Regulatory Toxicology and Pharmacology最新文献_第4页

PBT/PMT assessment of active pharmaceutical ingredients 有效药物成分的PBT/PMT评价。

IF 3 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub Date : 2025-02-01 DOI: 10.1016/j.yrtph.2025.105772

Gemma Janer , Joanne Elmoznino , Andreas Häner , Irene Bramke

The EU Commission proposal for a new EU pharmaceutical legislation considers PBT (persistence-bioaccumulation-toxicity) and PMT (persistence-mobility-toxicity) criteria for pharmaceuticals. Under current environmental risk assessment guidance, a PBT assessment is required regardless of the predicted environmental concentrations. However, consumption volumes of pharmaceuticals are contingent on marketing approval by EMA and are therefore predictable and their toxicological potency is established prior to any regulatory approval. Consumption volume and toxicological potency of pharmaceuticals span many orders of magnitude and are strong risk determinants. Routine data generation to evaluate persistence, mobility and bioaccumulation hazards as a means of pinpointing pharmaceuticals of increased environmental concern is therefore of questionable added value.

We present options to derive action triggers for PBT and/or PMT screening using exposure predictions and toxicological potency data. Our simulations demonstrate that an exposure-based action limit can be established as a trigger for PMT assessment, while a combined trigger based on exposure levels and mammalian toxicity is proposed for PBT assessment. The proposed approach is conservatively designed to ensure that compounds with any potential risks a) of secondary poisoning (main concern for PBT substances) and b) to groundwater/drinking water (main concern for PMT substances) are targeted for full evaluation.

欧盟委员会提出了一项新的欧盟制药立法，考虑了药品的PBT（持久性-生物积累-毒性）和PMT（持久性-流动性-毒性）标准。根据目前的环境风险评估指导，无论预测的环境浓度如何，都需要进行PBT评估。然而，药品的消费量取决于EMA的上市批准，因此是可预测的，其毒理学效力在任何监管批准之前就已确定。药品的消费量和毒理学效力跨越许多数量级，是强有力的风险决定因素。因此，为评价持久性、移动性和生物蓄积性危害而产生的常规数据，作为确定日益引起环境关注的药物的手段，其附加价值值得怀疑。我们提出了使用暴露预测和毒理学效力数据来获得PBT和/或PMT筛查的行动触发因素的选择。我们的模拟表明，基于暴露的作用限值可以作为PMT评估的触发因素，而基于暴露水平和哺乳动物毒性的组合触发因素可以用于PBT评估。拟议的方法设计保守，以确保具有任何潜在风险的化合物a)二次中毒（主要关注PBT物质）和b)地下水/饮用水（主要关注PMT物质）是全面评估的目标。

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引用次数: 0

Comprehensive extractables and leachables sensitization analysis and practical application of a risk-based approach to sensitization assessment for parenteral drug products

IF 3 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub Date : 2025-01-28 DOI: 10.1016/j.yrtph.2025.105776

Patricia Parris , Geraldine Whelan , Martyn L. Chilton , Claire Beaumont , Anders Burild , Uma Bruen , Courtney Callis , Jessica Graham , Natalia Kovalova , Elizabeth A. Martin , Melisa Masuda-Herrera , Carsten Worsøe , Anissa Alami , Joel Bercu , Dvir Doron , Kristen Dusenbury , Qiang Fu , Troy Griffin , Jedd Hillegass , Esther Johann , Lee Nagao

The Extractables and Leachables Safety Information Exchange (ELSIE) Consortium added to the sensitization potency analysis of Parris et al. (2023) by including the Product Quality Research Institute (PQRI) extractable and leachable dataset (Johnson et al., 2024; Product Quality Research Institute, 2021). This analysis of the comprehensive E&L dataset showed 5% of chemicals (20/407) had experimental results demonstrating or were predicted to be potent (strong or extreme) sensitizers, supporting the previous conclusion, that potent sensitizers are of low prevalence and are not routinely observed as leachables in pharmaceutical products. By accounting for prevalence of sensitization in the overall E&L dataset, the probability of any potential leachable being more potent than the less than lifetime ICH M7 (10, 20, and 120 μg/day for human exposure of >1–10 years, >1–12 months, and <1 month respectively) and non-mutagenic ELSIE threshold values (35, 110, and 180 μg/day for human exposures of >10 years to lifetime, >1–10 years, and ≤1 year respectively) (Masuda-Herrera et al., 2022) was considered. The M7 and ELSIE thresholds are anticipated to provide ≥95% coverage of induction of sensitization, supporting the use of these thresholds to set the Safety Concern Threshold (SCT).

