Drug Administration Research Articles

Prediction of adverse drug reactions using demographic and non-clinical drug characteristics in FAERS data

The presence of adverse drug reactions (ADRs) is an ongoing public health concern. While traditional methods to discover ADRs are very costly and limited, it is prudent to predict ADRs through non-invasive methods such as machine learning based on existing data. Although various studies exist regarding ADR prediction using non-clinical data, a process that leverages both demographic and non-clinical data for ADR prediction is missing. In addition, the importance of individual features in ADR prediction has yet to be fully explored. This study aims to develop an ADR prediction model based on demographic and non-clinical data, where we identify the highest contributing factors. We focus our efforts on 30 common and severe ADRs reported to the Food and Drug Administration (FDA) between 2012 and 2023. We have developed a random forest (RF) and deep learning (DL) machine learning model that ingests demographic data (e.g., Age and Gender of patients) and non-clinical data, which includes chemical, molecular, and biological drug characteristics. We successfully unified both demographic and non-clinical data sources within a complete dataset regarding ADR prediction. Model performances were assessed via the area under the receiver operating characteristic curve (AUC) and the mean average precision (MAP). We demonstrated that our parsimonious models, which include only the top 20 most important features comprising 5 demographic features and 15 non-clinical features (13 molecular and 2 biological), achieve ADR prediction performance comparable to a less practical, feature-rich model consisting of all 2,315 features. Specifically, our models achieved an AUC of 0.611 and 0.674 for RF and DL algorithms, respectively. We hope our research provides researchers and clinicians with valuable insights and facilitates future research designs by identifying top ADR predictors (including demographic information) and practical parsimonious models.

Youth e‐cigarette use drops to recent low level: Good news

Half a million fewer U.S. youth reported current use of e‐cigarettes in 2024 compared to 2023, according to new data from the National Youth Tobacco Survey (NYTS) released today by the U.S. Food and Drug Administration (FDA) and the U.S. Centers for Disease Control and Prevention (CDC). The nationally representative data featured in Morbidity and Mortality Weekly Report (MMWR) includes findings on e‐cigarette and nicotine pouch use among U.S. youth, two categories of tobacco products the FDA and CDC are monitoring closely, particularly regarding youth use and appeal.

US FDA Advisory Panel Members’ Assessment of Premarket Approval Process and Suggestions for Improvement

The manufacturing and marketing of medical devices is regulated by the US Food and Drug Administration (FDA), and the FDA premarket approval (PMA) process evaluates the safety and effectiveness of medical devices. The PMA process includes a detailed scientific, regulatory and quality system review and is critical to ensure that novel devices are safe, effective, and meet the needs of patients. To survey current voting members serving on panels of the FDA's Medical Devices Advisory Committee to better characterize panel decision-making and identify steps for improvement. This qualitative survey study included 36 questions that were mailed to FDA device panelists regarding their opinions on the influence of sources of information, pivotal trial design, quality of evidence, panel composition and internal deliberative process, time allocation, and impartiality of the FDA. The survey was mailed to the members of all 18 FDA device panels in January and February 2017. Data were collected from January to May 2017 and analyzed from 2018 to 2019. Respondents read and returned the aforementioned paper survey, while nonrespondents did not. The main outcomes included panel members' perceptions, and their implications for process improvement. χ2 or Fisher exact tests were used to test differences between subgroups. Of 64 of 92 panel members who responded (69.6%), 38 of 64 (59.4%) were male, 3 of 63 (4.8%) were Black respondents, 46 of 63 (73.0%) were White respondents, and 36 of 60 (60.0%) were in academic practice. The mean (range) panel service was 6.8 (1-22) years with 3.9 (1-19) meetings attended. Overall, respondents considered information presented by the FDA unbiased, and 28 of 61 (45.9%) believed that pivotal trials were frequently well-designed, 55 of 62 respondents (88.7%) suggested FDA consult panel members preemptively regarding trial design and 54 of 64 (84.4%) regarding the device label. Most indicated that prior FDA approval of another device serving the same medical purpose (43 of 62 [69.4%]) or approval in other countries with comparable regulatory regimes, such as Canada and Europe (39 of 62 [62.9%]), would make them more likely to recommend approval. Respondents rated written information (50 of 60 [83.3%]), live presentations (43 of 58 [74.1%]), and prior professional knowledge (41 of 60 [68.3%]) as the most important sources of information in deciding whether to recommend approval. Additionally, 52 of 58 respondents (89.7%) recommended that a panel member-only executive session would allow more clarity and honesty in deliberations, and 33 of 59 (55.9%) believed a three-fourths majority appropriate for recommending approval, which would be a deviation from the current system in which an overall vote is reported without designation of a vote threshold. In this survey study of FDA device panel members, respondents wanted improved study designs, more relevant clinical data, including from other countries, involvement of panelists in study design and device label development, and inclusion of an executive session. Demographically, panels could be made more diverse.

