Applicatiion of Almost ideal demand system for a pharmaceutical

This thesis is an application of the Almost Ideal Demand System approach of Deaton and Muellbauer,1980, for a particular pharmaceutical, Citalopram, in which GORMAN´s (1971) multi-stage budgeting approach is applied basically since it is one of the most useful approach in estimating demand for differentiated products. Citalopram is an antidepressant drug that is used in the treatment of major depression. As for most other pharmaceuticals whose the patent has expired, there exist branded and generic versions of Citalopram. This paper is aimed to define its demand system with two stage models for the branded version and five generic versions, and to show whether generic versions are able to compete with the branded version. I calculated the own price elasticities, and it made me possible to compare and make a conclusion about the consumers’ choices over the brand and generic drugs. Even though the models need for being developed with some additional variables, estimation results of models and uncompensated price elasticities indicated that the branded version has still power in the market, and generics are able to compete with lower prices. One important point that has to be taken into consideration is that the Swedish pharmaceutical market faced a reform on October 1, 2002, that aims to make consumer better informed about the price and decrease the overall expenditures for pharmaceuticals. Since there were not significantly enough generic sales to take into calculation before the reform, my paper covers sales after the reform.

The pharmaceutical industry, intellectual property rights and access to medicines in Pakistan

The pharmaceutical industry in Pakistan is worth around US$ l.18 billion, with annual growth in 2010 approaching 10 per cent (Khan, 2012). There are more than 650 registered companies, including 31 multinationals, which in 2006 had a market share in value terms of 53.3 per cent, with national firms controlling the remaining 46.7 per cent (IMS Health, 2007). In 2007 medicines worth about US$100 million were exported. Medicines are a vital component of healthcare, and Pakistan spends around three-quarters of its healthcare budget on medicines (WHO, 2004). This chapter provides an overview, from a public health perspective, of the national pharmaceutical market and the development of drug policies and regulation. Pakistan adopted a Trade Related Aspects of Intellectual Property Rights (TRIPS) compliant patent regime in 2000, and the intersection between patents and public health is a central policy challenge. This chapter highlights key issues related to intellectual property, Free Trade Agreements (FTAs), and production and access to medicines.

Patenting Strategies of the EU Pharmaceutical Industry -Crossroad between Patent Law and Competition Policy. Research Papers in Law, 1/2011

From the Introduction. The pharmaceutical sector inquiry carried out by the European Commission in 2008 provides a useful framework for assessing the relationship between the patent system on the one hand and competition policy and law on the other hand. The pharmaceutical market is not only specifically regulated. It is also influenced by the special characteristics of the patent system which enables pharmaceutical companies engaged in research activities to enter into additional arrangements to cope with the competitive pressures of early patent application and the delays in drug approval. Patents appear difficult to reconcile with the need for sufficient and adequate access to medicines, which is why competition expectations imposed on the pharmaceutical sector are very high. The patent system and competition law are interacting components of the market, into which they must both be integrated. This can result in competition law taking a very strict view on the pharmaceutical industry by establishing strict functional performance standards for the reliance on intellectual property rights protection granted by patent law. This is in particular because in this sector the potential welfare losses are not likely to be of only monetary nature. In brief, the more inefficiencies the patent system produces, the greater the risk of an expansive application of competition law in this field. The aim of the present study is to offer a critical and objective view on the use or abuse of patents and defensive strategies in the pharmaceutical industry. It shall also seek to establish whether patents as presently regulated offer an appropriate degree of protection of intellectual property held by the economic operators in the pharmaceutical sector and whether there is a need or, for that matter, scope for improvement. A useful starting point for the present study is provided by the pharmaceutical sector competition inquiry (hereafter “the sector inquiry”) carried out by the European Commission during the first half of 2008. On 8 July 2008, the Commission adopted its Final Report pursuant to Article 17 of Regulation 1/2003 EC, revealing a series of “antitrust shortcomings” that would require further investigation1.

Is Australia ready for biosimilars?

