ICh guideline M3(R2) on non-clinical safety studies for the conduct of human clinical trials and marketing authorisation for pharmaceuticals

Introduction:
This summary will provide an overview of the ICh guideline M3(R2) on non-clinical safety studies for the conduct of human clinical trials and marketing authorization for pharmaceuticals. The guideline outlines the international standards for harmonizing non-clinical safety studies to support human clinical trials and marketing authorization for pharmaceuticals. The guidance aims to reduce animal use, promote ethical drug development, and facilitate timely clinical trials.

Key Points:

* The guideline emphasizes the importance of harmonizing non-clinical safety studies to support clinical development and marketing authorization for pharmaceuticals.
* The document applies to the usual situations encountered during pharmaceutical development, with specific guidelines for biotechnology-derived products, products for life-threatening diseases, and innovative therapeutic modalities.
* General principles include characterizing toxic effects, estimating safe starting doses, and designing studies appropriate for the stage of development.
* high dose selection for general toxicity studies should consider maximum tolerated dose (MTD), maximum feasible dose (MFD), or exposure margins, limited to 1000 mg/kg/day or 2000 mg/kg/day, depending on exposure multiples.
* Pharmacology studies, toxicokinetic and pharmacokinetic studies, and various toxicity studies (acute, repeated dose, genotoxicity, carcinogenicity, reproduction toxicity, etc.) should be conducted based on the stage of development and specific product attributes.
* Exploratory clinical trials, local tolerance studies, and immunotoxicity, photosafety testing, and non-clinical abuse liability should be addressed on a case-by-case basis.
* Continuing efforts to improve harmonization and reduce animal use are encouraged.

Main Message:
The ICh guideline M3(R2) on non-clinical safety studies for the conduct of human clinical trials and marketing authorization for pharmaceuticals promotes international harmonization, ethical drug development, and efficient use of resources. By following this guidance, pharmaceutical companies can ensure appropriate non-clinical safety studies are conducted to support clinical development and marketing authorization while minimizing animal use and promoting timely access to new treatments.

“ICh Guideline M3(R2) on Non-Clinical Safety Studies for the Conduct of human Clinical Trials and Marketing authorisation for Pharmaceuticals.” European Medicines agency, December 2009.