Medical research without patents: It's preferable, it's profitable, and it's practicable.

This article addresses the question of the possibility of medical research without patents, a major issue in healthcare research and policy. We discuss and evaluate the relevant scientific, economic, societal, and moral aspects of our system of funding and organizing the research, development, manufacture and sale of prescription drugs. The focus is on the patent practices of big pharmaceutical companies. We analyze and critically assess the main features and impacts of these practices. In a positive sense, we propose an approach to organizing and funding drug research that prioritizes its public interest rather than its privatization through patenting. For these purposes, we first demonstrate that producing prescription drugs through patenting has serious drawbacks. Second, we develop a concrete alternative (medical research without patents) that is shown to be scientifically, socially and morally preferable, economically and financially profitable, and socio-politically and organizationally practicable.

Recent Developments and Applications of Microbial Levan, A Versatile Polysaccharide-Based Biopolymer.

Polysaccharides are essential components with diverse functions in living organisms and find widespread applications in various industries. They serve as food additives, stabilizers, thickeners, and fat substitutes in the food industry, while also contributing to dietary fiber for improved digestion and gut health. Plant-based polysaccharides are utilized in paper, textiles, wound dressings, biodegradable packaging, and tissue regeneration. Polysaccharides play a crucial role in medicine, pharmacy, and cosmetology, as well as in the production of biofuels and biomaterials. Among microbial biopolymers, microbial levan, a fructose polysaccharide, holds significant promise due to its high productivity and chemical diversity. Levan exhibits a wide range of properties, including film-forming ability, biodegradability, non-toxicity, self-aggregation, encapsulation, controlled release capacity, water retention, immunomodulatory and prebiotic activity, antimicrobial and anticancer activity, as well as high biocompatibility. These exceptional properties position levan as an attractive candidate for nature-based materials in food production, modern cosmetology, medicine, and pharmacy. Advancing the understanding of microbial polymers and reducing production costs is crucial to the future development of these fields. By further exploring the potential of microbial biopolymers, particularly levan, we can unlock new opportunities for sustainable materials and innovative applications that benefit various industries and contribute to advancements in healthcare, environmental conservation, and biotechnology.

Current status and vision of local pharmaceutical industries in Saudi Arabia: The focus on nanomedicines.

Background: Pharmaceutical nanomedicine products are expected to impact the global pharmaceutical market and healthcare system significantly. Since 2000, the Food and Drug Administration (FDA) and European Medicines Agency (EMA) have approved over 80 nanomedicine products for marketing; an additional double that number is currently being tested in clinical trials. The nanomedicine market is expected to reach USD 350.8 billion by 2025 from USD 138.8 billion in 2016. This demonstrates the importance of nanotechnology to the delivery of pharmaceuticals. The main benefits of employing nanotechnology to distribute therapeutic agents include reducing the undesired toxicity from non-specific distribution and increasing patient adherence, which can indirectly minimize the burden on the country's healthcare system. Such products are expected to gain a significant economic impact on Saudi Arabia's pharmaceutical drugs market once they get developed locally. Method: A descriptive and cross-sectional study, including a web-based questionnaire and a complete categorization of pharmaceutical products formed by the national industries in Saudi Arabia, was utilized to investigate the current and future direction of pharmaceutical manufacturing exploiting nanotechnology in the Kingdom. Results: The survey showed an apparent lack of willingness within the national pharmaceutical industries, as the majority (≈ 86%) of the leading Saudi companies cannot enable nanotechnology-based medicines in their manufacturing. However, more than 93% of the national pharmaceutical industries, upon the basis of the responses, agreed that the development of pharmaceutical products with nanotechnology is an important step toward solving various complications associated with conventional forms of the available medicine. Conclusion: National pharmaceutical industries in Saudi Arabia will need to get closer to manufacturing nanomedicines by partnering with international pioneer companies. In addition, empowering the local research and development (R&D) centers in nano delivery systems could facilitate translating their R&D outcomes into novel advanced and commercialized products. This could imitate the direction of the global pharmaceutical market and share its revenue which will positively reflect on the Kingdom's economy.

Bioactive molecules from fungal endophytes and their applications in pharmaceutical industries: challenges and future scope.

