Surgical instrumentation of cardiovascular telemetry device has minimal impact on the general toxicology data interpretation in Cynomolgus monkeys

Abstract

Increasing numbers of general toxicology studies with integrated implanted cardiovascular (CV) telemetry are being conducted due to the constrained supply of nonhuman primates and demands for higher method sensitivities as per ICH S7B Q&A. However, limited information is available for the potential impact of surgical instrumentation on the toxicology data. In this study, we reviewed the reports of implanted CV telemetry studies conducted in cynomolgus monkeys from 2017 to 2022 at our facility. The instrumentation had no impact on food consumption, respiration, pulse oximetry, neurological parameters, ophthalmology, troponin I, urinalysis, immunophenotyping, or organ weights. There was a low probability of needing to exclude animals from studies due to instrumentation-related technical (4.8 %) or health issues (0.8 %). Incidences were low (0.3 % to 2.6 %) to have instrumentation-related in-life or laboratory findings. Pathology findings were regional, rarely associated with clinical pathology changes, non-adverse, and clearly distinguishable from the test article effects in the studies examined. They were limited to localized effects (fibrosis and low-grade inflammation) associated with a foreign body reaction in the area immediately in contact with the device. Also, thrombus formation (0.2 %) was noted when the femoral artery was used for blood pressure catheter placement. Changing from intramuscular to intra-peritoneal placement greatly reduced the incidence of unusable ECG data and abnormal clinical signs. Use of the internal iliac artery for catheter placement also eliminated thrombus formation and the subsequent health impact. In conclusion, implanted telemetry integrated into a nonhuman primate toxicology study does not compromise the study objectives, study execution, or toxicology data interpretation.