European Medicines Research Articles

Les cellules CAR-T anti-CD19 : prototypes du médicament vivant

Chimeric antigen receptors (CARs) are synthetic receptors that determine the specificity and functions of transduced T cells. They bind cell surface antigens through their extracellular domain and initiate via their intracellular domain cytolytic functions, cytokine secretion and proliferation. The CAR thus specifies the properties of a living drug that is programmed to exert anti-tumor and immunoregulatory effects.After establishing a method to stably integrate foreign genes in primary T lymphocytes in the early 1990s, we identified combinatorial signaling modules that could sustain a prolonged T cell function [17], which underpins an essential feature of a living drug. We further identified CD19 as a promising molecular target, which, based on encouraging preclinical results in mice [30], paved the way for clinical trials.The first clinical studies in patients with relapsed, refractory leukemias and lymphomas, which all made use of CAR T cells produced in the academic setting, yielded remarkable clinical response that were soon confirmed at several centers [2]. CAR T cells targeting CD19 were the first living drugs to be approved by the US Food and Drug Administration in 2017 and the European Medicines Agency in 2018.CD19 CARs have thus spawned a new class of drugs and inspired new applications to treat cancer and autoimmune diseases with engineered immune cells, warranting sustained efforts to lower their cost and increase their availability in equitable fashion.

7650 Thionamide Induced Pancreatitis and Agranulocytosis, a Rare Case of Concurrence

Abstract Disclosure: J. Lin: None. J. Shariff: None. Introduction: Thionamides are considered first line in the treatment of Graves’ Disease due to their efficacy and safety. We present a case of Graves’ in which methimazole resulted in not only agranulocytosis but also pancreatitis. Case Report: A 29yo female was diagnosed with Graves’ 5 months postpartum by her PCP. Her labs at diagnosis revealed a TSH <0.01 uIU/mL, free T4 of 6.4 ng/dL, and positive TRAb. She was started on methimazole 10mg and propranolol 20mg three times a day by her PCP. One month after starting treatment, she presented to the ED due to throat pain/fevers and was diagnosed with tonsilitis. She was given a 10mg dose of dexamethasone and sent home with antibiotics. No labs were drawn that visit. She went to her PCP 3 days later due to persistent symptoms and nausea/vomiting. A CBC revealed she had a WBC of 0.7 K/uL and an absolute neutrophil count (ANC) of 0.1 K/uL. Her last dose of methimazole had been the day prior to seeing her PCP. It was recommended she be seen in the ED due to concern for agranulocytosis where she was started on antibiotics and a CT abdomen pelvis with contrast revealed she had acute pancreatitis. She was admitted and started on filgrastim 5mcg/kg daily for thionamide-induced agranulocytosis. Her pancreatitis improved with conservative measures. Her propranolol was resumed at 30mg three times a day with symptom improvement. On her fifth hospitalization day, her ANC had recovered to 2.22 K/uL, WBC was 6 K/uL. Her free T4 was 1.65 ng/dL, free T3 4.1 pg/mL, TSI >40 IU/L. This change was suspected to be from propranolol, steroids, iodine load from her CT, and prior methimazole use. It was strongly recommended she pursue surgery that hospitalization given inability to treat her Graves’ medically. The patient refused, stating she wished to consider her options further outpatient. She would be seen one week later in a satellite ED. Her free T4 was 5.9 uIU/mL, T3 >30 pg/mL, TSH <0.010 uIU/mL. She left against medical advice. She subsequently declined further endocrine follow-up. Clinical Lessons: Thionamide-induced agranulocytosis is a rare but known complication of use, with some studies showing a prevalence as low as 0.2-0.5% [1]. Pancreatitis is a lesser-known complication of thionamides. There are several case reports of its occurrence, with the European Medicines Agency even listing it in the potential adverse reaction. Absolute risk of occurrence remains low, some studies showing <0.4% [1]. This case shows a rare concurrence of two uncommon complications from thionamide use and brings awareness to both pancreatitis and agranulocytosis as potential adverse events.

