Species selection for nonclinical safety assessment of drug candidates: Examples of current industry practice
Rostam Namdari, Keith Jones, Samuel S. Chuang, Steven Van Cruchten, Zuhal Dincer, Noel Downes, Lars Friis Mikkelsen, Joanna Harding, Sven Jäckel, Björn Jacobsen, Jacqueline Kinyamu-Akunda, Andréanne Lortie, Sofiene Mhedhbi, Susanne Mohr, Michael Schmitt, Helen Prior
Abstract
In drug development, nonclinical safety assessment is pivotal for human risk assessment and support of clinical development. Selecting the relevant/appropriate animal species for toxicity testing increases the likelihood of detecting potential effects in humans, and although recent regulatory guidelines state the need to justify or dis-qualify animal species for toxicity testing, individual companies have developed decision-processes most appropriate for their molecules, experience and 3Rs policies. These generally revolve around similarity of metabolic profiles between toxicology species/humans and relevant pharmacological activity in at least one species for New Chemical Entities (NCEs), whilst for large molecules (biologics) the key aspect is similarity/presence of the intended human target epitope. To explore current industry practice, a questionnaire was developed to capture relevant information around process, documentation and tools/factors used for species selection. Collated results from 14 companies (Contract Research Organisations and pharmaceutical companies) are presented, along with some case-examples or over-riding principles from individual companies. As the process and justification of species selection is expected to be a topic for continued emphasis, this information could be adapted towards a harmonized approach or best practice for industry consideration.