Nitrosamines in ICH S9

Hi Nitrosamines Exchange Team,

I would like to take opinion in regard to allowance of ICH Q3A and ICH Q3B limits for nitrosamine impurities, when drug belongs to ICH S9 category.

Although EMA has clearly stated “For products intended for advanced cancer only as defined in the scope of the ICH S9 guideline, N-nitrosamine impurities should be controlled according to ICH Q3A(R2) and ICH Q3B(R2) guidelines, as specified in the Q&A document for the ICH S9 guideline”

Can we take this leverage with all other geographies and does any one have experience with any Regulatory agency who has rejected this approach or reluctant to accept this approach

We have asked FDA about this in case of several drugs. But they have not provided a clear response. I would like to know if anybody heard something positive from any agency regarding S9 and nitrosamines.

Thanks @ASrinivasan for sharing your experience

Health Canada has suggested us to control nitrosamine as per ICHQ2B in Finished product for one of the molecule falls under ICH S9. Same is mentioned in the Health Canada guidance on nitrosamine as well.

Thanks for sharing your experience @hgajjar

I have reproduced USFDA’s response provided in AAM/CHPA/PhRMA Questions for May 4th FDA-Industry Meeting to Discuss Nitrosamine Impurities in Pharmaceuticals, hope this helps.

  1. Does FDA accept ICH S9 approaches for management of potential nitrosamine
    impurities in therapeutics for advanced cancer therapies?
    Yes, the ICH S9 approach, where set limits for genotoxic impurities are not considered
    appropriate for pharmaceuticals intended to treat patients with advanced cancer, is acceptable.
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Thanks @Muzaffar for sharing this. This indicates may be most agencies will allow the approach of ICHS9 for Nitrosamine impurities.

If nitrosamine impurities could be flexed in terms of market availability and shortage. Then definitely, nitrosamine impurities in ICH S9 drugs should be allowed with their approach …Because altogether these drugs are meant to advanced cancer treatments.

I was part of the meeting and also the scribe who took all the notes :smile: The issue is that there are differences between advanced cancer and drugs which are used for maintenance.


Thanks for bringing this. This is really interesting.

At one of the instance we have reached EMA for clarity- EMA responded that- The drug can be classified as ICH S9 only when it is treated for patients with advanced cancer.

Now for maintenance therapy- the drug used for advanced cancer maintenance therapy shall be ICH S9?

Another point to be noted is a drug can be used for advanced cancer for one indication and for general cancer for another indication. Will that drug still falls under ICH S9?