Regulatory Agencies Research Articles

Insurance coverage for mental illness: A review through a lens of bioethics and the MHCA, 2017

Introduction: Health insurance coverage can serve as protection against catastrophic health expenditures. Section 21 (4) of the Mental Healthcare Act, 2017 (MHCA) mandates insurance coverage for mental illness to be on par with that for physical illness. Despite this, anecdotal evidence shows persons with mental health conditions are routinely denied or face difficulties in obtaining medical insurance coverage due to their mental illness. Method: We undertook an analysis of all insurance policy documents published on the Insurance Regulatory and Development Authority of India (IRDAI) webpage for the year 2020-21 to examine their relevance to mental illness and to examine how the policy wording adheres to Section 21 (4) of the MHCA and the core principles of bioethics. Results: We sourced 459 health insurance policies for the year 2020-21 from the IRDAI webpage. Of these, 268 relevant insurance policies were analysed in depth for their adherence to the MHCA guidelines and principles of bioethics. Of the policies analysed (n=268), we found six policies (from two insurance providers) explicitly excluded mental illness across all domains, in direct contradiction of the MHCA and the subsequent guidance issued by the IRDAI. Most insurance policies excluded coverage for injuries due to attempted suicide or self-injury (n=224) or alcohol consumption/substance use (n=267). Out-patient services were included in 23 policies.>/p> Discussion: Health insurance policies continue to contain discriminatory terms for mental illness thus violating the principle of parity put forth by the MHCA and at odds with core principles of bioethics. Sustained advocacy efforts are required to ensure insurance providers abide by the principles of parity in letter and in spirit to remove differential or discriminatory terms for mental illness in their policies in compliance with Section 21 (4) the MHCA.

Classification of Cell Therapy Products by Cell Manipulation Degree and Functions Performed: Analysis of International Regulatory Approaches

INTRODUCTION. The degree of processing (manipulation) of cells included in a cell product and the functions performed after administration (homologous/non-homologous use) determine the classification of the cell product as a transplant or an advanced therapy medicinal product (ATMP) and, hence, the regulatory aspects of the product’s life cycle. Currently, the legislation of the Eurasian Economic Union (EAEU) and the Russian Federation does not sufficiently explain the terms ‘minimal manipulation’ and ‘homologous/non-homologous use’, which may lead to the use of cell products with unproven safety and efficacy in humans.AIM. This study aimed to compare Russian and international approaches to the interpretation of the terms ‘minimal manipulation’ and ‘homologous/non-homologous use’ for classifying cell products and determining their regulatory pathways, with stromal vascular fraction (SVF) products used as an example.DISCUSSION. This article reviews and summarises the regulatory approaches of the Russian Federation, the EAEU, the United States (US), and the European Union (EU) that are based on the classification of cell products according to the degree of cell manipulation and the functions performed after administration. The authors have analysed and compared the regulatory acts and approaches of the countries under consideration, with SVF products as a case study. The article highlights general aspects of interpreting the terms ‘minimal manipulation’ and ‘homologous/ non-homologous use’ and demonstrates the difference in regulatory approaches across several countries, which lies in the classification of enzymatic processing and selective collection of cells as substantial or minimal manipulation.CONCLUSIONS. The mechanism for regulating cell products depends on the degree of cell manipulation (substantial or minimal) and the intended use (homologous or non-homologous). A common principle adopted by regulatory agencies in the US, EU, EAEU, and Russia is to classify manipulation as minimal if the manipulated cells preserve their biological characteristics and physiological function. A defining characteristic of the homologous use of cells or tissues is their administration to perform their inherent functions in the body. In Russia, the regulatory acts for ATMPs and for transplants list the procedures classified as minimal manipulation. According to international standards, preparations based on minimally manipulated SVF cells are classified as ATMPs when used non-homologously. The lack of comprehensive and clear explanations of the terms ‘minimal manipulation’ and ‘homologous/non-homologous use’ in the legislation of the EAEU and the Russian Federation necessitates the development of relevant guidelines providing specific examples.

