Digital technologies to unlock safe and sustainable opportunities for medical device and healthcare sectors with a focus on the combined use of digital twin and extended reality applications: A review.

Medical devices have increased in complexity where there is a pressing need to consider design thinking and specialist training for manufacturers, healthcare and sterilization providers, and regulators. Appropriately addressing this consideration will positively inform end-to-end supply chain and logistics, production, processing, sterilization, safety, regulation, education, sustainability and circularity. There are significant opportunities to innovate and to develop appropriate digital tools to help unlock efficiencies in these important areas. This constitutes the first paper to create an awareness of and to define different digital technologies for informing and enabling medical device production from a holistic end-to-end life cycle perspective. It describes the added-value of using digital innovations to meet emerging opportunities for many disposable and reusable medical devices. It addresses the value of accessing and using integrated multi-actor HUBs that combine academia, industry, healthcare, regulators and society to help meet these opportunities. Such as cost-effective access to specialist pilot facilities and expertise that converges digital innovation, material science, biocompatibility, sterility assurance, business model and sustainability. It highlights the marked gap in academic R&D activities (PRISMA review of best publications conducted between January 2010 and January 2024) and the actual list of U.S. FDA's approved and marketed artificial intelligence/machine learning (AI/ML), and augmented reality/virtual reality (AR/VR) enabled-medical devices for different healthcare applications. Bespoke examples of benefits underlying future use of digital tools includes potential implementation of machine learning for supporting and enabling parametric release of sterilized products through efficient monitoring of critical process data (complying with ISO 11135:2014) that would benefit stakeholders. This paper also focuses on the transformative potential of combining digital twin with extended reality innovations to inform efficiencies in medical device design thinking, supply chain and training to inform patient safety, circularity and sustainability.

Integrated Devices: A New Regulatory Pathway to Promote Revolutionary Innovation.

Policy Points Current medical device regulatory frameworks date back half a century and are ill suited for the next generation of medical devices that involve a significant software component. Existing Food and Drug Administration efforts are insufficient because of a lack of statutory authority, whereas international examples offer lessons for improving and harmonizing domestic medical device regulatory policy. A voluntary alternative pathway built upon two-stage review with individual component review followed by holistic review for integrated devices would provide regulators with new tools to address a changing medical device marketplace.

Percutaneous electrical nerve field stimulation for adolescents with irritable bowel syndrome: Cost-benefit and cost-minimization analysis.

Abdominal pain drives significant cost for adolescents with irritable bowel syndrome (IBS). We performed an economic analysis to estimate cost-savings for patients' families and healthcare insurance, and health outcomes, based on abdominal pain improvement with percutaneous electrical nerve field stimulation (PENFS) with IB-Stim® (Neuraxis). We constructed a Markov model with a 1-year time horizon comparing outcomes and costs with PENFS versus usual care without PENFS. Clinical outcomes were derived from a sham-controlled double-blind trial of PENFS for adolescents with IBS. Costs/work-productivity impact for parents were derived from appropriate observational cohorts. PENFS was associated with 18 added healthy days over 1 year of follow-up, increased annual parental wages of $5,802 due to fewer missed work days to care for the child, and $4744 in cost-savings to insurance. Percutaneous electrical field nerve stimulation for adolescents with IBS appears to yield significant cost-savings to patients' families and insurance.

Pediatric parenteral nutrition and hydroperoxide toxicity: Evaluation of the effectiveness of photoprotection medical devices.

