Bedside manufacturing as the next step in personalized medicine: medical progress and legal challenges.

Bedside manufacturing is having a revival in healthcare, with a promise to revolutionize personalized medicine through on-site drug production. While this concept holds considerable promise, it also encounters a complex web of legal uncertainties. The current regulatory framework in Switzerland and the EU, which includes the Swiss Therapeutic Products Act and the EU directives, regulations, and guidelines, fails to adequately address its distinct challenges. Rising new technologies underscore the urgent need for regulatory reform. These technologies highlight the pressing demand for comprehensive legal frameworks that can reconcile the rapid pace of innovation with the imperatives of patient safety and product efficacy. Legal concerns extend beyond mere compliance; they encapsulate quality assurance, and liability in cases of human error. This study outlines the call for a recalibrated legal landscape that prioritizes patient-centered care while fostering the growth of bedside manufacturing. It is crucial for the legal system to evolve in tandem with these medical advancements, ensuring a secure, efficacious, and equitable integration of bedside manufacturing into healthcare.

Assessing the efficacy of large language models in spinal health information dissemination.

•Examines AI's role in spinal health education.•Stresses multidisciplinary AI evaluations.•Advocates for stringent AI healthcare regulations.

Nanostructured Medical Devices: Regulatory Perspective and Current Applications.

Nanomaterials (NMs) are having a huge impact in several domains, including the fabrication of medical devices (MDs). Hence, nanostructured MDs are becoming quite common; nevertheless, the associated risks must be carefully considered in order to demonstrate safety prior to their immission on the market. The biological effect of NMs requires the consideration of methodological issues since already established methods for, e.g., cytotoxicity can be subject to a loss of accuracy in the presence of certain NMs. The need for oversight of MDs containing NMs is reflected by the European Regulation 2017/745 on MDs, which states that MDs incorporating or consisting of NMs are in class III, at highest risk, unless the NM is encapsulated or bound in such a manner that the potential for its internal exposure is low or negligible (Rule 19). This study addresses the role of NMs in medical devices, highlighting the current applications and considering the regulatory requirements of such products.

Shaping the Future of Coffee: Climate Resilience, Liberica's Rise, and By-Product Innovation-Highlights from the International Coffee Convention 2023 (ICC2023).

The International Coffee Convention 2023 comprehensively addressed the contemporary challenges and advancements in the coffee industry, emphasizing sustainability, health, and innovation. This convention gathered experts and stakeholders to explore diverse aspects of coffee, ranging from the potential of underutilized species like Coffea liberica in terms of climate resilience to the innovative use of coffee by-products. The convention featured presentations and discussions, employing both empirical research and analytical reviews to explore various topics, including the health benefits of coffee, the advancements in traceability and authentication methods, and the impact of global regulatory changes on coffee production and trade. The key findings highlighted the importance of biodiversity in coffee production as a response to climate change, the significant health benefits and sustainability potential of coffee by-products, and the evolving landscape of coffee consumption patterns driven by technological innovations. The convention also stressed the need for alignment in global coffee trade regulations, particularly concerning deforestation and traceability. The 2023 convention underscored the complexity and interconnectivity of the coffee industry's challenges and opportunities. It concluded with a forward-looking perspective, emphasizing the need for continued research, sustainable practices, and collaborative efforts to shape the future of the coffee industry. The community is looking forward to furthering these discussions at the next International Coffee Convention in 2024.

Global Regulatory Frameworks for the Use of Artificial Intelligence (AI) in the Healthcare Services Sector.

The healthcare sector is faced with challenges due to a shrinking healthcare workforce and a rise in chronic diseases that are worsening with demographic and epidemiological shifts. Digital health interventions that include artificial intelligence (AI) are being identified as some of the potential solutions to these challenges. The ultimate aim of these AI systems is to improve the patient's health outcomes and satisfaction, the overall population's health, and the well-being of healthcare professionals. The applications of AI in healthcare services are vast and are expected to assist, automate, and augment several healthcare services. Like any other emerging innovation, AI in healthcare also comes with its own risks and requires regulatory controls. A review of the literature was undertaken to study the existing regulatory landscape for AI in the healthcare services sector in developed nations. In the global regulatory landscape, most of the regulations for AI revolve around Software as a Medical Device (SaMD) and are regulated under digital health products. However, it is necessary to note that the current regulations may not suffice as AI-based technologies are capable of working autonomously, adapting their algorithms, and improving their performance over time based on the new real-world data that they have encountered. Hence, a global regulatory convergence for AI in healthcare, similar to the voluntary AI code of conduct that is being developed by the US-EU Trade and Technology Council, would be beneficial to all nations, be it developing or developed.