Advancements in Virtual Bioequivalence: A Systematic Review of Computational Methods and Regulatory Perspectives in the Pharmaceutical Industry

Background/Objectives: The rise of virtual bioequivalence studies has transformed the pharmaceutical landscape, enabling more efficient drug development processes. This systematic review aims to explore advancements in physiologically based pharmacokinetic (PBPK) modeling, its regulatory implications, and its role in achieving virtual bioequivalence, particularly for complex drug formulations. Methods: We conducted a systematic review of clinical trials using computational methods, particularly PBPK modeling, to carry out bioequivalence assessments. Eligibility criteria are emphasized during in silico modeling and pharmacokinetic simulations. Comprehensive literature searches were performed across databases such as PubMed, Scopus, and the Cochrane Library. A search strategy using key terms and Boolean operators ensured that extensive coverage was achieved. We adhered to the PRISMA guidelines in regard to the study selection, data extraction, and quality assessment, focusing on key characteristics, methodologies, outcomes, and regulatory perspectives from the FDA and EMA. Results: Our findings indicate that PBPK modeling significantly enhances the prediction of pharmacokinetic profiles, optimizing dosing regimens, while minimizing the need for extensive clinical trials. Regulatory agencies have recognized this utility, with the FDA and EMA developing frameworks to integrate in silico methods into drug evaluations. However, challenges such as study heterogeneity and publication bias may limit the generalizability of the results. Conclusions: This review highlights the critical need for standardized protocols and robust regulatory guidelines to facilitate the integration of virtual bioequivalence methodologies into pharmaceutical practices. By embracing these advancements, the pharmaceutical industry can improve drug development efficiency and patient outcomes, paving the way for innovative therapeutic solutions. Continued research and adaptive regulatory frameworks will be essential in navigating this evolving field.

Lecanemab's Path Forward: Navigating the Future of Alzheimer's Treatment in Europe Amidst the EMA's Rejection.

Lecanemab (Leqembi©, Biogen), a humanized anti-amyloid-beta monoclonal antibody, has been approved for early-stage Alzheimer's disease (AD) in several countries, including the US and Japan. However, the European Medicines Agency (EMA) recently issued a negative opinion on its marketing authorization, reflecting concerns over the clinical value and manageability of anti-amyloid treatments. This decision highlights the ongoing disconnect between research advancements and clinical practice, where the focus on biological markers over tangible clinical improvements remains contentious. Despite promising biological effects, lecanemab's clinical outcomes have been modest, raising questions about its therapeutic role. The EMA's refusal underscores the need to address doubts surrounding the real-world effectiveness and safety of such treatments, especially concerning amyloid-related imaging abnormalities (ARIAs), a common side effect observed in clinical trials. The recent approval of lecanemab by the UK's Medicines and Healthcare products Regulatory Agency, despite the National Institute for Health and Care Excellence's rejection on cost-effectiveness grounds, further fuels the debate on the feasibility of anti-amyloid therapies. This commentary emphasizes the importance of real-world data on lecanemab's impact on cognitive decline, daily functioning, and side-effect management. As the global clinical use of lecanemab increases, continuous and standardized reporting on its outcomes is crucial for guiding future regulatory decisions and for potentially bridging the gap between research and practice in AD treatment.

Exploiting Legal Reserve Compensation as a Mechanism for Unlawful Deforestation in the Brazilian Cerrado Biome, 2012–2022

