ISO 15189 is a sufficient instrument to guarantee high-quality manufacture of laboratory developed tests for in-house-use conform requirements of the European In-Vitro-Diagnostics Regulation.

The EU In-Vitro Diagnostic Device Regulation (IVDR) aims for transparent risk-and purpose-based validation of diagnostic devices, traceability of results to uniquely identified devices, and post-market surveillance. The IVDR regulates design, manufacture and putting into use of devices, but not medical services using these devices. In the absence of suitable commercial devices, the laboratory can resort to laboratory-developed tests (LDT) for in-house use. Documentary obligations (IVDR Art 5.5), the performance and safety specifications of ANNEX I, and development and manufacture under an ISO 15189-equivalent quality system apply. LDTs serve specific clinical needs, often for low volume niche applications, or correspond to the translational phase of new tests and treatments, often extremely relevant for patient care. As some commercial tests may disappear with the IVDR roll-out, many will require urgent LDT replacement. The workload will also depend on which modifications to commercial tests turns them into an LDT, and on how national legislators and competent authorities (CA) will handle new competences and responsibilities. We discuss appropriate interpretation of ISO 15189 to cover IVDR requirements. Selected cases illustrate LDT implementation covering medical needs with commensurate management of risk emanating from intended use and/or design of devices. Unintended collateral damage of the IVDR comprises loss of non-profitable niche applications, increases of costs and wasted resources, and migration of innovative research to more cost-efficient environments. Taking into account local specifics, the legislative framework should reduce the burden on and associated opportunity costs for the health care system, by making diligent use of existing frameworks.

Developing and testing a new tool to foster wind energy sector industrial skills.

The wind energy sector has seen an increasing growth in the last decade and this is foreseen to continue in the next years. This has posed several challenges in terms of skilled and prepared professionals that have always to be up to date in an industry that is constantly changing. Thus, teaching tools have gained an increasing interest. The present research reviewed the state of the art in terms of digital interactive training tools pinpointing that the existing options do not feature the user involvement in the development of the training material. Hence, the main aim of this paper is to develop and test an innovative method based on gamification to increase wind energy sector industrial skills, providing a digital interactive environment in the form of a new user-friendly software that can allow its users to train and contribute to the teaching and learning contents. The first methodological step deals with the associated background studies that were required at strategy implementation and development stages, including market analysis and technology trade-offs, as well as the general structure and the implementation steps of the software design. Obtained results pinpointed that with minimal use of web-based database and network connectivity, a mobile phone application could work in the form of a time-scored quiz application that remotely located staff at wind energy farms could benefit from. The technological innovation brought by this research will substantially improve the service of training, allowing a more dynamic formative management contributing to an improvement in the competitiveness and a step towards excellence for the whole sector.

Novel indicators to better monitor the collection and recovery of (critical) raw materials in WEEE: Focus on screens.

Currently, in the European Union (EU), e-waste chain performance is assessed by technical indicators that aim to ensure system compliance with collection and recovery targets set by the WEEE Directive. This study proposes indicators to improve WEEE flow monitoring beyond the current overall weight-based approach, including complementary flows and treatment performance. A case study focused on the screen category in France is presented. In 2017, the collection rate of cathode-ray tube screens (CRT) was 68%, while for flat panel display (FPD) generated only 14% was collected. CRT screens have less precious and critical materials than FDP. Thus, elements like cobalt and gold highly concentrated in FPD, have a collection rate two to four times lower than elements such as copper (37%) which represents a high proportion in CRTs. Recycling is the main treatment in France. Nevertheless, the recycling rate per element varies significantly due to the low collection, and also the lack of technology and/or secondary raw materials market. The elements with higher recycling rates are base metals such as copper (28%), followed by precious metals like silver (23%), and gold (13%). Except for palladium, the recycling rate of the critical raw materials targeted in the study ranged from 6% (cobalt) to 0% (e.g. neodymium and indium). The results stress the need for indicators to support the development of WEEE chain from waste management to secondary (critical) raw materials suppliers.

