Control of Nitrosamine Impurities in Human Drugs; Guidance for Industry; Availability

Issuing agencies

Abstract

The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled "Control of Nitrosamine Impurities in Human Drugs." This guidance recommends steps manufacturers of active pharmaceutical ingredients (APIs) and drug products should take to detect and prevent unacceptable levels of nitrosamine impurities in pharmaceutical products. The guidance describes two general structural classes of nitrosamine impurities: small-molecule nitrosamine impurities (i.e., nitrosamine impurities that do not share structural similarity to the API), and nitrosamine drug substance-related impurities (NDSRIs), which share structural similarity to the API and are generally unique to each API. The potential root causes of small-molecule nitrosamine impurities and NDSRI formation, detection of nitrosamine impurities, and recommendations for risk assessments, testing, and implementation of controls and other appropriate strategies to prevent or reduce the presence of small-molecule nitrosamine impurities and NDSRIs are provided. This guidance revises the final guidance of the same name issued on February 24, 2021.