Tissue-Agnostic Targeting of Neurotrophic Tyrosine Receptor Kinase Fusions: Current Approvals and Future Directions.

NTRK fusions are oncogenic drivers for multiple tumor types. Therefore, the development of selective tropomyosin receptor kinase (TRK) inhibitors, including larotrectinib and entrectinib, has been transformative in the context of clinical management, given the high rates of responses to these drugs, including intracranial responses in patients with brain metastases. Given their promising activity in pan-cancer cohorts, larotrectinib and entrectinib received U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) approval for tissue-agnostic indications in patients with advanced solid tumors harboring NTRK fusions. The safety profiles for both drugs are quite manageable, although neurotoxicity driven by the on-target inhibition of normal NTRK can be a concern. Also, on- and off-target resistance mechanisms can arise during therapy with TRK inhibitors, but they can be addressed with the use of combination therapy and next-generation TRK inhibitors. More recently, the FDA approved the use of repotrectinib, a second-generation TRK inhibitor, in patients with NTRK fusions, based on data suggesting clinical efficacy and safety, which could offer another tool for the treatment of NTRK-altered cancers. In this review, we summarize the current evidence related to the use of TRK inhibitors in the tissue-agnostic setting. We also elaborate on the safety profiles and resistance mechanisms from a practical perspective.

Inquérito telefónico sobre a utilização de medicina herbal em Portugal e aferição da validade científica dos usos reportados

Introduction: Portugal has a long tradition of plants and herbal preparations for medicinal purposes (herbal medicines - HMs), but few studies on their use today. The professions of phytotherapy have recently been regulated, enabling more efficacy and safety. Objectives: 1) assess the use of HMs in Portugal, including attitudes, behaviors, sources of information, acquisition methods and role of HMs in health management, and identify the most used plants and targeted conditions. 2) evaluate them according to scientific evidence. Material and methods: a structured telephone interview. Scientific validity was assessed using the monographs of European Medicines Agency (EMA) and systematic reviews. Results: in this sample of 272 individuals, HMs are considered mainly for prevention or minor health problems. Family knowledge is the main information source and supermarkets/herb shops the main places of purchase, infusions being the preferred form. Two cases of mild adverse effects were reported. Most targeted conditions are flu, cold, cough, digestive discomfort and insomnia. The most used plants are: eucalyptus, elderberry, thyme, lemon, peppermint, echinacea, lemon balm, chamomile, valerian and passionflower. Conclusions: HM is mainly used for mild pathologies and chronic conditions. Its uses are mostly supported by scientific evidence. More attention to HMs from the medical community is important, in collaboration with phytotherapy and naturopathy professionals.

Novel imaging techniques for tumor margin detection in basal cell carcinoma: a systematic scoping review of FDA and EMA-approved imaging modalities.

Mohs micrographic surgery (MMS) is the gold standard for removing basal cell carcinomas (BCCs) due to its ability to guarantee 100% margin evaluation through frozen section histopathology, offering the highest cure rate among current treatments. However, noninvasive imaging technologies have emerged as promising alternatives to clinical assessment for defining presurgical margins. This systematic scoping review examines the efficacy of these imaging modalities, focusing on those approved for clinical use by the United States Food and Drug Administration (FDA) or the European Medicines Agency (EMA). A systematic search of EMBASE, Scopus, PubMed, and the Cochrane Public Library databases identified 11 relevant studies out of 2123 records, encompassing 644 lesions across five imaging techniques. The findings suggest that dermoscopy, high-frequency ultrasound (HFUS), optical coherence tomography (OCT), line-field optical coherence tomography (LC-OCT), and reflectance confocal microscopy (RCM) show potential in detecting BCC margins, which could enhance MMS by providing better preoperative planning, informing patients of expected defect size, aiding in reconstruction decisions, and reducing overall procedure costs. This review discusses the benefits and limitations of each technique, offering insights into how these innovations could influence the future of BCC management. Emerging imaging techniques could enhance MMS by improving BCC margin assessment and reducing costs. Their adoption will depend on price and ease of use.

