Made available in DSpace on 2016-12-12T20:34:13Z (GMT). No. of bitstreams: 1 Dissertacao Paulo em 17-9.pdf: 465544 bytes, checksum: 33b5b1a2b098715556b9cc2171800076 (MD5) Previous issue date: 2007-10-22 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / In order to contribute for the evaluation of the Brazilian policies on generic drugs and their social relevance, this study investigated, by means of a case study on a public health unit, the knowledge that prescribers, dispensers, and users possess on generic drugs and their confidence on those drugs. First, the study investigated the history of the production and use of drugs in Brazil, from the colonial times to the present days. Then, by means of an examination of the legislation, the study investigated the characteristics of the Brazilian National Policy on Drugs, drawing a distinction between generic, similar and brand name drugs. Data were also obtained on the production and sales of drugs in Brazil. After that, by means of a case study, information was collected on the attitudes of health professionals and patients towards generics (knowledge, confidence, use, etc.). Subjects of this study were 62 patients of a policlinic in São José, Santa Catarina, Brazil, plus 14 prescribers (11 doctors and 3 dentists) and 2 dispensers (pharmacists), all of which work at the policlinic. The data were collected by means of questionnaires. Patients had a great difficulty to distinguish the classes of drugs based on the Law 9787/99 (Law of Generic Drugs). Most of them have the wrong conception that generics are cheaper than similar drugs. Prescribers also were also confused by the definitions of generic and similar drugs presented in the legal text. On the other hand, most of them are aware of the fact that generic drugs have the obligation to be cheaper than brand-name drugs only. Most of the prescribers rely on the quality of generic drugs, but they do not always make their prescriptions using the Brazilian Common Denomination, which would facilitate the acquisition of generics by patients. The pharmacists could easily identify drug classes, as presented in the legal text. They were also knowledgeable about the fact generics are normally more expensive than similar drugs. This research allowed for the following general findings, among others: a) Brazilian national policy for generics has warranted safety and efficacy of drugs, by establishing accurate criteria for the certification of the centers that test bioequivalence/bioavailability and pharmaceutical equivalence; b) the national policy for generics has favored the development of the Brazilian drug industry, because most the great majority of the generics sold in Brazil are produced by national laboratories; c) the national policy for generics has attended the principle of rational drug use, because it presupposes surveillance and control of drug production, prescription, and dispensing; d) generics are cheap enough to provoke a significant reduction on the cost of some treatments and bring some economy for the government concerning the acquisition of pharmaceuticals; e) in the last ten years, raises in drug prices caused a reduction in the consumption of drugs in Brazil, but it is probable that the increase in the use of generics forces a decrease in the price of brand name drugs; f) new public campaigns seem necessary in order to restate the distinctions among drug classes and to reinforce prescribers confidence in generics / Como forma de contribuir para a avaliação da política nacional de medicamentos genéricos e sua relevância social, este trabalho investigou, mediante estudo de caso em uma unidade pública de saúde, o conhecimento que têm prescritores, dispensadores e usuários relativamente aos medicamentos genéricos e a confiança que neles depositam. Para situar historicamente a pesquisa, traçou-se inicialmente um histórico da produção e uso de medicamentos no Brasil, desde os tempos coloniais até os dias atuais. A seguir, mediante exame da documentação oficial, procurou-se conhecer as características da Política Nacional de Medicamentos, distinguindo medicamentos genéricos de similares e de referência e obtendo também dados sobre a produção e comercialização de medicamentos no País. Depois, mediante estudo de caso, buscou-se obter informações quanto à relação de profissionais da saúde e usuários com os medicamentos genéricos (conhecimento, confiança, uso, etc.). Foram informantes da pesquisa 62 usuários da Policlínica Municipal de Campinas - São José/SC, 14 prescritores (11 médicos e 3 cirurgiões-dentistas) e 2 dispensadores (farmacêuticos), todos atuantes na Policlínica. Os dados foram colhidos mediante a aplicação de questionários. Os usuários tiveram bastante dificuldade para distinguir as classes de medicamentos a partir do texto da Lei 9.787/99 (Lei dos Genéricos). Mais da