含亚硝胺杂质的药品对我国仿制药参比制剂可及性的影响

doi:10.5246/jcps.2025.01.007

中国药学(英文版) ›› 2025, Vol. 34 ›› Issue (1): 75-81.DOI: 10.5246/jcps.2025.01.007

• 【药事管理与临床药学专栏】 • 上一篇

含亚硝胺杂质的药品对我国仿制药参比制剂可及性的影响

杨东升, 牛剑钊, 冯玉飞, 刘年, 马玲云^*()

中国食品药品检定研究院, 北京 100050

收稿日期:2024-09-21 修回日期:2024-10-11 接受日期:2024-11-12 出版日期:2025-02-20 发布日期:2025-02-20
通讯作者: 马玲云

Effects of nitrosamine impurities on the availability of Reference Listed drugs in China

Dongsheng Yang, Jianzhao Niu, Yufei Feng, Nian Liu, Lingyun Ma^*()

National Institutes for Food and Drug Control, Beijing 100050, China

Received:2024-09-21 Revised:2024-10-11 Accepted:2024-11-12 Online:2025-02-20 Published:2025-02-20
Contact: Lingyun Ma
Supported by:
Subject construction funding project of Institute for Chemical Drug Control (Grant No. 2024HYZX42) in National Institutes for Food and Drug Control, Beijing, China.

摘要/Abstract

摘要：

参比制剂是我国仿制药上市申请和一致性评价中使用的对照药品, 对仿制药的研发具有极其重要的作用。我国参比制剂具有多种来源, 其质量和市场可及性也受到各种因素和突发事件制约, 例如亚硝胺杂质事件。药品中被报道可能出现亚硝胺类杂质是近年来医药领域的新热点问题。目前, 因可能存在亚硝胺杂质而被报道的药品共有5类: 沙坦类、含二甲双胍类、雷尼替丁类、利福平类和酒石酸伐尼克兰片。本文介绍了美国和欧盟药品监管机构对含亚硝胺杂质药品的不同控制措施, 并结合实际分析其对我国参比制剂市场可及性和质量产生的影响, 为国内外仿制药生产企业和药品监管机构提供参考。

关键词: 参比制剂, 亚硝胺类杂质, 食品药品监督管理局, 欧洲药品管理局, 可及性

Abstract:

The Reference Listed drug (RLD) plays a critical role in the development and research of generic medicinal products, serving as the comparator product used in the marketing authorization application of new generic medicinal product and re-evaluation of generic medicinal product. In China, RLDs are sourced from various origins, but their quality and market availability can be constrained by multiple factors, including emergent issues such as nitrosamine impurities. Five classes of medicinal products have been reported to be at risk for containing nitrosamine impurities: sartan-based medicines, metformin-containing products, ranitidine medicines, rifampicin medicines, and Champix. This paper explores the control strategies implemented by drug regulatory agencies in the United States and the European Union to manage nitrosamine impurities and assesses their impact on the market availability and quality of RLDs in China. The aim is to offer valuable insights for generic drug manufacturers and regulatory bodies both domestically and internationally.

Key words: Reference Listed drugs, Nitrosamine impurities, Food and Drug Administration, European Medicines Agency, Availability

Supporting:

杨东升, 牛剑钊, 冯玉飞, 刘年, 马玲云. 含亚硝胺杂质的药品对我国仿制药参比制剂可及性的影响[J]. 中国药学(英文版), 2025, 34(1): 75-81.

Dongsheng Yang, Jianzhao Niu, Yufei Feng, Nian Liu, Lingyun Ma. Effects of nitrosamine impurities on the availability of Reference Listed drugs in China[J]. Journal of Chinese Pharmaceutical Sciences, 2025, 34(1): 75-81.

图/表 5

Figure 1. The affected RLDs of nitrosamine impurities in the published Chinese comparator product directories.

Table 1. Summary of the metformin-containing RLDs influenced by nitrosamine impurities.

Table 2. Summary of the RLDs of ranitidine medicines influenced by nitrosamine impurities.

Table 3. Summary of the RLDs of rifampicin medicines influenced by nitrosamine impurities.

Table 4. Summary of the RLDs of champix medicines influenced by nitrosamine impurities.

参考文献 17

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含亚硝胺杂质的药品对我国仿制药参比制剂可及性的影响

Effects of nitrosamine impurities on the availability of Reference Listed drugs in China

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