Our safety pharmacologystudies assist in the prediction of potential adverse effects of new chemical entities and biotechnology-derived products prior to first administration to man. For human pharmaceuticals, the ICH guidelines (ICH S7A and S7B) recommend performing a core battery of in vivo safety pharmacology tests as well as an in vivo and in vitro evaluation into the potential for delayed ventricular repolarisation (QT prolongation). Our studies conform to worldwide regulatory guidelines and can be monitored for GLP compliance by our Quality Assurance Unit. The specific studies to be conducted and the experimental design should be based on the properties and intended action of the compound under evaluation.
Core Battery Services
Our
Core Battery services incorporate:
- Central Nervous System - Detection of effects on motor activity using a modified Irwin test or a functional observation battery.
- Cardiovascular System - Measure effects on cardiac parameters (e.g. blood pressure, heart rate and ECG) in conscious (telemetered) or anaesthetised animals.
- Respiratory System - Measure effects on ventilatory parameters (respiratory rate, tidal volume) to provide an assessment on the general respiratory function of conscious animals. Measure effects on lung mechanics (resistance, compliance) in anaesthetised animals to provide an assessment on the efficacy of compounds on obstructive or restrictive disorders.
Ventricular Repolarization Services
Our
Ventricular Repolarization services incorporate:
- In Vivo QT Assay - Measures indices of ventricular repolarization such as QT interval. This assay is typically designed to meet the objectives of both ICH S7A and S7B and in doing so will reduce the use of animals.
- In Vitro IKr Assay - Testing of compounds for interactions with the hERG channel to identify potential risk of QT prolongation in humans. Such tests can be used as a screen in development candidate selection using conventional or automated (Rapid ICE) ion channel electrophysiology, or they can be monitored for GLP compliance to meet requirements for regulatory submission.
Formulation Analysis
Regulatory bodies are increasingly aware of the importance of being able to demonstrate
proof of exposure in test systems. Forming part of in vitro and in vivo service areas, our Formulation Analysis support group provides services to help validate proof of exposure. This includes method development, method validation, a stability assessment in vehicle, and the analysis of formulation samples taken during the in-life phase.
Supplemental and Follow-up Studies
We also offer a range of supplemental studies to help evaluate potential adverse effects on organ systems not addressed in the core battery:
- Renal/Urinary System
- Autonomic Nervous System
- Gastrointestinal System
- Other organ systems, e.g. skeletal muscle, drug dependency, immune and endocrine functions
And we can assist you with follow-up studies for further investigations which may be required due to observations from in vivo and in vitro QT assays:
- Human cardiac sodium channel in vitro
- Cardiac action potential assays in vitro (Purkinje fibre)
- Langendorff-perfused isolated heart in vitro