EMA Adopts Draft ICH Guideline, Calls for Submission of Rat Carcinogenicity Studies

The European Medicines Agency (EMA) has released for consultation a new document from the International Conference on Harmonisation (ICH), a move intended to continue the development of an existing international standards in the hopes of eventually phasing out the use of rats in preclinical carcinogenicity studies.

The standard, Draft ICH guideline S1 - Regulatory notice on changes to core guideline on rodent carcinogenicity testing of pharmaceuticals , remains in the early stages of ICH's development process.

The standards-setting body is a collaboration between the regulatory authorities of the US (Food and Drug Administration), Japan (Ministry of Health, Labour and Welfare) and EU (EMA).

The guideline was recently explored by ICH in a concept paper released for consultation in May. In that paper, regulators called for a "comprehensive and integrated approach to addressing the risk of human carcinogenicity of pharmaceuticals … without compromising safety." The details of the plan, including whether non-rodent models of carcinogenicity could be used to properly assess the risk to human patients, remained to be worked out, ICH noted at the time.

The changes were-and remain-under consideration, but EMA's adoption of the concept paper for consideration on 17 December 2012 gives the plan a better path forward for eventual adoption. Regulators and outside groups, including animal rights groups like People for the Ethical Treatment of Animals (PETA), have increasingly been calling for new regulatory science initiatives to reduce or replace the use of animals in preclinical safety testing.

The good news: "The outcome of the 2-yr rat carcinogenicity study can be predicted with reasonable assurance at the two extremes of the spectrum," ICH's document notes. The bad news: It's going to take a lot of work to prove that such a system is reliable.

The EMA/ICH draft guideline calls for sponsors to submit their Carcinogenicity Assessment Documents (CADs) for "all investigational small molecule pharmaceuticals subject to a two-year rat carcinogenicity study under current ICH S1A Guideline as well as for those with ongoing rat carcinogenicity studies, provided that dosing has not exceeded 18 months duration." This submission is voluntary.

Regulators plan to assess and evaluate data from approximately 50 CADs to determine whether the results from the completed rat-based study conform with results from non-rat-based ones.

Eventually, it is hoped that sponsors would be able to provide regulatory authorities with a CAD, which would then form the basis of a waiver that would allow them not to conduct a 2-year rodent study, and instead rely on other studies.

Comments on the draft guideline are due to EMA by 1 April 2013.