metade deles têm a percepção equivocada de que os genéricos são mais baratos que os similares. Já os prescritores também confundiram as definições para medicamento genérico e similar oferecidas no texto legal. Por outro lado, a maioria dos prescritores mostraram-se cientes de que os genéricos têm por obrigação serem mais baratos apenas que os medicamentos de referência. A maioria dos prescritores confiam na qualidade dos medicamentos genéricos, mas nem sempre fazem suas prescrições usando a DCB, o que facilitaria a aquisição de genéricos pelos pacientes. Os dispensadores identificaram sem dificuldade as classes de medicamentos, a partir do texto legal. Também sabem que os genéricos geralmente têm preço mais elevado que os similares. Entre outras, o trabalho permitiu as seguintes constatações gerais: a) a política nacional de genéricos tem garantido a segurança e eficácia dos medicamentos, mediante o estabelecimento de critérios apurados para certificação dos centros que realizam os testes de bioequivalência/biodisponibilidade e equivalência farmacêutica; b) a política de genéricos tem favorecido o desenvolvimento da indústria nacional de medicamentos, pois a grande maioria dos genéricos consumidos no País são produzidos por laboratórios nacionais; c) a política de genéricos tem favorecido ao princípio de uso racional de medicamentos, pois prevê acompanhamento e controle da produção, da prescrição e da dispensação de medicamentos; d) os genéricos são suficientemente baratos para provocar redução considerável no custo de alguns tratamentos e propiciar ao poder público alguma economia na aquisição de medicamentos; e) nos últimos dez anos, aumentos acima das taxas de inflação provocaram uma redução no consumo de medicamentos no País, mas é provável que o crescimento que se vem verificando no uso dos genéricos provoque uma queda no preço dos medicamentos de referência; f) parecem ser necessárias novas campanhas estabelecendo a distinção entre as classes de medicamentos e reforçando, nos prescritores, a confiança nos genéricos

Made available in DSpace on 2010-04-20T21:00:13Z (GMT). No. of bitstreams: 4 Jose Antonio Lopes.pdf.jpg: 14118 bytes, checksum: c889b29f5f70038e9202ed5ff58975d8 (MD5) Jose Antonio Lopes.pdf.txt: 99454 bytes, checksum: 3a0d9e5475dc749d8ee501b09eeee580 (MD5) Jose Antonio Lopes.pdf: 583370 bytes, checksum: 8f59c41f14df7e84775fb3ddcb57e4a6 (MD5) license.txt: 4886 bytes, checksum: 2af242f47fcec166b0886a2531cbaf60 (MD5) Previous issue date: 2009-01-16T00:00:00Z / The aim of this document is to evaluate the price behavior in the Brazilian market for drugs that are market leader in its segment after the presence of competitors such as similar and generics drugs. According to some American studies, leading drugs reacts positively in relation to price variance when generic competitors are introduced in the market after patent expiration of original brands. Leading drugs accommodate share growth of the followers, turning towards an inelastic market segment that is less sensitive to changes in the leading drug prices. This behavior is not aligned with the economic common sense that expects price reduction of leading brands when facing new competitors in a specific market. The results of this study related to the Brazilian pharmaceutical market, demonstrates that leading drugs reacts positively in relation to price variance when losing market share for generic and similar brands. On the other hand, a fierce competition among similar and generic brands leads their price to go down and its dispersion relatively to the leader price tends to go up. / O objetivo desse trabalho é avaliar o comportamento da variável preço para os medicamentos líderes de mercado no Brasil após a entrada de concorrentes similares e posteriormente a instituição dos medicamentos genéricos no Brasil. Segundo estudos realizados no mercado norte-americano, os medicamentos originais reagiriam à entrada de concorrentes genéricos de forma positiva no que se refere à variação de seu preço de comercialização. Dessa forma, os medicamentos originais se concentrariam nos segmentos de mercado mais inelásticos e com menor sensibilidade a possíveis alterações no seu preço de venda. Tal comportamento contradiz a intuição econômica comum de que a entrada de novos concorrentes em um mercado levaria a redução de preços por parte da empresa dominante. Os resultados desse trabalho, sobre o mercado farmacêutico brasileiro, indicam que as marcas líderes respondem positivamente em relação a aumento de seus preços quando da perda de participação de mercado para marcas seguidoras como genéricos e similares. Por outro lado, quando da presença de um aumento de competição entre as marcas seguidoras, se verifica uma diminuição de preços dessas marcas e um aumento da dispersão relativa dos preços das marcas seguidoras em relação à marca líder.

