Regulatory Toxicology and Pharmacology最新文献_第3页

Commentary on FDA's shift from animal testing and implications for drug attrition – The time to act is now 评论FDA从动物试验的转变和对药物损耗的影响-现在是采取行动的时候了。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-06-25 DOI: 10.1016/j.yrtph.2025.105896

Eckhard von Keutz

引用次数: 0

Assessment of human breast milk contamination with lead, mercury, cadmium, and arsenic and associated health risks in northeastern Algeria 阿尔及利亚东北部人类母乳铅、汞、镉和砷污染及相关健康风险评估

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-06-24 DOI: 10.1016/j.yrtph.2025.105891

Meriem Imen Boussadia , Mohamed Amine Kerdoun , Ali Boudebbouz , Zinette Bensakhri , Abdeldjalil Youcefi , Sadek Atoussi , Rabah Zebsa

{"title":"Assessment of human breast milk contamination with lead, mercury, cadmium, and arsenic and associated health risks in northeastern Algeria","authors":"Meriem Imen Boussadia , Mohamed Amine Kerdoun , Ali Boudebbouz , Zinette Bensakhri , Abdeldjalil Youcefi , Sadek Atoussi , Rabah Zebsa","doi":"10.1016/j.yrtph.2025.105891","DOIUrl":"10.1016/j.yrtph.2025.105891","url":null,"abstract":"<div><div>Lead (Pb), mercury (Hg), cadmium (Cd), and arsenic (As) pose global food safety concerns, with infants being particularly vulnerable due to exposure from maternal body burden. This study assessed health risks associated with exposure to Cd, Pb, Hg and As through breast milk consumption among women residing in Guelma, northeastern Algeria. Eighty-four breast milk samples were collected and analyzed using atomic absorption spectrometry, following microwave-assisted acid digestion. The mean concentrations of toxic metals in breast milk were as follows: Pb (15.77 ± 9.54 μg/L) > Hg (3.26 ± 2.50 μg/L) > Cd (2.75 ± 2.39 μg/L) > As (0.35 ± 0.73 μg/L). The Target Hazard Quotient (THQ) for Hg exceeded the safety threshold of 1 across all age groups, with 83 %, 82 %, and 49 % of samples surpassing this limit for 1-month, 6-month, and 12-month-old infants, respectively. Similarly, the Hazard Index (HI) exceeded 1 in all age groups, indicating significant non-carcinogenic risks. Furthermore, the Total Carcinogenic Risk (TCR) for all metals surpassed the acceptable limit (TCR = 1 × 10<sup>−4</sup>), with Cd posing a particularly high risk, as 82 % of samples exceeded the carcinogenic threshold. These findings highlight both carcinogenic and non-carcinogenic risks from infant exposure to toxic metals via breast milk, underscoring the urgent need for nationwide monitoring programs, stricter industrial emission controls, and further research into maternal dietary exposure.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"162 ","pages":"Article 105891"},"PeriodicalIF":3.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144491991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The safety of monosodium glutamate demonstrated in 28-day and 90-day dietary toxicity studies with Sprague-Dawley rats 在28天和90天的Sprague-Dawley大鼠饮食毒性研究中证实了味精的安全性。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-06-24 DOI: 10.1016/j.yrtph.2025.105897