Strategies for Traceability to Prevent Unauthorised GMOs (Including NGTs) in the EU: State of the Art and Possible Alternative Approaches.

The EU's regulatory framework for genetically modified organisms (GMOs) was developed for "classical" transgenic GMOs, yet advancements in so-called "new genomic techniques (NGTs)" have led to implementation challenges regarding detection and identification. As traceability can complement detection and identification strategies, improvements to the existing traceability strategy for GMOs are investigated in this study. Our results are based on a comprehensive analysis of existing traceability systems for globally traded agricultural products, with a focus on soy. Alternative traceability strategies in other sectors were also analysed. One focus was on traceability strategies for products with characteristics for which there are no analytical verification methods. Examples include imports of "conflict minerals" into the EU. The so-called EU Conflict Minerals Regulation requires importers of certain raw materials to carry out due diligence in the supply chain. Due diligence regulations, such as the EU's Conflict Minerals Regulation, can legally oblige companies to take responsibility for certain risks in their supply chains. They can also require the importer to prove the regional origin of imported goods. The insights from those alternative traceability systems are transferred to products that might contain GMOs. When applied to the issue of GMOs, we propose reversing the burden of proof: All companies importing agricultural commodities must endeavour to identify risks of unauthorised GMOs (including NGTs) in their supply chain and, where appropriate, take measures to minimise the risk to raw material imports. The publication concludes that traceability is a means to an end and serves as a prerequisite for due diligence in order to minimise the risk of GMO contamination in supply chains. The exemplary transfer of due diligence to a company in the food industry illustrates the potential benefits of mandatory due diligence, particularly for stakeholders actively managing non-GMO supply chains.

The Role of Artificial Intelligence in Echocardiography: A Clinical Update.

PURPOSE OF REVIEW: In echocardiography, there has been robust development of artificial intelligence (AI) tools for image recognition, automated measurements, image segmentation, and patient prognostication that has created a monumental shift in the study of AI and machine learning models. However, integrating these measurements into complex disease recognition and therapeutic interventions remains challenging. While the tools have been developed, there is a lack of evidence regarding implementing heterogeneous systems for guiding clinical decision-making and therapeutic action. RECENT FINDINGS: Newer AI modalities have shown concrete positive data in terms of user-guided image acquisition and processing, precise determination of both basic and advanced quantitative echocardiographic features, and the potential to construct predictive models, all with the possibility of seamless integration into clinical decision support systems. AI in echocardiography is a powerful and ever-growing tool with the potential for revolutionary effects on the practice of cardiology. In this review article, we explore the growth of AI and its applications in echocardiography, along with clinical implications and the associated regulatory, legal, and ethical considerations.

Real-world evidence for regulatory decision-making: updated guidance from around the world.

Leveraging the value of real-world evidence (RWE) to make informed regulatory decisions in the field of health care continues to gain momentum. Improving clinical evidence generation by evaluating the outcomes and patient experiences at the point-of-care would help achieve the ultimate aim of ensuring that effective and safe treatments are rapidly approved for patient use. In our previous publication, we assessed the global regulatory landscape with respect to RWE and provided a review of the regional availability of frameworks and guidance through May 2021 on the basis of 3 key regulatory elements: regulatory RWE frameworks, data quality guidance, and study methods guidance. In the current review, we have updated and elaborated upon recent developments in the regulatory RWE environment from a regional perspective under the same 3 regulatory elements stated above. In addition, we have also included a new category on procedural guidance. The review also discusses the perceived gaps and potential opportunities for future development and harmonization in this field to support framework establishment in regions without pre-existing RWE policies. Additionally, the article reviews current developments of health technology assessment (HTA) bodies pertaining to RWE and discusses the status of evidentiary alignment among regulators and HTA agencies.