[pt] O objetivo deste estudo é o de comparar o desempenho do paradigma SCP (Mason, 1939; Bain, 1956, 1968), e de Porter (1980) na indústria farmacêutica brasileira no período de 1999 a 2002. Não se pretende, portanto, analisar a aplicabilidade ou robustez destes modelos ou mesmo criticá-los, mas tão somente testar sua aderência à realidade brasileira. Para a pesquisa, foram consideradas as 50 empresas da indústria farmacêutica brasileira com maior faturamento em reais no ano de 2002, representando 91% do faturamento total e 90% das unidades vendidas. Os dados foram retirados de Cohen (2004) e têm como fonte a base de dados do Pharmaceutical Market Brazil- PMB. Com base na técnica estatística de Modelo de Equações Estruturais e nos passos descritos por Hair et al (1998) para sua aplicação, testaram-se as variáveis selecionadas, determinaram-se as cargas em cada um dos modelos por meio da utilização do LISREL e, por fim, compararam-se os resultados apurados para os dois modelos teóricos. Concluiu-se, reservadamente, a despeito da qualidade da amostra, de pequena quantidade de casos, e do número de variáveis usadas para medir os construtos, que as estratégias das empresas têm influência mais importante no desempenho que o ambiente, confirmando estudos anteriores, e que esta influência é igual nos dois modelos testados. Uma sugestão para melhoria dos resultados diz respeito à troca da amostra pelo universo dos laboratórios, o que aumentaria a possibilidade de aderência dos modelos, sem que isso, necessariamente, venha a implicar relação direta com técnicas gerenciais. Outra, sem dúvida, seria a manutenção da amostra, mas com reavaliação das variáveis de teste. / [en] This study aims at comparing the performance of SCP (Mason, 1939; Bain, 1956, 1968) and Porter´s (1980) models in the Brazilian pharmaceutical industry between 1999 and 2002. The intension is not, therefore, to analyze the applicability or robustness of these models or even to criticize them, but just to test its adherence to the Brazilian reality. For the research, the 50 companies with greater revenue in reais in the year of 2002, in the pharmaceutical industry, are considered. They represent 91% of the total industry revenue and 90% of the industry sold units. Data are collected after Cohen (2004), which source is the Pharmaceutical Market Brazil-PMB data base. Based on the statistical technique of Structural Equations Model - SEM and using the stages described by Hair et al (1998) for its application, the selected variables are tested, the models are designed and calculated by means of LISREL and, at the end, results are compared. The conclusion, with reserves, is that, despite the quality of the sample - having small number of cases and proporcional great number of variables used to measure the constructs - the companies strategies show greater influence on the performance than the industrial structure, confirming previous studies, and that this influence is same in the two tested models. A suggestion for the improvement of the results concerns changing the used sample for the universe of the laboratories, what would increase the possibility of adherence of the models, without implicating direct relationship with managerial techniques. Other sugestion is to maintain the sample, but with revaluation of the test variables.

Sammanfattning Titel: Alvedon vs det generiska läkemedlet Pamol - En studie om konsumentens kännedom, trovärdighet och dess påverkan av prisskillnader inför ett köpbeslut. Datum: 2021-05-25 Nivå: Kandidatuppsats  Författare: Darja Faily & Nader Albanna Handledare: Christine Tidåsen Examinator: Klaus Solberg Søilen Syfte: Syftet med denna studie är att undersöka konsumenters preferens och uppfattning av de generiska paracetamol-läkemedlen Alvedon och Pamol. Detta mäts genom att undersöka variablerna kännedom, trovärdighet och pris.  Forskningsfråga: “Finns det en skillnad på trovärdighet och kännedom mellan det generiska paracetamol-läkemedlen Pamol och Alvedon?” samt “Kan de generiska paracetamol-läkemedlen påverka konsumentens köpbeslut av dess stora prisskillnader?”.  Teoretiskt referensram: Tidigare forskning och teorier gällande kännedom, trovärdighet och prisets påverkan på konsumentens köpbeslut.  Metod: Primär- och sekundärdata har samlats in genom trianguleringsmetoden, det vill säga både av en kvalitativ och kvantitativ metod. De kvantitativa metoden genomfördes med en webbenkät, med urvalsstorleken 236 individer. I den kvalitativa metoden, genomfördes  fokusgruppsdiskussion med två grupper, bestående av fyra deltagare i respektive grupp.   Slutsats: Baserat på primär- och sekundärdata och hypotesprövningar kan vi dra slutsatsen att kännedomen och trovärdigheten förekom högst hos varumärket Alvedon, i jämförelse med Pamol. Dessutom att varumärkenas stora prisskillnad var en avgörande roll för konsumentens köpbeslut när pris förekom som en faktor. Nyckelord: Kännedom, Trovärdighet, Köpbeslut, Pris, Alvedon, Pamol, Generiska läkemedel / Abstract Title: Alvedon vs det generiska läkemedlet Pamol - En studie om konsumentens kännedom, trovärdighet och dess påverkan av prisskillnader inför ett köpbeslut Date: 2021-05-25 Level: Bachelor Thesis in Science in Business Administration and Economics and International Marketing  Author: Darja Faily & Nader Albanna Supervisor: Christine Tidåsen  Examiner: Klaus Solberg Søilen Purpose: The purpose of this study is to investigate consumers preferences and perceptions of the generic-paracetamol drugs Alvedon and Pamol. By examining the variables knowledge, credibility and price. To review whether consumers prefer the branded drug Alvedon or the generic drug Pamol.  