Introduction Of Generic Drugs Research Articles

Attitude to reproduced disease modifying therapies in patients with relapsing-remitting multiple sclerosis: results of a medical and sociological study

The problem of an adequate choice of a treatment method in multiple sclerosis (MS) remains one of the most urgent in modern neurology. The number of patients and the cost of drugs are increasing, leading to an increased MS societal burden. However, treatment costs can be reduced due to the introduction of generic drugs, including domestic ones, which price is significantly lower.Objective: to assess the attitude of Russian patients to the reproduced disease modifying therapies (DMTs) and features influencing an attitude to the replacement from the original to the reproduced drug.Patients and methods. We interviewed 300 patients from six regions of the Russian Federation, receiving interferon beta-1a 44 μg, interferon beta-1b, glatiramer acetate, and teriflunomide, who had an experience of switching from an original drug to a domestic biosimilar drug or generic not earlier than 2009.Results and discussion. The majority of patients (63%) do not notice any changes due to drug replacement from the original to the generic one, some (28%) experience a deterioration in their well-being, and others (7%) experience an improvement in their condition. Young patients (up to 30 years) are relatively less likely to notice a deterioration in well-being after drug replacement. The clinical deterioration after drug replacement is much more often experienced by the patients whose drug was replaced in a pharmacy (74% of cases) and not by the attending clinician (only 54% of cases of deterioration). The majority (87%) of patients with relapsing-remitting MS (RRMS) did not interrupt the treatment after replacement; 13% of respondents reported that they had stopped taking the drug. Among them, there were much more patients whose drug was replaced in a pharmacy, and not due to clinician recommendation (more than 80% of such cases). Adverse reactions to a new drug are another reason for drug withdrawal (20% of all withdrawals). Patients receiving interferon beta-1b have a higher negative attitude towards domestic DMTs: 52% of the respondents gave negative feedback (compared to 20–35% in other groups). Relatively higher loyalty to Russian DMTs was observed in patients receiving interferon beta-1a (20% of negative feedback, which is noticeably lower than in other groups) and teriflunomide (a relatively higher proportion of positive feedback to Russian drugs – 25% compared to 11–16% in other groups). The majority (76%) of the respondents noted that they are interested in learning more about the development and registration of new Russian drugs.Conclusion. The majority of RRMS patients do not tend to have a negative attitude towards Russian DMTs. Consequently, the proportion of ratings in favor of Russian DMTs exceeds the weight of ratings against them. The key priority in the formation of loyalty to Russian DMTs should be changing the perception of adverse reactions. This will significantly increase the adherence to therapy and the quality of the provided treatment.

Outcomes Associated with Generic Drugs Approved Using Product-Specific Determinations of Therapeutic Equivalence.

We sought to examine rates of clinical outcomes among patients before and after market introduction of generic versions of five drugs approved using product-specific equivalence determinations. We used data from a large national insurer to identify patients who initiated a study (acarbose tablets, salmon calcitonin nasal spray, enoxaparin injection, vancomycin capsules, venlafaxine extended-release tablets) or control drug (nateglinide, glimepiride, alendronate, fondaparinux, metronidazole, sertraline, paroxetine) in each calendar month between 2003 and 2012 and to determine rates of claims-based proxies for lack of effectiveness outcomes following initiation. We used segmented time-series analyses to evaluate level (short-term) and slope (longer-term) changes in outcomes upon introduction of a generic study or control drug. Among study drugs, we observed three increases (one with p<0.05) and three decreases (two with p<0.05) in the level of outcome rates. All changes in slope indicated decreases in outcomes from the brand-only to the generic period; four had p<0.05. For control drugs, we observed positive level changes for eight of nine drug-outcome pairs; two had p<0.05. We observed negative slope changes for eight out of nine pairs; six had p<0.05. We observed a significant increase in level change following the introduction of generic bupropion versions that were later found to be not bioequivalent (p<0.01). We did not find evidence that introduction of generic drugs approved using product-specific therapeutic equivalence determinations was associated with worse clinical outcomes than those among initiators of the brand-name versions of the same products. We observed similar patterns for control drugs.

