best strategy to achieve a robust answer to the investigation question, it does not guaranty the treatment efficacy in the clinical practice, since in the real world there are concomitant treatments, comorbidities, adherence and persistence challenges. But, to make informed treatment decision for a real life patient, we need to have evidence of the treatment efficacy, what has been called treatment effectiveness. This work aims to review fingolimod effectiveness, using as source of information abstracts, posters and manuscripts. This unorthodox strategy was developed because more than half of the published experience with fingolimod is still on abstracts and posters. Only a small part of the studies reviewed are already published in peer reviewed journals. Fingolimod seems to be, at least, as effective and safe as it was on clinical trials, and with its long term experience no new safety signals were observed. In the Portuguese hospital perspective, early treatment with fingolimod is expected to result in better clinical outcomes associated with a more efficient healthcare resources allocation.

Alergias a alimentos ou a derivados usados como excipientes em medicamentos

Aditivos químicos têm como principal objetivo melhorar os produtos industrializados, como fármacos, conferindo-lhes cor, aroma, textura, conservação, entre outros. Os aditivos utilizados na indústria farmacêutica são denominados excipientes, completando a massa ou o volume especificado no medicamento. São considerados substâncias inativas, uma vez que não apresentam propriedades curativas ou preventivas de doenças ou dos seus sintomas. No âmbito deste trabalho, foi realizado uma revisão bibliográfica sobre os excipientes naturais e sintéticos mais usados na indústria farmacêutica, agrupando-os mediante a sua função específica. Assim, foi feita uma breve descrição sobre alguns dos excipientes mais utilizados nas formulações farmacêuticas, nomeadamente os antioxidantes, os corantes, os edulcorantes e os conservantes, que visam garantir a conservação do produto em condições viáveis. Uma vez que os excipientes são considerados substâncias inativas, são vistos como inofensivos para a saúde. No entanto, é cada vez mais evidente que os excipientes não são sempre inertes e podem apresentar riscos para o desenvolvimento de reações alérgicas, podendo promover alterações mais prejudiciais. As reações alérgicas associadas aos excipientes são consideradas raras, visto que são incorporadas baixas concentrações destes em formulações farmacêuticas, tendo surgido, no entanto, diversos casos associados aos diferentes excipientes anteriormente referidos. Dependendo do excipiente e da sensibilidade do indivíduo, as alergias podem originar dermatites de contacto, prurido, urticária, edema, reações anafiláticas, entre outros. É importante salientar que o excesso de aditivos pode originar problemas de saúde, normalmente em indivíduos suscetíveis e na população pediátrica, sendo necessário aplicar cuidados adicionais que promovam uma maior vigilância e orientação no uso de medicamentos.

Curricular training report: 7 months as a study coordinator at Blueclinical LTD

The present report describes in detail the activities undertaken under the coordination of clinical and observational studies during the curricular internship at Blueclinical Ltd., inserted in the Master of Pharmaceutical Biomedicine. Blueclinical Ltd.company operates in three different areas: R&D consultancy, management and coordination of trial centers, and a phase I unit. The curricular internship had the duration of seven months during which I was able to perform different tasks relating to coordination of clinical trials in Centro Hospitalar do Baixo Vouga, E.P.E., (CHBV) in Aveiro, Portugal. This academic internship allowed me to develop theoretical and practical skills in the field of clinical trials and observational studies. I also had the opportunity to further the knowledge I gained throughout my academic journey. During this internship, I had the opportunity to interact with different health professionals and develop my knowledge in the field of several therapeutic indications. I also could interact with distinct monitors and sponsors. This experience allowed me to improve time management, communication and problems resolution skills.

Propriedades antioxidantes de constituintes fenólicos de macroalgas marinhas

Desde tempos remotos que as macroalgas marinhas são utilizadas por comunidades humanas, nomeadamente as orientais, como parte importante da sua dieta alimentar. A composição química das diferentes macroalgas marinhas (algas castanhas – Phaeophyta, algas vermelhas – Rhodophyta e algas verdes – Chlorophyta) confirma que além de terem um valor nutricional satisfatório podem ser uma fonte muito interessante de compostos bioativos como, por exemplo, os compostos fenólicos. Quimicamente os compostos fenólicos caracterizam-se por apresentarem um ou mais grupos hidroxilo ligados a um anel aromático. Estes compostos englobam desde moléculas simples até moléculas poliméricas de grandes dimensões. A maioria dos compostos fenólicos apresenta atividade antioxidante. O interesse pelo estudo de metabolitos secundários das macroalgas com propriedades antioxidantes surgiu, numa primeira fase, como uma tentativa de encontrar substitutos para os antioxidantes sintéticos usados como aditivos alimentares (nomeadamente o BHA e o BHT) que demonstravam possuir efeitos carcinogénicos. No entanto, rapidamente a comunidade científica reconheceu que a aplicação de novos compostos fenólicos naturais é muito mais vasta. Sabe-se hoje que é crucial para a promoção da saúde de um indivíduo que se verifique a manutenção do equilíbrio entre a produção de radicais livres e as respetivas defesas antioxidantes. Quando esse equilíbrio se altera e ocorre uma acumulação de radicais livres no organismo, este entra em stress oxidativo, situação que pode conduzir a danos dos lípidos celulares, proteínas e ácidos nucleicos, o que favorece o aparecimento de diversas doenças e acelera o envelhecimento celular. Assim, atualmente existe um crescente interesse por parte da indústria farmacêutica e da indústria da cosmética no estudo dos compostos fenólicos isolados de macroalgas. De entre estes, destacam-se os florotaninos, que para além das propriedades antioxidantes têm demonstrado possuir outras atividades farmacológicas importantes, tais como atividade antibacteriana, anti-viral, antineoplásica, anti-hipertensora e anti-diabética. Este trabalho consiste numa revisão bibliográfica sobre os diversos compostos fenólicos com atividade antioxidante isolados de macroalgas marinhas e que demonstraram vantagens na sua incorporação, quer em formulações cosméticas, quer em medicamentos, debatendo as suas ações farmacológicas, mecanismos de ação e possíveis aplicações futuras.