Shintaro Yoshida, Huichia Chao, Keigi Chin, Masanori Kohmura

{"title":"The safety of monosodium glutamate demonstrated in 28-day and 90-day dietary toxicity studies with Sprague-Dawley rats","authors":"Shintaro Yoshida, Huichia Chao, Keigi Chin, Masanori Kohmura","doi":"10.1016/j.yrtph.2025.105897","DOIUrl":"10.1016/j.yrtph.2025.105897","url":null,"abstract":"<div><div>The commonly used flavor enhancer monosodium glutamate (MSG) has been part of the human diet for many years and has undergone safety evaluation by several international scientific committees and regulatory agencies. Numerous studies exist on MSG but many of these studies are not consistent or representative of how humans are exposed to MSG (<em>i.e.</em>, ingestion of food). Two GLP-compliant dietary rodent studies were summarized in evaluations performed by EFSA (2017) and JECFA (2022) but were never published. In the first study, groups of Sprague-Dawley rats (10 rats/sex/group) were fed diets containing 0 ppm (basal diet) or 50,000 ppm MSG for 29 days. In the second study, groups of Sprague-Dawley rats (20 rats/sex/group) were fed diets containing 0 (basal diet), 0.5, 1.5, or 5 % (w/w) MSG for 92–96 days. Animals in both studies underwent clinical examinations, hematology and biochemistry tests, full necropsies, and histopathological examination. No toxicologically significant findings were reported in either study. In the 28-day study, there were no adverse effects observed at 5100 mg/kg bw/day (males) and 4800 mg/kg bw/day (females). In the 90-day study, a no-observed-adverse-effect level (NOAEL) was identified as the highest dose tested of 3170 mg/kg bw/day (males) and 3620 mg/kg bw/day (females) or more.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"162 ","pages":"Article 105897"},"PeriodicalIF":3.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comparison of whole transcriptome and targeted RNA sequencing for ecological high-throughput transcriptomics 生态高通量转录组学全转录组和靶向RNA测序的比较

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-06-24 DOI: 10.1016/j.yrtph.2025.105898

Daniel L. Villeneuve , Mackenzie Nash , Adam Biales , Kendra Bush , Garrett Evensen , Logan Everett , Jonathan Haselman , Monique Hazemi , Michelle Le , Helen Poynton , Bruce Seligmann , Leah Wehmas , Joanne Yeakley , Kevin Flynn

{"title":"Comparison of whole transcriptome and targeted RNA sequencing for ecological high-throughput transcriptomics","authors":"Daniel L. Villeneuve , Mackenzie Nash , Adam Biales , Kendra Bush , Garrett Evensen , Logan Everett , Jonathan Haselman , Monique Hazemi , Michelle Le , Helen Poynton , Bruce Seligmann , Leah Wehmas , Joanne Yeakley , Kevin Flynn","doi":"10.1016/j.yrtph.2025.105898","DOIUrl":"10.1016/j.yrtph.2025.105898","url":null,"abstract":"<div><div>In 2019, the US EPA organized a federal government challenge aimed at identifying and evaluating low cost, high-throughput, RNA sequencing technologies that could support the aims of a new program in ecological high-throughput transcriptomics. Innovators worldwide were invited to demonstrate their solutions in an open competition. Each responding Solver was provided a set of nine pooled RNA samples from each of four species of aquatic organisms (n = 36 samples total). Five Solutions submitted by three Solver teams were evaluated according to a pre-defined scoring rubric that considered accuracy, precision, transcriptome coverage for each species, cost per sample, and throughput. A targeted approach (TempO-Seq) that employed sentinel gene sets representing 5–11 % of the whole transcriptome was ranked as the top solution. However, all were viable approaches and had specific strengths and weaknesses. In a follow up investigation, transcriptomic points of departure based on a sentinel gene set were generally found to fall within a factor of 10 or less of those based on whole transcriptome sequencing. Results support the conclusion that a wide range of sequencing technologies and approaches are suitable for the work. Detailed and transparent reporting of the approaches used will help support uptake in science-based decision-making.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"162 ","pages":"Article 105898"},"PeriodicalIF":3.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144491989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Percutaneous absorption of climbazole: In vitro data from human skin 克里巴唑的经皮吸收：来自人体皮肤的体外数据。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-06-24 DOI: 10.1016/j.yrtph.2025.105895