EU and US Approaches to Delayed Access to Generic Drugs by Enforcement of a Patent or SPC Procured by Fraud

This article examines the impact of pharmaceutical patent protection on the introduction of generic drugs on the market. Basing itself on the Court of Justice of the European Union (CJEU) AstraZeneca case and US case law it examines, in particular, the way in which pharmaceutical companies may have created artificial barriers to entry for the market launch of generic drugs, so as to maintain market dominance by way of “life cycle management strategies”. Moreover, it compares the different ways, in which the EU and US have chosen to address the problem of the abuse of regulatory procedures by fraud with its purpose of delaying generic drug approvals. It also seeks to answer the question of whether the existence of a legal entitlement to a patent under the rules of patent law excludes competition-law liability.

Tendencias de consumo de medicamentos ansiolíticos e hipnóticos en una población colombiana, 2008-2013

IntroductionIn Latin America, psychotropic medications are the third most marketed drug group, especially antidepressants (35%) and anxiolytics (5%). The objective of this study was to determine the trends in the consumption and the costs of anxiolytic and hypnotic drugs in a population of patients enrolled in the Health System of Colombia. Material and methodsA descriptive, observational study was performed using the data recorded inprescriptions for any anxiolytic or hypnotic drug prescribed to outpatients in the period between January 2008 and December 2013 in a population of 3.5 million people. Sociodemographic, pharmacological variables, overall costs, and cost per thousand inhabitants per day (CHD), were also recorded. ResultsThe number of patients who received the drugs studied varied from 11,097 to 19,231 between 2008 and 2013. The most used drugs were clonazepam (44.1% of formulations), alprazolam (31.2%), and lorazepam (13.2%). The invoiced value of anxiolytics increased from US$ 207,673.63 in 2008 to US$ 488,977 in 2013, an increase of 135.4%. The CHD was US$ 0.31 for benzodiazepines, and US$ 0.02 for zaleplon, zolpidem and zopiclone (Z drugs) for 2008, and US$ 0.36 and US$ 0.02 in 2013 respectively. The CHD declined after 2010 following the introduction of generic drugs. ConclusionsPatients receiving benzodiazepines in Colombia are mostly women, average age 55 years, with very low frequency in defined daily doses per thousand inhabitants when compared with other countries.

Assessment of Generic Psychotropic Drugs Therapy Costs in Poland

Provision of cost-effective drug treatment is of particular importance in patients with psychiatric diseases. Most of the therapies in question requires life-long treatment and consists of more than one medicine. Introduction of generic drugs is one of the major strategies for reducing contribution of costs of medications to total healthcare costs. The primary evidence required both by FDA and EMA for marketing approval of a new generic drug is acceptable bioequivalence between the generic drug product and its corresponding reference product. The price of the generic drug is estimated to be 25% lower comparing with the reference product. In the present study a comprehensive cost analysis of a two-year psychotropic drug treatment in one of high reference Polish psychiatric hospitals has been performed. The total real costs have been compared with predictable costs of treatment with reference products if used instead of the available generic drugs. Our study due to the comprehensive analysis of both the availability and costs of psychotropic medicinal products in Poland.

Brazilian pharmaceutical industry and generic drugs policy: Impacts on structure and innovation and recent developments

When generic drugs were introduced into the Brazilian market, the main aim was to decrease prices and minimize public health expenditure. However, in addition to this effect, this policy brought about unintended changes to the industrial structure. In this paper, we evaluate the unplanned impacts from the introduction of generic drugs, particularly with respect to the business scale and innovation. Our main results show a large increase in market share in favor of domestic companies, but just a small increase in R&D expenditure and innovation within those companies. Such an increase in the business scale represented a window of opportunity for national firms, but the recent mergers and acquisitions by foreign firms have challenged their position. The weak competitiveness of domestic firms stems from their poor technological capabilities, which are an outcome of a successful ‘demand pull’ industrial policy without the support of a ‘technological’ industrial policy.