Exposure of parenteral nutrition (PN) to light induces hydroperoxide (HPO) formation whose toxicity, especially in pediatrics, is documented. In this context, we evaluated the efficacy of photoprotection medical devices used in our institution to protect PN from degradation after two different exposures to light. A mixed oil lipid emulsion (Smoflipid®) in standard or opaque syringes and a ternary PN mixture bags (Numetah®) with or without opaque overwrap were exposed for at least 420 min to a xenon lamp. Samples of Smoflipid® in standard or opaque syringes were also exposed for 24 h to conditions reproducing those of a neonatal intensive care unit. The use of opaque syringes for Smoflipid® administration or opaque overwraps for Numetah® administration reduced HPO formation by an average of 14% and 40%, respectively, compared to standard conditions after at least 420 min to a xenon lamp. When Smoflipid® samples were administered with standard or opaque syringes and exposed to a phototherapy lamp, the fold-change in the HPO concentration increased, respectively, by 6.3 or 5.4 at 24 h compared with syringes unexposed to phototherapy lamp. Although the observed differences were non-significant, it nonetheless appears prudent to use photoprotection of PN during administration, particularly in patients with immature or compromised antioxidant capacity.

A comprehensive roadmap for MedTech innovations uptake into the public healthcare system in India.

Background: The burden of communicable, non-communicable diseases and reproductive maternal, newborn, child & adolescent health in India, reflects the necessity to develop tailored solutions. The plethora of MedTech innovations has provided healthcare facilities with more effective, affordable and accessible healthcare for people across the country. However, in spite of the Make-in-India scheme in the country, the indigenously developed healthcare technology is far from making an impact on the healthcare system. Objective: To present a roadmap for MedTech innovations for their successful deployment into the public healthcare system. Methodology: In addition to the literature review, recommendations were included from several stakeholders such as innovators, manufacturers, policymakers, subject matter experts, funding organizations, State health officials etc. Results and conclusion: The journey of healthcare innovation from need identification to ideation, to prototyping and validation has paved the way towards the de novo design that caters to unmet needs. Innovations at the advanced technology readiness level (TRL 7/8 and above) demand a holistic and multidisciplinary approach which includes clinical validation, regulatory approval and Health technology assessment. The deployment of healthcare technology into the public healthcare system must consider resources (e.g., time, staff, budget, investment policies), ethical concerns (privacy, security, regulations, ownership), governance (policy, accountability, responsibility etc.), and Skills (capabilities, culture, etc.). The technologies are considered for field trials before the uptake in the public health system. Technology can be a key tool in achieving Universal Health Coverage but its use has to be strategic, judicious, and cognizant of issues around privacy and patient rights.

Safety profile of herbal medicines submitted for marketing authorization in Tanzania: a cross-sectional retrospective study.

BACKGROUND: The popular use of herbal medicines necessitates national regulatory authorities to have efficient mechanisms for the control of these products including marketing authorization (MA) and safety follow-up. Herbal medicines like conventional medicines require assessment of efficacy, safety and quality information before MA can be granted. However, the complete proof of safety is mainly based on the history of the long-term traditional use. Herbal medicines can cause adverse reactions due to various factors and thus require clinical trials to ensure their safety. Herbal medicines treatment practices involve combinations of different plants to achieve the desired effect while multiple herbal components have been known to cause herbal-herbal toxicity and interactions due to variety of complex active ingredients in plants. Compliance with regulatory requirements on herbal medicines has been shown to be difficult for manufacturers since different countries have different regulatory requirements with wide variations which results in the MA of very few herbal medicines. Limited studies on dossiers of marketing authorization of herbal medicines have been performed in other countries, with no studies in African regulatory system settings. The aim of this study is to determine the type of safety documentation that is submitted on herbal medicines application dossiers to support MA in Tanzania. METHODS: A cross-sectional retrospective study of herbal medicines dossiers submitted at the Tanzania Medicines and Medical Devices Authority from 2009 to 2020 was conducted. RESULTS: As many as 75% of the herbal products applications were combination products made by more than one herbal substance or plant. Out of 84 dossiers subjected to analysis the majority did not provide evidence of preclinical (55%) and clinical safety data (68%). Evidence of safety data in humans was mostly from the literature (70%) and not manufacturers' clinical studies. Quality parameters with safety implications were not included in 48% and 23% of the active herbal substance and finished product specifications, respectively. CONCLUSION: Analysis of the herbal medicine dossiers submitted showed major deficiencies of safety data to support MA. Manufactures need to provide evidence to support the safety of their products for evidence-based regulatory decisions and to avoid multiple reviews of the applications.