This research investigates the illegal Vegetation Suppression Authorization (VSA) for Legal Reserve Compensation (LRC) in Tocantins, Brazil, between 2012 and 2014. The VSA is a license issued by state environmental agencies that authorizes the removal or clearing of native vegetation. This infraction resulted from the state environmental agency’s mistaken interpretation of Resolution 07/2005 of the State Environmental Council and the Native Vegetation Protection Law, which operates nationally and takes precedence over state resolutions and laws. The study area focuses on eight municipalities contained in the Formoso, Pium, and Javaés river basins. The methodology examines irregular VSA-LRC cases through geospatial data analysis, multitemporal analysis using remote sensing data, and economic assessments in both the origin and destination areas of the compensatory reserve. The results showed that among the 217 VSA-LRC applications during the period, 93 had corresponding geospatial data, indicating that 57.1% of the geospatial data were missing. This discrepancy between the authorized area and the available geospatial information restricts the oversight capability of the regulatory agency. A decade-long deforestation analysis of VSA-LRCs using remote sensing data considered three phases: 2012–2014 (application and issuance of VSA-LRCs), 2015–2018 (operational issuance), and 2019–2022 (post-expiration of VSA-LRCs). The results revealed a total VSA-LRC area of 343.291 km2 (34,329.10 ha), with 229.1169 km2 (22,911.69 ha) of deforestation. Notably, 54.877 km2 (5487.70 ha) of this deforestation occurred in 2019–2022, after the VSA-LRC had expired. The analysis of the LRC origin and destination areas demonstrates a unidirectional strategy, from economically more valuable areas to less valuable ones, according to land market dynamics. Therefore, this investigation concludes the need for greater administrative transparency, the development of a reliable geospatial data system for monitoring, and policy changes and actions to enhance environmental protection.

Views on the Development and Use of a New Digital Adverse Drug Event Reporting Platform in Australia: A Qualitative Study.

Reporting of adverse drug events (ADEs) to regulatory authorities remains low, particularly among consumers. To explore stakeholders' views on the development and use of a digital platform to improve ADE reporting by consumers to the regulatory authority in Australia, i.e., the Therapeutic Goods Administration. A qualitative study was conducted using semi-structured interviews, focus group discussions (FGDs), and co-design workshops with consumers, healthcare professionals (HCPs), and regulators. The interview recordings were transcribed verbatim, coded, and analysed thematically according to the Capability, Opportunity, Motivation, Behaviour model. Findings of the FGDs and co-design workshops were incorporated to enhance and complement the insights gathered from the interviews. A total of 39 participants took part in the study (54 % consumers, 41 % HCPs, and 5 % regulators). Uncovered themes related to ADE reporting in general were: difficulty recognizing ADEs and health literacy, awareness about reporting ADEs (Capability); visibility of ADE reporting, professionals' views on consumer ADE reporting, consumer education (Opportunity); the common good, benefit to the reporter, identifying ADEs worth reporting, and concern about reporting (Motivation). Additional identified themes specific to a new digital platform were: physical abilities (Capability); features that facilitate intuitive use, convenience and accessibility, user experience, integration with existing systems, trust, sharing experiences with others (Opportunity); and concern about using a reporting platform, and feedback loop (Motivation). A cross-section of attitudes and values were obtained regarding ADE reporting in general and a new ADE reporting digital platform for consumers in Australia, which will inform its development, implementation and evaluation.

Shifting Under Pressure: Timing Practices within Regulatory Information Disclosure Programs

Research examines the process through which regulatory agencies and other powerful third parties publicly disseminate information about organizations in order to reduce the information asymmetry between those organizations and their dispersed or less powerful stakeholders. These disclosure programs are presumed to work by mobilizing stakeholders to pressure organizations for change. Prior studies focus on organizations’ resistance to that external pressure, often drawing from theories of institutional forces and organizational legitimacy. Instead, the present study examines the public disclosure process itself, and adapts research on organizational learning and collective attention focus to develop new theory regarding how organizations may selectively time their practices to influence these disclosures in their favor. Results suggest that organizations may respond to disclosure programs and other governance structures when actively monitored, but may drift out of compliance during intervening periods. Findings also suggest that strong governance outside of the regulatory disclosure process can help to reduce these problems. The study contributes to corporate governance, organizational learning, and other literatures by developing new theory regarding the timing of organizational responses to regulatory interventions, and by providing evidence that overlapping forms of oversight may mitigate the limitations within any one particular governance mechanism.