地域を守る医療ガバナンスの課題

In recent years, public hospitals in Japan's rural areas, which are the main providers of medical care in rural areas, have been experiencing worsening financial conditions. In response, in 2007, the Ministry of Internal Affairs and Communications issued public hospital reform guidelines to local municipalities, requesting that they improve public hospital management as quickly as possible. Because the worsening fi nancial position of public hospitals is linked to their special organizational structure of strong ties with local governments, the guidelines urged making hospitals managerially independent from municipalities. However, in rural areas that would be especially strongly affected by the guidelines, the issue of medical care is an administrative issue of high public interest, and public hospitals and municipalities are linked inseparably. Consequently, whether the independence of public hospitals from municipalities as proposed by the guidelines is suitable for rural areas persists as an important research subject. This study, which was conducted to clarify management improvement measures for public hospitals in rural areas and benefi cial governance structures necessary to enable such measures, examined Oguni-Town in Yamagata Prefecture, which improved management of public hospitals without making them independent from municipalities. Measures adopted and implemented by the Oguni public hospital during 2008.2011, including the implementation of a change in the classification of hospital beds, promotion of medical examinations, and introduction of generic drugs, raised medical practice income and contributed to the improvement of management. These measures were developed through cooperation and the exchange of ideas among medical personnel of various specialties and local government officials. Such collaboration is a method that has been emphasized by Oguni-Town throughout its town planning activities. Through the use of common methods, administrative support for public hospital reform was obtained readily. Because the protection of medical care in rural areas is an important part of community building, it can be argued that maintaining a close relation between medical care providers and the community is important.

On the Topic of Bioavailability/Bioequivalence-Challenges with Polymorphic Metabolism

The topic Bioavailability/Bioequivalence (BA/BE) which is a primary driving force for the introduction of generic drugs of small molecules has been discussed for several decades now [1-5]. BA/BE studies also are important for the development of new drugs as API manufacturing process and formulation options keep changing during the entire drug development paradigm. It is needless to say that BA/ BE considerations has gone through phases of considerable debate amongst pharmaceutical scientists, academic researchers, regulators and key opinion leaders. While on one hand it could be argued that there is no one single approach that could satisfy the need/requirements for all the stake holders, on the other hand there need to be an uniform yard stick to allow consistency in BA/BE assessment. Hence, the application of average bioequivalence criteria using geometric means of peak concentration (Cmax), [a measure of rate of absorption] and geometric means of area under the plasma/serum/blood concentration curve vs. time (AUCinf) [a measure of the extent of absorption] for the parent compound between test and reference formulation has been well accepted. In order for a test formulation to be bioequivalent with the reference formulation geometric means and the 90% confidence intervals of both Cmax and AUCinf ratios of test/reference should be contained within 80 -125%.

Análise comparativa da concentração industrial e de turnover da indústria farmacêutica no Brasil para os segmentos de medicamentos de marca e genéricos

Este artigo analisa a evolução da estrutura do segmento de medicamentos de marca e genéricos no Brasil a partir de 1997. Após a entrada dos medicamentos genéricos, constatou-se que não houve diminuição significativa da concentração na indústria farmacêutica brasileira, porém, o mesmo não ocorreu em nível mundial, verificando-se um aumento da concentração a partir de 2001, impulsionado pelo expressivo processo de fusões e aquisições nos últimos anos da década de 1990. Em relação ao turnover, notou-se que este foi muito baixo para o grupo das maiores empresas em ambos os segmentos de medicamentos. Entretanto, observa-se um elevado turnover com a entrada dos genéricos, mostrando o fortalecimento da indústria nacional. Verifica-se que o processo de fusões e aquisições entre empresas nacionais é pouco significativo, o que pode ser uma alternativa para as pequenas empresas farmacêuticas aumentarem a sua participação no mercado brasileiro.

Generika: Qualität, Wirksamkeit, Sicherheit und Austauschbarkeit

Since the introduction of generic drugs to the pharmaceutical market a sometimes emotional debate exists whether they are well-investigated and of high quality. There is some uncertainty about whether evidence of bioequivalence is enough to guarantee efficacy and safety of generic drugs. Some physicians ask the question if competent authorities are able to ascertain that the pharmaceutical quality of generics is acceptable. Doctors and patients sometimes are ill at ease about the interchangeability of innovator and generic products. This article describes how the European Union legislation ensures that a generic drug is only approved if its risk-benefit relationship is favourable and that it is essentially similar to the innovator product. In this context pharmacokinetic parameters are accepted as surrogates for clinical results because bioequivalence means therapeutic equivalence as well. For most drugs, current bioequivalence testing generally enables clinicians to routinely substitute generic for innovator products. Published findings, however, suggest that particular drugs may not be ideally suited for generic substitution when a patient is already on that drug. These are the so called critical dose medicinal products (drugs with a narrow therapeutic range). When starting a new therapy with any generic drug, however, its similarity to the innovator drug in terms of efficacy, safety and quality is guaranteed.