The biosimilars market is potentially the single fastest growing pharmaceutical sector with an estimated worth of US$67bn in global sales by 2020. This market generally refers to larger molecule, biological, protein-based pharmaceuticals which have lost its patent. This has stimulated the emergence of non-conventional pharmaceutical investors such as Fujifilm and Samsung as well as host countries such as Brazil, Mexico, China, India, South Korea, Turkey and Russia, which view biosimilars as a key macroeconomic driver of growth. Internationally, the European Medicines Agency has led the regulation of the quality, safety and efficacy of biosimilars; however, many countries have developed their own biosimilar regulatory frameworks. Despite the similarity of these with European guidelines, differences do exist across jurisdictions and have implications for cross-jurisdictional registration and regulation. The consideration of biosimilar regulation, however, demands attention beyond quality, safety and efficacy. The potential implications of extended patent protection, international trade and globalisation require a congruent policy approach to their regulation. Notwithstanding the fact that Australia is a relatively small pharmaceutical market and that there are only 14 biosimilar products currently approved for use, Australia’s geographical proximity to pharm-emerging countries and its trade relation with the major pharmaceutical markets have positioned Australia in a unique position to influence international development and regulation of biosimilars. Australia’s National Medicines Policy (2000) potentially provides the foundation for a partnership approach to biosimilar regulation, minimise duplication of regulatory efforts while at the same time fostering a viable pharmaceutical industry.

Impactos concorrenciais da entrada dos medicamentos genéricos no mercado farmacêutico brasileiro de 2003 a 2007

Em 1999, o mercado de medicamentos genéricos foi criado no Brasil. Com isso, iniciou-se uma nova fase do mercado farmacêutico brasileiro. Através de dados cedidos pela ANVISA sobre o mercado varejista brasileiro, objetivou-se testar em até que ponto a política de medicamentos genéricos tem logrado êxito. Foram utilizados dados em painel para analisar o impacto da entrada dos medicamentos genéricos sobre a estrutura do mercado, assim como o impacto nos preços e na quantidade vendida entre 2003 e 2007. Os resultados foram favoráveis à diminuição da concentração dos mercados relevantes da amostragem e também ao aumento da quantidade comercializada. Em relação aos preços, o modelo se mostrou pouco significativo, provavelmente pela política de medicamentos genéricos ser um instrumento indireto de controle de preços. De qualquer forma, os resultados encontrados parecem sugerir o bom andamento da política de medicamentos genéricos, o que é um alívio em se tratando de um mercado tão essencial para o bem-estar da população.

