ELIZABETH TOCCE
Global Applications, Development & Innovations Leader – Pharmaceutical Solutions at IFF

Abstract

Choosing the right nitrosamine risk mitigation strategy in a constantly evolving market – fuelled by emerging science and innovative technologies – can be challenging, especially when a development pipeline faces multiple routes of possible nitrosamine contamination. One such pathway occurs when an active pharmaceutical ingredient (API) containing a vulnerable amine reacts with nitrite under certain conditions, leading to the formation of API-based nitrosamines (1). Choosing low nitrite excipients is one tool that may reduce the risk of nitrosamine formation, especially when a vulnerable amine is present in the formulated drug product (2-5). Such an approach carries minimal risks and should form part of a holistic strategy to reduce the risk of nitrosamine formation. But why? Read on to uncover the role of low nitrite excipients in nitrosamine control and key considerations that drug manufacturers can bear in mind when planning their nitrosamine mitigation strategies.

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 ...
...