Ultrahigh-Performance Supercritical Fluid Chromatography-Mass Spectrometry in the Clinical Lipidomic Analysis.

Ultrahigh-performance supercritical fluid chromatography-mass spectrometry (UHPSFC/MS) method is optimized for the high-throughput quantitation of lipids in human serum and plasma with an emphasis on robustness and accurate quantitation. Bridged ethylene hybrid (BEH) silica column (100×3mm; 1.7μm) is used for the separation of 17 nonpolar and polar lipid classes in 4.4min using the positive ion electrospray ionization mode. The lipid class separation approach in UHPSFC/MS results in the coelution of all lipid species within one lipid class in one chromatographic peak, including two exogenous internal standards (IS) per lipid class, which provides the optimal conditions for robust quantitation. The method was validated according to European Medicines Agency and Food and Drug Administration recommendations. UHPSFC/MS combined with LipidQuant software allows a semiautomated process to determine lipid concentrations with a total run time of only 8min including column equilibration, which enables the analysis of 160 samples per day.

A Review and Comparative Case Study Analysis of Real-World Evidence in European Regulatory and Health Technology Assessment Decision Making for Oncology Medicines

ObjectivesReal-world evidence (RWE) is valuable in supporting regulatory and health technology assessment (HTA) decisions; however, the actual contribution to approvals remains elusive. This study aimed to review RWE approaches and use in oncology medicine approvals in Europe and understand cohesion and discrepancy in the acceptance of the RWE by the European Medicines Agency (EMA) and European HTA bodies. MethodsThis scoping review involved a search of the EMA database, National Institute for Health and Care Excellence (NICE), Gemeinsamer Bundesausschuss (G-BA), and Haute Autorité de Santé (HAS) websites to identify final reports and appraisals for oncology medicines with references to RWE. The selection was guided by research terms associated with RWE study designs, data sources, and outcomes. Qualitative analysis was used to systemize the data. Case studies assessed by more than one agency were selected for comparative assessment of RWE approach, use, and acceptability. ResultsRWE was mainly leveraged as an external control for indirect treatment comparisons or contextualization to support clinical trial results by the EMA, NICE, G-BA, and HAS. However, this approach was mostly rejected due to methodology biases. Comparative assessment of RWE acceptability for the same oncology medicines across agencies suggests discrepancies between EMA and European HTA bodies and among NICE, G-BA, and HAS. ConclusionsThere is diverging acceptance of RWE in EMA and European HTA bodies with no clear consensus on the most effective way to leverage RWE in approvals. With the introduction of the joint European Union Joint Clinical Assessment in 2025, it is crucial for European HTA bodies and EMA to develop synergetic standards for the use of RWE to ensure equitable and timely access to medicines.

Phosphodiesterase4 inhibitors in dermatology : Role in the treatment of skin diseases

Chronic inflammatory skin diseases are of great social and medical importance and require effective drug therapy. Phosphodiesterase4 (PDE4) inhibitors represent apossible therapeutic option by regulating inflammatory processes. PDEs cause the release of proinflammatory cytokines by interfering with signaling pathways. The PDE4 inhibitors apremilast (treatment of psoriasis and Behçet's disease), roflumilast (treatment of chronic obstructive pulmonary disease), and crisaborole (treatment of atopic dermatitis) are currently approved in Europe. Apremilast is used for second-line treatment of plaque psoriasis and psoriatic arthritis and has afavorable side effect profile. Topical PDE4 inhibitors are currently being researched and have not yet been approved by the European Medicines Agency (EMA). The topical PDE4 inhibitor crisaborole was approved by the EMA in 2020 as atopical treatment alternative to glucocorticoids and calcineurin inhibitors. Although the substance has shown good tolerability in studies and also alleviates the accompanying itching, it did not find its way onto the German market. BEHçET'S DISEASE: Apremilast is approved for the treatment of Behçet's disease in adults with refractory, severe oral ulcers. Case studies have also demonstrated the efficacy of systemic PDE4 inhibition in other skin diseases (including blistering autoimmune dermatoses, lichen planus, and acantholytic genodermatoses). The substances are also being researched and used to treat extracutaneous inflammatory diseases.