Medicinal plants are an important source of bioactive compounds and have been used to isolate various bioactive compounds having industrial applications. The demand for plants derived bioactive molecules is increasing gradually. However, the extensive use of these plants to extract bioactive molecules has threatened many plant species. Moreover, extracting bioactive molecules from these plants is laborious, costly, and time-consuming. So, some alternative sources and strategies are urgently needed to produce these bioactive molecules similar to that of plant origin. However, the interest in new bioactive molecules has recently shifted from plants to endophytic fungi because many fungi produce bioactive molecules similar to their host plant. Endophytic fungi live in mutualistic association within the healthy plant tissue without causing disease symptoms to the host plant. These fungi are a treasure house of novel bioactive molecules having broad pharmaceutical, industrial, and agricultural applications. The rapid increase in publications in this domain over the last three decades proves that natural product biologists and chemists are paying great attention to the natural bioactive products from endophytic fungi. Though endophytes are source of novel bioactive molecules but there is need of advanced technologies like clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9 (CRISPR-Cas9) and epigenetic modifiers to enhance the production of compounds having industrial applications. This review provides an overview of the various industrial applications of bioactive molecules produced by endophytic fungi and the rationale behind selecting specific plants for fungal endophyte isolation. Overall, this study presents the current state of knowledge and highlights the potential of endophytic fungi for developing alternative therapies for drug-resistant infections.

Vaccine technology transfer in a global health crisis: Actors, capabilities, and institutions.

The COVID-19 pandemic, which featured international pharmaceutical firms seeking to build global manufacturing networks to scale-up the supply of vaccines, has generated heightened interest in understanding the role of firm-to-firm technology transfer. While considerable attention has been given to tracking the extent of international vaccine technology transfer, we know little about how partnerships were established and work in practice. Understanding the challenges that such projects face, and how such challenges may be overcome, is crucially important. This paper provides an account of the partnership between the British-Swedish multinational pharmaceutical company AstraZeneca, the vaccine developer that has engaged in the most technology transfer and built the widest global manufacturing network, and Bio-Manguinhos, a public laboratory linked to Brazil's Ministry of Health. The case study demonstrates the importance of capabilities and regulatory flexibility. Moreover, the analysis highlights the role of political factors that affect the process of technology transfer, and innovation more broadly. Because of the risks involved and the need to quickly mobilize existing capabilities and build new ones, as well as the imperatives of coordinating among manufacturing and regulatory processes and allocating resources to make such arrangements feasible, technology transfer projects need to be enabled politically. Looking forward, the case study has implications for initiatives to expand technology transfer for broadened production of vaccines in the Global South.

Bioethics and sociology: the place of social studies of science and technology / Bioética e sociologia: o lugar dos estudos sociais da ciência e tecnologia / Bioética y sociología: el lugar de los estudios sociales de la ciencia y tecnología

The social sciences have integrated the analytical and normative practices of bioethics. However, with some exceptions, the proposals have been epistemically limited to the methodological scope and strictly directed to biomedical care practices. Taking some data on the strategies of production of new drugs by the pharmaceutical industry, this essay intends to demonstrate the possible contributions of the social studies of science and technology to a theoretical-methodological foundation of bioethical analyzes around global health issues, such as the production and distribution of technologies. We conclude that at least three types of analyzes would benefit from this proximity: analyzes of the epistemological integrity of the health sciences; ethical-political analyzes around the access and security of new and old health technologies; and ethical-philosophical analyzes of harmful attitudes of the scientific community and health professionals in relation to health care.(AU)

As ciências sociais têm integrado as práticas analíticas e normativas da bioética. No entanto, com algumas exceções, as propostas têm sido epistemicamente limitadas ao âmbito metodológico e estritamente direcionadas às práticas de cuidado biomédico. Tomando alguns dados sobre as estratégias de produção de novos medicamentos pela indústria farmacêutica, este ensaio pretende demonstrar as possíveis contribuições dos estudos sociais da ciência e tecnologia para uma fundamentação teórico-metodológica das análises bioéticas em torno de questões globais em saúde, tais como a produção e distribuição de tecnologias. Concluímos que pelo menos três tipos de análises se beneficiariam dessa proximidade: análises da integridade epistemológica das ciências da saúde; análises ético-políticas em torno do acesso e segurança de novas e antigas tecnologias em saúde; e análises ético-filosóficas de posturas nocivas da comunidade científica e dos profissionais de saúde em relação à assistência à saúde.(AU)