A "Trojan horse" strategy to reverse drug-resistance in brain tumors

Los gliomas malignos representan una de las formas más agresivas de los tumores del sistema nervioso central (SNC). De acuerdo con la clasificación de los tumores cerebrales de la Organización Mundial de la Salud (OMS), los astrocitomas han sido categorizados en cuatro grados, determinados por la patología subyacente. Es así como los gliomas malignos (o de alto grado) incluyen el glioma anaplásico (grado III) así como el glioblastoma multiforme (GBM, grado IV),estos últimos los más agresivos con el peor pronóstico (1). El manejo terapéutico de los tumores del SNC se basa en la cirugía, la radioterapia y la quimioterapia, dependiendo de las características del tumor, el estadio clínico y la edad (2),(3), sin embargo ninguno de los tratamientos estándar es completamente seguro y compatible con una calidad de vida aceptable (3), (4). En general, la quimioterapia es la primera opción en los tumores diseminados, como el glioblastoma invasivo y el meduloblastoma de alto riesgo o con metástasis múltiple, pero el pronóstico en estos pacientes es muy pobre (2),(3). Solamente nuevas terapias dirigidas (2) como las terapias anti-angiogénicas (4); o terapias génicas muestran un beneficio real en grupos limitados de pacientes con defectos moleculares específicos conocidos (4). De este modo, se hace necesario el desarrollo de nuevas terapias farmacológicas para atacar los tumores cerebrales. Frente a las terapias los gliomas malignos son con frecuencia quimioresistentes, y esta resistencia parece depender de al menos dos mecanismos: en primer lugar, la pobre penetración de muchas drogas anticáncer a través de la barrera hematoencefálica (BBB: Blood Brain Barrier), la barrera del fluido sangre-cerebroespinal (BCSFB: Blood-cerebrospinal fluid barrier) y la barrera sangre-tumor (BTB: blood-tumor barrier). Dicha resistencia se debe a la interacción de la droga con varios transportadores o bombas de eflujo de droga ABC (ABC: ATP-binding cassette) que se sobre expresan en las células endoteliales o epiteliales de estas barreras. En segundo lugar, estos transportadores de eflujo de drogas ABC propios de las células tumorales confieren un fenotipo conocido como resistencia a multidrogas (MDR: multidrug resistance), el cual es característico de varios tumores sólidos. Este fenotipo también está presente en los tumores del SNC y su papel en gliomas es objeto de investigación (5). Por consiguiente el suministro de medicamentos a través de la BBB es uno de los problemas vitales en los tratamientos de terapia dirigida. Estudios recientes han demostrado que algunas moléculas pequeñas utilizadas en estas terapias son sustratos de la glicoproteína P (Pgp: P-gycoprotein), así como también de otras bombas de eflujo como las proteínas relacionadas con la resistencia a multidrogas (MRPs: multidrug resistance-related proteins (MRPs) o la proteína relacionada con cáncer de seno (BCRP: breast-cancer resistance related protein)) que no permiten que las drogas de este tipo alcancen el tumor (1). Un sustrato de Pgp y BCRP es la DOXOrubicina (DOXO), un fármaco utilizado en la terapia anti cáncer, el cual es muy eficaz para atacar las células del tumor cerebral in vitro, pero con un uso clínico limitado por la poca entrega a través de la barrera hematoencefálica (BBB) y por la resistencia propia de los tumores. Por otra parte las células de BBB y las células del tumor cerebral tienen también proteínas superficiales, como el receptor de la lipoproteína de baja densidad (LDLR), que podría utilizarse como blanco terapéutico en BBB y tumores cerebrales. Es asi como la importancia de este estudio se basa en la generación de estrategias terapéuticas que promuevan el paso de las drogas a través de la barrera hematoencefalica y tumoral, y a su vez, se reconozcan mecanismos celulares que induzcan el incremento en la expresión de los transportadores ABC, de manera que puedan ser utilizados como blancos terapéuticos.Este estudio demostró que el uso de una nueva estrategia basada en el “Caballo de Troya”, donde se combina la droga DOXOrubicina, la cual es introducida dentro de un liposoma, salvaguarda la droga de manera que se evita su reconocimiento por parte de los transportadores ABC tanto de la BBB como de las células del tumor. La construcción del liposoma permitió utilizar el receptor LDLR de las células asegurando la entrada a través de la BBB y hacia las células tumorales a través de un proceso de endocitosis. Este mecanismo fue asociado al uso de estatinas o drogas anticolesterol las cuales favorecieron la expresión de LDLR y disminuyeron la actividad de los transportadores ABC por nitración de los mismos, incrementando la eficiencia de nuestro Caballo de Troya. Por consiguiente demostramos que el uso de una nueva estrategia o formulación denominada ApolipoDOXO más el uso de estatinas favorece la administración de fármacos a través de la BBB, venciendo la resistencia del tumor y reduciendo los efectos colaterales dosis dependiente de la DOXOrubicina. Además esta estrategia del "Caballo de Troya", es un nuevo enfoque terapéutico que puede ser considerado como una nueva estrategia para aumentar la eficacia de diferentes fármacos en varios tumores cerebrales y garantiza una alta eficiencia incluso en un medio hipóxico,característico de las células cancerosas, donde la expresión del transportador Pgp se vió aumentada. Teniendo en cuenta la relación entre algunas vías de señalización reconocidas como moduladores de la actividad de Pgp, este estudio presenta no solo la estrategia del Caballo de Troya, sino también otra propuesta terapéutica relacionada con el uso de Temozolomide más DOXOrubicina. Esta estrategia demostró que el temozolomide logra penetrar la BBB por que interviene en la via de señalización de la Wnt/GSK3/β-catenina, la cual modula la expresión del transportador Pgp. Se demostró que el TMZ disminuye la proteína y el mRNA de Wnt3 permitiendo plantear la hipótesis de que la droga al disminuir la transcripción del gen Wnt3 en células de BBB, incrementa la activación de la vía fosforilando la β-catenina y conduciendo a disminuir la β-catenina nuclear y por tanto su unión al promotor del gen mdr1. Con base en los resultados este estudio permitió el reconocimiento de tres mecanismos básicos relacionados con la expresión de los transportadores ABC y asociados a las estrategias empleadas: el primero fue el uso de las estatinas, el cual condujo a la nitración de los transportadores disminuyendo su actividad por la via del factor de transcripción NFκB; el segundo a partir del uso del temozolomide, el cual metila el gen de Wnt3 reduciendo la actividad de la via de señalización de la la β-catenina, disminuyendo la expresión del transportador Pgp. El tercero consistió en la determinación de la relación entre el eje RhoA/RhoA quinasa como un modulador de la via (no canónica) GSK3/β-catenina. Se demostró que la proteína quinasa RhoA promovió la activación de la proteína PTB1, la cual al fosforilar a GSK3 indujo la fosforilación de la β-catenina, lo cual dio lugar a su destrucción por el proteosoma, evitando su unión al promotor del gen mdr1 y por tanto reduciendo su expresión. En conclusión las estrategias propuestas en este trabajo incrementaron la citotoxicidad de las células tumorales al aumentar la permeabilidad no solo de la barrera hematoencefálica, sino también de la propia barrera tumoral. Igualmente, la estrategia del “Caballo de Troya” podría ser útil para la terapia de otras enfermedades asociadas al sistema nervioso central. Por otra parte estos estudios indican que el reconocimiento de mecanismos asociados a la expresión de los transportadores ABC podría constituir una herramienta clave en el desarrollo de nuevas terapias anticáncer.

