Abstract
The PDE/OEL for a pharmaceutical is set by determining the Point of Departure (POD) based on non-clinical or clinical toxicity studies of the issued substance and considering the uncertainties. If the toxicological information required for setting the PDE/OEL is not available, the following approaches can be proposed.
In the absence of toxicological information;
-The Threshold of Toxicological Concern (TTC) approach can be used to evaluate the issued substances without toxicological information. For mutagenic substances, the TTC value is specified in the ICH M7 guideline. Although TTC values for non-carcinogens are already available in the field of food safety assessment, there are no established TTC values for pharmaceuticals. As the TTC approach is generally considered to be conservative, it may be appropriate to use the read-across approach for evaluation where relevant toxicological information for structural analogues are available.
In the absence of information on toxicological information conducted in the route setting the PDE/OEL;
-Route extrapolation based on bioavailability should be considered. Regarding TTCs for non-carcinogenic substances, which have essentially been developed from oral toxicological information, TTCs for the management of impurities in parenteral pharmaceuticals are not applicable.
This presentation will introduce TTCs for non-carcinogens, read-across approach used in the evaluation of general substances, and route extrapolation of TTC as a reference for PDE/OEL settings of pharmaceuticals lacking sufficient toxicological information.
