Guidance

Medicines: marketing authorisation holders submission of Nitrosamine risk evaluation

MAHs should review their manufacturing processes to identify and, if found, to mitigate risk of presence of nitrosamine impurities.

Overview

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

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

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:

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.

Step 1 MHRA Excel Table template (MS Excel Spreadsheet, 19.9KB)

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.

Published 18 December 2019
Last updated 12 February 2020 + show all updates
  1. Updated information about formats to be used for submission and provided an Excel spreadsheet template.

  2. First published.