Analysis of nonclinical NOAEL
toxicity, ICH
SECONDARY
The determination of a NOAEL in toxicology studies conducted to support the clinical dosing of new drugs to oncology patients is not a required endpoint in ICH S9 [When assessing criteria for justifying the starting dose in clinical studies, it is important to understand species sensitivity to the compound with the more sensitive species most often being used. In preparing to conduct the analysis for using the alternative NOAEL approach, the submitted products were evaluated for how often a NOAEL was determined or justified in both the rodent and non-rodent toxicity studies. Using the criteria outlined for assessing an alternative NOAEL-based starting dose, 66 (72%) of the products were suitable for the exercise.There were 26 products that did not meet the criteria for the NOAEL-based starting dose assessment (Table Primary and secondary DLTs preventing NOAEL determination in animals and patient DLTs for these compounds