Nitrosamines: Assessing The Risk To Pharma Products

By Daniel Regan, Associate Principal Scientist, Product Development, and Eric Peterson, Sr. Scientist, Product Development

Nitrosamines, classified as Class 2A carcinogens, pose a significant and growing challenge for the pharmaceutical industry due to their detection in various drug products over the last few years. Regulatory bodies like the FDA and EMA now mandate comprehensive risk assessments beyond simple product release screening, requiring manufacturers and CDMOs to understand and mitigate the potential for nitrosamine growth under storage conditions.

Three critical risk factors drive nitrosamine formation: the presence of a secondary amine (in the API, a degradation product, or a contaminant); environmental conditions conducive to the reaction (temperature, pH, catalysts, etc.); and the presence of a nitrosating agent (such as nitrites). The biggest hidden sources of nitrites often include excipients, solvents, and traces from inadequate equipment cleaning. A robust, science-driven strategy is essential to address this. This includes a staged risk assessment starting with simple screening, moving to a detailed paper-based evaluation using supplier data, and then establishing a confirmatory testing and targeted mitigation strategy if necessary. Understanding these risks early in development is key to ensuring compliance and, most importantly, patient safety. See how to implement a structured, science-driven process to identify, evaluate, and mitigate these risks.