A narrative review of veterinary pharmacovigilance situations and prospects in East African countries

BackgroundVeterinary pharmaceuticals must be safe and effective for treating and preventing diseases in animal sectors. Strict adherence to regulations at every stage of production, storage, and administration is necessary as the global sector grows in order to lower the possibility of adverse veterinary drug events. Strong pharmacovigilance regulatory systems are critical in monitoring and managing safety concerns related with veterinary pharmaceuticals.ObjectiveThis review aimed to investigate the implementation of veterinary pharmacovigilance, collaborative initiatives, and reporting practices within the veterinary sector across East African countries.MethodsA thorough search was performed using online platforms such as Google Scholar, PubMed, the Web of Sciences, and regulatory Web sites. The search strategies relied heavily on selecting relevant published findings related to veterinary pharmacovigilance status, veterinary adverse drug event reporting practice, and collaborative efforts in veterinary pharmaceutical sectors within the East African landscape. This article search approach confirmed the inclusion state of veterinary pharmacovigilance and associated collaborative initiatives in the region.ResultsIn comparison to more developed regions, the review indicated that the veterinary pharmacovigilance system in East African countries was still in its early state. A strong legislative foundation and a large commitment from the veterinary profession are needed to establish a nationwide veterinary pharmacovigilance system. The review reveals a significant lack of consistency in the infrastructure of veterinary pharmacovigilance among the countries of East Africa. Tanzania, Kenya, and Ethiopia have some institutional processes for veterinary pharmaceutical safety, but they lack thorough documentation, which suggests that this systems still require improvement. The analysis emphasizes how inadequate the reporting systems are for adverse veterinary medication events in the majority of East African nations. Given the challenges East Africa faces, customized strategies are required to guarantee the safety and oversight of veterinary medications and improve veterinary pharmacovigilance. For systems to be more effective, veterinary pharmaceutical legal frameworks must be strengthened and stakeholder collaboration must be improved. Stakeholders include legislators, law enforcement, customs officials, regulatory organizations, scientists, pharmaceutical businesses, veterinarians, farmers, and the general public.ConclusionA multidisciplinary strategy is needed to solve current gaps in veterinary pharmacovigilance and improve overall veterinary drug safety in East Africa. It is feasible to create more reliable methods for tracking and guaranteeing the safety of veterinary medications by combining the efforts of numerous stakeholders, including as legislators, regulatory agencies, veterinary practitioners, and the general public.

Drone Regulation and AI Law: Assessing the Intersection of the EU Legal Frameworks for Unmanned Aircraft and Artificial Intelligence

Drones are becoming a more familiar sight in the skies. This growth has potential implications for all aspects of society. To ensure safe, secure and sustainable drone activities, regulatory authorities have been revoking, amending or introducing laws. The primary focus has been on aviation safety rules for the design, manufacture and operation of these unmanned aircraft. These rules do not directly address other domains. This paper assesses how the EU’s drone-specific safety-based rules interact with the EU’s AI legal framework that is currently being developed. While drone rules do not address AI directly, they do indirectly as, for example, autonomous drone operations are permitted in the single European sky. The general AI legal framework also applies to drone activities, despite such not being mentioned. This paper brings together the sector-specific EU drone rules and the EU’s generalAI legal framework to understand what the term ‘AI’ means within the context of drone operations, and assesses whether there are any inconsistencies, contradictions, overlaps or lacunae. This will determine the applicability and suitability of applying the general AI legal framework to a specific technology (drones) and sector (aviation), and whether the drone rules can contribute to the regulation of AI more generally.

Kind, Firm, and Fair Medical Regulation: A Systems Approach and Six Ethical Principles

ABSTRACT Background: Regulatory processes can be stressful, anxiety provoking, and complicated for the health professional involved, the institutions they work for, and for the regulators. Methods: This paper uses a case study to describe a systems approach to comprehensively identify the agents (ie: the complainant, the health professional concerned, the regulator dedicated to the case, the institution, the healthcare profession, the public, and the regulatory authority) and 6 ethical issues that emerge during the regulatory process: potential to cause harm, not in the best interest of a person, affects autonomy, unjust, not truthful, and loss of trust. Results: A systems approach lends to a mental model in which there are dynamic interactions across these elements accompanied by positive and negative feedback loops that maintain overall stability of the whole system. Conclusions: The process can be further refined and kinder to those concerned by developing a sensitive approach to improve assessment of risks, using feedback to improve the regulatory process, adapting transparent procedures, not causing undue delays to the process, embedding regulatory activities in a patient safety system, minimizing individual blame, using non-legalistic, non-threatening and respectful communications, and directing the different actors to a support network for guidance and advice.