New cancer medicines in Europe 2010–2020: comparison of medicines with or without extensions of indications

IntroductionDuring the last decade, extensions of therapeutic indications have been one of the most common methods to extend the lifecycle of a medical product in the post-authorisation phase and to...

Drifting Too Far From Shore: Paternal Valproate Statement by the European Medicines Agency (EMA).

Drifting Too Far From Shore: Paternal Valproate Statement by the European Medicines Agency (EMA).

N-Acetyl-L-Cysteine (NAC) Blunts Axitinib-Related Adverse Effects in Preclinical Models of Glioblastoma.

Axitinib is a tyrosine kinase inhibitor characterized by a strong affinity for Vascular Endothelial Growth Factor Receptors (VEGFRs). It was approved in 2012 by Food and Drug Administration and European Medicines Agency as a second line treatment for advanced renal cell carcinoma and is currently under evaluation in clinical trial for the treatment of other cancers. Glioblastoma IDH-wild type (GBM) is a highly malignant brain tumor characterized by diffusely infiltrative growth pattern and by a prominent neo-angiogenesis. In GBM, axitinib has demonstrated a limited effectiveness as a monotherapy, while it was recently shown to significantly improve its efficacy in combination treatments. In preclinical models, axitinib has been reported to trigger cellular senescence both in tumor as well as in normal cells, through a mechanism involving intracellular reactive oxygen species (ROS) accumulation and activation of Ataxia Telangiectasia Mutated kinase (ATM). Limiting axitinib-dependent ROS increase by antioxidants prevents senescence specifically in normal cells, without affecting tumor cells. We used brain tumor xenografts obtained by engrafting Glioma Stem Cells (GSCs) into the brain of immunocompromised mice, to investigate the hypothesis that the antioxidant molecule N-Acetyl-L-Cysteine (NAC) might be used to reduce senescence-associated adverse effects of axitinib treatment without altering its anti-tumor activity. We demonstrate that the use of the antioxidant molecule N-Acetyl-Cysteine (NAC) in combination with axitinib stabilizes tumor microvessels in GBM tumor orthotopic xenografts, eventually resulting in vessel normalization, and protects liver vasculature from axitinib-dependent toxicity. Overall, we found that NAC co-treatment allows vessel normalization in brain tumor vessels and exerts a protective effect on liver vasculature, therefore minimizing axitinib-dependent toxicity.

Anti-inflammatoires non stéroïdiens en prescription médicale facultative : mise au point dans la prise en charge de la douleur aiguë

Non-steroidal anti-inflammatory drugs (NSAIDs) are the second most widely used class of analgesics in France, after paracetamol. Some NSAIDs are available over the counter (OTC), without a prescription, on the advice of a pharmacist. NSAIDs have recently been the subject of safety alerts from France's Agence nationale de sécurité du médicament et des produits de santé (ANSM), highlighting a risk of worsening certain bacterial infections. This signal has not been confirmed by the European Medicines Agency (EMA) although a "risk of complications due to masking of symptoms of infection" has not been ruled out. These divergent messages can be confusing for healthcare professionals. This literature review, based on an analysis of nearly 200 scientific publications, considers the place of NSAIDs in the OTC management of migraine, tension headaches, postoperative analgesia, acute musculoskeletal and joint pain, dysmenorrhea, viral respiratory infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and their toxicity. The role of the pharmacist in dispensing NSAIDs without a prescription is also addressed. NSAIDs offer rapid and effective pain management in a context of increasingly challenging access to care. Their safety profile is reassuring and generally well established but could be strengthened by conducting an ad hoc study to rule on the safety signal issued by the ANSM definitively. Pharmacists have the knowledge and tools to ensure the safe dispensing and rational use of NSAIDs, with or without a prescription. The introduction of risk minimization measures, such as decision-support tools, could enable further progress in ensuring the safe dispensing of OTC NSAIDs.

Treatment patterns of goserelin 3.6 mg once monthly and 10.8 mg every three months in women with breast cancer: A real-world analysis.