Transcervical Fibroid Ablation (TFA): Current Status and New Developments

Abstract Aim Transcervical fibroid ablation offers a non-invasive alternative to traditional surgical options for the treatment of symptomatic uterine fibroids using real-time visualization using intrauterine ultrasound guidance. Purpose of Review To review the recent clinical literature on transcervical fibroid ablation (TFA) with the Sonata® System and discuss new developments in the use of such technology. Recent Findings Nearly six years since the Food and Drug Administration (FDA) approval in the United States (2018) and 14 years since receiving CE Mark in Europe, TFA with the Sonata system has been used to treat over 30,000 myomas in more than 10,000 procedures world-wide. Data regarding pregnancy outcomes, timing of pregnancy, route of delivery, neoadjuvant use of GnRH analogues and whether TFA is an effective treatment for adenomyosis remain fertile areas for investigation. Significant complications have been rarely reported.

Infection and infestation-related adverse events of biologics in psoriasis: insights from the Food and Drug Administration Adverse Event Reporting System (FAERS)

ABSTRACT Objective The study aims to thoroughly assess the adverse events related to infections and infestations associated with biological agents used for psoriasis using the U.S. Food and Drug Administration’s Adverse Event Reporting System (FAERS) database. Methods We analyzed FAERS data from the first quarter of 2004 to the fourth quarter of 2023. The study included TNF-α inhibitors (etanercept, infliximab, adalimumab), IL-12/23 inhibitors (ustekinumab), IL-23p19 inhibitors (guselkumab), and IL-17 inhibitors (secukinumab, ixekizumab). We used disproportionality analysis and Bayesian methods to quantify the related adverse event (AE) signals. Results Most AEs related to infections and infestations are already listed on the drug packaging labels. Notably, TNF-α inhibitors are associated with a significantly higher incidence of tuberculosis-related diseases compared to other biological agents. In contrast, IL-17 inhibitors show a greater variety and number of fungal infection-related AEs than their counterparts. Furthermore, our study has identified new potential AEs that require the attention of clinicians. Conclusion In clinical practice, it is advisable to monitor the risks of infections and infestations in patients receiving biological agents for psoriasis to enable early detection and intervention. Our findings highlight the need for further epidemiological investigations to establish causality and guide clinical practice in managing these risks effectively.

The Design Features, Quality by Design Approach, Characterization, Therapeutic Applications, and Clinical Considerations of Transdermal Drug Delivery Systems—A Comprehensive Review