Deprescribing oral antidiabetics in elderly patients: Do electronic leaflets across the world address it?

Diabetes caused 6.7 million deaths in 2021, equating to one death every five seconds, with its global financial burden projected to rise from $1.32 trillion in 2015 to $2.12 trillion by 2030. Severe hypoglycemia necessitates interventions like deprescribing, behavioral strategies, and technology for prevention. Deprescribing aims to reduce unnecessary medication use, enhance rational prescribing, prevent prescribing cascades, and improve health outcomes in elderly patients. Evaluating electronic leaflets can support deprescribing based on patient-centered care and shared decision-making. ObjectiveTo analyze information on deprescribing in oral antidiabetic leaflets from national medicines regulatory authorities, focusing on elderly patients with type 2 diabetes. MethodsThis documental study analyzed electronic leaflets of oral antidiabetics from the official websites of nine Medicines Regulatory Authorities: Australia, Brazil, Canada, New Zealand, Singapore, South Africa, UK, USA, and EU, covering drugs listed in the WHO's Essential Medicines List 2023. The analysis focused on the alignment of deprescribing information with the Ontario deprescribing algorithm for oral antidiabetics developed by the Bruyère Institute in Canada. ResultsOut of 72 expected leaflets, 64 (88.9 %) were retrieved. Only 18 leaflets (28.1 %) explicitly discussed deprescribing oral antihyperglycemics. Hypoglycemia and drug interaction risks were addressed in 55 leaflets (85.9 %). Caution for use in patients over 65 was mentioned in 32 leaflets (50 %), and 23 leaflets (35.9 %) addressed the risks of tight glucose and HbA1c targets. ConclusionDespite a high retrieval rate, 11.1 % of leaflets were missing, and those available contained inconsistent deprescribing information. There are significant disparities in guidance across regulatory authorities. Standardized, updated leaflets that address deprescribing in frail older patients could enhance prescribers' confidence and support shared decision-making

Uncovering the Complexities of Drug Bans in India: Are Key Considerations Being Overlooked?

The use of fixed dose combinations (FDCs) in healthcare has significant public health implications, both positive and negative. Positive aspects include simplifying treatment regimens, improving patient adherence, and cost-effectiveness, particularly in resource-constrained settings. However, negative implications arise when FDCs are used without careful consideration, leading to irrational combinations, reduced treatment options, and potential overuse. Moreover, substandard FDCs and aggressive marketing can pose risks, such as antibiotic resistance and treatment failures. Mitigating the negative implications of FDCs requires a comprehensive strategy. Strengthening regulatory oversight, rigorous approval processes, and clear scientific evidence for FDCs’ benefits over single-drug formulations are essential. Transparency in the approval process, regular reviews, and postmarketing surveillance hold regulatory agencies accountable. Training and education for healthcare professionals, emphasizing evidence-based decision-making, and encouraging adverse event reporting can help ensure rational use. Pharmacovigilance programs, clinical practice guidelines, and national formularies aid in monitoring and guiding FDC use. Public awareness campaigns and patient engagement foster informed discussions and reporting. Research and development efforts should focus on optimizing FDC formulations and assessing cost-effectiveness. International collaboration to harmonize standards and prevent substandard FDCs’ global spread is crucial. Legal measures should be in place to deter misleading marketing and distribution of unsafe FDCs by pharmaceutical companies. In conclusion, addressing the negative implications of FDCs involves a multifaceted approach that spans healthcare professionals, regulators, pharmaceutical companies, and the public. By ensuring rational and safe use, FDCs can maximize their benefits while minimizing associated risks in the realm of public health.