391 Background: Goserelin is a gonadotropin-releasing hormone agonist used for ovarian function suppression in the treatment of pre- and peri-menopausal patients with breast cancer. Goserelin, administered as a subcutaneous implant, is available in doses of 3.6 mg once monthly or 10.8 mg every three months; goserelin 3.6 mg is approved in the US, and both the 3.6 mg and 10.8 mg doses are approved by Health Canada and the European Medicines Agency. A study utilizing US real-world evidence was conducted to characterize treatment patterns of patients treated with goserelin 3.6 mg and/or 10.8 mg. Methods: Electronic health record data of adult patients with a history of breast cancer and with ≥2 prescriptions of goserelin between 1 January 2017 – 31 December 2022 were identified through TriNetX. Index date was the initiation of goserelin administration. Patients were followed until 15 March 2024. Patient demographics, treatment adherence, and healthcare resource utilization (HCRU) were examined and summarized using descriptive analytics. Results: Overall, 3,620 patients were identified: 2,870 treated with goserelin 3.6 mg, 410 with goserelin 10.8 mg, and 340 who switched from goserelin 3.6 mg to 10.8 mg. Peak utilization of goserelin 10.8 mg (36.6%) and peak dosage switching (26.5%) occurred in 2020. Across groups, mean age at index date was 42.2–44.4 years, and patients were white (64.1–67.6%), black (11.8%–13.9%), Asian (8.0%–11.8%), and American Indian and/or Alaskan native (0.3%–2.9%). Of patients with known BMI, BMI mostly ranged between 18.5–24.9 kg/m 2 in all groups. Patients who switched from goserelin 3.6 mg to 10.8 mg had the longest median treatment duration (776 days) (Table). Patients treated with goserelin 10.8 mg remained on treatment for a median of 426 days; 74.4% of these patients were treatment-adherent (Table). In comparison, patients treated with goserelin 3.6 mg had a shorter median treatment duration (226 days) and were less adherent (56.4%) (Table). HCRU during the 12 months after index date was broadly similar across groups. Conclusions: Treatment with goserelin 10.8 mg every three months is associated with greater adherence and longer treatment duration, compared with 3.6 mg once monthly, in patients with a history of breast cancer. Patients who switched from goserelin 3.6 mg to 10.8 mg were treatment-adherent for nearly two years, consistent with clinical recommendations. Goserelin 3.6 mg (n = 2,870) Goserelin 10.8 mg (n = 410) Switched from goserelin 3.6 mg to 10.8 mg (n = 340) Median duration of treatment (days) 264 429 776 Median time to switch (days) — — 218 Patients adherent* to dosing schedule 1,608 (56.4%) 306 (74.4%) — Status as of March 15, 2024 Discontinued goserelin 2,018 (70.8%) 261 (64.3%) 173 (50.9%) Death 88 (3.1%) 10 (2.5%) 3 (0.9%) *Defined as: ≤36 days between prescriptions (3.6 mg) or ≤108 days between prescriptions (10.8 mg).

Current vaccination and immunization strategies in dermatology

Vaccinations are an important pillar of public health. They have high benefits for individuals and society as awhole by specifically preventing or mitigating infectious diseases. In many cases, they offer benefits that go beyond protection against the disease in question, e.g., protective cardiovascular effects. Vaccination recommendations in Germany are drawn up by the Standing Committee on Vaccination (STIKO), while the European Medicines Agency (EMA) is responsible for the approval of vaccines in the EU. Vaccinations may be carried out by physicians regardless of their specialty. In dermatology, vaccinations against varicella (chickenpox), herpes zoster, and human papillomavirus are established. The development of vaccines against other dermatologically relevant diseases and cancer vaccines is the subject of intensive research. Particularly in the case of immunosuppression, the physician must also take into consideration which vaccinations are possible and useful or contraindicated. TypeI or typeIV allergies to components of vaccinations are very rare, but reactions at the injection site often occur as adermatological side effect. Urticarial reactions are also possible, as does the worsening of underlying dermatological conditions such as psoriasis vulgaris.