Research question:  “Is there a difference in credibility and knowledge between the generic paracetamol- drugs Pamol and Alvedon?” and, “Can generic paracetamol drugs influence the consumer’s purchasing decision due to its large price differences?” Method: Primary and secondary data were collected by the triangulation method, by both a qualitative and quantitative method. The quantitative method was conducted with a web survey, with a sample size of 236 individuals. In the qualitative method, focus discussions were conducted with two groups, where they consisted of four participants in each group. Findings: Previous research and theories regarding knowledge, credibility and how price affects the outcome of consumers purchasing decisions. Conclusion: Based on primary and secondary data and hypothesis tests, we can conclude that the knowledge and credibility were highest at the Alvedon brand, in comparison with Pamol. In addition to the fact that the brands' large price difference was a decisive role in the consumer's purchasing decision when price appeared as a factor. Keywords: Knowledge, Credibility, Purchase Decision, Price, Alvedon, Pamol, Generic Drugs

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Thesis (MA)--Stellenbosch University, 2005. / ENGLISH ABSTRACT: This thesis is an explanatory study into civil society's increased influence in global governance. More specifically this situation is examined by looking at the generic medicine debate that came in the wake of the passing of the Medicines and Related Substances Act by the South African government in 1997. This debate gained worldwide attention and touched some of the prevailing inequalities between the developed world and the developing world in our globalised society. The research question that is addressed here is to what extent did civil society influence the signing of the Doha Declaration of the TRIPS Agreement and Public Health by the members of the World Trade Organisation (WTO) in 2001? In doing so, this thesis looks at the role of the US government, the South African government, the pharmaceutical industry, the WTO's TRIPS Agreement and civil society in the form of nongovernmental organisations like Treatment Action Campaign (TAC), Oxfam and Medecines Sans Frontieres (MSF). The study applies a constructivist approach in order to analyse how civil society used global advocacy networks to inform and communicate the normative concerns regarding South Africa and developing countries' lack of access to HIVand AIDS drugs. Moreover, it examines how civil society's use of moral authority challenged the regulative power of the WTO. The study concludes that civil society played a vital role in influencing the WTO member states' decision to sign the Doha Declaration on the TRIPS Agreement and Public Health. However, it was not only civil society's ability to set the agenda concerning the HIV/AIDS pandemic, but also the content of the normative concerns themselves that help explain its success. Consequently, the study further concludes that civil society's success in this specific case must be seen in light of its growing influence in challenging global governance. / AFRIKAANSE OPSOMMING: Hierdie tesis is 'n verduidelikende studie van die burgerlike samelewing se groeiende invloed in globale regering. Hierdie situasie word meer spesifiek ondersoek deur te kyk na die generiese medisyne debat wat gevoer is na die Suid-Afrikaanse Regering die Medisyne en Verwante Stowwe Wet van 1997 goedgekeur het. Hierdie debat het wêreldwye aandag geniet en het geraak aan sommige van die bestaande ongelykhede wat daar heers tussen die ontwikkelde en ontwikkelende wêreld in die geglobaliseerde samelewing. Die navorsingsvraag wat hier aangespreek word is tot watter mate die burgerlike samelewing die ondertekening van die Doha Verklaring van die TRIPS Ooreenkoms en Publieke Gesondheid deur lede van die Wêreld Handelsorganisasie (WHO) in 2001 beïnvloed het. Deur dit te doen, sal hierdie tesis kyk na die rol van die Amerikaanse regering, die Suid- Afrikaanse regering, die farmaseutiese bedryf, die WHO se TRIPS Ooreenkoms en die burgerlike samelewing in die vorm van nie-regerings organisasies soos die Treatment Action Campaign (TAC), Oxfam en Medecines Sans Frontieres (MSF). Die studie maak gebruik van 'n konstruktiwistiese benadering om 'n analise te doen van hoe die burgerlike samelewing globale ondersteunings netwerke gebruik het om die normatiewe besorgdhede wat heers oor die tekorte in Suid-Afrika en die ontwikkelende lande ten opsigte van toegang tot MIV en VIGS medisyne, toe te lig en te verkondig. Verder ondersoek die studie hoe die gebruik deur die burgerlike samelewing van morele gesag die regulerende mag van die WHO uitgedaag het. Die studie kom tot die gevolgtrekking dat die bugerlike samelewing 'n uiters belangrike rol gespeel het in die WHO lidlande se besluit om die Doha Verklaring van die TRIPS Ooreenkoms en Publieke Gesondheid te onderteken. Dit was egter nie net die burgerlike samelewing se vermoë om die agenda daar te stel ten opsigte van die MIV/VIGS pandemie nie, maar ook die inhoud van die normatiewe besorgdhede self wat bygedra het om hierdie sukses te verduidelik. Gevolglik kom die studie tot die verdere gevolgtrekking dat die burgerlike samelewing se sukses in hierdie spesifieke geval gesien kan word in die lig van sy groeiende invloed in die uitdaging van globale mag en gesag.