Catherine Champmartin, Matthieu Aubertin, Claire Seiwert, Frédéric Cosnier

{"title":"Percutaneous absorption of climbazole: In vitro data from human skin","authors":"Catherine Champmartin, Matthieu Aubertin, Claire Seiwert, Frédéric Cosnier","doi":"10.1016/j.yrtph.2025.105895","DOIUrl":"10.1016/j.yrtph.2025.105895","url":null,"abstract":"<div><div>Climbazole is an antifungal substance used as an active ingredient or antimicrobial preservative in pharmaceuticals and personal care products. It is classified by the EU as an acute toxicant (Category 4), and ECHA has recently confirmed its endocrine disruptor concern. Data on climbazole's skin permeability, and consequently its occupational risks, are limited.</div><div>The aim of this study was to generate percutaneous absorption data in line with OECD guidelines to support occupational exposure assessment. <em>In vitro</em> experiments using 4.1 μg/cm<sup>2</sup> [<sup>14</sup>C]-labelled climbazole were conducted on freshly excised human skin samples placed in Franz diffusion cells, monitoring absorption over 20 h. The absorption profile data were used to calculate key parameters, including steady-state flux, lag time, and skin permeability coefficient (K<sub>p</sub>). The dose distribution across various compartments, including the skin, was evaluated. The individual skin layers were isolated by sequential tape-stripping, followed by epidermis-dermis separation to more precisely measure radioactivity levels. This information was used to predict the potential for further absorption of the dose retained within the skin. The presence of climbazole metabolites in the receptor fluid was also investigated.</div><div>The K<sub>p</sub> was determined to be 4.7 x 10<sup>−3</sup> cm/h. Significant dermal absorption was measured, highlighting potential occupational risks. Climbazole is mainly absorbed with biotransformation: 67 % of the absorbed dose was detected as metabolites. These new percutaneous absorption data will enhance the assessment of the occupational risks associated with dermal exposure to climbazole.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"162 ","pages":"Article 105895"},"PeriodicalIF":3.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evaluating high-throughput assays for pesticide ecological risk assessment 评价农药生态风险评价的高通量分析方法

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-06-23 DOI: 10.1016/j.yrtph.2025.105892

Leah Sattler , Michelle Embry , Scott Glaberman

{"title":"Evaluating high-throughput assays for pesticide ecological risk assessment","authors":"Leah Sattler , Michelle Embry , Scott Glaberman","doi":"10.1016/j.yrtph.2025.105892","DOIUrl":"10.1016/j.yrtph.2025.105892","url":null,"abstract":"<div><div>Evaluating pesticide ecological risk is essential for regulation, but traditional vertebrate testing is resource-intensive and ethically challenging. New approach methodologies, such as high-throughput assays (HTAs), offer cost-effective, mechanistically explicit alternatives that reduce animal use. The US EPA's ToxCast program houses HTA data for chemical screening, but its use in ecological risk assessment (ERA) remains underutilized. We applied ToxCast data directly to ERA metrics, comparing assay-derived exposure–activity ratios to <em>in vivo</em> risk quotients (RQs) from regulatory assessments. Uniquely, our study focuses on pesticides and is risk-focused rather than hazard-focused, leveraging data drawn directly from the same standardized regulatory risk assessments that inform decision-making. While ToxCast assays generally underestimated risks compared to <em>in vivo</em> RQs—particularly for chronic endpoints—certain assays, such as cytochrome P450 assays, demonstrated strong alignment for herbicides and fungicides. In contrast, assay performance was weaker for neurotoxic insecticides and herbicides targeting photosynthesis, reflecting gaps in HTA coverage for these modes of action. Our findings underscore the potential of HTAs as complementary tools for ERA, particularly for screening and prioritization, though further assay development is needed for chronic and mode-of-action-specific risks. Integrating HTA data into risk metrics lays the groundwork for promoting more accurate, efficient, and ethical approaches to pesticide evaluation.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"162 ","pages":"Article 105892"},"PeriodicalIF":3.0,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144491990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A review of common approaches to determining allocation factors and relative source contribution factors for drinking water contaminants: caveats and areas for improvement 审查确定饮用水污染物的分配因素和相对来源贡献因素的一般方法：注意事项和需要改进的领域。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-06-18 DOI: 10.1016/j.yrtph.2025.105886