Curricular training report: clinical studies coordination in a clinical research organization vs an investigational site perspective

This report describes my experience of nine months as a trainee of a CRO (Eurotrials, Scientific Consultants), as well as a trainee of a clinical research site (Clinical Academic Center – Braga, Association). This document describes the European framework about clinical research and the Portuguese situation compared to similar countries. The activities developed during this internship are also described. These activities are divided in two phases. The first one occurred in Eurotrials, Scientific Consultants, a CRO specialized in clinical research and scientific advice. The first weeks were dedicated to intensive self-training needed to perform CTA tasks. These tasks included qualification, initiation and monitoring activities related to clinical trials, as well as the development of a quality management system. The second phase took place on 2CA-Braga, a clinical research center located in Hospital of Braga. Clinical studies coordination was the main focus of this second phase of my internship, as well as negotiation of clinical studies agreements. I had also the opportunity to participate in “1as Jornadas de Investigação Clínica e Inovação” (1st Clinical Investigation and Innovation Conference) organized by 2CA-Braga. Globally, this internship was a great opportunity to get knowledge and experience in the implementation and management of clinical trials, in a CRO and clinical research site perspectives. These two perspectives provided an interesting overview about the scientific needs of different players involved in clinical research. To conclude, this internship strengthened the knowledge acquired from my academic background, which make me able to face and overcome new challenges in the clinical research area.

Determinación de la flora micológica del maíz seco y su harina en la parroquía San Juan-cantón Gualaceo

El presente trabajo de tesis tuvo como finalidad evaluar la flora micológica del maíz seco y su harina producidos en la parroquia San Juan - Cantón Gualaceo con el fin de aportar con información sobre la calidad de estos alimentos. Además se evaluaron los siguientes factores para el desarrollo de la flora micológica: temperatura, actividad acuosa, almacenamiento; así como también el crecimiento en distintos medios de cultivos y el uso de la desinfección del grano como parte de la técnica de siembra. La detección, recuento y aislamiento de hongos se realizó de acuerdo a la técnica de recuento en placa por siembra en profundidad para la harina y en el caso del grano por la técnica de siembra directa, con y sin desinfección de la superficie del grano utilizándose el agar MEA (Agar Extracto de Malta), PDA (Agar Papa Dextrosa) y DRBC (Agar Rosa de Bengala Diclorán) y sometiendo a dos tratamientos térmicos (18°C vs 25°C). Se encontró que la micoflora presente en las muestras analizadas corresponde a los géneros Penicillium, Fusarium, Rhizopus, Aspergillus y levaduras, siendo el género predominante Penicillium tanto en el grano como en la harina. La temperatura óptima para el crecimiento fue 25°C; y a su vez el crecimiento fue mejor sin desinfectar las superficies del grano. El crecimiento micológico varió dependiendo del medio, siendo PDA el más óptimo para Penicillium y Rhizopus, mientras que para Fusarium y Aspergillus no hubo diferencia. Igualmente se encontró que la actividad acuosa influyó en forma proporcional al crecimiento micológico y que el almacenamiento controlado influyó positivamente en su disminución.

Curricular trainig report as study coordinator in Blueclinical Ltd.

The present report describes in detail the activities and knowledge aquired during my internship as study coordinator in Blueclinical – Investigação e Desenvolvimento em Saúde, Ltd., in order to obtain the master degree in Pharmaceutical Biomedicine. According to the type of services provided, Blueclinical is formed by three business units: Blueclinical Clinical Research Partnership, Blueclinical Phase I and Blueclinical Research and Development. The fact of belonging to such a company gave me the opportunity to be in touch with different areas of pharmaceutical development and to contact with different research teams, which for me was an added advantage to the integration and consolidation of knowledge, as well as in the development and improvement of soft and hard skills. The main activity developed was the coordination of clinical studies, in Unidade Local de Saúde de Matosinhos, E.P.E., which was one of the institutions that established a partnership with Blueclinical, Ltd. During my internship I was able to contact with various stages of development and coordination of clinical trials, which will be reported in this report.

