FDA and EMA to think about collaborative approaches for total impurities limits, if more than one nitrosamine impurities are observed in product
@Naiffer_Host @Yosukemino your comments on this topic is highly appreciable and it will helps to all pharma industries.
Dear Yuvraj,
The info you are asking is already very well explained in the guidelines.
Please refer to: Nitrosamines EMEA-H-A5(3)-1490 - QA Art. 5(3) Implementation_rev17(QA10) (europa.eu)
If there is any specific question of the methodology in the guidelines, feel free to ask.
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Dear @Yuvraj,
Thank you for asking me. As @Diego_HM explained, guidance shows the limit for multiple nitrosamines.
EMA:
- The total daily intake of all identified N-nitrosamines not to exceed the AI of the most potent Nnitrosamine identified, or
- Total risk level calculated for all identified N-nitrosamines not to exceed 1 in 100,000.
FDA(with/without NDSRI):
If more than one nitrosamine impurity (NDSRI(s) and/or small molecule nitrosamine(s)) is identified and the total level of nitrosamines exceeds the recommended AI limit for the most potent nitrosamine in the drug product based on the maximum daily dose, the manufacturer or applicant should contact the Agency. FDA also recognizes that if the recommended AI limits for the individual nitrosamines vary greatly, basing the total nitrosamine limit on the most potent individual nitrosamine limit might not be practical. In such cases, FDA encourages manufacturers to contact the Agency if proposing a nitrosamine limit other than the recommended AI of the most potent nitrosamine impurity detected.