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引用次数: 0

Control performance of Amphibian Metamorphosis Assays with Xenopus laevis 非洲爪蟾防治两栖动物变态试验的效果。

IF 3 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub Date : 2025-01-18 DOI: 10.1016/j.yrtph.2025.105773

James R. Wheeler , Raechel Puglisi , Adriana C. Bejarano , Zhenglei Gao , Laurent Lagadic , Scott Glaberman , Constance A. Mitchell , Natalie Burden , Valentin Mingo , Scott G. Lynn , Michelle R. Embry

The amphibian metamorphosis assay (AMA) is an in vivo screen to assess potential interactions of chemicals with the amphibian thyroid system. Tadpoles are exposed for 21-days, then assessed for development and growth after 7 days and at test termination. This paper presents data from studies performed to satisfy test orders from the US EPA's Endocrine Disruptor Screening Program. Data Evaluation Records were used to collate the control variability and performance of biological endpoints in AMAs conducted in different laboratories, then supplemented with recent studies. We examine the statistical power of AMA endpoint analysis and assess whether historical control data (HCD) can assist evidence-based interpretation of the endpoints, with 52 studies from 7 different laboratories. HCD can be used to understand assay performance post validation. The analysis identifies some need for flexibility in the interpretation of the Test Guidelines' performance criteria, including latitude with analytical variability and statistical analysis of late-stage animals. Additionally, more guidance is suggested for feed regiments and the selection criteria for batches of animals to initiate the assay. Potential Guideline refinements that improve interpretation of the data and have potential to reduce the number of vertebrate animals used in the conduct of AMAs are identified and discussed.

两栖动物变态试验（AMA）是一种体内筛选，以评估化学物质与两栖动物甲状腺系统的潜在相互作用。蝌蚪暴露21天，然后在7天后和试验结束时评估发育和生长情况。本文介绍了为满足美国环境保护局内分泌干扰物筛选计划的测试要求而进行的研究数据。数据评估记录用于整理在不同实验室进行的ama生物终点的控制变异性和性能，然后补充最近的研究。我们通过来自7个不同实验室的52项研究，检验了AMA终点分析的统计能力，并评估了历史对照数据（HCD）是否有助于对终点的循证解释。HCD可用于了解验证后的分析性能。该分析确定了在解释《试验指南》的性能标准方面需要一些灵活性，包括具有分析变异性的纬度和后期动物的统计分析。此外，建议对饲料团和开始试验的动物批次的选择标准提供更多指导。确定并讨论了潜在的指南改进，以改进对数据的解释，并有可能减少用于进行ama的脊椎动物的数量。

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引用次数: 0

A Comprehensive Safety Assessment of Algae Protein from Picochlorum for Human Consumption. 人类食用Picochlorum藻类蛋白的安全性综合评价。

IF 3 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub Date : 2024-11-28 DOI: 10.1016/j.yrtph.2024.105753

Tomal Dattaroy, Manish R Shukla

The current trend happens to be that consumers are seeking nourishing, high quality sustainable protein sources to meet their nutritional needs, thus establishing a clear intent to broaden their protein horizon. Microalgae protein holds great promise in becoming the next vegan protein option. In the present study, protein extracted from the microalga Picochlorum maculatum has been thoroughly evaluated for its safety for human consumption through a battery of in-vivo and in-vitro tests. Bacterial reverse mutation assay indicates that the test substance is non-mutagenic and studies comprising of in-vitro chromosomal aberration test and the in-vivo mammalian micronucleus test showed that the test item is non-clastogenic, and therefore, lacks genotoxicity. Based the results of an acute oral toxicity study, the test item can be classified as "Category 5" as designated in a globally harmonized system for classification of chemicals. Further, 28-day and 90-day repeated dose oral toxicity studies did not result in any mortality or morbidity throughout the experimental period; none of the animal groups used in the study showed any abnormal clinical signs, establishing a "No Observed Adverse Effect Level" of Algae Protein Powder at 3000 mg kg bw^-1. Moreover, the test item exhibited a positive impact on growth in test animals. Computational studies established extremely low allergenic potential of the test item.

