Control Strategies And Method Development For Nitrosamines In Active Pharmaceutical Ingredients (APIs) And Drug Products

As regulatory expectations evolve, nitrosamine risk assessments have become a critical component of late-phase drug filings with agencies such as the FDA, EMA, and others. Even when the assessed risk is low, regulatory guidance mandates the implementation of robust testing strategies to ensure compliance.

This paper explores the key elements involved in controlling nitrosamine impurities in both active pharmaceutical ingredients (APIs) and drug products. It provides an in-depth look at current regulatory requirements, advanced analytical methodologies, and real-world case studies to highlight the complexities and practical approaches to nitrosamine testing. Topics include an overview of nitrosamine control strategies, techniques for method development and validation, challenges in testing, and effective strategies for detecting Nitrosamine Drug Substance Related Impurities (NDSRIs). The paper also features seven detailed case studies that illustrate the application of these methods in various scenarios.