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APIC: Updated Nitrosamine Guidance

The Active Pharmaceutical Ingredients Committee (APIC) has published the 2nd revision of its nitrosamine risk management guidance for API manufacturers. This guidance document was first prepared in 2020 by the APIC Nitrosamines Task Force.

The structure of the document is extended to follow recent regulatory requirements (mainly EMA) regarding risk assessment principles, root causes considered, analytical testing, control and mitigation measures. This includes, but not limited to:

  • Comprehensive discussion on nitrosamine formation mechanisms
  • Extension of the scope from small nitrosamines toward Nitrosamine Drug substance related impurities (NDSRIs)
  • Approaches toward theoretical risk assessments with purge factor calculations (ability of a process to remove or reduce nitrosamines during the manufacture of APIs)
  • Guidance for detailed evaluation of risk from water
  • API testing, including methodology, with acceptable limit calculation
  • Implementation of suitable control/mitigation strategies

At last, but not least, a separate chapter is dedicated to incorporation of nitrosamine risk management into the quality management system.


Source:

APIC: Nitrosamine Risk Management: Guidance for API Manufacturers


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