News about GMP/cGMP


EMA: Q&A on Nitrosamines updated

EMA: Q&A on Nitrosamines updated

The European Medicines Agency EMA has further updated its Q&A on nitrosamine impurities. The document is intended to support marketing authorization holders of human medicinal products and considers the latest regulatory requirements (we reported).

The latest version of 21 September 2021 includes an update of

  • Question 10 “Which limits apply for nitrosamines in medicinal products?”
    N-nitroso-varenicline, NNV, was added to the table of specific nitrosamines with a limit of 37.0 ng/day.

This value was derived using structure-activity-relationship (SAR) /read-across approach using the TD50 of N-nitroso-1,2,3,6-tetrahydropyridine as point of departure.

The Step 2-template for responses to the EMA to confirm that a nitrosamine has been detected was updated, as well. It provides two options for alternative indication of limit values of newer nitrosamines not considered in the "Assessment report" (according to Article 5(3) of Regulation EC 726/2004) of the CHMP of June 2020:

  1. General class specific TTC (18 ng/day) in line with CHMP article 5(3) Q&A is being applied
  2. Substance specific AI limit (including SAR considerations) is being applied

All documents can be accessed via the EMA website on nitrosamine impurities.


EMA: Nitrosamine impurities