Medico-Legal Implications and Regulatory Frameworks of Regenerative Orthopaedics.

Regenerative orthopaedics has revolutionized traditional medicine, which represents a giant leap in science and research. The knowledge of the medico-legal implications and regulatory framework of this branch is vital for clinicians and researchers to go forward smoothly. This systematic review of the literature should shed light on these considerations and provide a comprehensive knowledge of the various implications and laws governing practice and research. The wide plethora of knowledge in the use of regenerative orthopaedics should be complemented by updated regulations and clinicians' grasp of knowledge on regenerative medicine. The review focused on peer-reviewed published articles concerned with the topic and outlined common medico-legal issues and the current regulatory frameworks in various countries. The articles suggest that developed nations like the US have faced several lawsuits in this field, and a few countries in Europe like Italy and Germany, which were frontrunners in this field based on research, have fallen back due to emerging legal and regulatory policies. Undoubtedly, regenerative orthopaedics holds the key to future orthopaedics, but the world is skeptical of this concept, and laws and regulatory frameworks can curb it if not guided well. In India, this field has received prime attention, but at a slow pace when compared to the laws. After reviewing 113 articles, we analysed eight critically in this systematic review to emphasize the comparative global frameworks, daily medico-legal problems, and solutions for the branch of regenerative orthopaedics.

Unmet Needs in Complicated Urinary Tract Infections: Challenges, Recommendations, and Emerging Treatment Pathways.

While urinary tract infections (UTIs) are one of the most common types of infections globally, the wide variety of presentations and of severity of disease can make it difficult to manage. The definition for uncomplicated UTIs (uUTIs) is generally regarded as UTIs in healthy, non-pregnant women whereas all other UTIs are considered complicated. There is, however, a lack of consensus definition of complicated UTIs (cUTIs), leading to global differences in management. In addition, the patients who develop complicated UTIs generally have other comorbidities that warrant more urgent intervention. One of the biggest challenges in treating cUTIs is the rise of antimicrobial resistance (AMR). While there have been recent drug approvals for new antibiotic to treat these resistant organisms, a multidisciplinary approach, including regulatory frameworks, provider education and public awareness campaigns, is crucial to limiting unnecessary treatments for asymptomatic bacteriuria (ASB) and uUTIs that can ultimately lead to more severe infections.

Current Status of PRP Manufacturing Requirements & European Regulatory Frameworks: Practical Tools for the Appropriate Implementation of PRP Therapies in Musculoskeletal Regenerative Medicine.

Providing accurate and up-to-date practical tools enabling oversight of platelet-rich plasma (PRP) legislation and of the appropriate standards to be implemented for its manufacture and use in Europe is a demanding task. This is due to rapid medico-technological advancements, slowness and disparity in legislation updates and enforcement between member states, and many reported gray-zone practices, notably for autologous PRP use. The levels of risk associated with blood manipulation processes generally dictate the manufacturing requirements for PRP preparations, which have gradually shifted toward good manufacturing practices (GMP) for standardization and overall quality enhancement. This work firstly outlines Western European and Swiss legislation for PRP products/preparations, providing key simplified information and recommendations for medical doctors seeking to implement this biological-based therapy for safe use in hospital settings, clinics, or private offices. This work secondly shows the importance of PRP-based product manufacturing standardization, which subsequently enables sound clinical evaluation of therapeutic interventions. Although the applicable legal bases provide guidelines for GMP manufacturing infrastructure and basic process design, paramount importance is set on the definition of workflows, technical specifications, and key parameters for PRP preparation and delivery. Overall, the development of simple and robust technologies and processes for PRP preparation is critical for guaranteeing the high therapeutic quality of the intervention, in collaboration with qualified GMP manufacturing platforms. Importantly, this work aims to serve as a practical tool for clinicians based in Western Europe who are willing to appropriately (i.e., administratively and technically) implement autologous PRP treatments in musculoskeletal regenerative medicine workflows, to ensure they make informed and optimal regulatory or process-based decisions.