Christopher W. Greene , M. Valcke , A.A. Soshilov , P. Levallois , H.M. Goeden

{"title":"A review of common approaches to determining allocation factors and relative source contribution factors for drinking water contaminants: caveats and areas for improvement","authors":"Christopher W. Greene , M. Valcke , A.A. Soshilov , P. Levallois , H.M. Goeden","doi":"10.1016/j.yrtph.2025.105886","DOIUrl":"10.1016/j.yrtph.2025.105886","url":null,"abstract":"<div><div>Relative Source Contribution (RSC) factors, or Allocation Factors (AF), in the 0–100 % range are commonly applied for calculating non-cancer health-based guidance values (HBGVs) for drinking water. The use of an RSC/AF allows consideration of non-water exposures when developing HBGVs. An RSC/AF value can be calculated from chemical-specific exposure data or assigned a default value based upon qualitative information or a lack of data. In this review, we analyzed RSC/AF procedures and outcomes from six agencies and 30 published scientific papers. For agency-derived RSC/AF values, default values with no rationale provided were most common, followed by default values informed qualitatively by data, non-default values informed qualitatively by data, and non-default values calculated from data. Data-based non-default RSC/AF values were uncommon due to insufficient exposure data for critical population groups. Furthermore, we found that the bases for RSC outcomes are poorly documented, making analysis of the decision process sometimes impossible. For RSC/AF values from the literature, we observed proportionally more data-calculated RSC/AF values compared to agency results. Our findings indicate a need to make better use of available exposure data, including allowing a wider range of default options and/or the use of modeling approaches. A decision matrix is proposed in this regard.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"162 ","pages":"Article 105886"},"PeriodicalIF":3.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

New artificial neural network models for risk assessment of skin sensitization using amino acid derivative assay, KeratinoSens™, human cell line activation test and in silico structural alert parameter 使用氨基酸衍生物试验、KeratinoSens™、人类细胞系激活试验和硅结构警报参数进行皮肤致敏风险评估的新人工神经网络模型。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-06-16 DOI: 10.1016/j.yrtph.2025.105882

Kosuke Imai, Yuri Hatakeyama, Shiho Oeda, Toshiyuki Ohtake, Tomomi Atobe, Morihiko Hirota

{"title":"New artificial neural network models for risk assessment of skin sensitization using amino acid derivative assay, KeratinoSens™, human cell line activation test and in silico structural alert parameter","authors":"Kosuke Imai, Yuri Hatakeyama, Shiho Oeda, Toshiyuki Ohtake, Tomomi Atobe, Morihiko Hirota","doi":"10.1016/j.yrtph.2025.105882","DOIUrl":"10.1016/j.yrtph.2025.105882","url":null,"abstract":"<div><div>In the next-generation risk assessment (NGRA) of skin sensitization, estimating the point of departure (PoD) is crucial. The murine local lymph node assay (LLNA) has been considered the ‘gold standard’ for evaluating the skin sensitizing potential of chemicals, with the LLNA EC3 values serving as the PoD for dermal quantitative risk assessment (QRA). This study presents artificial neural network (ANN) models that predict EC3 values, enhanced by integrating the Amino Acid Derivative Reactivity Assay (ADRA) to expand the applicability domain. Initially, descriptors derived from ADRA, based on both molar and gravimetric concentrations, showed significant correlations with LLNA EC3 values. We then constructed prediction models using ANN analysis, incorporating parameters from GL497-adopted methods. These models exhibited a strong correlation with LLNA EC3 values. The predicted EC3 values for molar and gravimetric concentrations correlated well with each other and with previous values from an ANN model using DPRA instead of ADRA. Additionally, the prediction accuracy of ANN models combined with “2 out of 3″ negative judgment for GHS classification was comparable to that of ITSv1/v2. Ultimately, this enables QRA for a broader range of substances using predictive EC3 values as PoDs without animal testing, paving the way for more effective risk assessments.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"162 ","pages":"Article 105882"},"PeriodicalIF":3.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144294843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Risk (Re)assessment of N-Methyl-N-nitrosophenethylamine for use in computing risk levels of N-Nitrosamine drug substance related impurities 用于计算n -亚硝胺类药物相关杂质风险水平的n -甲基-n -亚硝基苯基乙胺的风险（再）评估

