Nitrosamines risk assessment and batch results

Dear Community

I am coming back to you asking for a question on nitrosamines risk assessment issuance.

Could you please let me know whether you include routine batch analysis data? If yes, could you please explain the reason why?

To my understanding, we should report analysis results from confirmatory testing in order to support either omission or routine basis control. Once risk is confirmed, what about batch analysis? Should these results be reported in a risk assessment report?

Thank you in advance for your time to review the query and your kind feedback :slight_smile:

Once nitrosamines are detected above the 10%, the testing should go by inclusion into the specification wit the same criteria of the 10% of the anual batches for skip testing and batch per batch analysis if routine is needed.

That should be an inmediate action part of the internal CAPA plan and/or investigation + a regulatory requeriment.

The results should be available in the CoA for release.


Thank you very much for your input here


As per CEP 2.0 guidance Skip lot is not part of specification section 3.2.S.4.1:

Link: The CEP 2.0 guideline on requirements for the content of the dossier has been updated - European Directorate for the Quality of Medicines & HealthCare

"EDQM does not take position on skip testing unless if specifically foreseen in guidelines:
Example:- ICH Q3D for elemental impurities, ICH M7 for mutagenic impurities and EMA/425645/2020 for nitrosamine impurities. Therefore, any other reference to skip testing should not be reported in section 3.2.S.4.1".

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Once a specification is set and routinely applied, I think a quality system has other ways to deal with the data than updating the nitrosamine risk assessment with the new QC batch data every time a batch is released?

Of course often there will be an interim phase where root cause investigation or remediation verification is ongoing and overlapping with routine testing initiation and more often the data and conclusions are updated directly in nitrosamine reporting. But truly in the routine and when no changes trigger a risk assessment update, at most an annual update to couple back conclusions from the PQR should be more than enough? Or a onetime clarification in the report how the routine testing is done, evaluated and stored?

Some companies have reported having tested already hundreds of drug product batches of a drug product for a nitrosamine as monitoring action (temporarily or permanently), especially where skip testing was not accepted and batch to batch testing was done in the interim. Surely one cannot allocate resources to very frequently updating the risk assessment with this data and once when root cause and remediation verification is done, QC evaluation at batch level together with period PQR activities should be enough (whereas OOT/OOS can trigger a review in nitrosamine risk assessment terms).

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