目前的趋势是，消费者正在寻求营养丰富、高质量的可持续蛋白质来源，以满足他们的营养需求，从而建立了一个明确的意图，以扩大他们的蛋白质视野。微藻蛋白有望成为下一个纯素蛋白的选择。在本研究中，通过一系列体内和体外试验，对从微藻Picochlorum maculatum中提取的蛋白质进行了全面的安全性评估，以供人类食用。细菌反突变试验表明该试验物质不具有诱变性，体外染色体畸变试验和哺乳动物体内微核试验研究表明该试验项目不具有致裂性，因此不具有遗传毒性。根据急性口服毒性研究的结果，该测试项目可根据全球统一的化学品分类系统归类为“第5类”。此外，28天和90天的重复剂量口服毒性研究在整个实验期间没有导致任何死亡率或发病率；本研究使用的动物组均未出现任何异常临床症状，建立了3000 mg kg bw-1的藻类蛋白粉“未观察到不良反应水平”。此外，测试项目对实验动物的生长表现出积极的影响。计算研究证实该测试项目极低的致敏潜力。

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引用次数: 0

Considerations and derivations of permitted daily exposure limits for impurities from intravitreal pharmaceutical products 考虑并推导出玻璃体内药物杂质的每日允许接触限值。

IF 3 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub Date : 2024-11-22 DOI: 10.1016/j.yrtph.2024.105745

Yi Yu Rice , David G. Dolan , Suren B. Bandara , Ryan E. Morgan , Michael Garry , Joyce Tsuji

Intravitreal (IVT) injection is an uncommon route of parenteral administration for therapeutic medications, but one of the most important for the treatment of ocular diseases, especially those related to macular degeneration. Nonetheless, there are currently no regulatory guidelines that specifically address how to establish a permitted daily exposure (PDE) for impurities and residual process reagents in IVT pharmaceutical drug products given the unique vulnerability of ocular tissues. The establishment of PDEs for IVT administration is complicated by the limited understanding of metabolism and clearance of small molecular weight chemicals from the human vitreous humor (VH), a problem compounded by the limited IVT-specific toxicological data. In this paper, we describe a feasible and comprehensive methodology for deriving PDE limits for impurities and residual process reagents from IVT drug products, as exemplified by five case studies, including inorganic elements, formic acid, polyethylene glycols, acetic acid, and caprolactam. The five case studies were selected to cover compounds with a wide range of impurity sources and toxicological data availability. The proposed framework considers both local ocular and systemic toxicity endpoints and advances the goal of a harmonized, science-based approach for deriving IVT PDE limits.

玻璃体内注射（IVT）是一种不常见的非肠道给药途径，但却是治疗眼部疾病（尤其是与黄斑变性有关的疾病）最重要的途径之一。然而，鉴于眼部组织的特殊脆弱性，目前还没有专门针对如何确定静脉注射药物产品中杂质和残留工艺试剂的允许日暴露量（PDE）的监管指南。由于对人类玻璃体液（VH）中小分子量化学物质的代谢和清除了解有限，制定静脉注射用药的 PDE 变得更加复杂，而静脉注射用药的特定毒理学数据有限又加剧了这一问题。在本文中，我们介绍了一种可行且全面的方法，用于推导静脉注射药物产品中杂质和残留工艺试剂的 PDE 限值，并通过无机元素、甲酸、聚乙二醇、乙酸和己内酰胺等五个案例研究加以说明。选择这五个案例研究是为了涵盖杂质来源和毒理学数据可用性范围广泛的化合物。建议的框架同时考虑了局部眼部和全身毒性终点，并推进了以科学为基础的统一方法推导 IVT PDE 限值的目标。

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引用次数: 0

Carcinogenicity assessment of inotersen in Tg.rasH2 mice and Sprague-Dawley rats: Implications for 2′-MOE antisense oligonucleotides Inotersen 在 Tg.rasH2 小鼠和 Sprague-Dawley 大鼠中的致癌性评估：2'-MOE反义寡核苷酸的意义。

IF 3 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub Date : 2024-11-22 DOI: 10.1016/j.yrtph.2024.105743

Tae-Won Kim , Chris N. Papagiannis , Laura S. Zwick , Paul Snyder , Jeffery A. Engelhardt , Rosie Z. Yu , Christine M. Hoffmaster , Archit Rastogi , Scott P. Henry