Commercial probiotic products in public health: current status and potential limitations.

Consumption of commercial probiotics for health improvement and disease treatment has increased in popularity among the public in recent years. The local shops and pharmacies are brimming with various probiotic products such as probiotic food, dietary supplement and pharmaceuticals that herald a range of health benefits, from nutraceutical benefits to pharmaceutical effects. However, although the probiotic market is expanding rapidly, there is increasing evidence challenging it. Emerging insights from microbiome research and public health demonstrate several potential limitations of the natural properties, regulatory frameworks, and market consequences of commercial probiotics. In this review, we highlight the potential safety and performance issues of the natural properties of commercial probiotics, from the genetic level to trait characteristics and probiotic properties and further to the probiotic-host interaction. Besides, the diverse regulatory frameworks and confusing probiotic guidelines worldwide have led to product consequences such as pathogenic contamination, overstated claims, inaccurate labeling and counterfeit trademarks for probiotic products. Here, we propose a plethora of available methods and strategies related to strain selection and modification, safety and efficacy assessment, and some recommendations for regulatory agencies to address these limitations to guarantee sustainability and progress in the probiotic industry and improve long-term public health and development.

Supporting the Involvement of Adults with Cognitive Disabilities in Research: The Need for Reform.

This article examines current legal and ethical requirements concerning research about adults with cognitive disabilities. These requirements, the article argues, are complex, difficult to navigate, and inevitably act as a disincentive for research to be conducted. These requirements also do little to encourage active involvement by adults with cognitive disabilities in deciding whether to participate in research. The article argues that reforms are needed for State and Territory laws to require, wherever possible, adults to be supported to make their own decisions about research participation. State and Territory law reform is also required to clarify when, and on what basis, others may be appointed to make research participation decisions on behalf of adults with cognitive disabilities. The article concludes by seeking complementary reform of the National Health and Medical Research Council National Statement on Ethical Conduct in Human Research, which would result in it being more human rights compliant and simpler to apply.

Núcleo de Apoio à Saúde da Família: análise de uma década da produção normativa do Ministério da Saúde / Support Center for Family Health Care: analysis of a decade of normative production by the Ministry of Health

Resumo Introdução Trazemos à cena a Atenção Básica e o Núcleo Ampliado de Saúde da Família (NASF), equipe multiprofissional que proporciona suporte qualificado para os outros profissionais da Estratégia da Saúde da Família. Objetivo Descrever a trajetória de uma década de NASF (2008-2018) e sua expansão neste período. Método Análise de conteúdo de documentos produzidos pelo Ministério da Saúde (MS), entre janeiro a setembro de 2008. Os achados foram organizados em uma linha cronológica, com análise das ferramentas de trabalho mais frequentes e dados de implantação. Resultados Existem onze Portarias, treze materiais escritos e sete vídeos com conteúdo de suporte técnico-pedagógico para práticas. Ainda que exposto às sucessivas transformações legais, houve uma expansão considerável em 10 anos de existência, com ampliação de equipes e inserção de 19 categorias profissionais, apresentando múltiplas possibilidades de atuação. Os documentos apontam para atuação do NASF através do apoio matricial, embora a atual Política Nacional de Atenção Básica não o reconheça. Conclusão Conhecer a trajetória do NASF é relevante para compreendermos as mudanças que ocorreram e as propostas que surgirão. Uma década é pouco tempo para consolidar uma prática inovadora, em um país cujos direcionamentos por meio das mudanças normativas podem caminhar em uma velocidade bem maior.

