Janardhan, Kyathanahalli, Sura, Radhakrishna, Salian-Mehta, Smita, Flandre, Thierry, Palazzi, Xavier, Singh, Bhanu, Hukkanen, Renee Rosemary, Muthafar, Al-Haddawi, Bennet, Bindu, Laast, Victoria, Lee, Donna, Peterson II, Richard, Romeike, Annette, Schorsch, Frédéric and Guffroy, Magali (2022) Opinion on Not Terminating Control Animals in the Recovery Phase of Non-rodent Toxicology Studies. Toxicologic pathology.

Abstract

Nonclinical toxicology studies required to support human clinical trials of new drug candidates are generally conducted in a rodent and a non-rodent species. These studies typically contain a vehicle control group and low, intermediate, and high dose test article treatment groups. In addition, a dosing-free recovery phase is sometimes included in toxicity studies to demonstrate reversibility of toxicities observed during the dosing phase and may include additional animals in the vehicle control and one or more dose groups. Typically, reversibility is determined by comparing the test article-related changes in the dosing phase animals to concurrent recovery phase animals at the same dose level. Therefore, for interpretation of reversibility, it is not always essential to terminate the recovery vehicle control animals. In the absence of recovery vehicle control tissues, the pathologist’s experience, historical control database, digital or glass slide repositories, or literature can be used to interpret the findings in the context of background pathology of the species/strain/age. Therefore, in most studies, the default approach could be not to terminate recovery vehicle control animals. This manuscript provides opinions on scenarios that may or may not necessitate termination of recovery phase vehicle control animals in nonclinical toxicology studies involving dogs and nonhuman primates.

Item Type:	Article
Keywords:	Preclinical, Nonclinical, Controls, 3Rs, Dog, NHP, Recovery
Date Deposited:	05 Nov 2022 00:46
Last Modified:	05 Nov 2022 00:46
URI:	https://oak.novartis.com/id/eprint/47859