MAHs should review their manufacturing processes to identify and, if found, to mitigate risk of presence of nitrosamine impurities.
In accordance with the CHMP opinion under Article 5 (3) of Regulation (EC) No. 726/2004 on the presence of nitrosamine impurities in human medicinal products containing chemically synthesised active pharmaceutical ingredients, and as a precaution, MAHs should review their manufacturing processes to identify and, if found, to mitigate risk of presence of nitrosamine impurities.
MAHs should work with manufacturers of API and finished products in order to review the API and finished product manufacturing processes with respect to the arrangements for preventing nitrosamine formation as well as contamination or cross-contamination, taking into account their knowledge of the manufacturing processes as well as the potential sources of nitrosamine impurities.
The following guidance is for all UK Market Authorisation Holders (MAH) and should be followed to submit the outcomes of the Stage 1 nitrosamine risk evaluation required by March 2020 as detailed in the guidance CMDh practical guidance for Marketing Authorisation Holders of nationally authorised products (incl. MRP/DCP) in relation to the Art. 5(3) Referral on Nitrosamines
Article 5(3) Submission of Nitrosamine risk evaluation
Step 1 - Risk Evaluation
For all products licensed in the UK (including UK National licences and EU licences where UK is RMS or CMS) MAH should submit one of two templates supplied by CMDh depending on the risk evaluation outcome:
Step 1 no risk identified response template document
Step 1 risk identified response template document
Completed template filenames should begin with UK PL number.
For efficient processing please also provide a table with all submissions containing the following minimal requirements using the excel template below. There is no requirement for a separate cover letter to be sent with the templates and no other spreadsheets will be required by MHRA at step 1.
|UK PL Number (e.g. PL 12345/6789)||Product Name||Risk Identified (Yes/No)|
eCTD format should not be used and the The MAH should submit the completed forms as information updates:
Existing MHRA Portal users should use the General Product Licensing Submission form
CESP users can submit using the regulatory activity ID: G0008 - Follow-Up Measure/Information Update and subactivity ID H005 - Closing Documents
Bulks of up to 20 completed risk assessment forms will be accepted if supported by tabulated details of the bulk submission. Each bulk should be submitted as a separate submission.
Further guidance will be provided for step 2 submissions in a later update.