Managing Nitrite Impurities: A Supplier-Manufacturer Approach To Mitigating Nitrosamine Risk

By Dr. Sebastian Hickert, Dr. Ulrich Reichert, Dr. Joerg Schlingemann

The presence of nitrosamine drug substance-related impurities (NDSRIs) was discovered in the comprehensive assessment of active pharmaceutical ingredients (APIs), formulated drug products, and packaging materials. In light of these findings, regulatory bodies have issued guidance instructing pharmaceutical companies to assess chemical and biological products for the presence of nitrosamines and establish mitigation actions where necessary. It is crucial for drug manufacturers to develop robust nitrosamine control measures to safeguard patient health.

This white paper outlines the formation of nitrosamines, their prevalence and chemical precursors in pharmaceuticals, techniques for quantification, and approaches for managing nitrite impurities. Additionally, a case study demonstrating methods for preventing N-nitrosodimethylamine (NDMA) formation in metformin drug products is presented.