Nitrosamines challenges - 2023

Raphael Nudelman, Global Operations, Teva Pharmaceuticals, Netanya , Israel (raphael.nudelman@teva.co.il)

Nitrosamines were first identified as impurities in pharmaceuticals in 2018. At first the concern focused on small dialkyl nitrosamines (e.g. NDMA, NDEA, NDBA, etc.). In 2020 nitrosamines of API-like structures, also known as Complex nitrosamines or Nitrosamine drug substance-related impurities (NDSRIs), started to emerge and today the majority of nitrosamines being detected in pharmaceuticals are NDRSIs. Health Authorities have set very low limits for nitrosamines, exclusively based on the carcinogenicity potency data known for the small dialkyl amines. Industry finds its very challenging to stand to these low limits. At the same time, the understanding around the toxicology of NDSRIs is beginning to become clear and it is evident that NDSRIs are not potent mutagenic/carcinogenic substances as the small dialkyl nitrosamines. A major effort is currently being undertaken by Industry and Health Authorities to establish acceptable intakes for NDRSIs. This presentation will focus on the available scientific methods being currently utilized to set such acceptable intake limits