Building robust, proportionate, and timely approaches to regulation and evaluation of digital mental health technologies.

Demand for mental health services exceeds available resources globally, and access to diagnosis and evidence-based treatment is affected by long delays. Digital mental health technologies present an opportunity to reimagine the delivery of mental health support by providing innovative, effective, and tailored approaches that meet people's individual preferences and goals. These technologies also present new challenges, however, and efforts must be made to ensure they are safe and effective. The UK Medicines and Healthcare products Regulatory Agency and the National Institute for Health and Care Excellence have launched a partnership, funded by Wellcome, that explores regulation and evaluation of digital mental health technologies. This Viewpoint describes a series of key challenges across the regulatory and health technology assessment pathways and aims to facilitate discussions to ensure that approaches to regulation and evaluation are informed by patients, the public, and professionals working within mental health. We invite partners from across the mental health community to engage with, collaborate with, and provide scrutiny of this project to ensure it delivers the best possible outcomes.

Reports of tropane alkaloid poisonings and analytical techniques for their determination in food crops and products from 2013 to 2023.

Food safety is crucial to attaining food security and sustainability. Unsafe foods for human and animal consumption lead to product recalls and rejection, negatively impacting the global economy and trade. Similarly, climate change can adversely affect the availability of safe and nutritious food at the table. The changing climatic conditions and global food trade and transport can make the movement of toxic plants possible, resulting in food crops being increasingly invaded by some species of plants that produce toxic secondary metabolites, such as tropane alkaloids (TAs).Datura stramoniumfrom the Solanaceae plant family is an invasive and virulent plant that produces high amounts of two TAs, atropine and scopolamine. Various food poisoning events following accidental or deliberate ingestion of foods contaminated by atropine and scopolamine from seeds ofD. stramoniumhave been recorded in different locations globally. Due to these incidents, regulatory agencies require the development of plant toxin detection methods that can be used in the food chain as early as possible. This systematic review thus focuses on the TA determination techniques in food and feeds published between 2013 and 2023. A particular focus was given to the sample preparation methods, the improvements of each technique claimed, and data to support the performance of each method, especially the ability to measure at or below the maximum level. The review concludes with other technological advancements, including rapid spectroscopy, electrophoresis, and colorimetric methods, as well as the possibility of coupling with smartphones for use in on-farm detection and the challenges in applying them.

Inventory of the best-selling medicinal plants on the Lubumbashi markets (DR Congo) and authentication of samples from the 3 most popular species

Ethnopharmacological relevanceKnowledge of the high-sale medicinal plants and their authentication are essential parameters to ensure the safety of people using herbal medicine and to plan the safeguarding of medicinal species threatened with extinction. AimsThe present study, carried out in Lubumbashi, Democratic Republic of Congo, aimed to geolocate medicinal plant sales points, list the best-selling species, and authenticate samples of the most popular species on the market. MethodsA survey was conducted among the medicinal plant sellers in Lubumbashi’s markets and other public spaces, to identify the best-selling species. Samples of the species reported as the most sold were purchased for sales unit weight measurement, and authentication. For the 3 most popular plant species, the identity of 92 samples, purchased from some 25 herbalists, was assessed by combining the microscopic characteristics of powdered drugs with the HPTLC fingerprints of methanolic extracts; for each species, these samples were compared with 1 or 2 botanically authenticated reference samples. As abundant starch granules were detected by microscopy, some samples were suspected of heavy flour contamination, which was confirmed by an enzymatic determination of their starch content. ResultsA total of 108 herbalists (48.1 % women) with a median age of 37 years (range, 20 to 67 years), and a median seniority of 5 years (0.7 to 30) were interviewed. From a total of 514 purchased samples, 396 (77.0 %) corresponded to 56 species that could be identified, including 92 samples representing the 3 most frequently sold plant species. The identities of 118 samples (having 82 different vernacular names), could not be determined, due to the lack of voucher specimen Roots were the most sold organ (56.0 %; n = 514), mainly in powder form (78.7 %), and the median price was 21 USD/kg, at the time of the survey (01/2022). The identified specimens were, predominantly, the roots of Terminalia mollis M.A.Lawson (33.3 %), Securidaca longepedunculata Fresen (28.7 %), and stem barks of Nauclea pobeguinii Hua ex Pobég. (23.1 %); from the recorded sales figures, the amounts of material annually sold for these 3 species are estimated at about 5.7, 6.0, and 3.1 tons, respectively. Some sellers reported problems in identifying and/or preserving S. longepedonculata and T. mollis.Among the 92 samples analyzed for the three species, 18.5 % raised problems, including species substitutions (14/17), dilution with flour (1/17), dilution with flour and species substitution (1/17), and detection of a phytochemical variant (1/17), that could arise either from contamination by another species, a particular plant growth environment, or poor storage conditions. ConclusionThe confusion/adulteration rate measured here for highly popular species is quite alarming (18.5 %); but, indeed, roots, especially as powders, are often difficult to differentiate based on the coarse organoleptic examination practiced by herbal traders. Microscopic and phytochemical characteristics reported in this study, quite easy to obtain with basic laboratory equipment, should be systematically applied by the health products regulatory authorities to control the quality of herbals and ensure that patients get the drug desired for their treatment.