Ecosystem services accounts: Valuing the actual flow of nature-based recreation from ecosystems to people.

Natural capital accounting aims to measure changes in the stock of natural assets (i.e., soil, air, water and all living things) and to integrate the value of ecosystem services into accounting systems that will contribute to better ecosystems management. This study develops ecosystem services accounts at the European Union level, using nature-based recreation as a case study and following the current international accounting framework: System of Environmental-Economic Accounting - Experimental Ecosystem Accounting (SEEA EEA). We adapt and integrate different biophysical and socio-economic models, illustrating the workflow necessary for ecosystem services accounts: from a biophysical assessment of nature-based recreation to an economic valuation and compilation of the accounting tables. The biophysical assessment of nature-based recreation is based on spatially explicit models for assessing different components of ecosystem services: potential, demand and actual flow. Deriving maps of ecosystem service potential and demand is a key step in quantifying the actual flow of the service used, which is determined by the spatial relationship (i.e., proximity in the case of nature-based recreation) between service potential and demand. The nature-based recreation accounts for 2012 show an actual flow of 40 million potential visits to 'high-quality areas for daily recreation', with a total value of EUR 50 billion. This constitutes an important contribution of ecosystems to people's lives that has increased by 26% since 2000. Practical examples of ecosystem services accounts, as shown in this study, are required to derive recommendations and further develop the conceptual and methodological framework proposed by the SEEA EEA. This paper highlights the importance of using spatially explicit models for ecosystem services accounts. Mapping the different components of ecosystem services allows proper identification of the drivers of changes in the actual service flow derived from ecosystems, socio-economic systems and/or their spatial relationship. This will contribute to achieving one of the main goals of ecosystem accounts, namely measuring changes in natural capital, but it will also support decision-making that targets the enhancement of ecosystems, their services and the benefits they provide.

Dietary fibre in Europe: current state of knowledge on definitions, sources, recommendations, intakes and relationships to health.

Research into the analysis, physical properties and health effects of dietary fibre has continued steadily over the last 40-50 years. From the knowledge gained, countries have developed guidelines for their populations on the optimal amount of fibre to be consumed each day. Food composition tables from many countries now contain values for the dietary fibre content of foods, and, from these, combined with dietary surveys, population intakes have been determined. The present review assessed the uniformity of the analytical methods used, health claims permitted, recommendations and intakes, particularly from national surveys across Europe and around the world. It also assessed current knowledge on health effects of dietary fibre and related the impact of different fibre types on health. The overall intent was to be able to provide more detailed guidance on the types of fibre which should be consumed for good health, rather than simply a total intake figure, the current situation. Analysis of data indicated a fair degree of uniformity in the definition of dietary fibre, the method used for analysis, the recommended amount to be consumed and a growing literature on effects on digestive health and disease risk. However, national dietary survey data showed that intakes do not reach recommendations and very few countries provide guidance on the types of fibre that are preferable to achieve recommended intakes. Research gaps were identified and ideas suggested to provide information for more detailed advice to the public about specific food sources that should be consumed to achieve health benefits.

Changing paradigms in bioequivalence trials submitted to the EMA for evaluation - A clinical and regulatory perspective.

BACKGROUND: The selection of a robust bioequivalence (BE) study designs for registering a generic product remains still a hard task. This task is still challenging despite the fact that generic products are much needed by health care providers in economical terms. Thus, BE study designs could be a means to allow companies to reduce costs and reach the market earlier. We therefore investigated whether different approaches in various products assessed by the European Medicines Agency during the approval phase resulted in a reduction in resources required to show bioequivalence for different medicinal products. METHODS: European Public Assessment Reports (EPARs) for off-patent medicinal products authorised within the European Union (EU) through the centralised procedure during the period 2007-2015 were retrieved and reviewed to identify the clinical studies that resulted in fewer number of subjects, the number of centres or trial duration versus the two-period crossover design. RESULTS: 7 studies out of 108 were considered as having benefitted from having a different design. Differences noted included having a different dose allocation scheme, having a different number of dosing periods, having a different number of treatment arms, and having one study evaluating different strengths. Benefits noted included a decrease in the number of subjects and centres required, decreases in study duration and a reduced number of studies required to demonstrate bioequivalence. CONCLUSION: Bioequivalence studies can be designed in a specific manner to require fewer resources to carry out. Fewer resources required to register a medicinal product, could impart an advantage to companies (such as to be first on the market) or could even translate to making medicines more accessible (such as cheaper) to patients.