La bioéquivalence, une mesure de substitution de l'innocuité et de l'efficacité à différents stades du processus de développement des médicaments, est tout particulièrement importante lors du développement d'un médicament générique. Entre autres critères, la bioéquivalence garantit que les médicaments génériques sont équivalents aux produits innovateurs ou de références approuvés en termes d’efficacité clinique et d’innocuité tout en contournant le long cours et le coût élevé des essais chez les animaux et des essais cliniques chez les patients exigés pour les médicaments innovants. Malgré les avancées dans le développement d'approches robustes au cours des dernières décennies, la pratique actuelle de la bioéquivalence fait toujours l'objet de controverses. Le but de cette thèse est d'explorer certaines de ces controverses et de les aborder en proposant des approches nouvelles et alternatives. L'une des questions les plus controversées dans la pratique actuelle de la bioéquivalence est l'extrapolation des résultats d'études de bioéquivalence d'une population à une autre. La majorité des études de bioéquivalence portant sur des formes pharmaceutiques orales efficaces par voie systémique reposent sur les critères de pharmacocinétique obtenus chez des sujets sains, alors que la population cible est constituée de patients. Ceci est basé sur l'hypothèse que si deux produits sont bioéquivalents dans une population, ils devraient l'être dans une autre. L'extrapolation des résultats des études de bioéquivalence ne se limite pas à celle des sujets sains aux patients. Depuis 2007, une proportion croissante d'études de bioéquivalence pharmacocinétique portant sur des soumissions génériques nord-américaines ou européennes a été réalisée auprès de populations géographiques/ethniques autres que celles visées, en raison du coût moins élevé de ces études en dehors de l'Amérique du Nord et de l'Europe. Dans le premier volet de cette thèse, nous avons examiné si les résultats de la bioéquivalence obtenus dans une population géographique ou ethnique pouvaient être extrapolés à une autre. À cette fin, nous avons extrait les résultats des études de bioéquivalence pharmacocinétique disponibles publiquement et provenant de soumissions génériques à Santé Canada et à la Food and Drug Administration des États-Unis. Pour dix médicaments différents, nous avons calculé l'effet d’un repas normalisé sur le produit de référence et comparé les résultats obtenus chez deux populations ethniques, les indiens et les nord-américains. Cette approche novatrice est basée sur le raisonnement suivant: si l'effet d’un repas sur le produit de référence est le même chez les populations indienne et nord-américaine, le produit générique et sa référence qui se sont révélés bioéquivalents dans la population indienne devraient également l'être dans la population nord-américaine. Pour 90% des médicaments à l'étude, une différence statistiquement significative a été détectée entre les deux populations après un repas. Pour 30% de ces médicaments, la différence s'est révélée d'une pertinence clinique possible. Les résultats de cette étude ont mis en évidence que l’extrapolation des résultats de bioéquivalence d’une population à l’autre devrait possiblement être reconsidérée pour certains médicaments. Les défis dans le contexte de la bioéquivalence ne se limitent pas toujours aux études pivots où la performance d’un produit générique est comparée à celle de la référence. En effet, une étude pilote peut être menée afin d’établir un protocole d’étude approprié pour cette étude pivot. Par conséquent, les résultats inexacts provenant d'une étude pilote, tels qu'une estimation imprécise du moment ou de la durée d’administration optimale de la dose lors de la comparaison du produit testé par rapport à la référence, pourront affecter négativement les résultats de l’étude de bioéquivalence. Ceci est particulièrement crucial pour les produits indiqués pour un usage topique dermatologique dont les corticostéroïdes constituent un cas d’espèce. En effet, leur bioéquivalence est démontrée par une mesure pharmacodynamique, le blanchiment cutané, à différents temps après application topique. L’intensité du blanchiment est comparée entre le produit générique et le produit de référence à une durée d’administration spécifique d’une dose donnée, la DD50, soit la durée associée à 50% de l’effet maximal observé. Par conséquent, cette durée d’administration de la dose doit d’abord être déterminée dans le cadre d’une étude pilote. L’agence réglementaire américaine recommande l’utilisation d’une approche populationnelle basée sur la modélisation non linéaire à effets mixtes pour l'estimation de la DD50 et ce, quelle que soit la méthode d'analyse. Étant donné qu’il existe différents types de méthodes d’analyse non linéaire à effets mixtes, chaque commanditaire peut en choisir une différente. Dans le deuxième volet de cette thèse, nous avons examiné si les mêmes estimations de DD50 pouvaient être obtenues en utilisant différentes méthodes non linéaires à effets mixtes. À cette fin, nous avons ajusté les données de blanchiment de la peau d’onze études avec deux méthodes non linéaires à effets mixtes différentes : le maximum de vraisemblance avec maximisation de l’espérance (MLEM) et l'estimation conditionnelle de premier ordre (FOCE). Les résultats ont favorisé MLEM, compte tenu d’une meilleure puissance discriminative pour l’estimation de la DD50 de population et d’une meilleure minimisation de la variabilité interindividuelle. Bien que l'approche de la bioéquivalence fondée sur la pharmacocinétique ait contribuée de manière significative au développement de versions génériques de haute qualité des formes pharmaceutiques orales indiquées pour un effet systémique, la disponibilité de versions