As per EMEA Q&A guidance for Nitrosamine EMA/409815/2020 Rev.17, there is a interim limit table provided for Q22, upto 12 months a calculations of 13.3xAI* and >12 months 6.7xAI*
For the * following conditions given
*In any case the limit should not exceed 1.5 µg/day unless the established AI (Table 1, Q&A10) is > 1.5 µg/day or the nitrosamine concerns a category 5 according to CPCA or the nitrosamine is shown to be negative in an enhanced
Ames test (EAT).
My question is this * is applicable for AI value only or the calculation outcome of 13.3xAI
Example for N-Nitroso ciprofloxacin can i multiply appendix 1 AI of 1.5 mcg/day with 13.3 and get the applicable number of 19.95 mcg/day or the maximum overall interim limit of 1.5 mcg/day is only applicable in this case?
Can anyone please clarify * is applicable for AI only or the multiplication number outcome after putting specified factor of 13.3 or 6.7
According Q10 EMA guideline " The ‘less than lifetime’ (LTL) approach should not be applied in calculating the limits as described above but can only be considered after consultation with competent authorities as a temporary measure until further measures can be implemented to reduce the contaminant at or below the limits defined above. "
Then, if your agency agrees, you can propose a temporary limit.
For example, N-Nitroso ciprofloxacin is category 4, so according to the guideline you cite you cannot use limit above 1.5 µg/day unless you can show that N-Nitroso ciprofloxacin is negative in an enhanced Ames test (EAT).