Facile Modification of Medical-Grade Silicone for Antimicrobial Effectiveness and Biocompatibility: A Potential Therapeutic Strategy against Bacterial Biofilms.

A one-step modification of biomedical silicone tubing with N,N-dimethyltetradecylamine, C14, results in a composition designated WinGard-1 (WG-1, 1.1 wt % C14). A surface-active silicon-amine phase (SAP) is proposed to account for increased wettability and increased surface charge. To understand the mechanism of antimicrobial effectiveness, several procedures were employed to detect whether C14 leaching occurred. An immersion-growth (IG) test was developed that required knowing the bacterial Minimum Inhibitory Concentrations (MICs) and Minimum Biocidal Concentrations (MBCs). The C14 MIC and MBC for Gm- uropathogenic E. coli (UPEC), commonly associated with catheter-associated urinary tract infections (CAUTI), were 10 and 20 µg/mL, respectively. After prior immersion of WG-1 silicone segments in a growth medium from 1 to 28 d, the IG test for the medium showed normal growth for UPEC over 24 h, indicating that the concentration of C14 must be less than the MIC, 10 µg/mL. GC-MS and studies of the medium inside and outside a dialysis bag containing WG-1 silicone segments supported de minimis leaching. Consequently, a 5 log UPEC reduction (99.999% kill) in 24 h using the shake flask test (ASTM E2149) cannot be due to leaching and is ascribed to contact kill. Interestingly, although the MBC was greater than 100 µg/mL for Pseudomonas aeruginosa, WG-1 silicone affected an 80% reduction via a 24 h shake flask test. For other bacteria and Candida albicans, greater than 99.9% shake flask kill may be understood by proposing increased wettability and concentration of charge illustrated in the TOC. De minimis leaching places WG-1 silicone at an advantage over conventional anti-infectives that rely on leaching of an antibiotic or heavy metals such as silver. The facile process for preparation of WG-1 silicone combined with biocidal effectiveness comprises progress toward the goals of device designation from the FDA for WG-1 and clearance.

Plurigin Ovules and Plurigin Solution in the Treatment of Vulvovaginal Atrophy in Menopausal Women: A Retrospective Monocentric Observational Study.

Background and Objectives: Vulvovaginal atrophy (VVA) is a condition that affects a large number of women and can significantly impact their quality of life. While several treatments are currently available for VVA, there are potential risks associated with their use. Non-hormonal medical devices have been developed to treat VVA, offering a potential alternative to traditional hormone-based therapies. This study aimed to evaluate the safety and efficacy of the combined treatment with two medical devices, Plurigin Ovules and Plurigin Solution, used as an adjuvant in the treatment of VVA. Materials and Methods: This is a retrospective, observational study. Data were collected from medical records of all patients who received the combination treatment of both medical devices as part of normal clinical practice for the treatment of VVA. The performance of the medical devices was analyzed using the THIN Prep. A comprehensive physical examination and gynecological evaluation were conducted before the initiation of treatment (day 0), as well as at follow-up 1 (day 90), follow-up 2 (day 180), and follow-up 3 (day 270). Data analysis included descriptive analysis and statistical tests. Results: The study included 76 women (mean age: 59 years). At follow-up 3, 61% of the respondents demonstrated improved THIN Prep results and symptom resolution (p < 0.001; CI [0.5003, 0.7197]). Moreover, the percentage of patients reporting dyspareunia, burning, and irritation decreased over the course of the study, with the majority of patients reporting no symptoms at follow-up 3. Conclusions: The use of Plurigin Ovules plus Plurigin Solution may be an effective treatment option for VVA, improving vaginal health, alleviating symptoms, and improving sexual function, leading to improved quality of life for women suffering from this condition. However, the study has limitations, such as its retrospective nature, and further studies are needed to confirm the efficacy and safety of these devices.

Phyto-assisted synthesis of zinc oxide nanoparticles for developing antibiofilm surface coatings on central venous catheters.

