Swissmedic: Risk Assessment for Nitrosamine Drug Substance-Related Impurities (NDSRI)
Swissmedic has further specified risk assessment measures for Nitrosamine Drug Substance-Related Impurities (NDSRI). Initially identified in 2018, nitrosamine impurities, including those in antihypertensives, prompted ongoing evaluations and measures by Swissmedic to prevent such impurities.
International collaboration led to the development of the Carcinogenic Potency Categorization Approach (CPCA) and the Enhanced Ames Test (EAT) as tools to assess Nitrosamine risks and define acceptable intakes. Swissmedic relies on these tools to avoid impurities in medicinal products, emphasizing patient safety.
The impurities found in 2018 were simple nitrosamine compounds such as NDMA and NDEA, but subsequent analyses revealed more complex Nitrosamine drug substance-related impurities (NDSRIs) in both products and active substances. These can occur during manufacturing or storage, when active substances react with trace nitrites in excipients. Swissmedic's analyses identified NDSRIs even when the manufacturing process suggested no nitrosamine formation.
In summer 2023, international therapeutic product authorities updated guidelines to include a risk assessment model (CPCA), updated acceptable intakes (AI) for nitrosamines, and the Enhanced Ames Test (EAT) to determine permissible intakes. Swissmedic continues to follow EMA's published acceptable intakes, requiring marketing authorization holders to perform risk-based evaluations for products prone to nitrosylation and submit results.
For NDSRIs, lacking specific experimental data on carcinogenic potential, the CPCA was developed. Swissmedic prioritizes measures for CPCA categories with the highest potential risks to patient safety, requiring identification of preparations with potential NDSRIs in CPCA categories 1 and 2 by January 31, 2024. The results of analytical testing for these categories must be submitted to Swissmedic by September 30, 2024.
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