Hi Friends,
Recently I am getting emails from clients on an issue related to the N-nitrosoduloxetine (ND) interim limit. Not sure if any of you faced anything similar. This is about the information in Table 3 on the website (CDER Nitrosamine Impurity Acceptable Intake Limits | FDA), where interim higher limits are provided. Recently the interim limit for ND was removed. I just realized that the FDA advised one of my clients, “The interim limit applies to the lots you manufacture before the date provided”. However, today a client came to me with this recommendation from the FDA, “The updated limit applies to all batches distributed from January 1, 2025, onward, regardless of the manufacturing date.” And the nitrosamine has been removed from Table 3. Now, my perception is that the information in the second advice is inline with the website information. But, I would have taken any of these recommendations at face value if they were not contradictory. Giving two different advice to two groups ion the same drug is really not the best scenario. Again, clarity and agreement within the FDA itself, better transparency in the written documents may be helpful. Let me know what your experience is. Again, these interim limits have nothing to do with safety, they are based on what the Agency is seeing in the products that are marketed. So, even with the current Table 3, dont draw any safety conclusions from these numbers.
The recently initiated recall of duloxetine appears to be based on the interim limit.
https://www.accessdata.fda.gov/scripts/ires/index.cfm?Product=212850
https://www.accessdata.fda.gov/scripts/ires/index.cfm?Product=212704
https://www.accessdata.fda.gov/scripts/ires/index.cfm?Product=212020
I am really worried that this drug with many other anti-depressants may disappear if the FDA does not give a break on the nitrosamines.
I agree with you, @ASrinivasan. I searched the recall of pharmaceuticals due to nitrosamines contamination on Enforcement report. When sorted by event ID, 15 of the 37 recalls since 2022 were related to duloxetine, despite the use of recommended interim limits. Duloxetine has been repeatedly withdrawn. 
03-23-2025_enforce_rpt.pdf (224.2 KB)
Yosukemino San, this class will disapper if agencies do not stop. Fluoxetine is not in a great shape either.
@ASrinivasan we are getting similar inquiries from manufacturers in China.
Naiffer, I am not surprised. With Duloxetine though I am seeing some of the reformulation work out through things are still at the fringe.