Toxicological Risk Assessments: Impurities/Degradants, Extractables, and Leachables 

Our American and European Board-certified toxicologists use both traditional toxicological approaches and advanced computational tools (i.e., QSAR) to provide robust, tailored solutions aligned with global regulatory requirements to ensure patient safety. 

Services:

• Specification limit evaluations in alignment with ICH guidelines and in consideration of reference listed drug levels, and preparation of toxicological justifications which assess risk associated with the route, frequency, and magnitude of exposure 

• Conduct impurity, residual solvent, and E&L qualification involving Permissible Daily Exposure (PDE), Tolerable Intake (TI), Acceptable Intake (AI), and Threshold of Toxicological Concern (TTC) derivations in alignment with ICH and other guidelines (e.g. ISO) as needed 

• Preparation of surrogate justification and selection for E&L/impurity compounds lacking toxicity data and requiring a read-across approach  

• Genotoxic evaluation of structural alerts in impurities/degradants and residual solvents in the API and/or drug product consistent with ICH M7 recommended approaches for initial assessment of impurities, using FDA-validated in silico toxicology software (e.g., Leadscope, Multicase) which includes both expert rule- and statistical-based models 

• Providing support for toxicity testing of impurities/degradants, including study design, CRO selection, and study placement, as well as review of protocols and reports 

• Impurity purge evaluations in which purge factors are determined throughout the manufacturing process to assess its ability to remove impurities (e.g., via reaction, solubility, or volatility) and ensure patient safety 

• Comprehensive safety evaluation of laboratory E&L study data for pharmaceuticals and medical devices to identify and address potential risks in accordance with ICH Q3E draft guidance 

• Toxicological risk assessments conducted using both provided data and literature-based safety data on the identified compound(s) in the API/drug product and in accordance with ICH and regional guidance (e.g., FDA, Health Canada, EMA)