Swissmedic updated requirements for dealing with potential nitrosamine impurities in medicinal products

Risk assessments regarding NDSRI with CPCA

Unlike nitrosamines with a simple structure, there are no specific experimental data on NDRSIs that would enable determination of the carcinogenic potential. For this reason, the Carcinogenic Potency Categorization Approach (CPCA) was developed. Based on a structural comparison with nitrosamines with known carcinogenic potential, risks can be identified and, on the basis of the chemical structure, safe intakes can be defined. The total points are calculated on a decision tree, which then results in the risk category for the relevant substance.

Swissmedic is prioritising measures for the CPCA categories that have the highest potential risks to patient safety: Marketing authorisation holders must identify preparations with the potential to form NDSRIs in CPCA categories 1 and 2 by 31 January 2024.

Analytical testing for NDRSIs in category 1 or 2

Preparations from CPCA categories 1 or 2 must be analysed using validated and sufficiently sensitive methods. The results of these tests must be provided to Swissmedic by 30 September 2024.

Q&A is also updated.
As required for marketed products, confirmatory testing data are expected if N-Nitroso derivatives of the API (i.e. the directly nitrosylated API) of CPCA Cat.1 or 2 can theoretically form. However, if experimental evidence shows that the N-Nitroso derivative of the API is unlikely to form, the MAH/applicant should contact Swissmedic to clarify if analytical data are required.


Thanks a lot Yosukemino for sharing this useful update; this is extremely useful. Having been through the content of the revised information, I can see that the scope of the Swiss Medic original request from september 2023 or timelines are unchanged ? e.g: Swiss Medic is still focussing on API secondary amines with NDSRIs category 1 and 2.
Would other members agree?
I can see mostly some clarifications for hypothetical NDSRIs that are not able to be formed based on recent practical experiments.

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Yes, while the web page text doesn’t explicitly say so, from the attached documents to it I believe the message that the systematic testing requirement for NDSRIs of CPCA cat. 1-2 is limited to N-nitroso APIs and not includes N-nitroso API impurities is maintained.