Alianças estratégicas e suas implicações para a configuração de capacidades tecnológicas: evidências da indústria farmacêutica multinacional

Esta dissertação examina as capacidades tecnológicas (sistema técnico-organizacional, molécula e medicamento) disponibilizadas em alianças estratégicas pela indústria farmacêutica multinacional, assim como as principais implicações das alianças estratégicas para a indústria farmacêutica em termos de configuração de suas capacidades tecnológicas . Essas questões são examinadas à base de evidências empíricas secundárias sobre alianças estratégicas em uma amostra de 25 companhias multinacionais da indústria farmacêutica, pertencentes a três grupos: companhia farmacêutica de grande porte (big pharma); companhia biofarmacêutica de grande porte (biofarma) e companhia pequena de pesquisa . A literatura relacionada oferece uma grande quantidade de estudos sobre alianças estratégicas e capacidades tecnológicas na indústria farmacêutica multinacional. Porém, o tema das implicações de tais alianças estratégicas para mudanças na configuração de capacidades tecnológicas ainda carece de mais fundamentação empírica, pela perspectiva de gestão de empresa e, mais precisamente, pela perspectiva de estratégia empresarial baseada em competências dinâmicas. Essa dissertação baseia-se em extensiva e sistemática coleta de evidências empíricas relativas às alianças estratégicas implementadas por 25 companhias da indústria farmacêutica e, publicadas durante o período de 1993 a 2003. Tais evidências empíricas foram coletadas a partir de três bancos de dados: Business & Industry; Galé e Dialog . Com relação aos resultados, foi encontrado que: Em termos de participações com capacidades tecnológicas ingressantes em alianças estratégicas: (i) as 'big pharmas' ingressaram com 11 % das 169 capacidades tecnológicas; (ii) as biofarmas ingressaram com 44% das 143 capacidades tecnológicas; (iii) as companhias pequenas de pesquisa ingressaram com 72% das 95 capacidades tecnológicas . 2 Em termos de implicações das alianças estratégicas para a mudança na configuração de capacidades tecnológicas que ingressaram em alianças estratégicas, foi encontrado que: (i) as 'big pharmas' aumentaram a proporção em moléculas (16% para 55%); (ii) as biofarmas aumentaram a participação em moléculas (22% para 32%) e sistema técnico-organizacional para pesquisa de molécula (49% para 55%); (iii) as companhias pequenas de pesquisa inseriram-se a uma nova atividade (comercialização de medicamento no mercado farmacêutico) a partir do aumento da participação em medicamentos (3% para 29%). Adicionalmente, atualizaram sistemas técnico-organizacionais para pesquisa de molécula . As evidências sugerem que o critério de escolha por companhia parceira e por mecanismo de aliança estratégica foi condicionado aos objetivos e às necessidades de cada grupo de companhia da indústria farmacêutica. Por fim, enquanto as companhias integradas, 'big pharmas' e biofarmas, principalmente, as primeiras, têm adaptado o modelo de negócio "Fully Integrated Pharmaceutical Company" com a adoção de alianças estratégicas para complementação de capacidades tecnológicas, as companhias pequenas de pesquisa capitalizam as suas capacidades tecnológicas através das alianças estratégicas e ingressam no mercado farmacêutico com a comercialização de medicamentos adquiridos por meio de alianças estratégicas. Portanto, as evidências sugerem que a busca por complementação de base de conhecimento para competir no mercado globalizado, tem implicado ainda que, informalmente, uma alteração na organização das atividades tecnológicas inovadoras, especialmente, em termos de produtos (medicamentos) .

