In September 2019 EMA began a review under Article 5(3) of Regulation (EC) No 726/2004 to provide guidance to MAHs on how to avoid the presence of nitrosamine impurities in human medicines. As part of this review, the MAHs were requested to review their authorised human medicines containing chemically synthesised active substances for the possible presence of nitrosamines and test all products at risk, regardless of their registration procedures.

This risk evaluation should follow 3 steps:

Step 1: conduct a risk evaluation to identify products at risk of N‑nitrosamine formation or (cross‑) contamination and report the outcome by 26 March 2020 at the latest.
Step 2: perform further confirmatory testing on the products identified to be at risk of N‑nitrosamine formation or (cross-) contamination and report confirmed presence of nitrosamines as soon as possible.
Step 3: apply for any necessary changes to the manufacturing process resulting from this review using the established regulatory procedures.


Human medicines containing chemically synthesised active substances and approved via the National, MRP or DCP procedure route, should undergo risk evaluation regarding the presence of nitrosamine impurities, as outlined in ANSM’s published information note. Conclusions of the risk evaluation are reported online via ANSM’s newly developed web application, the steps for reporting are as follows:

  • Each MAH receives a confidential code (MAH code), which allows them to access the reporting application via the ANSM website
  • The coding system: MAH code-MAA number, should be followed to access the form
  • The MAH completes the form associated with each medicinal product (form pre-filled in some sections)

The required information is similar to that required by the European authorities in the EMA Excel table. The cover letter templates are the same as published by the EMA and CMDh and are available via the ANSM application; the risk analysis should be available upon request.

In summary, the risk evaluation reporting notification to ANSM can be submitted online and should be completed no later than the 26 March 2020. The outcome should also be submitted along with the covering letter signed by the qualified person to:

If the outcome of the risk evaluation is positive, confirmatory testing is required (Step 2) and the MAH should follow the timetable as notified during Step 1. If the confirmatory testing results show a content of nitrosamines above the acceptable limit, the ANSM should be informed immediately.

Regarding Steps 2 and 3, the ANSM will publish further information at a later stage.

For more detailed information, please refer to the ANSM website:


For centralised procedures the outcome should be submitted to the EMA as per the EMA procedure.


Please contact us directly for queries on how EUDRAC can assist you.

11 February 2020