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M3(R2): Guidance on Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals

Description - Figure 1: Recommended High does selection for general toxicity studies

1. MTD. 2. Exposure saturation. 3. MFD. 4. Mean exposure margin 50x clinical*.

Are/were any of the above situations met? Yes. Tested dose level is considered adequate. No. 1000 milligram per kilogram limit dose reached? No. Additional Studies might be warranted. Tested dose level is considered adequate. Yes. Mean exposure margin ≥10x clinical? Yes. Human dose <1 gram per day? No. Human Dose <1 gram per day? No. In completed or subsequent studies: 2000 milligram per kilogram does level tested? No. MFD or mean exposure margin ≥10x clinical? No. Additional studies might be warranted. MFD or mean exposure margin ≥10x clinical? Yes. Tested dose level is considered adequate. 2000 milligram per kilogram does level tested? Yes. Exposure animals ≥ humans? Yes. Tested dose level is considered adequate. No. Consider testing up to MFD. *For the US: see additional recommendations in section 1.5.