SAFETY ASSESSMENT

Porsolt is the ideal partner for evaluating the Safety of your next drug candidate. Our scientists rely on a very strong knowledge and expertise of safety pharmacology evaluations to advance your program successfully from early screening to regulatory submission.

Our  safety pharmacology program complies with International Conference on Harmonisation (ICHS7) Guidelines and provides the  interpretations needed to advance your program successfully in full compliance with GLP standards.

ICH S7 Regulatory Package

> Cardiovascular System : Blood pressure, heart rate, electrocardiograms (ECGs), ventricular pressure and pulmonary, and echocardiography

> Respiratory System: Respiratory rate, tidal and minute volumes

> Central Nervous System (CNS): Functional observation battery | Irwin screen

> in vitro Electrophysiology: Cloned human potassium channels (hERG)

 Behavioral pharmacology studies for investigating Abuse & Dependence Potential

> Early indicators of abuse liability

> Dedicated in vivo models for evaluating drug abuse liability

> Assessment of withdrawal symptoms

> Telemetry recording

> GLP compliant protocols

 

Follow-up studies

> Renal function

> Autonomic nervous system

> Gastrointestinal system

> Cardiovascular studies in anesthetized animals

> ex vivo studies : Spontaneously beating right atrium, Stimulated left atrium

> Cardiomyocytes Cor4U®/iCell²®

Functional toxicity assays

> Hepatotoxicity

> Nephrotoxicity

> Neurotoxicity

> Cardiotoxicity

Learn more on our Safety Pharmacology Services

CNS safety pharmacology is designed to identify behavioral and neurological effects of a test substance.

The basic test used is the Irwin Test, often coupled with Activity Meter and Rotarod. Additional tests are also available, although not part of the core battery defined in ICH S7A, to help discharge any perceived risks relevant to potential CNS safety concerns with a test substance.

Cardiovascular safety pharmacology defined in ICH S7A aims to assess the effects of a test substance on cardiovascular function. The subsequent ICH S7B focused on arrhythmogenic risk and QT prolongation. Both in vitro electrophysiological studies and in vivo assays in non-rodent telemetered animals are recommended. In addition to the core battery, there are other cardiovascular risk factors and a broad evaluation of hemodynamic parameters in anesthetized large animals is highly recommended. Depending on the effects observed during the core battery studies, or during phase1, additional follow-up studies can be proposed.

The identification of abuse and dependence liability is an important issue for CNS safety pharmacology.

Regulatory bodies in both the US and Europe are working to produce standard guidelines. In both cases the approach is based on looking for similarities with known drugs on abuse. This leaflet describes the strategy and the main procedures available at Porsolt for assessing abuse and dependence liability.

Respiratory safety pharmacology as described in ICH S7A core battery aims to evaluate the effects of a test substance on pulmonary function.

The basic procedure uses whole body plethysmography.

Several supplementary and follow-up studies can be designed to further evaluate the effects on respiratory function.

In addition to the three main vital systems (central nervous, cardiovascular and respiratory systems), the effects of a test substance on other important physiological functions should be assessed on the basis of its known chemistry, pk/pd or previously reported preclinical or clinical effects.

At Porsolt, the selection and design of the tests to be performed is carried out in close collaboration with our clients.