Composition differences between organic and conventional meat: a systematic literature review and meta-analysis.

Demand for organic meat is partially driven by consumer perceptions that organic foods are more nutritious than non-organic foods. However, there have been no systematic reviews comparing specifically the nutrient content of organic and conventionally produced meat. In this study, we report results of a meta-analysis based on sixty-seven published studies comparing the composition of organic and non-organic meat products. For many nutritionally relevant compounds (e.g. minerals, antioxidants and most individual fatty acids (FA)), the evidence base was too weak for meaningful meta-analyses. However, significant differences in FA profiles were detected when data from all livestock species were pooled. Concentrations of SFA and MUFA were similar or slightly lower, respectively, in organic compared with conventional meat. Larger differences were detected for total PUFA and n-3 PUFA, which were an estimated 23 (95 % CI 11, 35) % and 47 (95 % CI 10, 84) % higher in organic meat, respectively. However, for these and many other composition parameters, for which meta-analyses found significant differences, heterogeneity was high, and this could be explained by differences between animal species/meat types. Evidence from controlled experimental studies indicates that the high grazing/forage-based diets prescribed under organic farming standards may be the main reason for differences in FA profiles. Further studies are required to enable meta-analyses for a wider range of parameters (e.g. antioxidant, vitamin and mineral concentrations) and to improve both precision and consistency of results for FA profiles for all species. Potential impacts of composition differences on human health are discussed.

The use of animal by-products in a circular bioeconomy: Time for a TSE road map 3?

In 2005 and 2010, the European Commission (EC) published two subsequent 'Road Maps' to provide options for relaxation of the bans on the application of animal proteins in feed. Since then, the food production system has changed considerably and demands for more sustainability and circularity are growing louder. Many relaxations envisioned in the second Road Map have by now been implemented, such as the use of processed animal proteins (PAPs) from poultry in pig feed and vice versa. However, some legislative changes, in particular concerning insects, had not been foreseen. In this article, we present a new vision on legislation for increased and improved use of animal by-products. Six current legislative principles are discussed for the bans on animal by-products as feed ingredients: feed bans; categorization of farmed animals; prohibition unless explicitly approved; approved processing techniques, the categorization of animal by-products, and monitoring methods. We provide a proposal for new guiding principles and future directions, and several concrete options for further relaxations. We argue that biological nature of farmed animals in terms of dietary preferences should be better recognised, that legal zero-tolerance limits should be expanded if safe, and that legislation should be revised and simplified.

Covid-19 related factors to food security and dietary diversity among urban households in western Oromia, Ethiopia.

