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EMA: Updated Q&A on Nitrosamines 2022

The European Medicines Agency (EMA) has published a revised version 12 of its Q&A on nitrosamines for marketing authorisation holders dated 10 October 2022. The revision includes an update of Q&A 10 on the limits for nitrosamines in medicinal products and introduces a new Q&A 21 on the approach to control presence of nitrosamine while the AI is being established.

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

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