ANVISA Ver 2- Guide for Controlling Nitrosamines in Active Pharmaceutical Ingredients and Medicines

ANVISA published today Version 2 of Guide 50/2021 "Guia sobre o Controle de Nitrosaminas em Insumos Farmacêuticos Ativos e Medicamentos "

Guide attached here:
Guia nº 50/2021 – versão 2 - Original (989.8 KB)

Guide No 50/2021 - Version 2 - English version (Machine translated by Google) (2.1 MB)

A few days ago @PauloEliandro posted about the official approval of the guidance and immediate reaction to Brazil industry.

Something that really catches my eye in the guidance is the use of ‘Less-than-lifetime’ approach.

The applicability of the LTL concept to nitrosamines has been discussed internationally, however, there is still no consensus on the safety of its use as a starting point for the calculation of acceptable limits.
Thus, analytical methods must be developed and validated so that their sensitivity (limit of quantification) is adequate for the concentrations presented in the limits tables, the absence of nitrosamines during the confirmatory tests, discussed in item 5 of this guide, should not be based on the limits obtained through the LTL approach

I am curious to hear the reaction from @AmandaGuiraldelli @PauloEliandro @acpavia @fernandaw @andresaopedro @roberta_drekener @Mariah


Hi Naiffer,
Indeed Anvisa has a different position in this version of the guideline when compared to the first one which did not give any restrictions to the use of LTL. They mention that their concern related to this is the possibility of overwhelming the repair capacity of the DNA, due to exposure from other sources like polypharmacy, food and the environment.
They do however mention that although LTL should not be used as a starting point when defining the limit, it can be used when shown that the lifetime limits are analytically impracticable.
The LTL paper which used NDEA as a surrogate was already a good start in showing that the same principles should apply to nitrosamines, and LTL is conservative enough, but additional studies may potentially be needed to reduce the concerns regulators currently have.