Background: This study aims to assess factors associated with food security and dietary diversity among poor urban households of western Oromia, Ethiopia, after the outbreak of the Covid-19 pandemic. Method: A cross-sectional, community-based study was conducted in May to June 2021 with 361 poor urban households in the Horo Guduru Wollega zone, western Oromia, Ethiopia. A pre-tested structured questionnaire was used to collect primary data. Twenty-four hour reminder points were used to assess household dietary diversity, and household food security was assessed using the Household Food Insecurity Access Scale tool. Data were evaluated using the statistical software SPSS version 25.0. Results: This study showed a prevalence of food insecurity in households of 59.6%. The mean and standard deviation of household dietary diversity values were 4.19 ± 1.844. Family size (AOR = 8.5; 95% CI:3.295-21.92), monthly income (AOR = 3.52; 95% CI; 1.771-6.986), dietary diversity (AOR = 8.5; 95% CI; 3.92-18.59), knowledge (AOR = 3.0, 95% CI = 1.08-)8.347), attitude (AOR = 8.35, 95% CI:3.112-22.39) and practices against Covid-19 (AOR = 2.12; 95% CI:1.299-11.4) were factors significantly associated with food insecurity. Variables like educational status (AOR = 3.46; 95% CI:1.44-8.312), increased family size after the Covid-19 pandemic (AOR = 2.26; 95% CI:1.02-5.04), food security (AOR = 6.7; 95% CI:4.01-19.01), knowledge (AOR = 3.96; 95% CI:1.57-10.0), attitude (AOR = 3.9; 95% CI:1.75-8.82) and practices toward coronavirus (AOR = 2.23; 95% CI:2.18-23.95) were predictors significantly associated with dietary diversity. Conclusion: This study concluded that family size, monthly income, and dietary diversity were factors contributed to household food security. On the other hand, variables such as educational status, family size, and food security were highly relevant factors for dietary diversity after the outbreak of the Covid-19 pandemic. Knowledge, attitudes, and practices were also variables related to both household food security and dietary diversity. Therefore, immediate interventions such as nutrition-specific interventions can be suggested to address food insecurity and problems of inadequate food intake in poor urban households. In addition, governmental and non-governmental organizations should raise awareness and policies to support those at higher risk by developing affordable, sustainable and targeted social protection systems that ensure food security and adequate dietary intake at the household level.

Quality assessment of raw and pasteurized milk in Gondar city, Northwest Ethiopia: A laboratory-based cross-sectional study.

Milk is a complete and highly nutritious source of food for human beings. However, in many developing countries, including Ethiopia, the quality of milk products has become a major health concern for consumers, particularly for infants and children. Therefore, the aim of the present study was to assess the quality of raw and pasteurized milk marketed in Gondar city, Northwest Ethiopia. A laboratory-based cross-sectional study was conducted on 90 milk samples. The samples were chosen using a simple random sampling technique. For statistical analysis, ANOVA and the Pearson correlation coefficient were used. The specific gravity of pasteurized milk, farm milk, and milk vendors were found to be 1.021, 1.027, and 1.026, respectively. Farm milk, milk vendors, and pasteurized milk had fat contents of 3.38%, 3.22%, and 3.09%, respectively. The total bacterial count in pasteurized milk, farm milk, and milk vendors was found to be 7.08, 6.73, and 6.94 log10 CFU/mL, respectively. In raw milk, hydrogen peroxide (7.7%), formalin (7.7%), and water (3.8%) were found, whereas in pasteurized milk, hydrogen peroxide (50%), formalin (50%), and water (19.8%) were found. Based on the findings of this study, the quality of both raw and pasteurized milk was found to be poor as per the milk quality standards. This may cause significant public health-related problems. Therefore, an appropriate intervention should be conducted to improve the quality of milk.

Bisphenols, but not phthalate esters, modulate gene expression in activated human MAIT cells in vitro.

One route of human exposure to environmental chemicals is oral uptake. This is primarily true for chemicals that may leach from food packaging materials, such as bisphenols and phthalate esters. Upon ingestion, these compounds are transported along the intestinal tract, from where they can be taken up into the blood stream or distributed to mucosal sites. At mucosal sites, mucosal immune cells and in the blood stream peripheral immune cells may be exposed to these chemicals potentially modulating immune cell functions. In the present study, we investigated the impact of three common bisphenols and two phthalate esters on mucosal-associated invariant T (MAIT) cells in vitro, a frequent immune cell type in the intestinal mucosae and peripheral blood of humans. All compounds were non-cytotoxic at the chosen concentrations. MAIT cell activation was only slightly affected as seen by flow cytometric analysis. Phthalate esters did not affect MAIT cell gene expression, while bisphenol-exposure induced significant changes. Transcriptional changes occurred in ∼ 25 % of genes for BPA, ∼ 22 % for BPF and ∼ 8 % for BPS. All bisphenols down-modulated expression of CCND2, CCL20, GZMB and IRF4, indicating an effect on MAIT cell effector function. Further, BPA and BPF showed a high overlap in modulated genes involved in cellular stress response, activation signaling and effector function suggesting that BPF may not be safe substitute for BPA.