Transdermal drug delivery systems (TDDSs) are designed to administer a consistent and effective dose of an active pharmaceutical ingredient (API) through the patient’s skin. These pharmaceutical preparations are self-contained, discrete dosage forms designed to be placed topically on intact skin to release the active component at a controlled rate by penetrating the skin barriers. The API provides the continuous and prolonged administration of a substance at a consistent rate. TDDSs, or transdermal drug delivery systems, have gained significant attention as a non-invasive method of administering APIs to vulnerable patient populations, such as pediatric and geriatric patients. This approach is considered easy to administer and helps overcome the bioavailability issues associated with conventional drug delivery, which can be hindered by poor absorption and metabolism. A TDDS has various advantages compared to conventional methods of drug administration. It is less intrusive, more patient-friendly, and can circumvent first pass metabolism, as well as the corrosive acidic environment of the stomach, that happens when drugs are taken orally. Various approaches have been developed to enhance the transdermal permeability of different medicinal compounds. Recent improvements in TDDSs have enabled the accurate administration of APIs to their target sites by enhancing their penetration through the stratum corneum (SC), hence boosting the bioavailability of drugs throughout the body. Popular physical penetration augmentation methods covered in this review article include thermophoresis, iontophoresis, magnetophoresis, sonophoresis, needle-free injections, and microneedles. This review seeks to provide a concise overview of several methods employed in the production of TDDSs, as well as their evaluation, therapeutic uses, clinical considerations, and the current advancements intended to enhance the transdermal administration of drugs. These advancements have resulted in the development of intelligent, biodegradable, and highly efficient TDDSs.

A holistic approach to address female genital schistosomiasis in Ghana and Madagascar: the FGS Accelerated Scale Together Package

Women and girls who have been infected with the blood fluke Schistosoma haematobium can experience the chronic form of urogenital schistosomiasis, called female genital schistosomiasis (FGS). Some FGS symptoms resemble sexually transmitted infections. As a result, women and girls seeking treatment are often misdiagnosed and stigmatized. The FGS Accelerated Scale Together (FAST) Package project implemented a holistic approach to address FGS combining proven interventions in training, mass drug administration, diagnosis, and treatment as well as community awareness to address FGS in four selected districts in Ghana and Madagascar. The FAST Package was supported by an FGS National Committee who provided guidance on integration at the national level. Using an implementation research design, researchers worked closely with government counterparts in the programs for neglected tropical diseases in both countries. Baseline cross-sectional surveys and qualitative methodologies collected information on schistosomiasis and FGS awareness, experience with health seeking behaviors and knowledge of schistosomiasis prevention amongst community members and teachers. FAST Package interventions included healthcare provider training delivered in online and in person formats; development of an Educators’ booklet to support schistosomiasis/FGS awareness creation among teachers, healthcare providers and community members; suspected FGS case detection; and advocacy for the provision of praziquantel in the primary health care system. Endline results included a cross-sectional survey and qualitative methodologies amongst community members and teachers, including Photovoice for women of reproductive health age exposed to FGS. This paper presents a description of the FAST Package project, the value of its holistic approach, and selected results from both countries. It discusses the lessons learnt highlighting some of the challenges and opportunities for integration within the health system.

Molecular xenomonitoring reveals Anopheles funestus and An. rivulorum as the primary vectors of lymphatic filariasis in coastal Kenya