Las ciencias integran las prácticas analíticas y normativas de la bioética. Sin embargo, con algunas excepciones, las propuestas han sido epistémicamente limitadas al ámbito metodológico y rigurosamente dirigidas a las prácticas del cuidado biomédico. Tomando algunos datos sobre las estrategias de producción de nuevos medicamentos por la industria farmacéutica, este ensayo pretende demostrar las posibles contribuciones de los estudios sociales de la ciencia y la tecnología para una fundamentación teórico-metodológica de los análisis bioéticos sobre de cuestiones globales de salud, tales como la producción y distribución de tecnologías. Concluimos que al menos tres tipos de análisis se beneficiarían de esa proximidad: análisis de la integridad epistemológica de las ciencias de la salud, análisis ético-políticos sobre el acceso y la seguridad de nuevas y antiguas tecnologías de salud y análisis ético-filosóficos de posturas nocivas de la comunidad científica y de los profesionales de salud con relación a la asistencia de la salud.(AU)

Local pharmaceutical research and development capacity in a developing country: a qualitative exploration of perspectives from key stakeholders in Ethiopia.

PURPOSE: Despite its importance in ensuring sustainable healthcare, there are huge challenges with pharmaceutical research and development (R&D) especially for developing countries mainly due to the high investment costs naturally associated with such activities. In this regard, the pharmaceutical sector in Ethiopia, the most populous nation in East Africa, faces numerous challenges. The current study aimed at assessing the R&D capacity of the local pharmaceutical manufacturers from the perspectives of key informants working in the companies and supporting government offices and education institutions. METHODS: A qualitative study design employing in-depth interviews using semi-structured interview guides with flexible probing techniques was used for data collection. The study involved purposively selected participants who represented major stakeholders such as managers in the R&D departments of pharmaceutical manufacturers, officers and leaders in concerned government agencies and researchers in a local university. All transcribed interviews were subjected to thematic analysis and the Qualitative Data Analysis software in family R (RQDA) was used for data analysis. RESULTS: A total of 14 participants were involved in the study and three major themes were identified from the interviews. Current R&D capacity, opportunities and challenges for involvement in R&D were the major themes. Under current R&D capacity, the weak R&D status of local pharmaceutical plants and minimal university-industry linkage were identified. The challenges of pharmaceutical R&D in Ethiopia included weak governmental and managerial support; difficult procurement processes for R&D input; and the high cost of R&D. Availability of trainable human power and planned government incentives were identified as the opportunities. CONCLUSION: Overall, there is a low level of R&D capacity in local pharmaceutical industries and timely interventional strategies should be implemented through collaboration of academia, research institutions and pharmaceutical industries.

Removal of the EMA orphan designation upon request of the sponsor: cui prodest?

PURPOSE: Various incentives are provided by the European Medicines Agency (EMA) to facilitate the development and marketing of orphan drugs. A 10-year period of market exclusivity is reserved to an orphan medicinal product. Sometimes, the sponsor renounces the designation before the expiration of that standard period. Our aim was to focus on these premature withdrawals. METHODS: We retrieved all the molecules included in the Community Register of Orphan Medicinal Products for Human Use from 2000 to November 2020. We considered the active substance, therapeutic indication, sponsor, year of designation, year of approval of the corresponding medicinal product, and that of the withdrawal of the orphan designation, if occurred. RESULTS: Overall, 2350 orphan designations were approved from 2000 to November 2020. Of these, 141 have been marketed. Premature withdrawal of orphan designation concerned 23 drugs (20 being antineoplastic agents), corresponding to 16 medicinal products. These withdrawals occurred after almost 2 years (range <1-7 years). CONCLUSIONS: A not negligible fraction of marketed orphan medicinal products underwent premature removal of their orphan designation. No motivation is requested by the EMA for this renouncement, although the peculiarity of the orphan medicinal products would need a greater transparency. We can only speculate about possible compensations in support of this decision, for instance in terms of commercial agreements between pharmaceutical companies, giving way to alternative products, as a couple of examples suggest. An open debate on this topic among members of academia, regulatory bodies, price and reimbursements committees, and pharmaceutical industry representatives will be welcome.

Monitoring and controlling bacteria in pharmaceutical industries water system.

