The following updates have been added to this guidance:
- Updated information following the passing of the deadline for the submission of steps 1, 2 and 3.
- The deadlines of the call for review (steps 1, 2 and 3) for medicines containing chemically synthesised and biological active substances have passed.
- Any MAH that has not notified the MHRA about identified nitrosamine impurities should report them as a matter of priority in line with the CHMP’s Article 5(3) opinion as well as any updates to previous notifications, using the response templates and available reporting mechanisms previously established.
- Guidance has been added for MAHs regarding step 2 submission requirements where nitrosamines are determined to be non-mutagenic.
- For nitrosamine impurities that are classified as non-mutagenic based on in-vivo mutagenicity studies, the submission of step 2 confirmatory testing is not required, and these impurities should be controlled according to ICH Q3A and ICH Q3B guidelines.
- To allow nitrosamine outcomes to be correctly recorded for each Marketing Authorisation, Marketing Authorisation Holders are asked to continue making step 2 submissions for these products. The cover letter should indicate that the identified nitrosamine is non-mutagenic and that therefore no test data are provided.
- Additional guidance about lifecycle management is provided under the heading Lifecycle Management. MAHs are expected to continue to review and re-visit the outcome of the risk evaluation as and when new information becomes available. This includes:
- Changes to known root causes which may also affect the product in question, including when a new Acceptable Intake (AI) limit is published for the product in question.
- Changes in the product lifecycle that may require a revision of the risk evaluation and may change the outcome of the risk evaluation.
Further information is available at the link below.
Source: MHRA