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

doi:10.5246/jcps.2025.01.007

Abstract

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:

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.

Figures/Tables 5

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.

References 17

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