CMHP meeting from January: N-nitroso-Mefanamic Acid & N-Nitroso-Folic Acid

New Scientific Knowledge & Development
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The European committee for Medicinal Products for Huma Use (CHMP) held its January meeting on 24/27 Jan 2022.

Report attached:
IDRAC_341767_18-Mar-2022_CHMP 24_27-Jan-2022 Meeting.pdf (3.3 MB)

  • CMDh question to Safety Working Party (SWP) to determine the acceptable intake for nitrosamine N-nitroso-Mefanamic Acid based on lifetime daily exposure including information on the points of departure and methodology used.

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  • Update on Q&A for marketing authorization holders/applicants on the CHMP Opinion for the Article 5(3) of Regulation (EC) No 726/2004 referral on nitrosamine impurities in human medicinal products (EMA/409815/2020 Rev.6).
    CMDh question to SWP to determine the acceptable intake for N-Nitroso-folic acid based on
    lifetime daily exposure including information on the points of departure and methodology
    used.
    Action: For adoption
    The CHMP adopted the updated Q&A on nitrosamines.
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Hi Naifer,

Thanks for the information. Regarding the Folic acid nitrosamine is the one with:

CAS Number: 29291-35-8

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CAS Number: 26360-21-4

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Can we have confirmation please?

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@Diego_HM It’s unclear what conformation CMHP was referring to. I was hoping @AndyTeasdale or @David might have some additional insights.

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One of these is a Nitrosamide, the second is a Nitrosamine

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Thanks Andrew, I should had put my question as “nitroso compound”. My doubt was also related that when information is looked for this compounds the only difference in the naming is that the 2nd one is indicated as N10-nitroso folic acid because of the numbering, and the IARC indicate as “N-nitroso folic acid” to be the nitrosoamide. Thus better to be sure.

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Is there any limit already published? i understood it was already included into the currente Q&A document that is nothing included. was this stopped?

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For your information, EMA through AskEMA confirmed that the nitroso compound they were talking about is in fact:

Name : 2-[[4-[(2-amino-4-oxo-1H-pteridin-6-yl)methyl-nitrosoamino]benzoyl]amino]pentanedioic acid

CAS Number : 26360-21-4

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Also for your information and for more detail, the IARC in the past has defined “N-nitroso-folic-acid” to be the nitrosamide.

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N-Nitrosofolic Acid (IARC Summary & Evaluation, Volume 17, 1978) (inchem.org)

As for more info about the AI the SWP working group was asked to develop, is expected to be around Q2. Thus not into the Q&A document.

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