euro-toxicology-2016_scientifictracks-abstracts

Volume 6, Issue 6(Suppl)

J Clin Toxicol 2016

ISSN: 2161-0495, JCT an open access journal

Page 37

Notes:

Euro Toxicology 2016

October 24-26, 2016

conferenceseries

.com

Toxicology & Applied Pharmacology

October 24-26, 2016 Rome, Italy

Euro-Global Summit on

Change of rodent carcinogenicity testing

Gerd Bode

and

Jan Willem van der Laan

University of Gottingen, Germany

Medicines Evaluation Board, Netherlands

odent carcinogenicity studies are not meant to produce a toxicology result/tumor count, but to extrapolate (translate)

these data and develop a prediction of potential cancer risk for patients. If there is a real risk, then either no approval

can be granted or a rigid risk/benefit analysis will justify any treatment of humans. Altogether, there are too many positive

results from such long-term rat or mouse studies. The need for the 2 year rodent assay to assess a carcinogenic potential

is questioned already for years. From retrospective analyses of various datasets (PhRMA, FDA, JPMA and common

EU+FDA) it was concluded that based on genotoxicity and non-genotoxic mechanisms, detectable in pharmacology and

chronic toxicity data (usually present at the end of phase 2 in the development of a new pharmaceutical) the outcome of

the 2-yr rat carcinogenicity study can be predicted with reasonable assurance at the two extremes of the spectrum: Negative

predictions can be made when predictive carcinogenic signals are absent and positive predictions are possible when such

signals are present. In between a category of compounds still remain for which the outcome cannot be predicted with

sufficient certainty and where experimental studies may have added value to identify real hazards. These hypotheses are

being tested in an ongoing common exercise by agencies and industries. Such prospective evaluations are necessary to justify

any revision of the present recommendations of the ICH guideline S1. Until 2017, sponsors will be strongly encouraged

to submit carcinogenicity assessment documents (CADs) to drug regulatory agencies (DRAs) for all investigational

pharmaceuticals with ongoing or planned 2-yr rat carcinogenicity studies. The CAD would address the overall carcinogenic

risk of the investigational drug as predicted by the available knowledge and a rationale for why the conduct of long-term

studies would or would not add value to that assessment, in the latter case by a request of a “virtual” waiver. Drug regulatory

agencies will independently review the submitted documents and evaluate the degree of concordance with sponsors.

During this prospective evaluation period waiver requests will not be granted but the data are intended solely for collecting

experience. Submitted CADs will finely be compared to the real outcome of the 2-yr carcinogenicity studies and/or any other

factors of a weight of evidence evaluation. Main objective will be the assessment of accuracy of the predictions, with emphasis

on the “Virtual” waivers. This paper will inform about the details of the retrospective analyses leading to the new hypothesis

and will report about preliminary results of this prospective exercise. Hopefully, further contributing participation can be

stimulated.

Gerd Bode et al., J Clin Toxicol 2016, 6:6(Suppl)