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FDA: Control of Nitrosamine Impurities

The FDA published the second revision to the industry guidance on "Control of Nitrosamine Impurities in Human Drugs".

Update compared to the guidance of 2021:

  • New section that describes nitrosamine drug substance-related impurities (NDSRIs) - NDSRIs are a class of nitrosamines sharing structural similarity to the API. NDSRIs can be generated during the manufacturing process or during storage of a finished drug.
  • Potential root causes of NDSRIs
  • Mitigation strategies to prevent or reduce the presence of NDSRIs

The guidance describes two general structural classes of nitrosamine impurities:

  • Small-molecule nitrosamine impurities (they do not share structural similarity to the API)
  • NDSRIs that share structural similarity to the API and are generally unique to each API

NDRSIs are also addressed in the guidance “Recommended Acceptable Intake Limits for Nitrosamine Drug Substance-Related Impurities (NDSRIs)“ (August 2023).

Weblink to acceptable limits: FDA/CDER Nitrosamine Impurity Acceptable Intake Limits


Source:

PDA/FDA Joint Regulatory Conference 2024
Tina Kiang, Ph.D., Director, Division of Regulations and Guidance, FDA/OPQ/OPPQ

FDA: Control of Nitrosamine Contamination in Pharmaceuticals for Human Use

 

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