We have developed one tablet formulation for EU/US market and its containing amide group.
Now during risk assessment, we found that one of the excipient microcrystalline cellulose has given declaration that…
Nitrites and Nitrates are known to be generated as impurities during the manufacturing process. They have analysed Nitrites and Nitrates and found to be less than 4.5 ppm and less than 17.3 ppm respectively. While Nitrosamines are not detected.
Other excipients and API has given Nitrosamine free as a declaration.
Now, My question is that…
Sholud We go for Nitrosamine impurities analysis for our tablet or risk assessment is acceptable by authority.
Plz try to solve my query.
@Jigarshah_172 While I cannot comment on the regulatory acceptance. It’s a consensus that risk assessment should be conducted. The risk assessment will inform of the theoretical potential of forming nitrosamines, the theoretical concentrations (assuming 100% conversion of Nitrites in the formulation), the risk of impuritie’s API on forming nitrosamines along the process, purging conditions (if applicable), etc.
Every regulatory guidance out there calls for the Risk Assessment as an essential part of the Nitrosamina mitigation strategy.
Thanks for the prompt reply.
All the excipients have given Nitrosamine free declaration including API.
But only MCC has given this. In MCC declaration Nitrosamine is Not detected.
So, My question is that…
Should i go for Nitrosamine analysis by FDA method or take a chance with risk assessment first.
@Jigarshah_172, Even if the Excipient Manufacturers gives declaration for absence of Nitrosamine impurities and if the excipients contains Nitrite/Nitrate impurities, the probability of Nitrosamine impurity/ies formation in Finish product can not be ruled out.
Based on the molecular structure of API used in Finish product, the evaluation has to done whether there are chances of formation of Nitrosamine impurity/ies /NDSRIs due to presence of secondary/tertiary amine groups present in the molecule. This should be a part of Risk Assessment and based on this, whether to analyse the finish product (as per FDA) for these Nitrosamine impurity/ies/NDSRIs can be decided.
This will be informative to me.
Thank you, Sir.