Inotersen, a 2′-O-(2-methoxyethyl) modified antisense oligonucleotide (2′-MOE ASO), is approved for the treatment of hereditary transthyretin-mediated amyloidosis (hATTR). It underwent a comprehensive nonclinical safety evaluation, including safety pharmacology, repeat-dose toxicity, genotoxicity, reproductive and development toxicity, and carcinogenicity studies. Tumorigenic potential was assessed through dedicated carcinogenicity studies in transgenic rasH2 (Tg.rasH2) mice and Sprague Dawley (SD) rats. In the 26-week Tg.rasH2 mouse study, inotersen and a mouse-active surrogate (ISIS 401724) were administered as weekly subcutaneous (SC) doses up to 80 mg/kg and 30 mg/kg, respectively. Proinflammatory effects and ASO accumulation in the liver and kidney, both well-documented class effects, were observed; however, no treatment-related neoplasms were noted. Similarly, the mouse surrogate did not induce any treatment-related neoplasms. In the 2-year SD rat carcinogenicity study, inotersen was administered as weekly SC doses up to 6 mg/kg. The primary dose-limiting effect at doses ≥2 mg/kg/week was an increased incidence of chronic progressive nephropathy (CPN), which contributed to decreased survival at the 6 mg/kg/week dose level. Notably, no renal neoplasia was associated with the increased CPN. Increasing mononuclear cell infiltrates at the injection site were linked to an increased incidence of subcutaneous fibrosarcoma at doses ≥2 mg/kg/week. This inflammation-associated injection site tumor in rats administered inotersen has limited relevance for humans. Additionally, the long-term assessment of ASO effects in rats is somewhat limited due to the ASO exacerbation of CPN and its impact on survival. There was no evidence of genotoxicity in vitro or in vivo at limit doses. Collectively, these data support a conclusion that a single carcinogenicity assessment in the Tg.rasH2 mouse, along with data from chronic toxicology studies in the rodent and nonrodent, is sufficient to assess carcinogenic potential for this drug class.

Inotersen是一种2'-O-（2-甲氧基乙基）修饰的反义寡核苷酸（2'-MOE ASO），已被批准用于治疗遗传性经甲状腺素介导的淀粉样变性（hATTR）。该药物经过了全面的非临床安全性评估，包括安全性药理学、重复剂量毒性、遗传毒性、生殖和发育毒性以及致癌性研究。通过对转基因 rasH2（Tg.rasH2）小鼠和 Sprague Dawley（SD）大鼠进行专门的致癌性研究，对其致癌潜力进行了评估。在为期 26 周的 Tg.rasH2 小鼠研究中，inotersen 和小鼠活性替代物（ISIS 401724）的每周皮下注射（SC）剂量分别高达 80 毫克/千克和 30 毫克/千克。观察到了促炎效应以及 ASO 在肝脏和肾脏中的蓄积，这两种效应都是有据可查的一类效应；但是，没有发现与治疗相关的肿瘤。同样，小鼠代用品也没有诱发任何与治疗相关的肿瘤。在为期 2 年的 SD 大鼠致癌性研究中，伊诺替生的每周 SC 剂量最高为 6 毫克/千克。当剂量≥2 毫克/千克/周时，主要的剂量限制效应是慢性进行性肾病（CPN）的发病率增加，这导致了 6 毫克/千克/周剂量水平的存活率下降。值得注意的是，肾脏肿瘤与 CPN 的增加无关。注射部位单核细胞浸润的增加与剂量≥2 毫克/千克/周时皮下纤维肉瘤发病率的增加有关。大鼠注射伊诺特生后出现的注射部位炎症相关肿瘤与人类的相关性有限。此外，由于 ASO 会加重 CPN 及其对存活率的影响，因此对 ASO 对大鼠影响的长期评估具有一定的局限性。在极限剂量下，体外和体内均无遗传毒性证据。总之，这些数据支持这样一个结论，即在 Tg.rasH2 小鼠中进行一次致癌性评估，再加上在啮齿类动物和非啮齿类动物中进行的慢性毒理学研究数据，就足以评估这类药物的致癌性。

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引用次数: 0

Enhancing reliability of embryo-fetal developmental toxicity studies: A proposed design of replicate studies 提高胚胎-胎儿发育毒性研究的可靠性：拟议的重复研究设计

IF 3 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub Date : 2024-11-20 DOI: 10.1016/j.yrtph.2024.105742

L. David Wise

Background

This report addresses the reliability of results from rat Embryo-Fetal Developmental Toxicity (EFDT) studies. Recent literature discusses the roles of reproducibility, replicability, and other influences on scientific reliability. Reproducibility is a re-analysis of the original data, while replicability addresses the same question with a separate study of some type. Concordance of rat and rabbit studies has been addressed previously, but replication of single-species EFDT studies was not found in the literature. A modest modification of the rat study is therefore proposed to assess replicability and possibly enhance reliability.