Medical devices such as Central Venous Catheters (CVCs), are routinely used in intensive and critical care settings. In the present scenario, incidences of Catheter-Related Blood Stream Infections (CRBSIs) pose a serious challenge. Despite considerable advancements in the antimicrobial therapy and material design of CVCs, clinicians continue to struggle with infection-related complications. These complications are often due colonization of bacteria on the surface of the medical devices, termed as biofilms, leading to infections. Biofilm formation is recognized as a critical virulence trait rendering infections chronic and difficult to treat even with 1,000x, the minimum inhibitory concentration (MIC) of antibiotics. Therefore, non-antibiotic-based solutions that prevent bacterial adhesion on medical devices are warranted. In our study, we report a novel and simple method to synthesize zinc oxide (ZnO) nanoparticles using ethanolic plant extracts of Eupatorium odoratum. We investigated its physio-chemical characteristics using Field Emission- Scanning Electron Microscopy and Energy dispersive X-Ray analysis, X-Ray Diffraction (XRD), Photoluminescence Spectroscopy, UV-Visible and Diffuse Reflectance spectroscopy, and Dynamic Light Scattering characterization methods. Hexagonal phase with wurtzite structure was confirmed using XRD with particle size of ∼50 nm. ZnO nanoparticles showed a band gap 3.25 eV. Photoluminescence spectra showed prominent peak corresponding to defects formed in the synthesized ZnO nanoparticles. Clinically relevant bacterial strains, viz., Proteus aeruginosa PAO1, Escherichia coli MTCC 119 and Staphylococcus aureus MTCC 7443 were treated with different concentrations of ZnO NPs. A concentration dependent increase in killing efficacy was observed with 99.99% killing at 500 µg/mL. Further, we coated the commercial CVCs using green synthesized ZnO NPs and evaluated it is in vitro antibiofilm efficacy using previously optimized in situ continuous flow model. The hydrophilic functionalized interface of CVC prevents biofilm formation by P. aeruginosa, E. coli and S. aureus. Based on our findings, we propose ZnO nanoparticles as a promising non-antibiotic-based preventive solutions to reduce the risk of central venous catheter-associated infections.

Suitability of R. pulmo Jellyfish-Collagen-Coated Well Plates for Cytocompatibility Analyses of Biomaterials.

Cytocompatibility analyses of new implant materials or biomaterials are not only prescribed by the Medical Device Regulation (MDR), as defined in the DIN ISO Norm 10993-5 and -12, but are also increasingly replacing animal testing. In this context, jellyfish collagen has already been established as an alternative to mammalian collagen in different cell culture conditions, but a lack of knowledge exists about its applicability for cytocompatibility analyses of biomaterials. Thus, the present study was conducted to compare well plates coated with collagen type 0 derived from Rhizostoma pulmo with plates coated with bovine and porcine collagen. The coated well plates were analysed in vitro for their cytocompatibility, according to EN ISO 10993-5/-12, using both L929 fibroblasts and MC3T3 pre-osteoblasts. Thereby, the coated well plates were compared, using established materials as positive controls and a cytotoxic material, RM-A, as a negative control. L929 cells exhibited a significantly higher viability (#### p < 0.0001), proliferation (## p < 0.01), and a lower cytotoxicity (## p < 0.01 and # p < 0.05)) in the Jellagen® group compared to the bovine and porcine collagen groups. MC3T3 cells showed similar viability and acceptable proliferation and cytotoxicity in all collagen groups. The results of the present study revealed that the coating of well plates with collagen Type 0 derived from R. pulmo leads to comparable results to the case of well plates coated with mammalian collagens. Therefore, it is fully suitable for the in vitro analyses of the cytocompatibility of biomaterials or medical devices.

Electromagnetic field therapy in cardiovascular diseases: A review of patents, clinically effective devices, and mechanism of therapeutic effects.