BackgroundLymphatic filariasis (LF) is an infectious neglected tropical disease caused by mosquito-borne nematodes such as Wuchereria bancrofti, Brugia malayi, and Brugia timori. Globally, LF affects 51 million people, with approximately 863 million at risk in 47 countries. In Kenya, filariasis is endemic along the entire coastal strip, and more recently, at the Kenya–Ugandan border. The World Health Organization (WHO) recommends mass drug administration to reduce disease transmission and morbidity. Monitoring the effectiveness of such interventions relies on robust surveillance, achieved through microscopic examination of microfilariae in nighttime blood, detection of circulating filarial antigens (CFA), and molecular xenomonitoring. We focused on molecular xenomonitoring along the Kenyan coast due to its noninvasive nature and the opportunity to identify new vectors.MethodsIn 2022, mosquitoes were collected from Kilifi, Kwale, and Taita-Taveta counties located within the LF endemic region in Kenya. Subsequently, genomic deoxyribonucleic acid (gDNA) was extracted from these mosquitoes for speciation and analysis of Wuchereria bancrofti infection rates. The impact of sociodemographic and household attributes on infection rates was assessed using generalized estimating equations.ResultsA total of 18,121 mosquitoes belonging to Culicinae (63.0%, n = 11,414) and Anophelinae (37.0%, n = 6707) subfamilies were collected. Morphological identification revealed that Anopheline mosquitoes were dominated by An. funestus (45.4%, n = 3045) and An. gambiae (42.8%, n = 2873). Wuchereria bancrofti infection rates were highest in Kilifi (35.4%; 95% CI 28.0–43.3%, n = 57/161) and lowest in Taita Taveta (5.3%; 95% CI 3.3–8.0%, n = 22/412). The major vectors incriminated are An. rivulorum, An. funestus sensu stricto, and An. arabiensis. Mosquitoes of the An. funestus complex were significantly associated with LF transmission (OR 18.0; 95% CI 1.80–180; p = 0.014). Additionally, a higher risk of transmission was observed outdoors (OR 1.74; 95% CI 1.08–2.82; p = 0.024) and in homesteads that owned livestock (OR 2.00; 95% CI 1.09–3.66; p = 0.025).ConclusionsIn this study, we identified An. funestus s.l. sibling species, An. rivulorum and An. funestus s.s., as the primary vectors of lymphatic filariasis along the Kenyan coast. These findings also highlight that a significant portion of disease transmission potentially occurs outdoors where indoor-based vector control tools, including long-lasting insecticidal nets and indoor residual spray, may not be effective. Therefore, control measures targeting outdoor resting mosquitoes such as zooprophylaxis, larval source management, and attractive sugar baits may have potential for LF transmission reduction.Graphical

Understanding the barriers and facilitators related to never treatment during mass drug administration among mobile and migrant populations in Mali: a qualitative exploratory study

IntroductionFive of the neglected tropical diseases use a strategy of preventative chemotherapy distributed via mass drug administration (MDA) for all eligible people living in endemic areas. To be successful, high...

Global research and current trends on nanotherapy in lung cancer research: a bibliometric analysis of 20 years

BackgroundLung cancer ranks as one of the most rapidly growing malignancies. Which is characterized by its poor prognosis and a low survival rate due to late diagnosis and limited efficacy of conventional treatments. In recent years nanotechnology has emerged as a promising frontier in the management of lung cancer, presenting novel strategies to enhance drug administration, improve therapeutic efficiency, and mitigate side effects. This research comprehensively evaluates the current state and research trends concerning the application of nanomaterials in lung cancer through bibliometric analysis.Materials and methodsWe employed a systematic approach by retrieving studies from the Scopus database that focused on nanomaterials and lung cancer between 2003 and 2023. Subsequently, we carefully selected relevant articles based on predetermined inclusion criteria. The selected publications were then subjected to bibliometric and visual analysis using softwares such as VOSviewer and Biblioshiny.ResultsA total of 3523 studies that meet inclusion criteria were selected for bibliometric analysis. We observed a progressive increase in the number of annual publications from 2003 to 2023, indicating the growing interest in this field. According to our analysis, China is the primary contributor to publication output among the countries. The “Ministry of Education of the People's Republic of China” was the most influential institution. Among the authors, "Dr. Jack A. Roth” and “Dr. Huang Leaf” had the highest number of publications and cited publications, respectively. The “International Journal of Nanomedicine” was found to be the most prolific journal in this field. Additionally, “Biomaterials” emerged as the most cited journal. Through keyword analysis, we identified five main research themes and future research directions; nono-immunotherapy and green synthesis are the hot topics in this research field.ConclusionOur study summarized the key characteristics of publications in this field and identified the most influential countries, institutions, authors, journals, hot topics, and trends related to the application of nanomaterials in lung cancer. These findings contribute to the existing body of knowledge and serve as a foundation for future research endeavors in this area. More effective efforts are needed in this field to reduce the burden of lung cancer and help achieve the United Nation’s Sustainable Development Goals.

