FDA initially were very keen on Elemental impurities and over the period switched to Nitrosamines in

the products that are arising due to the process contributors.

Recently FDA focus has shifted to the product related nitrosamines like - N-Nitroso Rasagiline etc.
The limits for such impurities are very very low as compared to the general nitrosamines like NDMA
NDEA etc.

Recently EMA has published a guidance on 27th July for the product specific limits where many of
the prone molecules limits have been recommended. If the molecule is prone to form Nitroso imp
and the limit is not mentioned in any of the guidance, we need to follow 18 ng AI limit.

So, as of now 3 rootcauses have been identified for the formation of genotoxic Nitroso imp-

1. Due to Process components

2. molecule containing tetrazole rings like Sartans
3. Molecue can form complex with Nitro group.

Basically there are 3 minimum conditions required to form the nitrosamines.

1. Nitrite/ Nitrate
2. Sec/Ter amines
3. Acidic environment