Non-invasive, home cage digital monitoring for improved safety pharmacology assessments in drug development: ICH S7A update considerations.

Non-invasive digital sensors are rapidly evolving in their capabilities and applications in both humans and animals. The dynamic and continuous biological insights they provide are likely to re-define our understanding of human and animal health and disease. For animal studies, the portfolio of measures is expanding and includes activity classification, locomotion, eating, drinking, social interaction, and even respiratory rate. Though these capabilities are most mature for rodents, there is precedent for their application in non-rodents as well. Preclinical safety pharmacology studies done in accordance with international guidance like International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) S7A protect healthy human volunteers and patients from acute, life-threatening harm to important organ systems including the central nervous (CNS), cardiovascular (CV), and respiratory systems. Though these studies have accomplished that aim, they are less effective at predicting subtle, progressive but no less impactful effects that occur commonly in patients. These assessments (particularly, studies of CNS function) have several potential weaknesses including the need to remove animals from their home cage, human observational bias, handling stress, discontinuous endpoints, short exposure times, and limited correlation to human patients. Continuous digital monitoring can mitigate many of these weaknesses through continuous monitoring, automation, quantitative outputs, and integration into other required studies of longer duration (e.g. repeat-dose general toxicity studies). Accordingly, there is a call to update ICH S7A to leverage advances in technologies like digital measures (DM) to improve the analytical rigor, translational relevance, and animal welfare management in safety pharmacology assessments.