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-06-16 DOI: 10.1016/j.yrtph.2025.105888

David R. Woolley , George E. Johnson , Kevin P. Cross

{"title":"Risk (Re)assessment of N-Methyl-N-nitrosophenethylamine for use in computing risk levels of N-Nitrosamine drug substance related impurities","authors":"David R. Woolley , George E. Johnson , Kevin P. Cross","doi":"10.1016/j.yrtph.2025.105888","DOIUrl":"10.1016/j.yrtph.2025.105888","url":null,"abstract":"<div><div>Management of N-Nitrosamine impurity levels in pharmaceutical drug substances and products is guided by ICH M7 where N-nitrosamines are defined as Cohorts of Concern. Regulatory agencies have suggested using read-across of rodent carcinogenicity TD50 values for structurally similar compounds to assess the potency of various data-poor N-nitrosamines. The TD50 for N-Methyl-N-nitrosophenethylamine (NMPEA) as reported in the CPDB with a harmonic mean TD50 value 7.88 μg/kg/day (or an Acceptable Intake (AI) level of 8 ng/day) did not follow the recommendations of ICH M7. Mixed tissues (oesophagus, forestomach, tongue, and nasal cavity) were combined into a single group termed “upper gastro-intestinal tract”. Upon examination of the original data, the oesophagus was considered the most sensitive organ of effect. The TD50 value for the oesophagus was recalculated to 40.1 μg/kg/day (or an AI of 40.1 ng/day). Subsequently, Benchmark Dose (BMD) analysis was performed on the same data set yielding a BMD10 of 3.06–17.6 μg/kg/day in rat (or Permitted Daily Exposure range of 306–1760 ng/day). Theses updated values are 5 times (or higher than) the current AI level of 8 ng/day and could result in significantly higher AI limits for marketed drug impurities that use NMPEA as a suitable analog (e.g., N-nitroso- nortriptyline) to derive an AI.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"162 ","pages":"Article 105888"},"PeriodicalIF":3.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144298736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Analysis of cellular and gene therapy product reviews in the United States 美国细胞和基因治疗产品评论分析。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-06-16 DOI: 10.1016/j.yrtph.2025.105885

Cheng-Fang Weng, Jhe-Yuan Dong, Shiuan-Fei Lin, Ai-Lei Jiang, Yu-Li Cheng, Lin-Chau Chang

{"title":"Analysis of cellular and gene therapy product reviews in the United States","authors":"Cheng-Fang Weng, Jhe-Yuan Dong, Shiuan-Fei Lin, Ai-Lei Jiang, Yu-Li Cheng, Lin-Chau Chang","doi":"10.1016/j.yrtph.2025.105885","DOIUrl":"10.1016/j.yrtph.2025.105885","url":null,"abstract":"<div><div>The emergence of cellular and gene therapy (CGT) products has profoundly transformed healthcare by addressing previously unmet medical needs. However, developing these innovative therapies presents complex regulatory challenges that require thorough examination. This study aimed to identify strategies to mitigate potential delays or rejections in the CGT approval process. By analyzing review documents from the United States Food and Drug Administration, we found that quality concerns were the primary focus of Complete Response letters and postmarketing commitments, while safety concerns predominantly shaped postmarketing requirements, reflecting persistent uncertainties around CGTs. The unique characteristics of CGTs were also evident in their individualized clinical trial designs. Although the regulatory landscape is intricate, the increasing diversity of CGTs and accumulated experience have clarified key product-specific challenges. To facilitate approvals, it is crucial for applicants to address these deficiencies early, while we recommend that regulatory authorities re-evaluate the scope of utilizing postmarketing requirements. Enhanced collaboration among academia, industry, and regulatory authorities is essential to identify balanced, effective strategies, while continuous information gathering and monitoring are vital to ensure the safe, long-term administration of approved CGTs.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"162 ","pages":"Article 105885"},"PeriodicalIF":3.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0