Preclinical study guidelines
for cardiovascular pharmacology & electrophysiology
Harmonized guidelines for cardiac safety studies
When it comes to drug development, preclinical studies are subjected to mandatory guidelines issued by the ICH, the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use.
This council combines experts from regulatory authorities and the pharmaceutical industry, who cover the scientific and technical aspects of drug registration. Current standards require preclinical safety studies to analyze the effect of your compound on all vital functions, i.e. cardiovascular, renal, pulmonary, gastrointestinal and neurological.
Cardiovascular safety studies have to be conducted in compliance with:
ICH S7A, the Guideline on safety pharmacology studies for human pharmaceuticals. Safety Pharmacology, as defined in guideline ICH S7A aims to assess potential adverse effects of a test substance on vital functions: cardiovascular, respiratory and central nervous system are considered as the vital organ systems that should be studied in the core battery.
ICH S7B, seen as an extension of the above S7A guideline. The S7B guideline focuses on the assessment of the effects of pharmaceuticals on ventricular repolarization and proarrhythmic risk. S7B details the guidelines on Safety Pharmacology studies to assess the potential for delayed ventricular repolarisation (QT interval prolongation) in human pharmaceuticals.
PhysioStim, ICH guidelines and GLP compliance all in one
A profound working knowledge of all applicable regulations and requirements
PhysioStim is a preclinical CRO for expert cardiac safety studies and assays. Our team has a profound working knowledge of all applicable regulations and requirements, which are integrated in our quality assurance policy. Our team also constantly monitors any evolutions in regulations in policies so your studies comply with all applicable requirements. The CIPA initiative below is one of those upcoming regulations:
Upcoming guidelines for preclinical safety studies
CIPA, the Comprehensive in Vitro Proarrhythmia Assay
The objective of the CiPA initiative is to facilitate the adoption of a new paradigm to assess the clinical potential of Torsades de pointe, which cannot be measured exclusively by potency of hERG block and not at all by QT prolongation.
The Comprehensive In Vitro Proarrhythmia Assay is currently being designed by expert working groups from:
- the FDA (Food and Drug Administration)
- the HESI (Health and Environmental Sciences Institute)
- the CSRC (Cardiac Safety Research Institute)
The CIPA pathway uses both in vitro and in silico technologies to improve risk assessment during drug development. The 3 main elements of the CIPA initiative:
- Develop voltage clamp protocols for core set of cardiac ion channel types responsible for both the depolarization and the repolarization process of cardiac action potential.
- Develop consensus in silico model to reconstruct electrophysiologic activity within a heart cell.
- Investigate capabilities of human stem-cell derived cardiomyocyte assays to confirm findings of in vitro and in silico assays.
PhysioStim, your expert in cardiac safety
MANDATORY PRECLINICAL STUDIES
GLP-certified preclinical ICH S7B & S7A-compliant assays
FOLLOW-UP STUDIES TO COMPLETE YOUR DATA
A wide range of in vitro and in vivo assays for cardiac safety studies
The right study model to guarantee excellence
A wide selection for reliable preclinical safety studies
The experts at PhysioStim go beyond standard study guidelines to conduct their safety studies. We provide a wide range of possibilities to conduct both mandatory and complementary studies and help your project move forward. PhysioStim has over 17 years of expertise in developing in vitro and ex vivo models to investigate potential drug-related cardiac adverse effects. We provide cellular models as well as tissue and organ models.