Quarantine and testing strategies to ameliorate transmission due to travel during the COVID-19 pandemic: a modelling study.

BACKGROUND: Numerous countries have imposed strict travel restrictions during the COVID-19 pandemic, contributing to a large socioeconomic burden. The long quarantines that have been applied to contacts of cases may be excessive for travel policy. METHODS: We developed an approach to evaluate imminent countrywide COVID-19 infections after 0-14-day quarantine and testing. We identified the minimum travel quarantine duration such that the infection rate within the destination country did not increase compared to a travel ban, defining this minimum quarantine as "sufficient." FINDINGS: We present a generalised analytical framework and a specific case study of the epidemic situation on November 21, 2021, for application to 26 European countries. For most origin-destination country pairs, a three-day or shorter quarantine with RT-PCR or antigen testing on exit suffices. Adaptation to the European Union traffic-light risk stratification provided a simplified policy tool. Our analytical approach provides guidance for travel policy during all phases of pandemic diseases. INTERPRETATION: For nearly half of origin-destination country pairs analysed, travel can be permitted in the absence of quarantine and testing. For the majority of pairs requiring controls, a short quarantine with testing could be as effective as a complete travel ban. The estimated travel quarantine durations are substantially shorter than those specified for traced contacts. FUNDING: EasyJet (JPT and APG), the Elihu endowment (JPT), the Burnett and Stender families' endowment (APG), the Notsew Orm Sands Foundation (JPT and APG), the National Institutes of Health (MCF), Canadian Institutes of Health Research (SMM) and Natural Sciences and Engineering Research Council of Canada EIDM-MfPH (SMM).

Meta-analyses of molecular seafood studies identify the global distribution of legal and illegal trade in CITES-regulated European eels.

Authentication of seafood products by means of molecular techniques has relevance for food sustainability and security, as well as international trade regulation, linked to transparency in food manufacturing. We focus on the molecular detection of the depleted European eel Anguilla anguilla, a species for which strict international trade regulations are in place since 2010, in studies conducted outside Europe. We found thirteen studies from nine countries (Canada, China, Japan, Malaysia, Peru, Singapore, South Korea, Taiwan, and USA) for which, on average, 59 ± 28% of the 330 sequenced eel samples comprised European eel. Only China, Japan, South Korea, and USA reported the import of European eel in the years prior to sampling. The authentication of eel products demonstrates a global, in part illegal, trade in European eel, covered up by incomplete or fraudulent labelling. This calls into question the compliance with existing national and international trade regulations and its implications for food safety and sustainability.

Operating, financial and investment impacts of Covid-19 in SMEs: Public policy demands to sustainable recovery considering the economic sector moderating effect.

Currently, many institutions and academics are working to establish strategies of economic recovery with the aim of mitigating the short- and long-term impacts of the COVID-19 crisis. The main aim of this study is to analyze how this crisis has impacted Spanish SMEs, considering their operating, financial, and investment activities. We also analyze the initiatives or public policies that SME managers consider necessary in order to face the effects of COVID-19. To do this, an empirical study has been carried out based on information from 612 Spanish SMEs, estimating a PLS research model and multigroup analysis that considers the activity sector as a moderating variable. The results are useful to companies and different economic and social agents, providing information to facilitate decision-making to overcome pandemic crisis mainly in the economic and strategic spheres.

The prehospital care experiences and perceptions of ambulance staff and Eastern European patients: An interview study in Lincolnshire, UK.

