New Approaches to Nitrosamine Detection and Mitigation

Nitrosamines remain a huge challenge to the pharmaceutical industry that encompasses all stages of the pharmaceutical development process. Process chemists need to develop new strategies to mitigate formation during API synthesis, formulation and manufacturing scientists and engineers need to establish the likelihood of nitrosamine formation and devise appropriate controls that will mitigate nitrosamine formulation in the drug product during manufacturing and storage, and analytical chemists need to develop methods to measure and predict nitrosamine formation in both the API and drug product.

The focus of this presentation is on developing new methods to establish risk assessment during product storage and new technologies to minimize the risk of nitrosamine formation in drug products.

Pharmaceutical scientists who would like to learn the latest developments in nitrosamine risk management strategy and mitigation in drug products. Specifically, analytical chemists who work in nitrosamine detection as well as formulators who focus on nitrosamine mitigation and control.

The focus of this presentation is on the development of new strategies for predicting nitrosamine formation on drug product storage. The presentation will start with an overview of ranitidine hydrochloride recalls, and motivate why it is important to understand how ranitidine hydrochloride degrades to NDMA in drug products. A mechanism to show how NDMA formation is caused by the presence of crystal defects will be presented. Next, our research on ranitidine hydrochloride has found that nitrosamine formation can be reduced by several orders of magnitude by forming high-quality crystals that are essentially unreactive. This is particularly relevant because the FDA just approved a reformulation of ranitidine hydrochloride without a clear understanding of why it degrades to form NDMA in drug products, or alternative methods to reduce NDMA formation. Finally, data on other compounds that could form nitrosamines in the solid state will be presented.