ADEs for different routes
We often get asked the question "The route of administration for our drug formulation is different than route of administration for the selected point of departure in the OEL Fastrac monograph. Does this make a difference in the ADE?"
Our response is as follows:
It is important to remember that the definition of an ADE, which as indicated in ISPE's Baseline Guide: Risk-Based Manufacture of Pharmaceutical Products (Risk-MaPP), is defined as:
"The daily dose a substance below which no adverse events are anticipated, by any route [emphasis added], even if exposure occurs for a lifetime."
When selecting the point of departure for a drug compound, the expert toxicologists at Affygility Solutions perform an adjustment factor analysis that examines all possible routes of administration, the species involved, the various PK/PD factors, and other relevant factors. Based on the results of this analysis, unless otherwise indicated in the OEL Fastrac monograph, the lowest ADE value for all possible routes of administration is selected. By selecting the lowest ADE value (for the most sensitive route in the most sensitive species) all other routes are protected.
In some rare cases, this may result in a more conservative ADE than necessary for your formulation, but it does provide the added benefit of not having to manage multiple ADEs for the same drug compound.
This approach is supported in the scientific literature as follows:
Please note: Unless otherwise indicated, the route of administration does not include ocular or pediatrics. If you need ADEs for these situations, contact Affygility Solutions.
For a more detailed discussion on this topic, watch the video below.