Glad to share the update posted on FDA NDSRI Webpage (revision 4). The update is in following:
Regards
Reena
Why is this limit revised? and in that case, we need to perform partial method validation for higher limit w.r.t analytical testing.
At first, the FDA decided the interim limit of varenicline as 185ng/day aside from 37ng/day. Then the interim limit was lifted because US manufacturers could adequately supply the market with varenicline at or below the acceptable intake limit of 37 ng per day. The 400ng/day is from CPCA and is the same as the limit by EMA. It looks more appropriate than read-across from NTHP(37ng/day).
The MDD of Chantix is 2mg. The range of test methods that the FDA recommended is 1-200 ppm. It covers 400ng/day.
N-nitroso-varenicline-FDA was already working on the acceptable limit for this NDSRI. Please see this link
FDA Updates and Press Announcements on Nitrosamine in Varenicline (Chantix) | FDA where In July 2021, FDA announced it would not object to certain manufacturers distributing varenicline tablets containing N-nitroso-varenicline above FDA’s acceptable intake limit, but below the interim acceptable intake limit of 185 ng per day.
Now as a continuous effort, the AI 400 ng/day is published by FDA as per the CPCA category.
See FDA NDSRI Webpage: Updated Information | Recommended Acceptable Intake Limits for Nitrosamine Drug Substance-Related Impurities (NDSRIs) | FDA
Regarding the method please follow the link (https://www.fda.gov/media/175552/download?attachment) wherein range of test methods that the FDA recommended is 1-200 ppm as shared by Yosukemino. It covers 400ng/day.
美国这个药品不是停产了吗，如何知道，美国可以提供符合37ng/天要求的产品？
FDA updated the Interim AI limit of N-nitroso-ciprofloxacin to 12,000 ng/day, @lucas10mauriz taught me. The AI of N-nitroso-ciprofloxacin is 1500 ng/day(CPCA Cat.4) simultaneously.
@Yosukemino, Thank you for sharing the post.
In this scenario, it’s a matter of weighing risks against benefits, and as the FDA states in its NDSRI Guidance:
“*If drug product batches already in distribution contain NDSRIs at levels above the FDA recommended AI limit, and manufacturing changes or recalls are likely to lead to a disruption in the drug supply, then manufacturers and applicants should immediately contact (…)”
