How to mitigate nitrosamine risk with low nitrite excipients

Introduction
The pharmaceutical industry faces the difficult task of controlling and minimising nitrosamine impurities to acceptable levels across the entire drug supply chain. This is a significant challenge given that nitrosamine impurities can be introduced into drug products through multiple routes, including during the manufacture of APIs, the production and storage of formulated drug products, or even via the packaging materials used (6). Understanding the pathways to nitrosamine formation is key to developing appropriate mitigation strategies because it raises questions like, “Do I need to lower the risk at every stage?” and “Do I need to look at the influence of my API?” or “Is the excipient contributing to the risk?” Here are some of the approaches helping to lower contamination risk.

Diverse strategies for nitrosamine risk mitigation
There are many ways to approach a nitrosamine mitigation strategy, each tailored to the specific drug product and how it is manufactured. Potential options include, but are not limited to:

• Reducing one of the reactive species (vulnerable amine or nitrosating agent)
• Modifying the manufacturing process so that these reactive species do not encounter each other
• Altering the environment of the reaction, such as the pH or mobile phase
• Adding a nitrite scavenger to neutralize the nitrosating agent.