A liquid chromatography - Tandem mass spectrometry method for determination of ocrelizumab in serum of patients with multiple sclerosis

Ocrelizumab is a second generation recombinant humanized IgG1 monoclonal antibody used for the treatment of multiple sclerosis that selectively target B cells expressing the CD20 antigen. This study aimed to develop and validate a UPLC-MS/MS method for quantification of ocrelizumab in human serum, which can be used in clinical applications for therapeutic drug monitoring.The analysis of ocrelizumab was performed using a bottom-up approach on a liquid chromatography coupled to tandem mass spectrometry detection. The method involved immunoglobulin precipitation with cold methanol followed by peptide digestion with trypsin. The resulting specific peptides were separated on an Acquity UPLC BEH C18 column at 55 °C using gradient elution. The method was validated according to European Medicines Agency (EMEA) guidelines and demonstrated intra- and inter-assay precision with coefficients of variation ranging from 1.6 % to 6.1 % and accuracies between 90.2 % and 107.2 %. Stability testing, including autosampler, long-term and freeze-thaw stability, showed no more than 15 % variation. The method was successfully applied to 169 patient samples, revealing ocrelizumab concentrations ranging from 0.5 to 21.8 mg/L in patients on 6-month dosing regimen and 20.5–65.0 mg/L in 16 patients receiving an initial two-week dose of 300 mg. The newly developed UPLC-MS/MS method met all criteria for accuracy, precision and stability, confirming its suitability for clinical use in monitoring ocrelizumab levels in multiple sclerosis patients.

Mitochondrial ribosomal proteins in metastasis and their potential use as prognostic and therapeutic targets.

The mitochondrion is an essential cell organelle known as the powerhouse of the cell. Mitochondrial ribosomal proteins (MRPs) are nuclear encoded, synthesised in the cytoplasm but perform their main functions in the mitochondria, which includes translation, transcription, cell death and maintenance. However, MRPs have also been implicated in cancer, particularly advanced disease and metastasis across a broad range of cancer types, where they play a central role in cell survival and progression. For some, their altered expression has been investigated as potential prognostic markers, and/or therapeutic targets, which is the focus of this review. Several therapies targeting MRPs are currently approved by the Food and Drug Administration and the European Medicines Agency for use in other diseases, revealing the opportunity for repurposing their use in advanced and metastatic cancer. Herein, we review the evidence supporting key MRPs as molecular drivers of advanced disease in multiple cancer types. We also highlight promising avenues for future use of MRPs as precision targets in the treatment of late-stage cancers for which there are currently very limited effective treatment options.

Schisandrin C prevents Regorafenib-Induced cardiotoxicity by recovering EPHA2 expression in cardiomyocytes.

Regorafenib, an oral multikinase inhibitor of angiogenic, stromal, and oncogenic receptor tyrosine kinases, has been approved for the treatment of metastatic colorectal cancer, gastrointestinal stromal tumors and hepatocellular carcinoma by the US Food and Drug Administration and European Medicines Agency. However, regorafenib-induced cardiotoxicity increases the risk of mortality. Despite reports that regorafenib can cause mitochondrial dysfunction in cardiomyocytes, the molecular mechanism of regorafenib-induced cardiotoxicity is much less known and there is an urgent need for intervention strategies. Here, we treated mice with vehicle or 200 mg/kg regorafenib daily for 42 days by gavage or treated cardiomyocyte lines with 8, 16 or 32 μM regorafenib, and we found that regorafenib could cause apoptosis, mitochondrial injury and DNA damage in cardiomyocytes. Mechanistically, regorafenib can reduce the expression of EPHA2, which inhibits AKT signaling, leading to cardiomyocyte apoptosis and cardiotoxicity. In addition, we showed that recovering EPHA2 expression via plasmid-induced overexpression of EPHA2 or schisandrin C, a natural product, could prevent regorafenib-induced cardiotoxicity. These findings demonstrated that regorafenib causes cardiomyocyte apoptosis and cardiac injury by reducing the expression of EPHA2 and schisandrin C could prevent regorafenib-induced cardiotoxicity by recovering EPHA2 expression, which provides a potential management strategy for regorafenib-induced cardiotoxicity and will benefit the safe application of regorafenib in clinic.