In recent years, electromagnetic field (EMF) therapy has gathered much attention for its protective effects on cardiovascular functions. From reviewing the literature, it is evident that exposure to specific EMF spectrums, such as static- and extremely low frequency (ELF)- EMFs, by EMF-generating devices can be considered as a safe method for therapeutic means in various cardiovascular diseases, including heart failure, cardiac arrhythmias, and hypertension. This review article will describe registered patents and non-invasive clinically effective devices that generate EMF to target various cardiovascular diseases based on their mechanism of therapeutic effects.

Mass spectrometry-based metabolomic analysis as a tool for quality control of natural complex products.

Metabolomics is an area of intriguing and growing interest. Since the late 1990s, when the first Omic applications appeared to study metabolite's pool ("metabolome"), to understand new aspects of the global regulation of cellular metabolism in biology, there have been many evolutions. Currently, there are many applications in different fields such as clinical, medical, agricultural, and food. In our opinion, it is clear that developments in metabolomics analysis have also been driven by advances in mass spectrometry (MS) technology. As natural complex products (NCPs) are increasingly used around the world as medicines, food supplements, and substance-based medical devices, their analysis using metabolomic approaches will help to bring more and more rigor to scientific studies and industrial production monitoring. This review is intended to emphasize the importance of metabolomics as a powerful tool for studying NCPs, by which significant advantages can be obtained in terms of elucidation of their composition, biological effects, and quality control. The different approaches of metabolomic analysis, the main and basic techniques of multivariate statistical analysis are also briefly illustrated, to allow an overview of the workflow associated with the metabolomic studies of NCPs. Therefore, various articles and reviews are illustrated and commented as examples of the application of MS-based metabolomics to NCPs.

New Method to Implement and Analysis of Medical System in Real Time.

The use of information technology and technological medical devices has contributed significantly to the transformation of healthcare. Despite that, many problems have arisen in diagnosing or predicting diseases, either as a result of human errors or lack of accuracy of measurements. Therefore, this paper aims to provide an integrated health monitoring system to measure vital parameters and diagnose or predict disease. Through this work, the percentage of various gases in the blood through breathing is determined, vital parameters are measured and their effect on feelings is analyzed. A supervised learning model is configured to predict and diagnose based on biometric measurements. All results were compared with the results of the Omron device as a reference device. The results proved that the proposed design overcame many problems as it contributed to expanding the database of vital parameters and providing analysis on the effect of emotions on vital indicators. The accuracy of the measurements also reached 98.8% and the accuracy of diagnosing COVID-19 was 64%. The work also presents a user interface model for clinicians as well as for smartphones using the Internet of things.

Nanosecond Pulsed Electric Field (nsPEF): Opening the Biotechnological Pandora's Box.

Nanosecond Pulsed Electric Field (nsPEF) is an electrostimulation technique first developed in 1995; nsPEF requires the delivery of a series of pulses of high electric fields in the order of nanoseconds into biological tissues or cells. They primary effects in cells is the formation of membrane nanopores and the activation of ionic channels, leading to an incremental increase in cytoplasmic Ca2+ concentration, which triggers a signaling cascade producing a variety of effects: from apoptosis up to cell differentiation and proliferation. Further, nsPEF may affect organelles, making nsPEF a unique tool to manipulate and study cells. This technique is exploited in a broad spectrum of applications, such as: sterilization in the food industry, seed germination, anti-parasitic effects, wound healing, increased immune response, activation of neurons and myocites, cell proliferation, cellular phenotype manipulation, modulation of gene expression, and as a novel cancer treatment. This review thoroughly explores both nsPEF's history and applications, with emphasis on the cellular effects from a biophysics perspective, highlighting the role of ionic channels as a mechanistic driver of the increase in cytoplasmic Ca2+ concentration.

Therapeutic Devices for Motor Symptoms in Parkinson's Disease: Current Progress and a Systematic Review of Recent Randomized Controlled Trials.

