The nitrosamine drug substance-related impurities (NDSRI) is a special class of nitrosamine impurities. Unlike traditional small-molecule nitrosamine impurities, NDSRI shares structural similarity to the API (having an API or an API fragment in the chemical structure) and is therefore unique to each API. Since the US Food and Drug Administration firstly issued a guidance on NDSRI in August 2023, this class of impurities has been paid more and more concern. For the safety of human medication, it must be strictly controlled. This article systematically introduced the formation mechanisms and main sources of NDSRI and deeply analyzed the control strategies of NDSRI from 4 dimensions: risk assessment, limit determination, analytical methods and elimination strategies in order to provide systematical references for the effective control of NDSRI.

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