Revision of the EMA Guideline on Nitrosamines

In revision 13 of document EMA/409815/2020 the Committee for Medicinal Products for Human Use (CHMP) introduced new maximum daily intake limits for six new nitrosamines:

• 3 API-specific nitrosamines
• 3 generic nitrosamines

Since the first discovery in 2018, the European Medicines Agency (EMA) has drawn up a series of documents and guidelines in order to prevent the uncontrolled presence of nitrosamines in medicines for human use. Indeed, the intake of medicines containing this type of substance has been linked, if uncontrolled, to the development of oncological diseases.

Article 5(3) of Regulation EC/2004/726, together with related documents, is the main point of reference for marketing authorisation holders. This Guideline is constantly updated, with the help of the CHMP, in order to prevent or limit the presence of nitrosamines and to improve the manufacturing process of medicines.

With Revision 13, dated 5 December 2022, of Question and answers for marketing authorisation holders/applicants on the CHMP Opinion for the Article 5(3) of Regulation (EC) No 726/2004 referral on nitrosamine impurities in human medicinal products, the following limits are introduced:

N-Nitrosamine (CAS Number)	ng/day	Source
N-nitroso-fluoxetine	100	Fluoxetine
N-nitrosoparoxetine	1300	Paroxetine
N-nitroso-diphenylamine NDPh (86-30-6)	78000	-
N-nitroso-mefenamic acid	78000	Mefenamic acid
N-nitroso-pyrrolidine NPYR (930-55-2)	1700	-
N-nitroso-diethanolamine NDELA (1116-54-7)	1900	-

LabAnalysis has already developed and validated several matrix-specific methods [LC-HRMS, LC-MS/MS, GC-MS/MS] for some of the new nitrosamines targeted by the European Medicines Agency (EMA). The laboratory makes its expertise available to search for API-specific and generic nitrosamines on all kinds of products.

For more information contact
sales.pharma@labanalysis.it

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