Non-clinical Safety Studies for the Conduct of Human Clinical Trials for Pharmaceuticals: ICH M3 and M3(R2)

Abstract

The extent of non-clinical safety testing to support clinical trials at different stages of development differed greatly between the EU, Japan and the USA prior to the adoption of the original ICH M3 guidance in 1997. The guideline achieved some notable harmonizations, but there was still significant disharmony, especially around the duration of dosing for non-rodents and the timing and extent of reproductive toxicology studies to support trials in women of childbearing potential. The inability to harmonise on these particular issues led to a reluctant acceptance of finalising the M3 guidance.

In 2006, a revision of ICH M3 commenced with an aim to remove the ­un-harmonised components. Although the M3 guideline is essentially concerned with the timing of non-clinical studies in relation to clinical development, further topics were also ­introduced by the Expert Working Group during the discussions. The ICH M3(R2) document was signed off by the regulators in June 2009. While the 2000 version of the guideline had 6 pages of text, the revision had 27. All the objectives had been largely met and with only one minor difference still in place.