Benjamin, Amanda, Gallacher, David J, Gintant, Gary, Greiter-Wilke, Andrea, Guillon, Jean-Michel, Kasia, Cheiko, Leishman, Derek, Levesque, Paul, Louttit, James, Prelle, Katja, Ratcliffe, Sian, Sannajust, Frederick, Ledieu, David, Vargas, Hugo and Valentin, Jean-Pierre (2015) Renal studies in safety pharmacology and toxicology: A survey conducted in the top 15 pharmaceutical companies. Journal of Pharmacological and Toxicological Methods.

Abstract

Introduction: What strategies are used to investigate renal toxicity in both ICH S7A compliant safety pharmacology studies and within repeat dose toxicity studies by large pharmaceutical companies today? Do single dose renal safety pharmacology studies have impact or utility in drug development or are we better placed to assess renal effects after multiple doses of compounds? How much mechanistic work is performed? What has the impact of the validation of the DIKI biomarkers been in terms on what companies are now measuring? What is the impact of renal/urinary safety study data upon progression of projects?
Methods: A short anonymous survey was conducted, by invitation, to safety pharmacology representatives of the top 15 pharmaceutical companies, as defined by 2012 R&D portfolio size. A series of multiple choice questions were designed to explore the strategies used to investigate renal effects in both ICH S7A compliant safety pharmacology studies and within toxicology studies. Results: A 67% response rate was obtained. Nine out of ten companies conduct renal excretory measurements in toxicology studies whereas only five out of ten conduct renal safety pharmacology studies; and all of those 5 also conduct the renal excretory measurements in toxicology studies. A variety of parameters are measured and/or calculated as part of these studies, on a case by case basis, including regulatory qualified and non-qualified DIKI biomarkers. Finally, only one company has used renal/urinary functional data alone to stop a project, whereas the majority of respondents combine renal data with other target organ assessments to form a larger decision-making set. Conclusion: This short survey has highlighted areas of similarity, e.g. urinary measurements are more commonly taken on repeat dose toxicity studies and renal safety pharmacology studies have little utility and also differences such as the differing use of DIKI biomarkers in urinary safety studies, in the way large pharmaceutical companies assessed renal function.

Item Type:	Article
Date Deposited:	26 Apr 2016 23:46
Last Modified:	26 Apr 2016 23:46
URI:	https://oak.novartis.com/id/eprint/20850