génériques pour les produits dermatologiques topiques demeure limitée et ce, par manque de méthodes acceptées par les agences réglementaires pour l'évaluation de la bioéquivalence de ces produits. Dans le troisième volet de cette thèse, une nouvelle approche pour l’évaluation de la bioéquivalence de formulations de crème topique d’acyclovir a été développée en utilisant une analyse basée sur un modèle de données d’exposition locales récupérées à partir d’échantillons de peau abrasée prélevés à une seule durée d’administration de la dose, la DD50 à l’aide de bandes adhésives. Un seul échantillonnage de peau effectué à la DD50 a non seulement assuré que les données pharmacocinétiques étaient recueillies à la durée d’administration de la dose ayant le meilleur pouvoir discriminant pour détecter une différence au niveau des formulations, mais a également permis de diminuer considérablement le nombre d'échantillons à analyser. Et surtout, cette nouvelle approche a permis de générer un profil pharmacocinétique au niveau même de la peau. Ce faisant, nous avons pu utiliser l'analyse compartimentale populationnelle et contourner les nombreuses hypothèses et calculs sophistiqués requis par les méthodes précédentes. Notre approche a également permis de générer de nouveaux paramètres pharmacocinétiques permettant de décrire la vitesse et le degré d’exposition cutanée pour l'évaluation de la biodisponibilité et de la bioéquivalence topiques. Finalement, cette méthode a le potentiel de discerner une formulation bioéquivalente d’une autre qui ne l’est pas. / Bioequivalence is a surrogate measure of safety and efficacy in different stages of drug development process with the most pronounced significance in the development of generic drugs. Bioequivalence, among other standards, ensures that generic drugs are equivalent to their approved innovator or reference products in terms of clinical efficacy and safety while circumventing the lengthy-time course and high cost of animal and clinical trials in patients required for innovator drugs. Despite the advancements in development of robust bioequivalence approaches over the past decades, there are still controversies in the current practice of bioequivalence. The aim of this thesis is to explore some of these controversies and address them by putting forward new and alternative approaches. One of the most controversial issues in the current practice of bioequivalence is the extrapolation of bioequivalence study results from one population to another. The majority of bioequivalence studies for systemic effective oral dosage forms are conducted based on pharmacokinetic endpoints in healthy volunteers whilst the targeted population is patients. This is based on the assumption that if two products are bioequivalent in one population, they should be bioequivalent in another one. The extrapolation of bioequivalence study results is not limited to that from healthy volunteers to patients. Since 2007, an ever-increasing proportion of pharmacokinetic bioequivalence studies for North American or European generic submissions have been performed in geographical/ethnic populations other than the intended ones, due to the lower cost of these studies outside North America and Europe. In the first part of this thesis, we investigated whether the bioequivalence results obtained in one geographical or ethnic population can be extrapolated to another one. To this purpose, we extracted pharmacokinetic bioequivalence studies results from generic submissions to Health Canada and the US Food and Drug Administration. We calculated food effect for ten different reference drug products and compared the results for each product between two ethnic populations, Indians and North Americans. This is based on the reasoning that if food effect is found to be the same between the Indian and North American populations, then the generic product and its reference that were found to be bioequivalent in the Indian population should also be bioequivalent in North American population. For 90% of the study drugs, statistically significant difference was detected in the food effect between two populations. For 30% of these drugs, the difference was found to be of possible clinical relevance. The results of this study raised a flag for extrapolating the bioequivalence results from one population to another. Challenges in the context of bioequivalence are not always limited to the pivotal studies where the performance of a generic product is compared to that of Reference. Prior to pivotal bioequivalence studies, a pilot study may be conducted to establish an appropriate study design for the pivotal bioequivalence study. Therefore, inaccurate results from a pilot study, such as inaccurate estimation of time point or dose duration for comparison of test versus reference, can affect the bioequivalence outcomes adversely. An example to this case is the comparison of the extent of skin blanching, the pharmacological effect of generic versus reference products of topical dermatological corticosteroids at specific dose duration, DD50, where the effect is half maximal. This dose duration should initially be determined in a pilot study. The US FDA 1995 Guidance document recommends the use of non-linear mixed effect population modeling for the estimation of DD50, irrespective of the method of analysis. Given the availability of different types of non-linear mixed effect modeling methods, each sponsor could choose a different one. In the second part of this thesis we investigated whether the same DD50 estimates can be obtained when different non-linear mixed effect modeling methods are used. To this purpose, we fitted the skin blanching data from eleven studies with two different non-linear mixed effect modeling methods, the Maximum Likelihood