Levantamento de dados sobre o conhecimento e informação acerca dos medicamentos genéricos em uma população de pacientes do serviço de saúde ambulatorial do Recife, Pernambuco, Brasil

Brazilian Federal Act 9,787/99, regulating generic medicines, includes rules for drug registration and provides for the population's access to safe, effective, high-quality, and low-cost medication. Four years after the introduction of generic drugs on the Brazilian market, we proposed to measure knowledge and information on generic drugs among the clientele at a public outpatient clinic in Recife, Pernambuco State, applying a questionnaire in 2000. 76.1% of the interviewees were women, 95.7% had heard of generic drugs, and 68.1% could define generic medication. Government action to publicize the properties of such medicines and their advantages for consumers has thus reached the vast majority of the population.

Clinical flow cytometry, a hypothesis-driven discipline of modern cytomics.

Recently, two major books have been published that summarize the historical aspects and recent achievements of practical flow cytometry (1,2). Both emphasize the role played by this newly developed technical discipline in the development of scientific (1) and diagnostic platforms during late 20th-century medicine (2). Indeed, the gray box called a flow cytometer is the result of a multidisciplinary collaboration between engineers, biophysicists, biochemists, histopathologists, molecular cytologists, hematologists, immunologists, and quality controllers, with a more recent contribution from physicians specializing in the human immunodeficiency virus (HIV), oncologists, and epidemiologists (Table 1). The foresight by the “fathers” has been astonishing (1). In his book, Howard Shapiro reminds us that flow cytometry, used to investigate cells in a flow system instead of on a static microscope, was put into practice by Coulter when he used impedance to count red cells. Rapid cell spectroscopy was introduced by Kamentsky to leukocyte differential counting with computer-assisted displays. Then optical cell counters, fluorescence dies, lasers, and photomultiplier tubes were added by Fulwyler and Jones. Immunologic concepts and reagents were introduced by the Herzenbergs and were fully primed to harvest the gems of the incipient monoclonal antibody revolution. The first commercial cytometer with precision engineering of the flow cells was launched by Goehde. These initial steps were duly followed by the release of a series of cytometers that showed increasing sensitivity, computerization, and practicality in research and routine laboratory work. This is illustrated by science historians Keating and Cambrosio in their book that blends the sociological aspects of medical technological developments with witness accounts (2). Flow cytometry currently is a colorful, practical discipline that has become available to medicine at the appropriate time for various pressing clinical applications, thus rewarding the scientists who had the vision to foresee these needs. These contributions established cytometry, including flow technology, image analysis, and advanced microscopy, among the leading trends of modern biomedicine and health care. After the launch of the Human Genome Project (3), two areas, genomics and proteomics, have been majestically promoted on both sides of the Atlantic and in the East (4). Genomics includes the identification of genes and gene regulatory processes, and proteomics investigates the abundance of proteins simultaneously with the changes associated with alterations of the functional state of the cell. Such a “pseudo-functional” approach aims to extend the study of quantitative changes during differentiation, proliferation, and signaling of different cell types (5). Clearly, there is an enormous, newly generated influx of information here, but it is not certain that a mere analysis of genes and protein structure, even in its extended format that includes the interaction of various biomolecules, will provide all of the necessary information to understand function and regulation at the level of living cells and organisms. Hence, the concept of cytomics has been introduced recently (6,7), for two reasons. First, cytomics is the cell-oriented analysis of molecules and their functions in cellular systems and/or organs, referred to as cytomes. Second, cytomics is the new, absolutely essential, interface between biosciences and clinical medicine. Importantly, advanced cytometry, including the traits defined in Table 1, represent the driving engine of cytomics. A new paradigm is that cytomics is the combined, interrelated force for cytometry, proteomics, and genomics (6,7). There are, however, significant differences between these three modern trends. First, it is in the realm of cytometry, with the major contribution of flow systems, where the appropriate functional analysis of cells, the display and regulation of functional molecules, and the differentiation pathways are successfully carried out. Animal models and human diseases provide targets for these studies. Second, it is the cytometric field where the diagnostic tests, for malignancies (cf. 8,9) and the cellular analysis of infectious diseases (10), currently harvest the richest crop of practical results, whereas in the fields of genomics and proteomics only the seeds are sown for the practically useful multiarray systems. Third, these two fields at their current developmental state, are essentially observational sciences that primarily document the observed heterogeneity. As a marked contrast, the research by flow cytometry has been, from the beginning, primarily