For your information new guidance from US FDA on LTL adjustments for nitrosamines:
This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on this topic. It does not establish any rights for any person and is not binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations.
This is big!!
Thank you for sharing.
I wonder if other FDA aligned authorities will follow suit?
Indeed quite big step forward! Thanks for sharing!
Mark, let’s just hope they do - but it would only make sense
Wow! Right?
First time FDA surprises industry in the good way.
Lets see if this is a sneak peek at what ICH M7 harmonization will bring… or if EMA will align soon.
Maybe all the pressure from experts and scientists has finally worked.
Great. This goes a step further than the application of LTL during CAPA, which is supported by the EMA. The important point is that the FDA will accept requests for consultation on the application of LTL and determine its acceptability on a case-by-case basis.
I found the link and information on the CDER page.
Application of Less-Than-Lifetime (LTL) Adjustment to Nitrosamine Impurities
The recommended AI limits in Tables 1 and 2 of this webpage reflect recommended lifetime AI limits that approximate an increased cancer risk of one additional case in 100,000 people. This risk is based on a conservative assumption of daily exposure to the impurity over a lifetime (70 years). As described in the Application of Less-Than-Lifetime Adjustment to Nitrosamine Impurities, consistent with the LTL framework described in International Council for Harmonisation (ICH) guidance for industry, M7(R2) Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk (July 2023), LTL adjustment factors may be applied to recommended lifetime AI limits for nitrosamine impurities in drug products intended for a less-than-lifetime duration of treatment. Refer to the Other Emerging Scientific and Technical Issues section of this webpage for LTL adjustment factors for individual nitrosamine impurities (see September 24, 2026: Application of Less-Than-Lifetime Adjustment to Nitrosamine Impurities).
* Chemical structure images provided by the National Institutes of Health/National Center for Advancing Translational Sciences.
In addition, a new footnote was added to Tables 1 and 2.
1 The recommended AI limits in this table were determined based on lifetime exposures. Refer to the Application of Less-Than-Lifetime Adjustment to Nitrosamine Impurities update on the Other Emerging Scientific and Technical Issues section of this webpage for additional information on adjustment factors for less-than-lifetime use.
Its good initiative by FDA
Good catch on this note, Yosuke-San