Background: Pharmacotherapy is the first-line treatment option for Parkinson's disease, and levodopa is considered the most effective drug for managing motor symptoms. However, side effects such as motor fluctuation and dyskinesia have been associated with levodopa treatment. For these conditions, alternative therapies, including invasive and non-invasive medical devices, may be helpful. This review sheds light on current progress in the development of devices to alleviate motor symptoms in Parkinson's disease. Methods: We first conducted a narrative literature review to obtain an overview of current invasive and non-invasive medical devices and thereafter performed a systematic review of recent randomized controlled trials (RCTs) of these devices. Results: Our review revealed different characteristics of each device and their effectiveness for motor symptoms. Although invasive medical devices are usually highly effective, surgical procedures can be burdensome for patients and have serious side effects. In contrast, non-pharmacological/non-surgical devices have fewer complications. RCTs of non-invasive devices, especially non-invasive brain stimulation and mechanical peripheral stimulation devices, have proven effectiveness on motor symptoms. Nearly no non-invasive devices have yet received Food and Drug Administration certification or a CE mark. Conclusion: Invasive and non-invasive medical devices have unique characteristics, and several RCTs have been conducted for each device. Invasive devices are more effective, while non-invasive devices are less effective and have lower hurdles and risks. It is important to understand the characteristics of each device and capitalize on these.

A framework for designing medical devices resilient to low-resource settings.

BACKGROUND: To date (April 2021), medical device (MD) design approaches have failed to consider the contexts where MDs can be operationalised. Although most of the global population lives and is treated in Low- and Middle-Income Countries (LMCIs), over 80% of the MD market share is in high-resource settings, which set de facto standards that cannot be taken for granted in lower resource settings. Using a MD designed for high-resource settings in LMICs may hinder its safe and efficient operationalisation. In the literature, many criteria for frameworks to support resilient MD design were presented. However, since the available criteria (as of 2021) are far from being consensual and comprehensive, the aim of this study is to raise awareness about such challenges and to scope experts' consensus regarding the essentiality of MD design criteria. RESULTS: This paper presents a novel application of Delphi study and Multiple Criteria Decision Analysis (MCDA) to develop a framework comprising 26 essential criteria, which were evaluated and chosen by international experts coming from different parts of the world. This framework was validated by analysing some MDs presented in the WHO Compendium of innovative health technologies for low-resource settings. CONCLUSIONS: This novel holistic framework takes into account some domains that are usually underestimated by MDs designers. For this reason, it can be used by experts designing MDs resilient to low-resource settings and it can also assist policymakers and non-governmental organisations in shaping the future of global healthcare.

Music-based techniques and related devices in neurorehabilitation: a scoping review.

Introduction:The music as a powerful, and versatile stimulus for the brain, is at the date sometimes used in neurorehabilitation and proposed as a promising complementary strategy provided in combination with other therapy in individuals with neurological disorders. Different techniques and devices have been developed in the field of the music-based neurorehabilitation.Areas covered:This scoping review analyzes the current scientific literature concerning the different techniques and devices used in the music-supported neurorehabilitation, also focusing on the devices used in music-based therapies in patients with neurological disorders: 46 studies met the inclusion criteria and were included.Expert opinion:Included studies, highlight the potentiality and the versatility of the music-based therapy in the rehabilitation of neurological disorders. The variety of existing techniques allow to applied the music-based therapy in different situations and conditions. Moreover, the wide range of used devices that ranging from the simple musical instruments to the more advanced technologies, allows to develop customized exercises based on the needs of the patient. This review may be considered as a starting point to better design future RCTs that would investigate the effectiveness of music therapy on neurological disorders.

Technology development of hyperthermic pressurized intraperitoneal aerosol chemotherapy (hPIPAC).

