On 01/05/2024, the European Medicines Agency (EMA) rolled out an update to Appendix 1 (EMA/154403/2024 /Rev. 4) of the Nitrosamines Guideline. In this Appendix the different nitrosamines that have an established Acceptable Intake (AI) are listed.
What’s new?
In this update, new nitrosamine drug substance-related impurities (NDSRIs) of high concern, such as N-nitroso-N-ethyl-benzylamine (NBEA), N-nitroso-desmethyl-edoxaban and N-nitroso-trientine Impurity 1, have been published. As well as other NDSRIs related to the manufacturing process of various medicines (Opipramol, Omecamtiv mecarbil, Mirabegron, Articaine, Fenfluramine, Dextromethorphan, Posaconazole, Rivaroxaban and Vibegron).
In addition, the AI value for N-nitroso-Lisinopril has been updated. It’s no longer considered a mutagenic impurity, and can therefore be controlled according to ICH Q3B.
What does this mean to you?
In recent years, significant concern has arisen due to the well-known carcinogenic potency of nitrosamine impurities. Consequently, regulatory agencies have reiterated the need for continuous review of Nitrosamine Risk Assessments. Therefore, when updates like this are published, it’s essential to pause and ensure that your reports comply with current regulations and that all potential risk factors have been accurately assessed.
This update particularly impacts medicines containing any of the active substances listed above in their formulation. If this applies to you, the first question to ask is, “Have I assessed the possible presence of these new NDRSIs?” If the answer is “no,” it’s crucial to promptly review your NRA, as there may be new risks that weren’t considered previously.
If you have already assessed these NDRSIs and identified a risk, your next step is to check whether the AI value used for calculating the acceptable limits has changed with this update. The limits may have changed significantly, potentially altering the conclusions of your confirmatory analysis results.
How can QbD Group assist you regarding this update?
Our expert team toxicologists and organic chemists is here to guide you through regulatory changes and ensure your Nitrosamine Risk Assessments are up-to-date and compliant.
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