Since 2018, the discovery of nitrosamine impurities — potent carcinogens including NDMA and NDEA — in widely used drug products has triggered more than 250 recalls and exposed pharmaceutical companies to substantial financial and reputational liability.
This 2023 report by Datwyler traces the origins of the nitrosamine crisis, from initial findings in blood pressure medications to the identification of contamination sources across APIs, excipients, recovered solvents, and primary packaging materials including container closure systems. It details the FDA and EMA regulatory response — including phased risk assessment timelines, acceptable intake limits, Pharmacopeia guidance chapters, and mandatory stability testing — and explains how nitrosamine risk assessment has now become a routine step in early drug development. Critically, the report addresses the well-established link between certain rubber accelerators used in polyisoprene elastomers and secondary amine formation, a known nitrosamine precursor. It explains why Datwyler's halobutyl-based elastomeric compounds — used for stoppers, plungers, and combiseal components in long-term drug contact applications — do not require sulphur accelerators in the curing process, effectively eliminating this packaging-related contamination pathway and providing pharmaceutical manufacturers with a defensible, future-proof approach to parenteral packaging compliance.