Mercado brasileiro de medicamentos genéricos: análise do desemprenho de uma subsidiária de laboratório estrangeiro

The pharmaceutical industry is a segment that is dominated by transnational companies. This characteristic is visible in Brazil, where there are only three domestic laboratories in the top ten pharmaceutical companies list. From the 1970s onwards, the world pharmaceutical market went through deep changes caused mainly to the increase of regulatory control and patent expiration that led to the advent of generic medicaments. In 1999, it was published the law that allowed the introduction of generic medicaments in Brazil, creating a new market that is currently dominated by domestic laboratories. This dissertation proposes to identify the reasons for a subsidiary of foreign laboratory does not achieve the leadership of this market. The literature is based on international political economy and international business concepts that means, relations between subsidiary and head office, domestic and foreign companies and government. Four propositions are presented and tested through multiple sources of evidences. The empirical research was mainly grounded in interviews with key persons and participant observation that allowed access to information, which would be not available for scientific investigation. The results indicate that the relationships considered in this study affect the subsidiary performance in generic medicament market in regard to its ability to make decisions, price competitiveness and wide portfolio creation. The respondents considered those three aspects as success critical factors. The results can be used for future research, aiming to wide the focus of the study about domestic laboratory dominance in generic medicament markets. Another suggestion is to follow this market evolution regarding to the internationalization process of domestic laboratories.

Sistemas microemulsionados como carreador lipídico para fármacos insolúveis

Several pharmaceutical products have been developed in recent years aiming to enhance the treatment of diseases by increasing the effectiveness of drugs. Many of these new products are based on new drug delivery systems. Among these, microemulsions, which were first studied in 1943 by Hoar and Schulman, is of great interest. Microemulsion can be defined as a thermodynamically stable, isotropic, translucent and transparent system of two immiscible liquids stabilized by a surfactant film located in the oil / water interface. The aim os this work was the incorporation of Amphotericin B and Simvasatin to a microemulsion system and analyzes its physicochemical properties and their therapeutical activity when incorporated into this system. Some very promising results were achieved as the reduction of the toxicity and maintenance of the efficacy of the Amphotericin B incorpored into a microemulsion, which was demonstrated in the in vitro pharmacotoxicological study. As for the incorporation of Simvastatin in microemulsion, it was observed a significant improvement in the potential antiinflammatory and anti-infective properties when the system was use to treat infected wounds (simvastatin pleiotropic effects). Therefore, it can be concluded that the incorporation of these drugs into microemulsion system reveal the potential of microemulsions as a promising and novel dosage form, qualifying them for future trials in order to make them available in the pharmaceutical market

Prodrugs for the treatment of neglected diseases

Recently, World Health Organization ( WHO) and Medicins San Frontieres (MSF) proposed a classification of diseases as global, neglected and extremely neglected. Global diseases, such as cancer, cardiovascular and mental (CNS) diseases represent the targets of the majority of the R&D efforts of pharmaceutical companies. Neglected diseases affect millions of people in the world yet existing drug therapy is limited and often inappropriate. Furthermore, extremely neglected diseases affect people living under miserable conditions who barely have access to the bare necessities for survival. Most of these diseases are excluded from the goals of the R&D programs in the pharmaceutical industry and therefore fall outside the pharmaceutical market. About 14 million people, mainly in developing countries, die each year from infectious diseases. From 1975 to 1999, 1393 new drugs were approved yet only 1% were for the treatment of neglected diseases [ 3]. These numbers have not changed until now, so in those countries there is an urgent need for the design and synthesis of new drugs and in this area the prodrug approach is a very interesting field. It provides, among other effects, activity improvements and toxicity decreases for current and new drugs, improving market availability. It is worth noting that it is essential in drug design to save time and money, and prodrug approaches can be considered of high interest in this respect. The present review covers 20 years of research on the design of prodrugs for the treatment of neglected and extremely neglected diseases such as Chagas' disease ( American trypanosomiasis), sleeping sickness ( African trypanosomiasis), malaria, sickle cell disease, tuberculosis, leishmaniasis and schistosomiasis.