AIM: This research aimed to monitor pharmaceutical water system by sampling water from all treatment stages, identify bacterial isolates from each phase and determine the most suitable methods to control them. METHODS AND RESULTS: Water samples were collected and examined from pharmaceutical water system in a pharmaceutical factory in Giza, Egypt during 12 months, once per month (from December 2017 to November 2018) from 15 points covering all stages of the treatment process starting from wells, pre-treatment points; treatment points ending with purified points which are the main source of water used in all pharmaceutical process. In all, 216 water samples were collected and examined, 156 isolates were selected according to morphological characteristics. VITEK system 2 (BioMérieux) was used for identification of all isolates resulting in 24 different identified bacteria. Antibiotic assay test using disc diffusion methods were carried out using seven antibiotics from different groups. Several disinfectants were also examined for efficacy against the isolates to control micro-organisms in water treatment stage and manufacturing area. The effect of different preservatives (parabens, acids and alcohols) in various pharmaceutical formulas was also tested on bacterial isolates, 63% of formulas were effective against all bacterial isolates. CONCLUSION: Ciprofloxacin was the most effective antibiotic, mixture of 0·45% peracetic acid plus 2·2% of hydrogen peroxide (Minncare 1%) was maximally effective disinfectant, and Cronobacter sakazakii was the most resistant micro-organism against 22·7% of tested preservatives. SIGNIFICANCE AND IMPACT OF THE STUDY: Controlling pharmaceutical manufacturing operation from pathogenic bacteria that affect the quality of drugs.

Value of shared preclinical safety studies - The eTOX database.

A first analysis of a database of shared preclinical safety data for 1214 small molecule drugs and drug candidates extracted from 3970 reports donated by thirteen pharmaceutical companies for the eTOX project (www.etoxproject.eu) is presented. Species, duration of exposure and administration route data were analysed to assess if large enough subsets of homogenous data are available for building in silico predictive models. Prevalence of treatment related effects for the different types of findings recorded were analysed. The eTOX ontology was used to determine the most common treatment-related clinical chemistry and histopathology findings reported in the database. The data were then mined to evaluate sensitivity of established in vivo biomarkers for liver toxicity risk assessment. The value of the database to inform other drug development projects during early drug development is illustrated by a case study.

Medicine adaptive pathways to patients (MAPPs): using regulatory innovation to defeat Eroom's law.

Eroom's Law is, literally, Moore's law in reverse. The pharmaceutical sector invests $50 billion annually in research for new medicines but, "the number of new drugs approved per billion US dollars spent has halved roughly every 9 years since 1950, falling around 80-fold in inflation-adjusted terms". Pharmaceutical companies have invested enormous sums in new molecular entities (NME) in the areas of unmet medical need identified by the World Health Organization (WHO), but the approval rates from phase I are only 7% for cardiovascular disease, dropping to 4% for Alzheimer's disease. The increasing cost of research & development (R&D) is not only a factor of research management quality, but also indicative of an industry trying to address therapeutic areas that have incredibly complex biological mechanisms with budget-crushing failure rates. Medicine adaptive pathways to patients (MAPPs) build on the stratification breakthroughs of personalized medicine to facilitate new types of clinical trials that adapt to a given patient's response. At their core, MAPPs will have a limited commercial marketing authorization for a patient group who has access to new therapeutic agents while validating additional clinical endpoints at the same time. This gives MAPPs a theoretical ability to run trials that fulfil both the efficacy requirements for authorization and the effectiveness needs of national health technology assessments (HTA) simultaneously, providing patients with needed therapies in the most efficient timescale and trial size possible. In order to move science forward and meet these daunting medical challenges for patients, new collaborative approaches to testing the efficacy and effectiveness of new improved medicines such as MAPPs should be embraced by regulators in close partnership with patients, payers, and practitioners. To not do so puts the entire healthcare value chain, and the future health of patients, at risk.

Conflitos de interesse na pesquisa, produção e divulgação de medicamentos / Conflicts of interest in the research, production and dissemination of medicines

Analisa o debate sobre os conflitos éticos dos artifícios utilizados pela indústria farmacêutica na pesquisa, produção e divulgação dos medicamentos. Três aspectos são examinados: o envolvimento dos profissionais de medicina com os representantes das indústrias farmacêuticas; o conflito de interesses quanto a sua atuação como patrocinadora de pesquisas científicas; a avaliação de fármacos em seres humanos. Verifica-se que a mensagem para promoção da saúde advém da medicalização; as grandes indústrias farmacêuticas não produzem exclusivamente mercadorias, mas, sobretudo, subjetividades. Dessa forma, descortina-se o tipo de ordem por elas estabelecida.

This paper analyzes the debate about the ethical conflicts of the methods used by the pharmaceutical industry in the research, production and dissemination of medicines. Three aspects are examined: the involvement of medical professionals with representatives of the pharmaceutical industry; the conflicts of interest regarding their role as sponsors of scientific research; and the evaluation of drugs on human beings. It is seen that the message for health promotion comes from medicalization; the major pharmaceutical industries do not exclusively produce merchandise, but especially subjectivities. In this way, the type of order established by them is revealed.