Nitrosamines and bioequivalence studies

Risk Assessment Strategy / Tools & Technology
#1

Dear Nitrosamines investigators,

What is your experience and knowledge regarding conducting a BE study for your generic products when your Drug substance of study is one of the known-to-contain nitrosamines?

Is it sufficient to submit IMPs with nitrosamines results lower than the AI either for the brand batch or the test batch?

Is it mandatory to submit your risk assessment and root-cause analysis to the drug authority where the BE study will be conducted?

Are there any guidelines or authority circulars that discuss this issue?

#2

When you look at Control of Nitrosamine Impurities in Human Drugs Guidance for Industry from the FDA, the responsibility lies with the manufacturer.

The test vs reference would be meaningless other than giving you a sense of security.

The requirement is seen at registration. You would need the full risk assessment at that point.