Toxicological Risk Assessment (TRA) - Overview
Impurities in medicinal drug substances (active pharmaceutical ingredient; API) or medicinal 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 its usage at unsafe levels.
Toxicological Risk Assessments of impurities and E&L are structured scientific evaluations involving hazard identification and risk characterization. For such risk assessment, Freyr uses recommended and validated tool(s) by requirements of ICH M7.
Freyr’s toxicology team has supported numerous global clients in the Toxicological Risk Assessments of impurities, and E&Ls, and addressed several simple to complex issues associated with impurities in drug substances, drug products, residual solvents, process impurities, and elemental impurities.
Following is the list of services offered by Freyr in the Toxicological Risk Assessments domain:
- Genotoxic Impurities Risk Assessment in Compliance with ICH-M7
- Toxicological Risk Assessment of Impurities in Drug Substance (ICH Q3A) and Drug Products (ICH Q3B)
- Toxicological Risk Assessment of Residual Solvents (ICH Q3C)
- Toxicological Risk Assessment of Elemental Impurities (ICH Q3D)
- Toxicological Risk Assessment of Extractables & Leachables (E&L) from Container Closure System (CCS)
- Impurities in Veterinary Medicinal Products (VICH GL18)
Toxicological Risk Assessment (TRA)
- Understanding the issue clearly and developing appropriate strategy in consultation with Sponsor.
- Use of highly scientific approaches and methodologies including read-across strategies/approaches to fill the data gaps.
- QSAR evaluation by using well-validated and Regulatory-accepted software tools by the recommendations of ICH M7 (statistical and expert rule-based evaluation).
- Expert reports generated by ICH M7 with complete supporting data/information and reports reviewed/approved by qualified toxicologists.
- 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).
- Highly experienced and board-certified team (American Board of Toxicology and European Registered Toxicologists).
- Clear understanding of the Toxicological Risk Assessment process for impurities and E&L with relevant Regulatory guidelines.
- 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.
