Determining Recommended Acceptable Intake Limits for N-nitrosamine Impurities in Pharmaceuticals: Development and Application of the Carcinogenic Potency Categorization Approach

Carcinogenic Potency Categorization Approach (CPCA): A Breakthrough in Drug Safety

The Carcinogenic Potency Categorization Approach (CPCA) is a cutting-edge methodology developed to assess and categorize N-nitrosamine impurities in pharmaceuticals based on their carcinogenic risk.

Key Features of CPCA

• Risk-Based Categorization
  - Categorizes nitrosamines into potency categories based on their chemical structure, focusing on the α-hydroxylation mechanism of metabolic activation.
• Training Dataset
  • Utilizes a training set of 81 nitrosamines to establish potency categories and Acceptable Intake (AI) limits.
• Structural Scoring System
  • Factors such as α-hydrogens and other activating or deactivating structural features are scored.
  • The total score determines a nitrosamine’s potency category and corresponding AI limit.
• Regulatory Efficiency
  • Facilitates AI limit determination without specific safety data, expediting regulatory reviews and drug safety assessments.
• Evolving Framework
  • CPCA is designed to adapt with new studies, ensuring ongoing improvements in nitrosamine risk evaluation.

Global Impact

The CPCA is gaining international adoption, contributing to enhanced drug safety, improved supply management, and streamlined regulatory processes. By providing a transparent and efficient methodology, it addresses a critical need in pharmaceutical safety.

This innovative approach is a significant step forward in safeguarding public health while ensuring regulatory compliance.

Source: https://www.fda.gov/drugs/spotlight-cder-science/determining-recommended-acceptable-intake-limits-n-nitrosamine-impurities-pharmaceuticals
Region: United States of America