Abstract Background We bring to the scene the Primary Health Care and the Support Center for Family Health (NASF) in Brazil, a multi-professional team that provides qualified support to other professionals in the Family Health Strategy. Objective Describe the trajectory of a decade of NASF (2008-2018) and its expansion in this period. Method: Content analysis of documents produced by the Ministry of Health, between January and September 2008. The results were organized in a chronological line, with analysis of the most frequent work tools and implementation data. Results There are 11 ordinances, 13 written materials, and 7 videos as technical and pedagogical support for Core Actions practices. Although exposed to successive legal changes, there has been a considerable expansion in these 10 years of existence, not only in the number of teams, but also in the insertion of 19 professional categories and their multiple possibilities of action. The documents point to NASF's strategy of action through matrix support, although the current National Primary Care Policy does not recognize it. Conclusion Knowing the trajectory of NASF is relevant for understanding the changes that have occurred and the proposals that will arise. A decade is little time to consolidate an innovative practice in a country whose direction through normative changes can move at a much greater speed.

Pesquisa e desenvolvimento de nanomedicamentos: olhar bioético / Nanodrug research and development: a bioethical approach / Investigación y desarrollo de nanomedicinas: desde la mirada bioética

Resumo Nanotecnologia é a utilização de materiais na escala nanométrica, em que estes adquirem características próprias. A área de pesquisa e desenvolvimento de novos nanomedicamentos é uma das mais promissoras atualmente, todavia essas partículas necessitam de avaliação particular e ainda não há consenso referente às testagens específicas a serem seguidas, o que dificulta a formação de uma legislação que garanta a segurança e eficácia destes medicamentos, além de um processo de registro mais eficaz. Assim, é necessária uma abordagem bioética da nanotecnologia e sua utilização em medicamentos, visando garantir que o progresso científico não acarrete impactos irreversíveis. Diante dessa problemática, busca-se promover uma discussão nanoética referente ao processo de pesquisa e desenvolvimento de nanomedicamentos, por meio de estudo qualitativo, exploratório-descritivo e de caráter analítico, utilizando revisão bibliográfica, análise documental e dados quantitativos disponíveis como técnicas de pesquisa.

Abstract Nanotechnology consist of using materials at the nanoscale, in which they acquire specific characteristics. Nanodrug research and development is one of the most promising fields today; however, these particles require particular evaluation. Moreover, studies lack consensus on which specific tests to follow, thus hindering the elaboration of legislation that ensure their safety and efficacy, as well as a more effective registration process. Thus, a bioethical approach to nanotechnology and its use in drug development is necessary to ensure scientific progress without irreversible impacts. Given this scenario, this article proposes a nanoethics discussion regarding nanodrug research and development by means of a qualitative, exploratory and descriptive analysis, based on literature review, documental analysis and quantitative data available.

Resumen La nanotecnología utiliza materiales nanométricos, en que estos adquieren características propias. El área de investigación y desarrollo de nuevas nanomedicinas es una de las más prometedoras en la actualidad, sin embargo, estas partículas requieren de una evaluación particular y aún no existe consenso en cuanto a las pruebas específicas que seguir, lo que dificulta establecer una legislación que garantice la seguridad y eficacia de estos medicamentos, además de un proceso de registro más efectivo. Por lo tanto, se necesita un enfoque bioético de la nanotecnología y su uso en medicamentos para garantizar que el avance científico no tenga impactos irreversibles. Ante esta problemática, se pretende promover el debate sobre la nanoética en el proceso de investigación y desarrollo de nanomedicinas a partir de un estudio cualitativo, exploratorio-descriptivo y analítico, que utiliza como técnicas de investigación la revisión bibliográfica, el análisis de documentos y los datos cuantitativos disponibles.

The Future Is Coming: Artificial Intelligence in the Treatment of Infertility Could Improve Assisted Reproduction Outcomes-The Value of Regulatory Frameworks.