Expectation Maximization (MLEM) and the First Order Conditional Estimation (FOCE). The results favored MLEM given its lower population DD50 estimates that would locate in a more discriminative portion of the Emax curve and better minimization of inter-individual variability. Although the pharmacokinetic-based bioequivalence approach has contributed significantly to the development of high-quality generic versions of systemic effective oral dosage form, the availability of generic versions of topical dermatological products remains constrained due to the limited methods accepted for bioequivalence evaluation of these products. In the third part of this thesis, a novel approach for the bioequivalence assessment of topical acyclovir cream formulations was developed based on the model-based analysis of local exposure data recovered from tape stripping of the skin at a single dose duration, DD50. Conducting the stripping procedure only at DD50 not only ensured that the PK data was collected at the dose duration that is most discriminative of formulation differences, but it also decreased the number of samples to be analyzed significantly. More importantly, our novel approach in generating the local PK profile in the skin (dermatopharmacokinetic profile) and the implementation of population compartmental analysis circumvented the numerous assumptions and sophisticated calculations that were inherent to previous methods, while yielding the PK parameters relevant for topical bioavailability and bioequivalence assessment (rate and extent of exposure to the skin). This method successfully concluded bioequivalence and its absence.

"Zimbabwe and South Africa are facing an HIV/AIDS epidemic of such proportions that the populations of these countries will markedly decline in the next ten years despite the existence of effective drugs to treat the symptoms of AIDS and dramatically lower the communicability of the virus. These drugs are under patent protection by companies in the developed world and the patents raise the prices above the level of affordability for HIV infected persons in South Africa and Zimbabwe. Zimbabwe has declared a national emergency on HIV/AIDS, apparently in conformance with TRIPS and has issued compulsory licenses to a local company that has started to manufacture and sell cheap anti-retroviral drugs. South Africa has not declared a national emergency and has not invoked the TRIPS flexibilities or utilized flexibilities inherent in its own legislation. However, while thousands of people die every week in the two countries, neither government has yet provided an effective HIV/AIDS policy. Extensive litigation and public pressure in South Africa has led the government to announce a policy of supplying free HIV drugs in public hospitals while the Zimbabwean government has announced the provision of the same drugs, also in public hospitals, apparently utilising the state of emergency. The TRIPS agreement under which the two governments undertook to protect international patents allows compulsory licensing under certain circumstances (not limited to a national emergency) and the Doha Declaration on TRIPS and Public Health, and subsequent agreements by the Ministerial Council of the WTO allow the manufacture and, in limited circumstances, the parallel importation of generic drugs. These provisions provide a theoretical mechanism for poor countries to ensure their citizens' rights of access to health (care). The research is aimed at identifying the extent of the effectiveness of the legal norms created by Articles 20 and 31 of TRIPS, the Doha Declaration and subsequent Council of Ministers' decisions, which together ostensibly provide a framework to allow provision of generic drugs. It is further aimed at investigating how the state of emergency in Zimbabwe has been utilised to provide cheap generic drugs to Zimbabweans and whether this would be an option for South Africa. A comparison of the legal provisions governing the provision of drugs in the two countries will also be undertaken to examine the extent to which international and national constitutional and legal provisions may be utilised to give effect to the right to health." -- Introduction. / Thesis (LLM (Human Rights and Democratisation in Africa)) -- University of Pretoria, 2004. / Prepared under the supervision of Dr. Enid Hill at the American University in Cairo. / http://www.chr.up.ac.za/academic_pro/llm1/dissertations.html / Centre for Human Rights / LLM

The aim of the diploma thesis is to describe and analyse information sources, which are useful for the molecules portfolio selection suitable for the future development of a generic drug. These information sources should be examined on the case study of the portfolio selection in a given therapeutic area. The topic of the diploma thesis is presented in the context of basic principles and functions of the generic farmaceutical industry and its information needs. The introductory chapter characterizes the farmaceutical industry in general and warn on a competitive environment, which the farmaceutical companies can succeed in thanks to the advanced methods of the business intelligence. The second chapter focuses on the differences betwen the generic and original pharmaceutical industry, a drug lifecycle is also introduced there. The next chapter specifies the methods of the business intelligence in the generic pharmaceutical industry on the ground of its information needs. The fourth chapter plays a key role. First of all, it introduces general characteristics of information sources used in the strategic portfolio management. Secondly, the detailed description and analysis of eight main information sources used by the generic companies within business intelligence follows. In the last chapter these...

