On 24 September 2026, the US Food and Drug Administration (FDA) published a guidance update, “Application of Less-Than-Lifetime Adjustment to Nitrosamine Impurities”, confirming that less-than-lifetime (LTL) adjustment factors may now be applied to recommended acceptable intake (AI) limits for nitrosamine impurities in drug products intended for a less-than-lifetime duration of treatment.
In short: manufacturers of drug products with short-term or intermittent dosing may now be able to justify higher nitrosamine AI limits, consistent with the LTL framework in ICH M7(R2), a position the FDA Center for Drug Evaluation and Research (CDER) had previously declined to adopt for nitrosamines.
The update sets out three LTL adjustment factors, applied to the recommended lifetime AI limit:
| Duration of treatment | Adjustment factor |
| 1 month or less | 80 x lifetime AI limit |
| More than 1 month to 12 months | 13.3 x lifetime AI limit |
| More than 1 year to 10 years | 6.67 x lifetime AI limit |
| More than 10 years to lifetime | No adjustment |
CDER attributes the change to new evidence, citing two recent publications (Felter et al., Regulatory Toxicology and Pharmacology, 2025 and 2026) developed in part through the Nitrosamines Research Program of the Health and Environmental Sciences Institute (HESI). These address the data gaps that previously prevented LTL adjustment for nitrosamines, including cumulative dose response, DNA repair capacity and polypharmacy.
The adjustment is not automatic. Treatment duration must reflect approved labelling, interim AI limits are excluded, and proposals for approved products generally require a prior approval supplement. CDER evaluates each proposal case by case.
Read the FDA guidance update: Application of Less-Than-Lifetime Adjustment to Nitrosamine Impurities (PDF) and the CDER nitrosamine AI limits page.
If you would like guided instructions on what this means for YOUR products, read our article from Senior Principal Scientist, David Ponting.
For support with nitrosamine risk assessment and acceptable intake decisions, see our nitrosamine impurity risk assessment solutions.