Rev.22
Updates to Q&A 10 to clarify the applicable AI limit to different administration routes and accepted in vivo study type. Update to Q&A 22 to highlight the expectations for the submission of variations to shelf-life and storage conditions as needed to comply with interim limit during CAPA implementation.
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Updates;
Q10.
The same risk approach is applicable to all routes of administration. Corrections to limits are generally not acceptable (“unless route-specific differences are justified by data” is removed from rev.21).
A negative result in a relevant well-conducted in vivo transgenic rodent (TGR) mutagenicity study (OECD 488) (it was “in vivo mutagenicity study” in rev.21) can allow control of the N-nitrosamine as a non-mutagenic impurity (NMI), i.e. according to ICH Q3A(R2) and ICH Q3B(R2) limits, irrespective of the limit calculated through option 1, 2 or 3.
Q22.
Changes in shelf life and storage conditions to comply with the interim AI are evaluated by the relevant authority and are expected to be introduced without delay and in accordance with the guideline on classification of variation (please refer to Q&A 13) is added.
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Important to flag that currently, the FDA does not accept the use of negative TGR studies to move the nitrosamines out of the cohort of concern and control at ICH Q3 levels.
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This is not a new addition in this update.
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you are right Wybon, i was confused with the updates 
well, i will discard my input on order to avoid any confusion
thanks a lot for your notice
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