BACKGROUND: Optimized drug delivery systems are needed for intraperitoneal chemotherapy. The aim of this study was to develop a technology for applying pressurized intraperitoneal aerosol chemotherapy (PIPAC) under hyperthermic conditions (hPIPAC). METHODS: This is an ex-vivo study in an inverted bovine urinary bladder (IBUB). Hyperthermia was established using a modified industry-standard device (Humigard). Two entry and one exit ports were placed. Warm-humid CO2 was insufflated in the IBUB placed in a normothermic bath to simulate body thermal inertia. The temperature of the aerosol, tissue, and water bath was measured in real-time. RESULTS: Therapeutic hyperthermia (target tissue temperature 41-43 °C) could be established and maintained over 30 min. In the first phase (insufflation phase), tissue hyperthermia was created by insufflating continuously warm-humid CO2. In the second phase (aerosolization phase), chemotherapeutic drugs were heated up and aerosolized into the IBUB. In a third phase (application phase), hyperthermia was maintained within the therapeutic range using an endoscopic infrared heating device. In a fourth phase, the toxic aerosol was discarded using a closed aerosol waste system (CAWS). DISCUSSION: We introduce a simple and effective technology for hPIPAC. hPIPAC is feasible in an ex-vivo model by using a combination of industry-standard medical devices after modification. Potential pharmacological and biological advantages of hPIPAC over PIPAC should now be evaluated.

[Analysis of regulatory status changes of drugs in France: 2010-2019]. / Analyse des modifications de statut réglementaire des médicaments en France : 2010­2019.

OBJECTIVES: The existence of borderline products between the status of a medicinal product and other less regulated products allows some products to have different statuses or even to change from one status to another. In order to quantify these changes, a review of medicines that have changed from drug status to other statuses (medical device, cosmetic product or food supplement) in France between 2010 and 2019 was performed. METHOD: The lists of medicinal products with archived or revoked marketing authorization (MA) from the French National Authority's Register of Medicinal Products were analyzed in order to identify the medicinal products withdrawn from the market between January 1, 2010 and September 30, 2019 that could be considered as products with a "potential for status change". Then, we searched on the official websites of the MA holders and other firms, for a possible return to the market with a different status, marketed by the same firm (self-change of status) or a different firm (hetero-change of status). RESULTS: Out of a list of 206 drugs identified as "with potential for status change", we detected a total of 101 status changes, including 36 auto-changes and 65 hetero-changes. These changes mainly concern vitamin or herbal drugs later marketed as food supplements (30 cases of auto-changes and 60 cases of hetero-changes). There are also 6 cases of switching to cosmetic product and 5 cases of switching to medical device. CONCLUSION: The existence of no clear distinction between the different statuses of health products facilitates their status changes. The increasing shift from "medicines" to less regulated products, the trivialization of their use by the public and their increasing consumption make them a fundamental issue of social pharmacology, requiring to raise the awareness of consumers and health professionals.

Medicinal plants and their preparations in the European market: Why has the harmonization failed? The cases of St. John's wort, valerian, ginkgo, ginseng, and green tea.

BACKGROUND: Botanical ingredients based on plants, algae, fungi or lichens have become widely available on the European Union market offering numerous preparations with considerable differences in classification. They are under the categories of food supplements, herbal medicinal products, cosmetics or medical devices. PURPOSE: The aim of the present work is to highlight how the European regulations concerning the different categories of botanicals can lead to different commercial choices such as time/cost for product development, application for a marketing authorisation, permitted indication (medical or health claim), and as a consequence, the same botanical products are sold in European Union as herbal medicinal products, food supplements, cosmetics or medical devices. Five different widely used botanicals, namely St. John's wort, valerian, ginkgo, ginseng, and green tea were selected to better explain the failure of harmonization through European Union. METHODS: A search of PubMed, ScienceDirect, European Medicines Agency and European commission web sites for medical devices and cosmetics, and European Food Safety Authority websites were conducted and the available information on regulation of herbal medicinal products, food supplements, medical devices and cosmetics in the European Union was collected. In addition, a market survey of all the sold botanical products in Europe was analysed by consultation of the medicines, medical devices, cosmetic and food agencies websites of the European countries. RESULTS: The current European legislation needs implementation and follow up because in the different countries the legal positions of the botanical products varied and it is possible to find the same product classified in the different categories, namely registered medicinal product including prescription only medicine, traditional herbal medicinal product, well established herbal medicinal products or food supplement, or medical device, or homoeopathic/anthroposophical medical product, cosmetic. CONCLUSIONS: There is an urgent need of harmonization, together with the implementation of interoperable vigilance databases, to avoid borderline options.