New Aspects of Mortellaro’s Disease: A Literature Review

Introduction. All over the word, hoof diseases, and Mortellaro’s disease in particular, are being among the most widespread and difficult to treat diseases in dairy cattle husbandry. They cause irreparable economic damage to the dairy industry by reducing the cattle reproductive ability indicators, feed conversion ratio, which compels to spend considerable amounts on treatment, prevention and culling of animals. Mortellaro’s disease is especially widespread in Europe and Western countries, but the current rate of national economy growth leads to the necessity to purchase the cattle abroad, which results in the increase of the Mortellaro’s disease incidence in Russia: at the farms where cattle has been imported, the percentage of the disease is 14.17±5.15% of the total number of hoof diseases in the herd. The aim of this review is to summarise the results of scientific research on the Mortellaro’s disease pathogenesis over the past 20 years.Materials and Methods. To achieve the stated objective, the criteria of inclusion into the search were defined. It was decided to include in the review the studies/reports presenting the results on: 1) the disease etiology and factors affecting the course of Mortellaro’s disease; 2) symptoms of Mortellaro’s disease manifestation in different species of farm animals; 3) the methods of Mortellaro’s disease treatment. The materials published in Elsevier, ASM Journal, Irish Veterinary Journal, Thieme, American Dairy Science Association, Epidemics, Schweiz Arch Tierheilkd, Journal of Clinical Microbiology, eLIBRARY.RU, Google Scholar have been investigated in the frame of the literature search. The search by the following keywords was done: interdigital dermatitis, Mortellaro’s disease, hoof diseases of cattle, contagious interdigital dermatitis. The time range of sources – those published within the period from 2003 to 2023.Results. In total, 44 articles have been analysed, 33 of which have been included in the present review. According to the studied materials, one of the prerequisites underlying the spread of Mortellaro’s disease in the Russian Federation is the import of the infected cattle, since the measures undertaken during the temporary housing and quarantine periods do not give the desired result. The animals get infected with the bacteria of the genus Treponema, which are localized deep in the hoof tissues, therefore, after the disease is endured, it turns into its chronic form. The specific symptoms of Mortellaro’s disease course in various cattle breeds have been established: in beef cows and buffaloes the interdigital dermatitis is characterised by a low level of pain symptom severity; in sheep – by the ulcerative lesions of the сoronary band, which progress and lead to the destruction of the abaxial hoof wall and loss of the hoof horn. The areas with the erosion are very painful, but the intercellular adhesive junctions are not lost, which allows for positive prognosis of the disease. The main indicators of productivity and fertility are reduced due to the disease, as is the immunity in general, and there is an estrous cycle delay. In the samples of patients sick with the digital dermatitis, an increase of the number of intact and degranulated mast cells is observed, compared to the healthy ones, which indicates that mast cells can play an important role in the pathogenesis of digital dermatitis. Nowadays, the Mortellaro’s disease treatment abroad and in Russia is based on the elimination of symptoms, and not the pathogen itself. The local treatment is mainly represented by the antiseptic baths, surgical treatment, local application of antibiotics to the wound. The experiments on antibiotic susceptibility of Treponema, which are the important step in the search for the specific treatment of Mortellaro’s disease, have been performed. The antibiotic susceptibility tests gave positive results (all isolates of Treponema were sensitive to tiamulin, valnemulin, tylosin, aivlosin, lincomycin, doxyclin), however, the difficulty lies in the method of drug administration into the source of Treponema localization, since the conventional ways of administration of antibiotics entail restrictions on the sale of milk and meat.Conclusion. The presented review of the scientific publications on Mortellaro’s disease made it possible to summarise the currently known results and identify the areas for further research. For example, it should be still investigated why the interdigital dermatitis requires the presence of many Treponema species rather than one? What role do representatives of the Mycoplasma, Porphyromonas and other bacteria play in the pathogenesis of the studied disease? And of course, there is a serious scientific gap in finding treatment of Mortellaro’s disease capable of eliminating the pathogen itself, rather than its symptoms. It should be mentioned that not all Treponema species can be cultivated, which also slows down the scientific process and makes the problem of Mortellaro’s disease treatment relevant worldwide.

