ISSUE NO. 13 — Safety Pharmacology Studies Review — A Review

Safety pharmacology studies are defined in the International Conference on Harmonization (ICH) S7A guidance as “those studies that investigate the potential undesirable pharmacodynamic effects of a substance on physiological functions in relation to exposure in the therapeutic range and above.” 

In other words, they are a set of tests focused on potentially adverse effects of pharmaceutical or biological agents, differing from traditional toxicology studies as they are typically concentrated on a single organ or physiological system.

In Issue 13 of The Altascientist, we take a look at the requirements, best practices, and core and supplemental study considerations, including:

• Cardiovascular system
• Central nervous system
• Respiratory system
• Species selection
• Routes of administration
• Dose level selection and duration
• Supplemental (follow-up) studies
• Safety pharmacology endpoints on traditional toxicology studies

Safety Pharmacology Endpoints

Safety pharmacology endpoints can be included in the regulatory single- or repeat-dose toxicology studies. In those instances, species selection is important, as administration by certain routes in certain species may not attain the level of exposure required.  

In some cases, combination studies, where integrated approaches examine the inter-relationships of drug-mediated effects on different organs, can be a practical approach for safety pharmacology studies. One example is the addition of FOB/Irwin’s Screen to rodent toxicology studies. The additional assessments are usually performed on a subset of animals, typically from the population of animals assigned to the evaluation of potential toxicity (generally between three to five animals/sex/group).

When designing integrated studies, it is important to consider that safety pharmacology requirements must not confound the interpretation of general toxicology endpoints, and vice versa. For example, surgery for implants may introduce pathological artifacts, while the extra handling and/or novel environments can induce stress artifacts. 

How Altasciences Can Support Your Safety Pharmacology Studies 

Safety pharmacology may or may not be required to move your molecule forward. Altasciences' experts can provide insight for the fundamental considerations in selecting and designing a suitable program of safety pharmacology. Establishing a specific roadmap which includes the core battery (cardiovascular, respiratory, and central nervous systems) is the starting point, with supplemental studies included when there is a cause for concern. Some safety pharmacology endpoints can be included in the regulatory single- or repeat-dose toxicology studies.

Consult with our scientists for a thorough review of your program requirements, and how we can assist you with a seamless transition to regulatory submission, and human clinical trials.

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