專利權具有獨占性，對一國產業發展具有重要影響，為了平衡該權利，各國專利法在給予發明人專利權的同時也加諸某些限制，以我國為例，於專利法第五十七條第一項列舉專利權效力所不及之情形有：(一)為研究、教學或試驗，實施其發明，而無營利行為者。此即所謂之「實驗例外」 (experimental use exception)條款。 實驗例外條款在各國司法實務運作上，最常被引起爭論者向來集中在處方藥市場中專利藥廠與學名藥廠間之競爭議題。因為學名藥廠為了能夠盡早進入市場，不免須在專利期間屆滿前實施原廠專利進行必要之研究、試驗，以符合各國對於藥物上市管理法令之要求。 雖然我國專利法與其他國家一樣也有試驗例外條款，但其中要件嚴格限定為「非營利行為」，從比較法之方式分析，該規定係受美國普通法之影響。美國普通法關於試驗例外係採取嚴格路線，必須行為人之試驗係出於非營利目的，單純追求真相、探求知識理論，或為滿足好奇心，才可主張普通法上之實驗例外，即始係不具營利色彩之公家機關、學術單位從事之試驗，只要背後具有實質的商業目的亦不得主張試驗例外。如此造成要成功適用試驗例外是愈來愈不可能。 國際間對於試驗例外之立法，除美國外，尚存在許多形式值得我國借鏡，以歐洲共同體專利規則草案(Proposal for a Council Regulation on a Community Patent)為例，其區分「私人且非商業性目的之行為」，以及「為試驗目的之行為」，後者要求必須係針對系爭專利技術本身所進行之試驗始非專利權效力所及，若係將該專利技術作為研究工具之用，仍非法之所許。這種區分方法不僅層次分明、無觀念上混淆之虞，判斷上也較具有可預測性。 美國於1984年通過Hatch-Waxman 法案鼓勵學名藥之發展，對於為滿足主管機關關於醫藥品上市要求之試驗，在專利法271(e)(1)明文規定排除在專利權效力之外，即所謂之「Bolar例外」。我國於九十四年二月五日亦增訂藥事法第四十條之二第五項：「新藥專利權不及於藥商申請查驗登記前所進行之研究、教學或試驗」關於Bolar例外之規定。惟或因立法匆促，致法條要件不符合實際狀況，例如限定「申請查驗登記前」之行為，實際上藥廠於提出查驗登記之申請後，往往在主管機關之要求下須進行其他試驗，這些行為均在立法者原欲保護之範圍內，僅因立法用語之不當，造成實務運用之困擾。 筆者最後從法律及商業管理觀點著眼，對國內立法提出下列修法建議，作為本研究之最終成果： 壹、對於專利法第五十七條第一項第一款修法之建議 一、刪除「教學」之行為態樣 二、刪除「而無營利行為」之要件 三、增列關於研究工具之專利則無本條之適用 四、放寬適用範圍為符合主管機關法規要求而實施他人專利亦有實驗例外之適用。 贰、對於藥事法修法之建議 一、刪除「申請查驗登記前」之要件，改以行為目的來限定範圍，即「為通過藥品查驗登記所進行之研究或試驗」，始有本款之適用。 二、明定「物品專利」及「方法專利」均有本條之適用