Drug-associated congenital anomalies of the external ear identified in the United States food and drug administration adverse event reporting system database

Congenital anomalies of the external ear can have a significant impact on a child’s development and quality of life. While genetic factors play a crucial role in the etiology of these anomalies, environmental factors such as drug exposure during pregnancy may also contribute to their occurrence. This study aims to investigate the association between drug exposure and congenital anomalies of the external ear using data from an adverse drug reaction report database. Using OpenVigil 2.1, we queried the FAERS database to retrieve adverse event reports from the first quarter of 2004 to the first quarter of 2024. To identify relevant cases, we used Medical Dictionary for Regulatory Activities terms focusing on congenital anomalies of the external ear. Drug generic names were sourced from the DrugBank database. To assess safety signals and rank drugs by their signal strength, we conducted a disproportionality analysis, generating reporting odds ratios (ROR) and proportional reporting ratios (PRR). A total of 20,754,281 AE reports were identified in the FAERS database from Q1 2004 to Q1 2024, of which 1763 were related to congenital anomalies of the external ear. Valproic acid (122 cases) was associated with the most cases, followed by mycophenolate mofetil (105 cases) and lamotrigine (65 cases). According to the disproportionality analysis, the top five drugs with the highest ROR and PRR were primidone (ROR: 397.05, 95% CI 147.21, 1070.9; PRR: 388.71, 95% CI 145.89, 1035.7), valproic acid (ROR: 239.46, 95% CI 123.75, 463.37; PRR: 236.42, 95% CI 123.82, 451.43), tapazole (ROR: 198.35, 95% CI 63.49, 619.67; PRR: 196.25, 95% CI 62.97, 611.67), nevirapine (ROR: 138.24, 95% CI 82.9, 230.51; PRR: 137.23, 95% CI 82.44, 228.44), and sebivo (ROR: 117.1, 95% CI 48.51, 282.67; PRR: 116.37, 95% CI 48.17, 281.12). This study identified several drugs significantly associated with congenital anomalies of the external ear in the FAERS database using disproportionality analysis. The findings can help healthcare professionals better recognize and manage drug-induced congenital anomalies of the external ear, particularly when prescribing high-risk medications. Further research is needed to elucidate the mechanisms underlying these associations and develop strategies for preventing and mitigating drug-induced congenital anomalies of the external ear.

Accelerated approvals: Early-phase success or premature authorization?

We compare the clinical trial success rates of products receiving US Food and Drug Administration (FDA) accelerated approval (AA) to those approved without using this pathway. Our findings raise important questions about how the AA pathway can best optimize early access to therapeutics that are ultimately proven safe and effective.

The First Triple Agonist for Antiobesity: Retatrutide

The prevalence of individuals with overweight and obesity has increased by 18% since 1990 and it is projected that by 2030, nearly 50% of US adults will have obesity. Lifestyle modifications, such as diet and exercise, typically lead to approximately 3–5% weight loss, whereas 5–15% weight loss is necessary to significantly impact obesity-associated comorbidities and improve overall health outcomes. In addition to lifestyle modifications, pharmacotherapy has been utilized as an adjunctive treatment to increase weight loss and improve health outcomes. The Food and Drug Administration has currently approved 6 drugs to treat overweight and obesity, with the recently approved drugs surging in popularity after demonstrating superior weight loss outcomes. Additionally, a number of agents are in the pipeline, offering promise of unprecedented degrees of weight loss. One such drug is retatrutide, which is a triple agonist targeting the glucagon-like peptide-1 receptor (GLP-1R), glucose-dependent insulinotropic polypeptide receptor, and glucagon receptor. Phase 1 and 2 clinical trials have demonstrated the safety, tolerability, and pharmacokinetics of retatrutide in patients with obesity and/or type 2 diabetes. The pharmacokinetics of retatrutide were dose proportional and its mean half-life of approximately 6 days supported a once-weekly dosing. The safety profile was similar to GLP-1R agonists and glucose-dependent insulinotropic polypeptide receptor/GLP-1R co-agonists, with gastrointestinal disorders being the most common adverse effects reported. Each trial demonstrated greater weight loss with retatrutide treatment in comparison to placebo, with greatest efficacy at higher doses. Overall, these clinical trials have demonstrated the superior efficacy of retatrutide as a weight loss medication in patients with overweight and obesity.