Background: EU enlargement after 2004 was a major factor in increasing Eastern European migration to the UK. This population requires access to high quality public services generally, and ambulance services more specifically. To understand how Eastern European migrants use ambulance care, this study explored the perceptions and experiences of ambulance staff and the Eastern European patients themselves. Methods: We undertook qualitative semi-structured interviews across Lincolnshire. Purposive and maximum variation sampling ensured that participants were knowledgeable about Eastern European patients' use of ambulance care and were demographically diverse. Data were analysed using framework analysis. Results: There were interviews with 15 ambulance staff and 12 Eastern European patients. A staff interviewee problematised "Health Tourism", which suggests that migrants deliberately exploit state-funded healthcare. However, most disagreed. Patient interviewees often undertook medical travel to access healthcare in response to perceived healthcare problems in the UK. Medical travel increased the likelihood of ambulance staff encountering foreign medication. Variable quality of, and access to, professional interpreters prompted patients to rely instead on informal interpreters. Patients did not register with GPs perhaps due to limited understanding of how the NHS worked. This led to inappropriate use of ambulance services. Recommendations for service delivery improvements included: Eastern European language information on how and when to use ambulance care; improving GP registration; and greater engagement between the ambulance service and Eastern European communities. Conclusions: Frequent medical travel can limit how Eastern Europeans acculturate to the NHS and anchor roots in the UK. Acculturation is about how migrant cultures adjust to the host country. This is not assimilation, where they dilute their cultural identity. Language and communication barriers, as well as inadequate availability and quality of interpreting services, can impede patient-staff dialogue in time-critical emergencies.

Data for the modelling of the future power system with a high share of variable renewable energy.

Energy and power system models have become necessary tools that provide challenges and technical and economic solutions for integrating high shares of Variable Renewable Energy. Models are focused on analysing strategies of power systems to achieve their decarbonisation targets. The data presented in this paper includes the model algorithm, inputs, equations, modelling assumptions, supplementary materials, and results of the simulations supporting the research article titled "Facing the high share of variable renewable energy in the power system: flexibility and stability requirements". The analysis is based on data from the system operator of one of the European Union member states (Spain). The developed model allows making projections and calculations to obtain the power generation of each technology, the international interconnections, inertia, emissions, system costs and flexibility requirements of new technologies. These data can be used for energy policy development or decision making on power capacity and the balancing needs of the future power system.

Advances in spray products for skin regeneration.

To date, skin wounds are still an issue for healthcare professionals. Although numerous approaches have been developed over the years for skin regeneration, recent advances in regenerative medicine offer very promising strategies for the fabrication of artificial skin substitutes, including 3D bioprinting, electrospinning or spraying, among others. In particular, skin sprays are an innovative technique still under clinical evaluation that show great potential for the delivery of cells and hydrogels to treat acute and chronic wounds. Skin sprays present significant advantages compared to conventional treatments for wound healing, such as the facility of application, the possibility to treat large wound areas, or the homogeneous distribution of the sprayed material. In this article, we review the latest advances in this technology, giving a detailed description of investigational and currently commercially available acellular and cellular skin spray products, used for a variety of diseases and applying different experimental materials. Moreover, as skin sprays products are subjected to different classifications, we also explain the regulatory pathways for their commercialization and include the main clinical trials for different skin diseases and their treatment conditions. Finally, we argue and suggest possible future trends for the biotechnology of skin sprays for a better use in clinical dermatology.

Approach to assess the performance of waste management systems towards a circular economy: waste management system development stage concept (WMS-DSC).

In this paper a novel holistic approach to assess the performance of waste management systems (WMSs) is presented. The so called WMS development stage concept (WMS-DSC) can be used by practitioners or decision makers to assess primarily the WMS at the municipal level. The WMS categorization into development stages notably enables a clear identification of symptoms, the causes of possible waste mismanagement and potential measures for improvement. The concept can be used to (i) assess the status quo of a WMS and, based on this, identify possible measures for implementation; (ii) check whether relevant system conditions to implement a specific measure are met; (iii) monitor the progress of a WMS; and (iv) compare the WMSs of different cities. The concept consists of five development stages: stage 1 - absence or lack of essential elements of waste management; stage 2 - reliable collection and improved landfill sites; stage 3 - separate collection and sorting; stage 4 - expansion of the recycling industry; and stage 5 - circular economy (CE), waste as a resource. While stage 1 describes the absence of or a very immature and malfunctioning WMS, stage 5 stands for a fully implemented CE. By equating the highest stage to the objectives that have evolved today globally for a sustainable CE, this concept can be used to identify targets and the most suitable steps for an individual WMS towards a future best practice of CE.•A holistic approach to assess waste management systems' performance is presented.•A benchmarking tool to estimate the circular economy (CE) evolvement in cities.•Usable for cities both in the Global North and South to identify CE potentials.

