Overview

Impurities in drug substances (Active Pharmaceutical Ingredient (API)) or drug products including Extractables and Leachables (E&L) not only affect the product quality but also pose a significant risk to the patient population. Toxicological Risk Assessment (TRA) of impurities, especially potential genotoxic impurities, is essential to control and/or limit the safe levels.  

TRAs of impurities and E&L are structured scientific processes involving hazard identification and risk assessment. For the assessment of genotoxicity (mutagenicity) potential, the application of computational methods like Quantitative Structure-activity Relationships (QSARs) by using validated and approved software tools coupled with expert judgment, is employed by ICH M7 recommendations.

With their vast experience, Freyr toxicologists have supported numerous global clients and addressed the issues associated with impurities in drug substances (ICH Q3A), drug products (ICH Q3B), residual solvents (ICH Q3C), process impurities, elemental impurities (ICH Q3D) including TRA of genotoxic impurities (ICH M7), and E&L. 

 

Freyr Expertise

  • Quality, scientific, read-across strategies/approaches
  • QSAR evaluation by using well-validated and Regulatory-accepted software tools by ICH M7 (statistical and expert rule-based evaluation)
  • Expert report by ICH M7 with full supporting data/information  
  • TRA and derivation of Acceptable Daily Intake (ADI) for ‘out-of-specification’ impurities including non-ICH Q3D elemental impurities
  • Planning and designing of nonclinical studies for the qualification of impurities including placement, monitoring, and review of study reports for Regulatory submissions
  • E&L risk assessment of Pharmaceuticals and Medical Devices (ISO10993-17, ISO10993-18, and ISO/TS 21726)   
 

Freyr Advantages

  • Highly experienced and board-certified team (American Board of Toxicology and European Registered Toxicologists)
  • Clear understanding of various Regulatory guidelines and processes
  • Comprehensive reports encompassing detailed evaluation and assessment of various hazards
  • Quick turnaround and priority delivery based on the urgency and requirement of the client
  • On-demand short-summary reports with ‘Go-No-Go’ decisions
  • Well-established and structured literature search strategy
  • Robust quality control checks right from document compilation to sign-off stages
  • 24x7 support for Regulatory and audit queries