Q&A 10: Which limits apply for nitrosamines in medicinal products?

• N-nitrosoduloxetine and 4-(Methylnitrosoamino)-1-(3-pyridinyl)-1-butanone (NNK), bothe with an acceptable intake of 100 ng/day, are now included.

Q&A 21: What is the approach to control the presence of nitrosamines until a substance specific AI is established?

• If new N-nitrosamines are identified without sufficient carcinogenicity data to establish a substance-specific limit, an AI (acceptable intake) agreed by the Non-clinical Working Party (NcWP) and adopted by the CHMP is required.
  
  In practice, this means that when competent authorities are notified about a product containing a new N-nitrosamine exceeding the TTC limit of 18 ng/day, no market actions may be required for batches with N-nitrosamine levels ≤178 ng/day at the MDD pending the agreement of the AI.The adoption of the t-AI is not automatic and is evaluated by the authorities at the time of notification. Use of the t-AI beyond 12 months will require additional consultation with competent authorities. The t-AI should not be used as a target for development of validated analytical methods to quantify new nitrosamines since the long-term limits adopted by CHMP might ultimately be lower than the t-AI.

Source:

EMA: Q&As for marketing authorization holders/applicants on the CHMP Opinion for the Article5(3) of Regulation (EC) No 726/2004 referral on nitrosamine impurities in human medicinal products