Safety pharmacology is a critical discipline within preclinical drug development. It focuses on evaluating the potential undesirable effects of a drug candidate on vital organ systems, particularly the cardiovascular, respiratory, and central nervous systems. This is essential for ensuring patient safety before a drug can progress to human clinical trials.

The primary goal of safety pharmacology is to identify potential risks associated with a drug's intended therapeutic effects or off-target actions. This involves assessing how a drug might affect:

Safety pharmacology studies are typically divided into core battery studies and follow-up studies. The core battery focuses on the three main organ systems, while follow-up studies are designed to investigate specific concerns identified in the core battery or based on the drug's mechanism of action.

The data generated from safety pharmacology studies is crucial for risk assessment. It helps determine safe starting doses for human clinical trials and informs the design of subsequent toxicology studies. Understanding how a drug affects vital functions in preclinical models allows researchers to predict potential adverse events in humans and implement appropriate monitoring strategies.

While in vivo studies remain central, in vitro assays (e.g., hERG channel assays for cardiac risk) and in silico modeling are increasingly used to screen drug candidates early and refine the design of in vivo studies. These methods can help prioritize compounds and reduce the number of animals used in testing, aligning with the principles of the 3Rs (Replacement, Reduction, Refinement).

Safety pharmacology studies are typically conducted after initial discovery and lead optimization, and before first-in-human (FIH) clinical trials. They are a mandatory part of the preclinical package submitted to regulatory authorities. The findings directly influence go/no-go decisions for advancing a drug candidate.