Rapid identification of fragrant rice using starch flavor compound via NIR spectroscopy coupled with GC–MS and Badh2 genotyping

The identification of fragrant rice varieties using near-infrared reflectance spectroscopy (NIRS) models has attracted extensive attention from regulatory authorities worldwide. In this study, 138 fragrant and 54 nonfragrant rice varieties were planted in the same region and distinguished using sensory evaluation, gas chromatography–mass spectrometry analysis, and betaine aldehyde dehydrogenase 2 (Badh2) genotyping. Then, the 2-acetyl−1-pyrroline (2-AP) content was assessed based on partial least-squares discriminant (PLS-DA) models generated after 2nd individually or combined with SNV/MSC/smoothing preprocessing successfully classified fragrant rice both in the calibration and predictive sets. Moreover, design of experiments (DoE)-based preprocessing selection was employed as an effective strategy to optimize the calibration models compared with the one variable at a time (OVAT) method. Further, Badh2 genotype sample screening assisted with identifying authentic fragrant rice and guaranteed the NIRS model's prediction accuracy in identifying fragrant rice. In conclusion, the high throughput PLS-DA multivariate method coupled with NIRS data was applied to identify fragrant rice varieties in routine monitoring and was effective, accurate, and rapid.

Resolution of Historically Discordant Ames Test Negative / Rodent Carcinogenicity Positive N-nitrosamines using a Sensitive, OECD-aligned Design.

The in vitro Bacterial Reverse Mutation (Ames) Test is crucial for evaluating the mutagenicity of pharmaceutical impurities. For N-nitrosamines (NAs) historical data indicated that for certain members of this chemical class the outcomes of the Ames Test did not correlate with their associated rodent carcinogenicity outcomes. This has resulted in negative outcomes in an OECD aligned Ames Test alone (standard or enhanced) no longer being considered sufficient by regulatory authorities to assess potential carcinogenic risk of NAs if present as impurities in drug products. Consequently, extensive follow-up in vivo testing can be required to characterise the potential mutagenicity and genotoxic carcinogenicity of NA impurities (i.e., beyond that defined in the ICH M7 guideline for non-NA impurities). We previously demonstrated that the mutagenicity of alkyl-nitrosamines can be detected by the appropriately designed, OECD aligned Ames Test and identified those conditions that contributed most to assay sensitivity. This OECD aligned Ames Test design was used to assess seven NAs, i.e. (methyl(neopentyl)nitrosamine, N-methyl-N-nitroso-2-propanamine, N-nitrosodiisopropylamine, bis(2-methoxyethyl)nitrosoamine, N-nitroso-N-methyl-4-fluoroaniline, dinitrosoethambutol, (R,R)- and mononitrosocaffeidine) that were reported to be negative in historical Ames Tests but positive in rodent carcinogenicity studies. All seven of the NAs were demonstrated to be mutagenic in the OECD aligned Ames test and therefore these compounds should no longer be considered as discordant (false negatives) with respect to the correlation of the Ames Test and rodent carcinogenicity. These results confirm the sensitivity of the OECD aligned Ames Test for the detection of NA mutagenicity and provides further support of its pivotal placement within the ICH M7 framework for the assessment of mutagenic impurities in pharmaceuticals to limit potential carcinogenic risk. In addition, we present data for 1-cyclopentyl-4-nitrosopiperazine, that indicates it could serve as a suitable positive control to provide further confidence in the sensitivity of the Ames Test for the NA chemical class.