Impact of educational interventions on adverse drug events reporting

Spontaneous adverse drug events (ADE) reporting is the main source of data for assessing the risk/benefit of drugs available in the pharmaceutical market. However, its major limitation is underreporting, which hinders and delays the signal detection by Pharmacovigilance (PhV). To identify the techniques of educational intervention (EI) for promotion of PhV by health professionals and to assess their impact. A systematic review was performed in the PUBMED, PAHO, LILACS and EMBASE databases, from November/2011 to January/2012, updated in March/2013. The strategy search included the use of health descriptors and a manual search in the references cited by selected papers. 101 articles were identified, of which 16 met the inclusion criteria. Most of these studies (10) were conducted in European hospitals and physicians were the health professionals subjected to most EI (12), these studies lasted from one month to two years. EI with multifaceted techniques raised the absolute number, the rate of reporting related to adverse drug reactions (ADR), technical defects of health technologies, and also promoted an improvement in the quality of reports, since there was increased reporting of ADR classified as serious, unexpected, related to new drugs and with high degree of causality. Multifaceted educational interventions for multidisciplinary health teams working at all healthcare levels, with sufficient duration to reach all professionals who act in the institution, including issues related to medication errors and therapeutic ineffectiveness, must be validated, with the aim of standardizing the Good Practice of PhV and improve drug safety indicators.

Farmácia magistral: sua importância e seu perfil de qualidade

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

T cells infiltrate the liver and kill hepatocytes in HLA-B(∗)57:01-associated floxacillin-induced liver injury.

Drug-induced liver injury is a major safety issue. It can cause severe disease and is a common cause of the withdrawal of drugs from the pharmaceutical market. Recent studies have identified the HLA-B(∗)57:01 allele as a risk factor for floxacillin (FLUX)-induced liver injury and have suggested a role for cytotoxic CD8(+) T cells in the pathomechanism of liver injury caused by FLUX. This study aimed to confirm the importance of FLUX-reacting cytotoxic lymphocytes in the pathomechanism of liver injury and to dissect the involved mechanisms of cytotoxicity. IHC staining of a liver biopsy from a patient with FLUX-induced liver injury revealed periportal inflammation and the infiltration of cytotoxic CD3(+) CD8(+) lymphocytes into the liver. The infiltration of cytotoxic lymphocytes into the liver of a patient with FLUX-induced liver injury demonstrates the importance of FLUX-reacting T cells in the underlying pathomechanism. Cytotoxicity of FLUX-reacting T cells from 10 HLA-B(∗)57:01(+) healthy donors toward autologous target cells and HLA-B(∗)57:01-transduced hepatocytes was analyzed in vitro. Cytotoxicity of FLUX-reacting T cells was concentration dependent and required concentrations in the range of peak serum levels after FLUX administration. Killing of target cells was mediated by different cytotoxic mechanisms. Our findings emphasize the role of the adaptive immune system and especially of activated drug-reacting T cells in human leukocyte antigen-associated, drug-induced liver injury.

Indian Patent Policy and Publich Health : implications from the Japanese Experience

The introduction of pharmaceutical product patents in India and other developing countries is expected to have a significant effect on public health and local pharmaceutical industries. This paper draws implications from the historical experience of Japan when it introduced product patents in 1976. In Japan, narrow patents and promotion of cross-licensing were effective tools to keep drug prices in check while ensuring the introduction of new drugs. While the global pharmaceutical market surrounding India today differs considerably from that of the 1970's, the Japanese experience offers a policy option that may profitably be considered by India today. The Indian patent system emphasizes the patentability requirement in contrast to the Japanese patent policy which relied on narrow patents and extensive licensing. R&D by local firms and the development of local products may be promoted more effectively under the Japanese model.