Pharmacology is the study of the mechanism by which substances act on a living system.
A core battery set of safety pharmacology studies was designed to investigate
effects on vital organ systems such as the central nervous system (CNS), cardiovascular
(CV) and respiratory system.
Although these are not always appropriate for biopharmaceuticals, the ICH
S6 guidelines do state that a safety pharmacology assessment should be made.
This can often be obtained within the main toxicity studies, for example obtaining ECG measurements in 4-week toxicology studies. However, more extensive studies are sometimes required when the product is pharmacologically active in the available models and product-specific issues deem them necessary.
The standard range of stand-alone safety pharmacology studies are detailed below.
- CNS - Modified Irwin dose-range
- CV - Telemetry (BP, HR, ECG) in a non-rodent species
- Respiration - Rate, tidal volume and minute volume
- In vitro hERG ion channel assay and Action Potential measurement
are available if required
Depending on the outcome of the core battery studies, additional follow-up studies may be required.
Further studies may also be required based on the therapeutic target or previous work done on similar classes of compound.
- Renal / urinary system
- Gastro-intestinal system
- Dependency potential
- Electrophysiology
- Autonomic nervous system and smooth muscle
- Neuromuscular function
- Assessment of antigenicity
- Endocrine function
- Other studies - e.g. drug interaction, measurement of blood parameters
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