UPDATE: Latest news from MHRA

The deadline for provision of the step 1 responses has been extended for an additional 6 months to 1 October 2020.

This deadline is subject to review in light of the ongoing Coronavirus (COVID-19) outbreak and any further changes will be communicated in due course.


With less than two weeks to go until the deadline for submission of Nitrosamine Risk Evaluation conclusion for Marketing Authorisation Holders (MAHs) – the risk evaluations are due to be submitted by 26th March 2020. (see note above).

The Coordination Group for Mutual Recognition and Decentralised Procedures – human (CMDh) has updated its practical guidance for Marketing Authorisation Holders of nationally authorised products (incl. MRP/DCP) in relation to the Art. 5(3) Referral on Nitrosamines (published 6th March 2020).

What is new?

The updates provide several clarifications, including:

  • Administrative aspects:
    • How to submit the outcome of the Step 1 Risk Evaluation
    • Where to place the outcome of the risk evaluation/risk assessment in the dossier.
    • Updated national contacts list and guidance in the Annex
  • What is expected at the time of submission of a new Marketing Authorisation Application (MAA) or during MAA assessment.
    • IMPORTANT! A missing risk evaluation/risk assessment (as appropriate) will be classified as a Major Objection which must be addressed before Day 210. If the applicant is not able to provide satisfactory information and justification on the benefit/risk profile of the product before Day 106, the procedure will remain in clock stop until the necessary data is provided.
  • NEW!! Question 1.9 – If at Step 1 a potential risk is identified because not all the relevant data are available, this risk evaluation is only done once, it cannot be amended and re-submitted if the outstanding data become available and it is then confirmed as no risk. It is expected that confirmatory testing is conducted.

A number of the questions and answers in the guidance document have also been edited and amended, and the clarifications can be viewed in the tracked changes version; the link to the guideline is provided below for ease of reference to see what has been updated:

CMDh practical guidance for Marketing Authorisation Holders of nationally authorised products (incl. MRP/DCP)in relation to the Art. 5(3) Referral on Nitrosamines

Where to Find the Latest Information and Guidance?

For national-specific advice, you should refer to the Annex at the end of the above-referenced guidance document.

The following are links to the other key sources of information on Nitrosamine Risk Evaluations:

European Medicines Agency (EMA):


European Directorate for the Quality of Medicines & Healthcare (EDQM):


Need Nitrosamine Risk Evaluation Support? Here’s how can S-cubed help you?

S-cubed is working with client companies, both MAHs and API manufacturers, to review their licensed medicines and manage the required risk evaluation process. We can help with liaising with contract manufacturers, and obtaining information to complete risk evaluations.

Any Questions?

If you have any questions on this topic, please don’t hesitate to ask! You can contact us through our website (www.s-cubed-global.com), via email (info@s-cubed-global.com), and telephone (S-cubed Ltd: +44 1235 77 22 60).