综合萃取物和浸出物致敏分析和基于风险的方法在肠外药物致敏评估中的实际应用。

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

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引用次数: 0

摘要

可提取和可浸出物安全信息交换（ELSIE）联盟通过纳入产品质量研究所（PQRI）可提取和可浸出数据集(Johnson等人，2024；产品质量研究所，2021)。对综合E&L数据集的分析显示，5%的化学品（20/407）的实验结果证明或预测为强致敏剂（强或极端），支持先前的结论，即强致敏剂的流行率低，并且在制药产品中不被常规观察到为可浸出物。通过考虑整个E&L数据集中的致敏率，考虑了任何潜在可浸出性比寿命较短的ICH M7（分别为10、20和120 μg/天，人类暴露于bb10 -10年、bb1 -12个月和10年至寿命、bb2 -10年和≤1年）更有效的可能性（Masuda-Herrera等人，2022）。预计M7和ELSIE阈值将提供≥95%的致敏诱导覆盖率，支持使用这些阈值来设置安全关注阈值（SCT）。

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

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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来源期刊

Regulatory Toxicology and Pharmacology 医学-毒理学

CiteScore

6.70

自引率

8.80%

发文量

147

审稿时长

58 days

期刊介绍： Regulatory Toxicology and Pharmacology publishes peer reviewed articles that involve the generation, evaluation, and interpretation of experimental animal and human data that are of direct importance and relevance for regulatory authorities with respect to toxicological and pharmacological regulations in society. All peer-reviewed articles that are published should be devoted to improve the protection of human health and environment. Reviews and discussions are welcomed that address legal and/or regulatory decisions with respect to risk assessment and management of toxicological and pharmacological compounds on a scientific basis. It addresses an international readership of scientists, risk assessors and managers, and other professionals active in the field of human and environmental health. Types of peer-reviewed articles published: -Original research articles of relevance for regulatory aspects covering aspects including, but not limited to: 1.Factors influencing human sensitivity 2.Exposure science related to risk assessment 3.Alternative toxicological test methods 4.Frameworks for evaluation and integration of data in regulatory evaluations 5.Harmonization across regulatory agencies 6.Read-across methods and evaluations -Contemporary Reviews on policy related Research issues -Letters to the Editor -Guest Editorials (by Invitation)