Development and safety of investigational and approved drugs targeting the RAS function regulation in RAS mutant cancers.

The RAS gene family holds a central position in controlling key cellular activities such as migration, survival, metabolism, and other vital biological processes. The activation of RAS signaling cascades is instrumental in the development of various cancers. Although several RAS inhibitors have gained approval from the United States Food and Drug Administration (FDA) for their substantial antitumor effects, their widespread and severe adverse reactions significantly curtail their practical usage in the clinic. Thus, there exists a pressing need for a comprehensive understanding of these adverse events, ensuring the clinical safety of RAS inhibitors through the establishment of precise management guidelines, suitable intermittent dosing schedules, and innovative combination regimens. This review centers on the evolution of RAS inhibitors in cancer therapy, delving into the common adverse effects associated with these inhibitors, their underlying mechanisms, and the potential strategies for mitigation.

Redefining chimeric antigen receptor T-cell (CAR-T) regulation: China's responses to address secondary cancer risks of CAR-T therapy.

Since the United States Food and Drug Administration (FDA) approved the first chimeric antigen receptor T-cell (CAR-T) therapy in 2017, it has marked a major breakthrough in cancer treatment, leading to a surge in global research and applications in this field. In recent years, China has made rapid progress, quickly catching up through heavy investment in CAR-T construction, preparation processes, and treatment strategies. China's CAR-T therapy market is driven by substantial pharmaceutical investment targeting its vast population, yet high therapy costs remain uncovered by basic medical insurance. In November 2023, FDA issued a warning about the risk of secondary cancers in patients undergoing CAR-T therapy, sparking global concern. In fact, the China National Medical Products Administration (NMPA) preemptively implemented a series of measures to address the safety concerns of CAR-T therapy, emphasizing the risk of secondary cancers and advising lifelong monitoring as part of the approval process for CAR-T products. Nevertheless, additional regulatory measures are needed to address emerging risks, particularly the threat of secondary cancers. The authors believe that raising the standards for Investigational New Drug (IND) approval and establishing a dynamic reporting and feedback system based on real-world data will strengthen regulatory oversight and support the sustainable growth of the CAR-T industry in China.

Quantitation of the DNA-dependent protein kinase inhibitor peposertib (M3814) and metabolite in human plasma by LC-MS/MS.

The DNA-dependent protein kinase (DNA-PK) is an abundant nuclear protein that mediates DNA double-strand break repair by nonhomologous end joining (NHEJ). As such, DNA-PK is critical for V(D)J recombination in lymphocytes and for survival in cells exposed to ionizing radiation and clastogens. Peposertib (M3814) is a small molecule DNA-PK inhibitor currently in preclinical and clinical development for cancer treatment. We have developed a high-performance liquid chromatography-mass spectrometry method for quantitating peposertib and its metabolite in 0.1 mL human plasma. After MTBE liquid-liquid extraction, chromatographic separation was achieved with a Phenomenex Synergi polar reverse phase (4μm, 2× 50 mm) column and a gradient of 0.1% formic acid in acetonitrile and water over an 8min run time. Mass spectrometric detection was performed on an ABI SCIEX 4000 with electrospray, positive-mode ionization. The assay was linear from 10 to 3000 ng/mL for peposertib and 1-300 ng/mL for the metabolite and proved to be both accurate (97.3%-103.7%) and precise (<8.9%CV) fulfilling criteria from the Food and Drug Administration (FDA) guidance on bioanalytical method validation. This liquid chromatography-tandem mass spectroscopy (LC-MS/MS) assay will support several ongoing clinical studies by defining peposertib pharmacokinetics.

