“The PDE represents a substance-specific dose that is unlikely to cause an adverse effect if an individual is exposed at or below this dose every day for a lifetime.”

• ICH Topic Q3C (R4). Impurities: Guideline for Residual Solvents (CPMP/ICH/283/95)
• VICH GL18 (R): Impurities: Residual solvents in new veterinary medicinal products, active substances and excipients (EMA/CVMP/VICH/502/99-Rev.1).
• ICH Q3D. Elemental Impurities. (Sept.2015)

STEPS OF THE DETERMINATION OF A PDE 

REFERENCE EQUATION

Appendices 3 of the ICH Q3C and VICH GL 18 guidelines present the following equation for the derivation of the PDE:

F1: to account for extrapolation between species

F2: to account for variability between individuals

F3: to account for toxicity studies of short-term exposure

F4: may be applied in cases of severe toxicity

F5: NOAEL vs LOAEL

We elaborate some cutomized PDE monographs with all calculation details and all bibliographic references linked to this calculations by complete reviewing of all relevant pharmaceutical and medical databases. Access directly to our database which contains more than 1,000 PDEs already developed.