Side-effects of Phytotherapeutics in Cancer Care - A Review of Inconsistencies in National and International Databases.

The interest in phytotherapy in patients with cancer is immensely high. When using herbal medicine, knowledge of potential side-effects is essential as part of counselling the patient. The aim of this study was therefore to collect information on the side-effects of popular medicinal plants and to compare different official and the most popular sources of information reporting the side-effects of phytotherapeutics. Four different databases were reviewed from 09 February 2021 to 01 March 2022. These were the German monographs of the German Federal Institute for Drugs and Medical Devices, the European monographs of the European Medicines Agency, the website About Herbs (https://www.mskcc.org/cancer-care/diagnosis-treatment/symptom-management/integrative-medicine/herbs) and the German Red List. A total of 171 medicinal plants were chosen from the German monographs. These plants were relevant for supportive cancer treatment, targeting symptoms e.g. pain, nausea, vomiting, mucositis or fatigue. Out of the 171 selected plants, only 20 were found in all four sources. The compilation of the data showed there to be a huge disparity in the number of plants listed by each database and the type and frequency of the side-effects described. The reasons for this are manifold: Lack of interest, different interest groups, different origins (Europe versus America) and no standardized terminology. Physicians should not rely exclusively on one source to inform themselves about potential side-effects of phytotherapeutics but should use several sources to ensure the best possible safety of the patient. Since there seems to be too few data on certain medicinal plants for which no side-effects have been documented, more clinical studies are needed.

The Challenges for EU User Testing Policies for Patient Information Leaflets.

Patient information leaflets (PILs) are essential tools in healthcare, providing crucial information about medication use. In the European Union, the European Medicines Agency (EMA) oversees the regulation and standardisation of PILs to ensure their readability and accessibility. However, challenges persist in ensuring these documents are comprehensible and user-friendly. This study employs a qualitative analytical approach, reviewing existing literature and regulatory documents to identify gaps in the EU user testing policies for PILs. It focuses on the diversity of participant samples, the independence of the testing process, and the robustness of user testing protocols. Findings indicate that current user testing practices often lack diversity and may be biased when pharmaceutical companies conduct their own tests. Additionally, there is a lack of user testing protocols for translated PILs, potentially compromising their accuracy and cultural relevance. To improve the efficacy of PILs, it is essential to include diverse and representative samples in user testing, mandate independent third-party evaluations, implement protocols for user testing on translated PILs, and ensure continuous updates to guidelines based on the latest best practices in health communication. These measures will enhance patient safety and understanding of medication information.

Inside out: Exploring edible biocatalytic biosensors for health monitoring

Edible biosensors can measure a wide range of physiological and biochemical parameters, including temperature, pH, gases, gastrointestinal biomarkers, enzymes, hormones, glucose, and drug levels, providing real-time data. Edible biocatalytic biosensors represent a new frontier within healthcare technology available for remote medical diagnosis. The main challenges to develop edible biosensors are: i) finding edible materials (i.e. redox mediators, conductive materials, binders and biorecognition elements such as enzymes) complying with Food and Drug Administration (FDA), European Food Safety Authority (EFSA) and European Medicines Agency (EMEA) regulations; ii) developing bioelectronics able to operate in extreme working conditions such as low pH (∼pH 1.5 gastric fluids etc.), body temperature (between 37 °C and 40 °C) and highly viscous bodily fluids that may cause surface biofouling issues. Nowadays, advanced printing techniques can revolutionize the design and manufacturing of edible biocatalytic biosensors.This review outlines recent research on biomaterials suitable for creating edible biocatalytic biosensors, focusing on their electrochemical properties such as electrical conductivity and redox potential. It also examines biomaterials as substrates for printing and discusses various printing methods, highlighting challenges and perspectives for edible biocatalytic biosensors.