A maturity assessment methodology for ISO 13485 implementation in the medical devices industry

PurposeThis study aims to develop a novel diagnostic methodology for implementing ISO13485:2016 and test its applicability to improve quality management systems (QMS) in the medical devices industry context.Design/methodology/approachFirst, a literature review on the topic was conducted. Second, insights gained from the literature and expert interviews were employed to develop the new maturity assessment methodology. Subsequently, the methodology was tested on a medical device manufacturer. Next, based on the evaluation of the intervention, actions were recommended to improve the QMS.FindingsResearch findings have developed a maturity assessment methodology comprising 52 certifiable requirements structured into four macro-requirements derived from ISO 13485:2016. Findings show that the methodology is valuable for aiding QMS implementation, and the diagnosed maturity levels corresponded with the company’s empirical perceptions of the requirement’s maturity.Practical implicationsEmpirical evidence validates the significance and practical utility of the proposed methodology, as evidenced by the company’s attainment of FDA (US Food and Drug Administration) approval after the intervention. Findings suggest that the methodology could be replicated within the medical products industry or adapted to assess other QMS, leveraging the organizational alignment with the international regulations of the sector and the ISO 9000 requirements.Originality/valueThe developed methodology fills existing gaps in both literature and practice within the medical devices industry, providing a valuable contribution by addressing the limited research on diagnostic methodologies designed for ISO 13485:2016 implementation. The article assists medical device enterprises in addressing QMS maturity levels as a metric for evaluating QMS requirements, which is an underexplored avenue in existing QMS evaluation approaches.

Navigating the online food environment: policy pathways for promoting food access, transparency, and healthy food choices online

The internet is drastically changing how U.S. consumers shop for groceries, order food from restaurants, and interact with food marketing. There is an urgent need for new policies to help ensure that the internet is a force for good when it comes to food access, transparency, and nutrition. This article outlines actions that federal agencies—like the U.S. Department of Agriculture (USDA), U.S. Food and Drug Administration (FDA), and Federal Trade Commission (FTC)—and state and local governments can take to improve the online food environment. We recommend policies in three settings: online grocery retail, online restaurant ordering, and marketing on social media and other online platforms. For example, USDA could finalize regulations increasing access to online WIC and remove barriers to accessing online SNAP by requiring large retailers to waive online delivery and service fees for SNAP purchases. FDA could improve access to nutrition information by issuing guidance describing what product information should be available at the online point of selection. FTC could give better guidance on appropriate tactics when marketing to children and collect better data on how companies are marketing food to children online. Finally, state governments could pass laws like New York’s recently introduced Predatory Marketing Prevention Act to address false and misleading advertising of unhealthy foods aimed at children and other vulnerable groups.

Modernizing Medical Device Regulation: Challenges and Opportunities for the 510(k) Clearance Process.

Nearly all medical devices reviewed by the U.S. Food and Drug Administration (FDA) are authorized via the 510(k) clearance process. Established in 1976, this review pathway bases authorizations on the comparability of new devices to previously authorized devices ("predicates"). This evaluation usually does not require clinical evidence of safety and effectiveness. Advocates of the 510(k) clearance process tout its support for device innovation and rapid market access, and critics of the 510(k) clearance process express that it may inadequately protect patient safety. In September 2023, the FDA issued 3 guidance documents that, if finalized, would significantly change medical device regulation. This article provides clinical and regulatory context for the proposed guidance documents, which focus on predicate selection, clinical testing requirements, and implantable devices, and identifies opportunities for further reforms that promote transparency and patient safety.