Simultaneous detection of multiple mycotoxins in agricultural products: Recent advances in optical and electrochemical sensing methods.

Mycotoxin contamination poses serious threats to human and animal health. Food and environmental systems are often simultaneously contaminated with multiple mycotoxins, a problem that is further exacerbated by the synergistic toxicological effects of these co-occurring mycotoxins. Consequently, the development of rapid detection methods capable of simultaneously identifying multiple mycotoxins in agricultural products is essential to prevent their entry into the food chain. Compared to standard detection methods, optical and electrochemical (EC) sensing methods have distinct advantages for the rapid detection of mycotoxins. This review comprehensively summarizes the latest advancements in the field of simultaneous detection of multiple mycotoxins using optical and EC sensing methods over the last 6years (2018-2024). First, the review introduces the classification and relevant principles of optical and EC sensing methods. Thereafter, it emphasizes innovative simultaneous detection strategies within these approaches. Finally, it discusses current challenges and offers a reference for further research. Currently, the main challenge lies in the mutual interference among targets, making the development of an interference-free detection platform essential. Furthermore, the ongoing development of integrated technology is expected to aid regulatory authorities in improving the quality of agricultural products for field applications.

Bispecific antibodies in follicular lymphoma.

Bispecific antibodies, specifically anti-CD20 T-cell engaging constructs, are poised to alter the treatment paradigm of multiple B-cell malignancies, including follicular lymphoma. Two CD20xCD3 bispecific antibodies, mosunetuzumab and epcoritamab, are now approved in the United States for third-line or later treatment of follicular lymphoma. A third agent, odronextamab, remains under review by regulatory agencies. In pivotal phase II trials, these bispecific antibodies demonstrated overall response rates of approximately 80%, with complete response rates of 60-70%, the majority of which have been durable at two years. Important safety signals included risk of infections, neutropenia, and cytokine release syndrome, which occurred in approximately half of patients, but was rarely high grade. Despite similar efficacy and toxicity profiles, key differences exist among agents, primarily relating to treatment duration, route of administration, and prophylactic corticosteroid use. Several ongoing studies are exploring bispecific antibodies in earlier lines of treatment, either as single agents or in combination with other active therapies. This novel class of agents is likely to play a pivotal role in improving outcomes for patients with follicular lymphoma.

Barriers to access to local produce in an early childhood setting in rural Appalachia

This case study examines young children’s access to fresh local produce in childcare settings in rural Appalachia. In-depth, semi-structured interviews with childcare center directors participating in farm to early care and education programming were conducted in the spring of 2023. Centering the per­spective of childcare directors, this research explores why farm to school programming is diffi­cult to implement. It specifically addresses the bar­riers preventing early childcare centers from pro­viding access to fresh and local produce to enrolled children. Eight primary obstacles to implementing farm to early care and education programming were identified: lack of staff; too wide a variety of tasks for directors; the “extra” work that fresh pro­duce requires; lack of knowledge about how to grow food; lack of required kitchen equipment; need for additional funding; unclear or out-of-date regulations about food safety; and a lack of paren­tal time. Limitations of the research include the specific geographic location of the study and the long-lasting implications of the COVID-19 pan­demic. Recommendations drawn from this case study include improving communication between childcare centers and regulatory agencies; creative use of alternative gardening practices; participating in a regional food hub; and improved funding.