Points to consider regarding the use and implementation of virtual controls in nonclinical general toxicology studies

Xavier Palazzi; Lennart T Anger; Theresa Boulineau; Armelle Grevot; Magali Guffroy; Kristin Henson; Natalie Hoepp; Matt Jacobsen; Vijay P Kale; John Kreeger; Joan H Lane; Dingzhou Li; Wolfgang Muster; Brianna Paisley; Lila Ramaiah; Nicola Robertson; Valerie Shultz; Thomas Steger Hartmann; Richard Westhouse

doi:10.1016/j.yrtph.2024.105632

Points to consider regarding the use and implementation of virtual controls in nonclinical general toxicology studies

Regul Toxicol Pharmacol. 2024 Apr 27:150:105632. doi: 10.1016/j.yrtph.2024.105632. Online ahead of print.

Authors

Xavier Palazzi¹, Lennart T Anger², Theresa Boulineau³, Armelle Grevot⁴, Magali Guffroy⁵, Kristin Henson⁶, Natalie Hoepp⁷, Matt Jacobsen⁸, Vijay P Kale⁹, John Kreeger¹⁰, Joan H Lane¹¹, Dingzhou Li¹², Wolfgang Muster¹³, Brianna Paisley¹⁴, Lila Ramaiah¹⁵, Nicola Robertson¹⁶, Valerie Shultz¹⁷, Thomas Steger Hartmann¹⁸, Richard Westhouse¹⁹

Affiliations

¹ Drug Safety Research and Development, Pfizer Inc, 445, Eastern Point Road, Groton CT, USA. Electronic address: xavier.palazzi@pfizer.com.
² Safety Assessment, Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA.
³ Nonclinical Drug Safety, Boehringer Ingelheim, 900 Ridgebury Road, Ridgefield, CT, 06877, USA.
⁴ Preclinical Safety, Novartis AG, Fabrikstrasse, Basel, Switzerland.
⁵ Preclinical Safety, AbbVie, 1 North Waukegan Road, R46G/AP13A-3, North Chicago, IL, 60064, USA.
⁶ Preclinical Safety, Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ, 07936, USA.
⁷ Nonclinical Drug Safety, Merck and Co., Inc., Rahway, NJ, USA.
⁸ Clinical Pharmacology and Safety Sciences, AstraZeneca, Biomedical Campus, 1 Francis Crick Ave, Cambridge, UK.
⁹ Nonclinical Safety, Bristol Myers Squibb, 1 Squibb Dr, New Brunswick, NJ, 08901, USA.
¹⁰ Non-Clinical Safety, GSK, 1250 S. Collegeville Rd, Collegeville, PA, USA.
¹¹ Translational Safety & Bioanalytical Sciences, Amgen, Inc., 1 Amgen Center Dr, Thousand Oaks, CA, 91320, USA.
¹² Global Biometrics & Data Management, Pfizer Inc, 445, Eastern Point Road, Groton CT, USA.
¹³ Pharmaceutical Sciences, F. Hoffmann-La Roche Ltd., Grenzacherstrasse 124, CH-4070, Basel, Switzerland.
¹⁴ iBAR ADMET, Eli Lilly and Company, 893 Delaware St, Indianapolis, IN, USA.
¹⁵ Preclinical Sciences and Translational Safety, Johnson & Johnson, 1400 McKean Road, PO Box 776, Spring House, PA, 19477, USA.
¹⁶ Non-Clinical Safety, GSK, Gunnels Wood Road, Stevenage, SG1 2NY, UK.
¹⁷ Nonclinical Development, Organon, 4000 Chemical Rd, Suite 500, Plymouth Meeting, PA, 19462, USA.
¹⁸ Investigational Toxicology, BAYER AG, Pharmaceuticals, Muellerstrasse 178, 13342, Berlin, Germany.
¹⁹ Toxicology and Pathology, Agios Pharmaceuticals, 88 Sidney Street, Cambridge, MA, USA.

PMID: 38679316
DOI: 10.1016/j.yrtph.2024.105632

Abstract

The replacement of a proportion of concurrent controls by virtual controls in nonclinical safety studies has gained traction over the last few years. This is supported by foundational work, encouraged by regulators, and aligned with societal expectations regarding the use of animals in research. This paper provides an overview of the points to consider for any institution on the verge of implementing this concept, with emphasis given on database creation, risks, and discipline-specific perspectives.

Keywords: 3Rs, animal use; Nonclinical; Toxicology; Virtual controls.