What is ICH?

The International Conference on Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use is a unique project that brings together the regulatory authorities of Europe, Japan and the United States and experts from the pharmaceutical industry to discuss scientific and technical aspects of product registration.

The ICH utlimately aims at achieving a more economical use of human, animal and material resources, and the elimination of unnecessary delay in the global development and availability of new medicines whilst maintaining safeguards on quality, safety and efficacy, and regulatory obligations to protect public health.


ICH & Safety Pharmacology

The ICH guidelines pertaining to safety pharmacology are numbered S7A and S7B. Both guidelines were developed as a reaction to the changing paradigm resulting from the appearance of more numerous and innovative compounds in the market.

While S7A introduces the nature and timing of preclinical studies during drug development, S7B is more oriented towards QT prolongation and cardiovascular toxicity.


S7A
S7A basically covers the selection and design of in vivo and in vitro safety pharmacology studies with particular consideration given to central nervous system, cardiovascular system and respiratory system.

It stipulates that safety pharmacology studies should be initiated prior to first human exposure, and use sensitive, validated animal models to predict the risk of human adverse effects. The need for GLP-compliance is underlined.
Click here for S7A original document

S7B
Document ICH S7B is entitled “The non-clinical evaluation of the potential for delayed ventricular repolarization (QT interval prolongation) by human pharmaceuticals”.

S7B focuses on cardiac arrhythmias as a risk to human subjects and patients. It describes a non-clinical testing strategy for assessing the potential of a test substance to delay ventricular repolarization.

It defines basic assays and complementary assays which should be given consideration in order to identify mechanisms of toxicity.

The guideline defines the goal of a cardiac safety profiling strategy as “attempting to relate the extent of delayed ventricular repolarization to the concentration of test substance and its metabolites to which the system is exposed”.

In-Vitro Ikr assay (hERG) and In-Vivo QT assay (ECG in canine) are now the two prerequisites to any Investigational New Drug (IND) application to be submitted to the FDA or Health Canada.

Click here for S7B original document