Infertility is a global health issue affecting women and men of reproductive age with increasing incidence worldwide, in part due to greater awareness and better diagnosis. Assisted reproduction technologies (ART) are considered the ultimate step in the treatment of infertility. Recently, artificial intelligence (AI) has been progressively used in the many fields of medicine, integrating knowledge and computer science through machine learning algorithms. AI has the potential to improve infertility diagnosis and ART outcomes estimated as pregnancy and/or live birth rate, especially with recurrent ART failure. A broad-ranging review has been conducted, focusing on clinical AI applications up until September 2022, which could be estimated in terms of possible applications, such as ultrasound monitoring of folliculogenesis, endometrial receptivity, embryo selection based on quality and viability, and prediction of post implantation embryo development, in order to eliminate potential contributing risk factors. Oocyte morphology assessment is highly relevant in terms of successful fertilization rate, as well as during oocyte freezing for fertility preservation, and substantially valuable in oocyte donation cycles. AI has great implications in the assessment of male infertility, with computerised semen analysis systems already in use and a broad spectrum of possible AI-based applications in environmental and lifestyle evaluation to predict semen quality. In addition, considerable progress has been made in terms of harnessing AI in cases of idiopathic infertility, to improve the stratification of infertile/fertile couples based on their biological and clinical signatures. With AI as a very powerful tool of the future, our review is meant to summarise current AI applications and investigations in contemporary reproduction medicine, mainly focusing on the nonsurgical aspects of it; in addition, the authors have briefly explored the frames of reference and guiding principles for the definition and implementation of legal, regulatory, and ethical standards for AI in healthcare.

"Constrained Medical Oxygen Supply Chain in India During COVID-19: Red-tapism, the Elephant in the Room?"

BACKGROUND: Recent disruption of medical oxygen during the second wave of coronavirus disease 2019 (COVID-19) has caused nationwide panic. This study attempts to objectively analyze the medical oxygen supply chain in India along the principles of value stream mapping (VSM), identify bottlenecks, and recommend systemic improvements. METHODS: Process mapping of the medical oxygen supply chain in India was done. Different licenses and approvals, their conditions, compliances, renewals, among others were factored in. All relevant circulars (Government Notices), official orders, amendments, and gazette notifications pertaining to medical oxygen from April 2020 to April 2021 were studied and corroborated with information from Petroleum and Explosives Safety Organization (PESO) official website. RESULTS: Steps of medical oxygen supply chain right from oxygen manufacture to filling, storage, and transport up to the end users; have regulatory bottlenecks. Consequently, flow of materials is sluggish and very poor information flow has aggravated the inherent inefficiencies of the system. Government of India has been loosening regulatory norms at every stage to alleviate the crisis. CONCLUSIONS: Regulatory bottlenecks have indirectly fueled the informal sector over the years, which is not under Government's control with difficulty in controlling black-marketing and hoarding. Technology enabled, data-driven regulatory processes with minimum discretionary human interface can make the system more resilient.

Regulatory frameworks can facilitate or hinder the potential for genome editing to contribute to sustainable agricultural development.

The advent of new breeding techniques (NBTs), in particular genome editing (GEd), has provided more accurate and precise ways to introduce targeted changes in the genome of both plants and animals. This has resulted in the use of the technology by a wider variety of stakeholders for different applications in comparison to transgenesis. Regulators in different parts of the world are now examining their current frameworks to assess their applicability to these NBTs and their products. We looked at how countries selected from a sample of geographical regions globally are currently handling applications involving GEd organisms and what they foresee as opportunities and potential challenges to acceptance of the technology in their jurisdictions. In addition to regulatory frameworks that create an enabling environment for these NBTs, acceptance of the products by the public is vitally important. We, therefore, suggest that early stakeholder engagement and communication to the public be emphasized to foster public acceptance even before products are ready for market. Furthermore, global cooperation and consensus on issues cutting across regions will be crucial in avoiding regulatory-related bottlenecks that affect global trade and agriculture.

Genetically modified organisms: adapting regulatory frameworks for evolving genome editing technologies.

Genetic modification of living organisms has been a prosperous activity for research and development of agricultural, industrial and biomedical applications. Three decades have passed since the first genetically modified products, obtained by transgenesis, become available to the market. The regulatory frameworks across the world have not been able to keep up to date with new technologies, monitoring and safety concerns. New genome editing techniques are opening new avenues to genetic modification development and uses, putting pressure on these frameworks. Here we discuss the implications of definitions of living/genetically modified organisms, the evolving genome editing tools to obtain them and how the regulatory frameworks around the world have taken these technologies into account, with a focus on agricultural crops. Finally, we expand this review beyond commercial crops to address living modified organism uses in food industry, biomedical applications and climate change-oriented solutions.