As part of the call for review process aimed at identifying and mitigating the risk of nitrosamine contamination in all medicinal products containing chemically synthesised or biological active substances, marketing authorisation holders (MAHs) who have identified and reported a potential risk during Step 1 are required to submit the results of the confirmatory studies as part of step 2 and to submit, for any changes that may become necessary, variations to the terms of the marketing authorisation (MA) as part of Step 3.
Please note that the results of the confirmatory studies (Step 2) and any variation to the marketing authorisation for the purposes of implementing the risk control and mitigation strategy (Step 3), should be submitted as soon as possible and finalised by 26 September 2022 for chemical medicinal products and by 1 July 2023 for biological medicinal products.
Regarding the timing and modalities for sending the results of the evaluations carried out as part of step 2, please refer to the information provided in the documents drawn up by the Coordination Group for Mutual Recognition and Decentralised Procedures (CMDh) and available at the following link: https://www.hma.eu/620.html.

The outcome of the confirmatory studies, as well as the notification of the submission of the MA variation, must be sent by e-mail to nitrosammine@aifa.gov.it, following the instructions specified below.  
For nationally authorised medicinal products, the subject of the email should be: ‘Outcome of confirmatory testing nitrosamines – Step 2’ followed by the result: ‘No nitrosamine detected’ or ‘nitrosamine detected’. Only in case of ‘nitrosamine detected’, the name of the medicinal product should be mentioned and it should be indicated if it is a biological medicinal product (by entering the word BIO).

For medicinal products authorised through Mutual recognition/Decentralised Procedures, please refer to the CMDh practical guidance for Marketing Authorisation Holders of nationally authorised products (incl. MRP/DCP) in relation to the Art. 5(3) Referral on Nitrosamines.
When the outcome of the evaluation is ‘No nitrosamine detected’, the results for multiple medicinal products can be grouped in a single template.
When the outcome of the evaluation is ‘Nitrosamine detected’, the results should be presented separately for each individual medicinal product.
All dosages and pharmaceutical forms of a medicinal product can be reported in a single template if the outcome of the evaluation is the same. Where different outcomes are obtained (for different dosages, pharmaceutical forms, packaging, etc.), different templates should be attached to the same e-mail according to the outcome.
If nitrosamines are detected at a level that exceeds the acceptable intake limit or the lifetime excess cancer risk of 1:100,000 or a new nitrosamine is identified, irrespective of the amount detected, the outcome of the assessment by AIFA (for national and IT-RMS procedures) should be awaited before submitting any variations to the terms of the MA in order to implement the proposed control strategy.
MAHs who have already sent the notifications related to Step 2 are not required to re-submit the results of the evaluations.