Toxicology Assessment: An Additional Step to Ensuring Patient Safety and Minimizing Delays in the Regulatory Approval Process
After extractables or leachables have been identified and quantitated, VR Analytical can facilitate a toxicological risk assessment through our association with Intertox Inc. Intertox is a science-based toxicology firm that specializes in risk management and will deliver submission-ready toxicology reports to support worldwide marketing authorization dossiers.
Potential toxicologic risks are first considered after extractables testing has produced a list of compounds that have the potential to leach into the drug product. An initial assessment identifies the higher-risk compounds that should be tracked during leachables testing using validated methods. If those compounds are detected, then a complete toxicological evaluation is warranted.
The final toxicology report for each leachable will include a comparison of detected concentrations against Safety Concern Threshold (SCT)-based Analytical Evaluation Thresholds (AETs). Where appropriate, Acceptable Daily Intakes (ADIs) and Maximum Allowable Concentrations (MACs) in the drug product will be determined and presented, based on data from toxicological studies. Consideration will be given to the potential impact that anticipated routes of exposure to the drug product may have on contaminant metabolism and toxicity, as well as to the potential effects of the agent on sensitive population groups such as in utero, infants and children, and immune-compromised groups. Where compound-specific data are insufficient, evaluations will incorporate the results of quantitative structure activity relationship (QSAR) analyses using accepted and validated models.