Ribociclib Succinate NDSRIs limit clarification related

Ribociclib Succinate drug substance would like to inform you that,. On January 15, 2024, EMA has published Appendix-1, EMA/25140/2024/Rev.2 and mentioned AI 400 (ng/day) in Appendix-1 for "Ribociclib Succinate Nitrosamine Impurity I (7-cyclopentyl-N,N-dimethyl-2-((5-(4-nitrosopiperazin-1-yl)pyridine-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide)”.

In other hand on January 15, 2024, EMA has published Q & A EMA/409815/2020 Rev.20 mentioned as “For products intended for advanced cancer only as defined in the scope of the ICH S9 guideline, nitrosamine impurities should be controlled according to ICH Q3A(R2) and ICH Q3B(R2) guidelines, as specified in the Q&A document to ICH S9 guideline”.

We request to you provide the clarity on Ribociclib Succinate NDSRIs limit, can we adopt ICH Q3A(R2) as per Q & A EMA/409815/2020 Rev.20 or AI 400 (ng/day) as per Appendix-1, EMA/25140/2024/Rev. 2.


I hope this message finds you well. I wanted to follow up on our my concern regarding [ [Ribociclib Succinate NDSRIs limit clarification related]
Please let me know your thoughts on the above said points.

I look forward to hearing from you soon.

Best regards,
Kapil Vaja

Hi Kapilvaja,

Do you have any analytical methods of Ribociclib succinate NDSRI ?

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Dear @kapilvaja - As per my knowledge Ribociclib cannot be categorized as into ICH S9 category. So better to follow published AI of 400 ng/day for specific nitrosamine mentioned.

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As per the FDA label of Ribociclib, is indicated or used in the treatment of advanced or metastatic breast cancer . As per my view we can consider the scope of the ICH S9 guideline.

A pharmaceutical classification into specifically ICH S9 should meet specific criteria.
Here Ribociclib is meant for both metastasis or advanced cancer.

You may seek further suggestions from regulatory or clinicians


Thanks for your response…