Our safety pharmacology studies 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. Detection of anti/pro
convulsive potential and abuse liability assessment. Detection of motor coordination
and spontaneous locomotor activity.
- Cardiovascular System - Measure effects on cardiac parameters (e.g.
blood pressure, heart rate and ECG) in conscious (telemetered) or anaesthetised
animals.
- Neuro-Cardio Combo System - Simultaneous assessment of CNS/CV system
on the same subject.
- 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.
Biodistribution Studies
Biodistribution studies are requested or recommended by several guidelines for the
pre-clinical safety evaluation of nevel gene therapy technologies and vaccines (CPMP/BWP/3088/99,
EMEA/CHMP/ICH/607698/2008, EMEA/CHMP/GTWP/125459/2006). Quantitative PCR (Q-PCR)
is considered the standard for the detection and quantification of specific gene
and vector sequences in the biodistribution studies given its robustness and sensitivity.
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