Exposure Margin & DRF Helper
Calculate NOAEL-linked HED, dose/exposure margins, and geometric dose levels for DRF studies.
Enter nonclinical and clinical AUC or Cmax as a pair in the same units.
Results
Enter the required dose, Km, and multiplier values.
This tool only calculates ratios from entered values. Selection of the NOAEL, relevant species, high-clinical-exposure scenario, and safety factor requires separate justification using the full nonclinical, pharmacology, and TK/PK evidence. An HED or calculated value is not an automatic starting dose or safety decision.
Basis: the FDA MRSD guidance flow from NOAEL through BSA-based HED to a user-selected safety factor, and the exposure/toxicity/TK study-design principles in ICH M3(R2).
Tool Guide
Definition
Exposure Margin & DRF Helper — Converts a nonclinical NOAEL dose to an HED using Km, calculates multiples over an expected high clinical dose and optional AUC/Cmax, and separately spaces DRF levels geometrically between entered endpoints.
Purpose
(1) Cross-check NOAEL-dose-to-HED arithmetic, (2) summarize nonclinical/clinical multiples by dose, AUC, and Cmax, (3) record an output using a user-selected safety factor, and (4) generate geometrically spaced candidate DRF doses.
How to Use
① In Margin mode, enter the NOAEL dose, test-species/human Km, expected clinical dose, and high-exposure multiplier. ② If available, enter nonclinical and clinical AUC or Cmax as pairs in the same units. ③ Optionally enter a justified safety factor; the tool does not recommend one. ④ In DRF mode, enter minimum/maximum doses and level count. Selection of the NOAEL, relevant species, exposure metric, safety factor, or starting dose is not automated.
Examples
Example) Rat NOAEL=60 mg/kg, Km=6, human Km=37, clinical dose=1 mg/kg, and high exposure=2× gives HED=9.7297 mg/kg, high clinical dose=2 mg/kg, and dose margin=4.8649×. A nonclinical/clinical AUC pair of 1,200/100 gives an AUC margin of 6×. Five DRF levels from 1–100 mg/kg are approximately 1, 3.1623, 10, 31.6228, and 100 mg/kg.