Safety evaluation study of lincomycin and spectinomycin hydrochloride intramuscular injection in chickens.

This study aimed to investigate the nonclinical safety of lincomycin and spectinomycin hydrochloride (LC-SPH) intramuscular (i.m) doses on target animals (chickens) to provide guidelines for dose level design and side effect monitoring in clinical trials. A total of 80 healthy Arbor Acres plus broiler chicks were completely randomized and blindly divided into four treatment groups (control, one-time dose, three-time dose, and five-time dose) of 20 chicks each (20 chickens per group). At the age of day 15, all chickens (except the control group) were administered LC-SPH intramuscularly (chest muscles) at different doses of 20 mg/kg.bw, 60 mg/kg.bw, and 100 mg/kg.bw respectively for 9 consecutive days recommended by veterinary international cooperation on harmonization (VICH) guidelines. The chickens had ad libitum access to antibiotic-free feed and water. Feeding chickens were observed twice a day throughout the study. The drug safety was evaluated by complete blood count, biochemical parameters, histopathological, clinical signs, body weight gain, and feed conversion ratio (FCR). Hence, considering the minor toxicity of 60 mg/kg, our results reveal that intramuscular injection of at least 20 mg/kg body weight has no effects on growth performance, clinical blood parameters, organ coefficient, and histopathological parameters. Thus, a combination of LC-SPH 20 mg/kg body weight i.m injection investigated safe followed daily administration for nine consecutive days in healthy chickens. It is concluded that the experimental results support the safety of 20 mg/kg body weight in combination for the further clinical research study.

Advanced Therapy medicinal products for autologous chondrocytes and comparison of regulatory systems in target countries.

Introduction: Autologous chondrocytes (ACs) are Human cell/tissue-based products used for the treatment of joint cartilage defects. Regulatory agencies have established regulations related to ACs to ensure their safety and efficacy. This study investigated the status and characteristics of ACs approved worldwide. Furthermore, the AC-related regulations were compared by country to provide reference materials for the development of product approval procedures. Methods: This study reviewed the current status of global AC products over the past 20 years by referring to the AC approval list provided on the International Society for Cell & Gene Therapy (ISCT) website. Based on the review report provided by the regulatory agencies that approved the products, major nonclinical/clinical data and product characteristics were reviewed; and the classification and definition of ACs and the approval review procedures were compared through the regulatory agencies' websites. The development status of ACs was also analyzed using a clinical trial registration site. Results: Eight ACs were approved during the study period in Europe, the US, Japan, Australia, and Korea. Two products were withdrawn owing to marketability problems. Human cell/tissue-based products in each country are classified and defined distinguished from biopharmaceuticals, but the approval process for both products is the same. The approval period differs by country, with an average of 282.4 days and the shortest being in Korea (115 days). On Clinical Trials.gov, we screened 46 clinical trials related to ACs, which were conducted in Europe (41%), Korea (20%), and the US (17%). The knee accounted for the largest portion of the indication (37/46, 80%), followed by the ankle or hip joints. Measurements of improvements in function and pain were the main endpoints used to evaluate the efficacy of ACs. Observational studies were conducted to confirm the long-term safety of these products. Conclusions: This is the first study comparing the current status and characteristics of globally approved AC products, as well as their classification and definition by country. In the past two decades, clinical trials have been conducted on the application of ACs in tissue engineering to treat joint cartilage defects. ACs are expected to be used for the treatment of cartilage defect diseases.