Safety pharmacology investigates potential undesirable effects of drugs on physiological functions, to predict safety before bringing to market.
We provide complete solutions to meet your GLP or non-GLP Safety Pharmacology needs. Our solutions allow for efficient data collection and analysis, in-line with ICH requirements, spanning in-vivo and ex-vivo applications.
Objectives of Safety Pharmacology Studies
The core battery of tests required per ICH guidelines S7A and S7B includes identification, evaluation, and investigation of the cardiovascular, respiratory, and central nervous systems.
Cardiovascular evaluation can be conducted in either anesthetized or freely moving, conscious animals. Wireless telemetry in conscious animals is the preferred method for ECG and blood pressure recording, as the data is not compromised by the effect of anesthetic. For ex vivo studies, isolatedHEART can be used to assess QT prolongation.
Respiratory evaluation studies the effects of novel therapeutic agents in conscious animals, predominately rodents. In such studies, there is a preference for conscious respiratory measurements, which fully encompass all aspects of the respiratory system’s function (i.e. the nervous system, muscular, and gas exchange components), thus providing physiologically relevant and translational outcomes.
Central nervous system (CNS) evaluation of core battery tests includes motor activity, behavioral changes, coordination, sensory/motor reflex responses, and body temperature. Neurological follow up studies evaluate electrophysiology (EEG/vEEG*), seizure, sleep, event related potentials (ERPs; AEP, VEP), learning and memory, ligand-specific binding, neurochemistry, and more. Wireless implanted telemetry is the preferred technique for data collection from unrestrained animals, particularly important for behavioral assessments.
Safety Pharmacology related hardware
Our easyTEL+ systems allow simultaneous acquisition of core battery and supplemental physiological measurements.
Transmitter acquires biopotentials (ECG, EEG, EMG, EOG), blood pressure (arterial, LVP), body temperature, and postural activity from conscious, freely moving rodents (200g or more) to large animals.
Our head-mounted rodentPACK system acquires up to 4 biopotentials and activity from conscious, freely moving subjects (50g or more). It can be used in combination with easyTEL+ to acquire additional physiological parameters (i.e. arterial pressure, LVP, body temperature).
easyTEL+ and rodentPACK use the same acquisition hardware, requiring only the consumables for a seamless transition between systems. Physiological endpoints can be acquired during behavioral testing (i.e. Elevated Plus Maze, Tail Suspension Test, Barnes Maze). Systems can be synchronized with video for vEEG studies.
emkaPACK4G jacketed telemetry monitors required physiological parameters in the core battery of tests per ICH guidelines S7A and S7B and is in line with the 3Rs* principles.
These include but are not limited to ECG, non-invasive blood pressure (i.e. tail cuff), respiratory endpoints (see below), temperature (i.e. skin or rectal), and activity from conscious subjects.
Invasive measurements such as arterial and/or left ventricular blood pressure, core body temperature or EEG, easyTEL+ implants are synchronized with physiological parameters from emkaPACK4G.
*Replacement, Reduction, Refinement
The non-invasive double chamber plethysmograph is a proven way to study pulmonary function in restrained, conscious animals. This technique has become the current industry standard as subjects are spontaneously breathing and evade any effects of anesthesia or other influences. A seal around the restraint creates a distinction between the nasal and thoracic cavities, providing true respiratory flow measurements that comply with ICH S7A Guidelines.
Whole Body Plethysmograph chambers are also commonly used to assess pulmonary function in conscious animals. The use of both techniques as part of the “core battery” tests provide useful and reliable information on pulmonary mechanics in safety pharmacology.
RIP bands (Respiratory Inductance Plethysmography) allow to measure respiratory endpoints non-invasively in large animals.
While ecgAUTO utilizes pioneering shape recognition to analyze large data sets of ECGs and detect arrhythmias in minutes, a separate module is available for RIP analysis. However, both data can be acquired at the same time.
emkaPACK4G uses up to 2 RIP bands (abdominal and thoracic) to derive tidal volume, minute volume, phase angle, etc. in large animals. The asynchronous movement between abdominal and thoracic breathing can be seen with the use of 2 RIP belts.
Possible endpoints include but are not limited to heart rate, interval analysis (i.e. RR, PR, QT, QRS, QTc), lung volume measurements (i.e. TV, MV, AVo), frequency, and phase angle with the use of ECG leads and RIP bands, respectively.
Automation and batch analysis shortens time from experimentation to reporting. Our software allows for cardiovascular, respiratory and neurological collection and analysis on a single, integrated platform.
To comply with regulatory requirements:
- GLP modules can be activated with each emka TECHNOLOGIES’ software
- Optional SEND export(s) available
- Dedicated validationspecialists can provide full service, or à la carte validation of our systems
Voice of the Customer
In a recent survey1, Simon Authier et al confirms that “The most frequently observed drug mediated effects included an increased heart rate, increased arterial blood pressure, hERG (IKr) block, decreased arterial blood pressure, decreased heart rate, QTc prolongation, and changes in body temperature”.