Methods

Regulatory guidelines were consulted and relevant literature was identified through online searches.

Results

Each replicate EFDT (r-EFDT) study in rats would consist of half the mated females of the definitive study. Studies would start at the same or different times in one testing facility. Separate shipments of animals (non-littermates) are required. All other procedures would be protocol-driven. The micro- and macro-environments of the animals would be held as constant as possible. Justification, design options, and interpretation methods are discussed.

Conclusion

Besides adding reliability, other benefits include reduced animal usage, and potentially reduced cost and time to final reports. By reducing the need for repeated studies due to questionable results, this modified study is viewed as a more efficient use of costly resources. The r-EFDT study design could easily be adapted to assess replicability of rabbit EFDT and some general toxicity studies. Future replicate studies are needed to critically evaluate replicability and the overall impact on study reliability.

背景：本报告探讨了大鼠胚胎-胎儿发育毒性（EFDT）研究结果的可靠性。最近的文献讨论了可重复性、可复制性以及对科学可靠性的其他影响因素的作用。可重复性是对原始数据的重新分析，而可复制性则是通过某种类型的单独研究来解决同一问题。以前曾讨论过大鼠和兔子研究的一致性，但在文献中没有发现单物种 EFDT 研究的可复制性。因此，建议对大鼠研究进行适度修改，以评估可重复性并可能提高可靠性：方法：参考监管指南，并通过在线搜索确定相关文献：在大鼠中进行的每项重复 EFDT（r-EFDT）研究将由最终研究中交配雌鼠的一半组成。研究将在同一试验设施的相同或不同时间开始。需要单独运送动物（非配对动物）。所有其他程序都将按规程进行。动物的微观和宏观环境将尽可能保持不变。结论：除了增加可靠性外，其他好处还包括减少动物用量，并有可能降低最终报告的成本和时间。由于减少了因结果可疑而进行重复研究的需要，这项修改后的研究被视为更有效地利用了昂贵的资源。r-EFDT研究设计可以很容易地用于评估兔EFDT和一些一般毒性研究的可重复性。今后需要进行重复研究，以严格评估可重复性以及对研究可靠性的总体影响。

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引用次数: 0

Target organ toxicity in Sprague Dawley rats following oral exposure to complex groundwater mixture: Assessment of dose-response relationships using histopathological and biochemical alterations 口服复合地下水混合物对 Sprague Dawley 大鼠靶器官的毒性：利用组织病理学和生化变化评估剂量-反应关系。

IF 3 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub Date : 2024-11-19 DOI: 10.1016/j.yrtph.2024.105744

B. Boamah , S. Siciliano , N. Hogan , M. Hecker , M. Hanson , P. Campbell , R. Peters , A.N. Al-Dissi , L.P. Weber

Exposure to contaminant mixtures from industrial legacy sites presents unique challenges that require novel approaches such as effects-directed toxicity assessment. This study characterized the target organ toxicity of groundwater from a legacy contaminated pesticide plant in male and female Sprague Dawley rats exposed to low impact (10% v/v) groundwater, high impact (0.01% v/v, 0.1% v/v, 1% v/v, and 10% v/v) groundwater or tap water (control) for 60 days. Rats exposed to high impact (1% and 10%) and 10% low impact groundwater mixture showed statistically significant increases in liver necro-inflammation relative to control. A statistically significant reduction was observed in plasma albumin of exposed rats (except 0.01% high impact) and alpha 2 macroglobulin (all exposed) when compared to the control. All groundwater-exposed rats showed glomerulopathy, but there were sex-specific differences in acute tubular necrosis. Testes showed germinal cell vacuolation, necrosis, reduced seminiferous epithelial height, and Sertoli syndrome in exposed rats, accompanied by reduced plasma testosterone and increased testicular malondialdehyde. Taken together, this sub-chronic oral exposure to groundwater from a contaminated industrial site caused dose-dependent hepatic and testicular toxicity, while nephrotoxicity was both sex-dependent and dose-dependent. This study provides support for the essentiality of using effects-driven approaches in the risk assessment of complex mixtures.

