Toxicological Risk Assessment (TRA) – An 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 unsafe levels.  

Toxicological Risk Assessment of impurities and E&L are structured scientific processes involving hazard identification and risk assessment. For the risk assessment in pharmaceuticals 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 Toxicological Risk Assessment and impurities in drug substances (ICH Q3A), drug products (ICH Q3B), residual solvents (ICH Q3C), process impurities, elemental impurities (ICH Q3D) such as TRA of genotoxic impurities (ICH M7), and E&L. 


Toxicological Risk Assessment (TRA) - Freyr Expertise

  • Quality scientific and 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 reports generated by ICH M7 with complete supporting data/information.  
  • Toxicological Risk Assessment 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 in Pharmaceuticals and Medical Devices (ISO10993-17, ISO10993-18, and ISO/TS 21726).   

Toxicological Risk Assessment (TRA) - Freyr Advantages

  • Highly experienced and board-certified team (American Board of Toxicology and European Registered Toxicologists).
  • A clear understanding of Toxicological Risk Assessment and E&L-relevant Regulatory guidelines and processes.
  • Comprehensive Toxicological Risk Assessment reports, encompassing detailed evaluation, hazard identification, and risk assessment.
  • Quick turnaround and priority delivery based on the urgency and requirement of the customer.
  • 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 the sign-off stage.
  • 24x7 Regulatory support for audit queries on Toxicological Risk Assessment reports.