Método rápido y biocompatible de extracción, saponificación y concentración de ácidos grasos poliinsaturados (PUFAS) por diferencias de solubilidad a partir de biomasa

La invención proporciona un método para preparar un concentrado de ácidos grasos poliinsaturados (PUFAS) a partir de biomasa que comprende: (a) extraer y saponificar la biomasa mediante tratamiento con un alcohol inferior y un hidróxido de metal alcalino a 75-90ºC; (b) enfriar la mezcla obtenida en (a) para obtener una fase líquida y una fase sólida; (c) filtrar la fase sólida a la temperatura de enfriamiento; (d) acidificar el filtrado; (e) extraer el filtrado acidificado con un disolvente orgánico; y (f) purificar el extracto destilando el disolvente; en el que en la etapa (a) el alcohol inferior es etanol absoluto y el hidróxido de metal alcalino es hidróxido sódico sólido; y el enfriamiento de la etapa (b) y la filtración de la etapa (c) se llevan a cabo a una temperatura de 0-4ºC. El concentrado de PUFAS así obtenido puede usarse en la industria agroalimentaria, farmacéutica o química.

Curricular internship report in medical writing at Blueclinical, Portugal

The contents of this report are a summary of the activities carried out during the 8-month internship as an Associate Medical Writer at Blueclinical Ltd, Matosinhos, Portugal. Mainly my activities were related to medical writing, particularly writing the clinical research protocols, clinical study reports, writing manuscript and preparing poster presentations. In addition to these activities, I also participated in performance of a clinical trial from beginning to end. During the period of its realization, I was able to familiarize myself with all the steps of the Phase I clinical trial.

Determinación de carbohidratos totales en bebidas analcohólicas consumidas por adolescentes en la ciudad de Cuenca y Nabón

Este trabajo presenta la determinación del contenido de carbohidratos totales en treinta bebidas analcohólicas altamente consumidas por adolescentes escolarizados de la ciudad de Cuenca y Nabón, por medio de la cual se identificaron las bebidas analcohólicas con el más alto contenido calórico que se consumen localmente y se realizó una comparación con lo declarado en sus respectivas etiquetas. Esta cuantificación se realizó mediante el método de Dubois, aplicado sin clarificación previa y utilizando la curva de calibración de sacarosa como patrón. Debido a la alta concentración de carbohidratos en las bebidas se realizaron diluciones sucesivas de cada muestra, para posteriormente aplicar el método de Dubois: a 1 mLde muestra diluida se añadió 500 µL de fenol y 2,5 mL de ácido sulfúrico concentrado; luego de una incubación en baño de hielo por 30 minutos, se realizó la medición de absorbancias en el espectrofotómetro a una longitud de onda de 490 nm. Tras los cálculos utilizando la curva de calibración, los resultados se expresaron en mg/L y en mg de carbohidratos totales por porción de bebida analcohólica (240 mL). De los resultados obtenidos se identificó al jugo FACUNDO NÉCTAR DE GUAYABA, la COLADA DE AVENA Y DE MAICENA, y el PULP NÉCTAR DE MANGO como aquellas con la concentración más elevada de carbohidratos totales. También se descartó la existencia de una relación entre la concentración de azúcar y el costo de la bebida (r=0,21; R2=0,012).Finalmente no se encontró una diferencia significativa entre los resultados obtenidos y los indicados en las etiquetas (t-test, P=0,19). El método utilizado en el análisis presenta varias ventajas como es la rapidez, sensibilidad a bajas concentraciones de azúcar, los reactivos son baratos y estables, entre otras. Además que las interferencias que presenta pueden ser evitadas sin ningún problema.

Determinación de macronutrientes en alimentos tradicionales de la ciudad de Cuenca

Los alimentos tradicionales de la ciudad de Cuenca representan un aporte de energía importante a la dieta, además pueden considerarse como alimentos sanos gracias a la combinación balanceada de ingredientes que contienen. La determinación de macronutrientes en estos alimentos permite elaborar una base de datos de composición local de los alimentos tradicionales de mayor consumo en la ciudad de Cuenca, de los cuales no se tienen datos. El contenido de macronutrientes presentes en los alimentos dependerá del proceso de elaboración al cual hayan sido sometidos, ya que estos pueden variar en cantidad con respecto a los ingredientes en estado crudo. Una porción promedio de la mayoría de los alimentos tradicionales estudiados aportan más de un 10% de una dieta diaria (2000 Kcal). Los alimentos tradicionales son usualmente consumidos como snacks por su alto contenido calórico sin embargo su consumo balanceado resulta más beneficioso por su contenido nutricional. Al estimar la ingesta de los alimentos tradicionales por medio de encuestas de consumo es posible establecer la ingesta diaria promedio, lo cual correspondió a un aporte de energía menor al 10 % de una dieta promedio de 2000 Kcal.