暴露于工业遗留场地的污染物混合物带来了独特的挑战，需要采用新的方法，如效应导向毒性评估。这项研究描述了受遗留农药厂污染的地下水对雄性和雌性 Sprague Dawley 大鼠靶器官的毒性，这些大鼠分别接触了低影响（10% v/v）、高影响（0.01% v/v、0.1% v/v、1% v/v 和 10% v/v）地下水或自来水（对照组）60 天。与对照组相比，接触高浓度（1% 和 10%）和 10% 低浓度地下水混合物的大鼠肝脏坏死性炎症在统计学上显著增加。与对照组相比，接触地下水的大鼠血浆白蛋白（0.01% 高浓度影响除外）和甲 2 巨球蛋白（所有接触者）在统计学上有明显降低。所有接触地下水的大鼠都出现了肾小球病变，但急性肾小管坏死存在性别差异。接触地下水的大鼠睾丸出现生殖细胞空泡、坏死、曲细精管上皮高度降低和 Sertoli 综合征，并伴有血浆睾酮降低和睾丸丙二醛增加。总之，亚慢性口服接触受污染工业场地的地下水会导致剂量依赖性的肝脏和睾丸毒性，而肾毒性则具有性别依赖性和剂量依赖性。这项研究证明，在对复杂混合物进行风险评估时，必须采用效应驱动法。

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引用次数: 0

Minimizing the risk of ethylene glycol and diethylene glycol poisoning in medications: A regulatory and pharmacopoeial response 将药物中乙二醇和二甘醇中毒的风险降至最低：监管和药典对策》。

IF 3 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub Date : 2024-11-18 DOI: 10.1016/j.yrtph.2024.105741

Pawan Kumar, Shruti Rastogi, Pawan Kumar Saini, Saurabh Sahoo, Rajeev Singh Raghuvanshi, Gaurav Pratap Singh Jadaun

Pharmaceutical and personal care products, including syrups and toothpastes, extensively use glycerin, sorbitol, and propylene glycol. However, past incidents of ethylene glycol (EG) and diethylene glycol (DEG) contamination in these products have raised serious health concerns. Recently, several child deaths linked to contaminated cough syrup consumption have heightened concerns regarding the safety of Indian pharmaceuticals. In response, Indian drug regulatory authorities and the Indian Pharmacopoeia have implemented several measures to enhance the quality, safety, and efficacy of pharmaceuticals manufactured in India. These measures encompass risk-based inspections of manufacturing facilities, rigorous quality control checks of medicinal products intended for export, and increased transparency in the supply chain of excipients prone to EG and DEG contamination. Further, the Indian Pharmacopoeia has updated monographs for five high-risk excipients: glycerin, propylene glycol, sorbitol solution (70%, both crystallizing and non-crystallizing), and liquid maltitol. These efforts are consistent with global regulatory standards and aim to ensure the overall quality and safety of pharmaceuticals produced in India.

包括糖浆和牙膏在内的医药和个人护理产品广泛使用甘油、山梨醇和丙二醇。然而，过去这些产品中出现的乙二醇（EG）和二甘醇（DEG）污染事件引起了严重的健康问题。最近，几起儿童死亡事件与饮用受污染的止咳糖浆有关，这加剧了人们对印度药品安全性的担忧。对此，印度药品监管机构和印度药典已采取多项措施，以提高印度生产的药品的质量、安全性和有效性。这些措施包括对生产设施进行基于风险的检查，对准备出口的医药产品进行严格的质量控制检查，以及提高易受 EG 和 DEG 污染的辅料供应链的透明度。此外，印度药典还更新了五种高风险辅料的各论：甘油、丙二醇、山梨醇溶液（70%，包括结晶型和非结晶型）和液体麦芽糖醇。这些努力符合全球监管标准，旨在确保印度生产的药品的整体质量和安全。

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引用次数: 0

Response to Letter to Editors submitted by PE Rasmussen, P Huntsman, TM Singer, MN Jacobs, and CC Trevithick-Sutton (Aug 2024) 对 PE Rasmussen、P Huntsman、TM Singer、MN Jacobs 和 CC Trevithick-Sutton 提交的致编辑信的回复（2024 年 8 月）。

IF 3 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub Date : 2024-11-16 DOI: 10.1016/j.yrtph.2024.105740

Adriana Oller , João Barroso , Pilar Prieto , Violaine Verougstraete , Katherine Heim , Rayetta Henderson

引用次数: 0