Finotti Cordeiro Cleydson, Lopardi Franco Lucas, Teixeira Carvalho Diogo, Bonfilio Rudy
Faculty of Pharmaceutical Sciences, Federal University of Alfenas (UNIFAL-MG), Alfenas, Minas Gerais, Brazil.
Crit Rev Anal Chem. 2024 Jul 26:1-21. doi: 10.1080/10408347.2024.2384046.
The presence of impurities in active pharmaceutical ingredients (APIs) and drug products represents a risk to patients' health. Such substances are related to diverse side effects and may have mutagenic potential. That's why it is necessary to establish acceptable limits for these by-products, to minimize the risk associated with medicinal therapy. This work focused on presenting a critical review of relevant points related to the presence of impurities in pharmaceuticals. The main legislation and guidelines from the FDA, EMA, ICH, and Pharmacopeias about the subject were evaluated, and recent articles related to the topic were searched in Scopus, ScienceDirect, PubMed, and Web of Science from 2013 to 2023. Additionally, the analytical techniques used for quantifying impurities were discussed, along with relevant tests for assessing the toxicological and mutagenic risks of these by-products. Recent legislation, including ICH Q3A (R2), ICH Q3B (R2), ICH M7 (R2), ICH Q3D (R2), ICH Q3C (R9), ICH Q3E, ICH Q6A, ICH M3 (R2), as well as FDA and EMA guidelines, highlights a comprehensive and effective framework for controlling impurities in pharmaceuticals. Despite this, there remains a lack of harmonization and standardized procedures across different regions. From the review of scientific literature, we observed that advancements in analytical techniques have significantly improved the sensitivity and selectivity in detecting impurities and degradation products. This underscores the ongoing commitment of health agencies and the pharmaceutical industry to ensure the safety and efficacy of medicinal products.
活性药物成分（API）和药品中杂质的存在对患者健康构成风险。此类物质与多种副作用相关，可能具有诱变潜力。这就是为何有必要为这些副产物设定可接受限度，以将药物治疗相关风险降至最低。这项工作着重对与药品中杂质存在相关的要点进行批判性综述。评估了美国食品药品监督管理局（FDA）、欧洲药品管理局（EMA）、人用药品注册技术协调国际会议（ICH）以及各药典关于该主题的主要法规和指南，并在Scopus、ScienceDirect、PubMed和Web of Science数据库中检索了2013年至2023年期间与该主题相关的近期文章。此外，还讨论了用于定量杂质的分析技术，以及评估这些副产物毒理学和诱变风险的相关测试。包括ICH Q3A（R2）、ICH Q3B（R2）、ICH M7（R2）、ICH Q3D（R2）、ICH Q3C（R9）、ICH Q3E、ICH Q6A、ICH M3（R2）在内的近期法规以及FDA和EMA的指南，凸显了一个控制药品中杂质的全面且有效的框架。尽管如此，不同地区之间仍缺乏协调统一和标准化程序。从科学文献综述中我们观察到，分析技术方面的进步显著提高了检测杂质和降解产物的灵敏度和选择性。这突显了卫生机构和制药行业为确保药品安全性和有效性所做出的持续努力。
