Safety pharmacology is the study of the possible undesirable pharmacodynamic (PD) effects of a substance in relation to the dosing within the substance’s therapeutic range and above. The International Committee for Harmonization (ICH) has published guidelines (ICH S7A and ICH S7B) for safety pharmacology which recommend a core battery and supplemental studies to evaluate adverse effects of new molecular entities on the main organ systems, including renal/urinary system, gastrointestinal system, autonomic nervous system, and some other systems. With years of experience in drug development, Creative Biolabs is dedicated to conducting standard safety pharmacology services and is skilled at predicting potential risks prior to clinical trials. We can design the supplemental safety pharmacology program complying with ICH S7A, ICH S7B and provide expert interpretations to advance clients’ program favorably.
Fig.1 Safety pharmacology study approaches. (Hamdam, 2013)
The objectives of safety pharmacology study involve: a. to identify undesirable PD properties of a substance that may relate to its human safety; b. to evaluate adverse PD and/or pathophysiological effects of a substance in toxicology and clinical settings; and c. to investigate the mechanism of adverse PD effects observed or suspected. Safety pharmacology is an important part of the drug development process and is applied to explore the drug’s underlying efficacy on vital functions. The influence of a drug candidate on vital functions in the safety pharmacology core battery would be investigated before first used in human beings. Notably, when there’s a cause for concern not addressed by the core battery or repeat-dose toxicity studies, supplemental safety pharmacology studies should be executed as appropriate. And these additional safety pharmacology studies may be warranted to supplement the understanding of potential undesirable effects of other organ systems under specific conditions.
Tab.1 Supplemental safety pharmacology studies. (Colerangle, 2017)
The safety pharmacology core battery aims to explore the effects on the test molecule in key biological processes. In some situations, the core battery should be supplemented or need not be implemented, based on scientific rationale. At Creative Biolabs, we can provide follow-up safety pharmacology services to exclude certain tests and scientifically justify certain systems before clinical trials, achieving the purpose of saving costs and time for clients.
Effects of the pharmaceuticals on the renal/urinary system can be assessed, parameters including protein, osmolality, pH, cytology, urinary volume, specific gravity, fluid/electrolyte balance, blood chemistry determinations, and any other tests clients required.
Effects of the pharmaceuticals on the autonomic nervous system can be assessed, including evaluating their abilities to bind to receptors relevant for the autonomic nervous system and ability to stimulate autonomic nerves directly as well as observing cardiovascular responses, functional responses to agonists/antagonists in vivo or in vitro, what’s more, baroreflex testing, and heart rate variability.
Effects of the pharmaceuticals on the gastrointestinal system can be assessed by gastric secretion, gastric pH measurement, gastrointestinal injury potential, transit time in vivo, ileal contraction in vitro, bile secretion, and pooling.
Effects of the pharmaceuticals on organ systems not investigated elsewhere should be considered to execute assessment when there’s a reason for concern, including evaluations of influences of pharmaceuticals on central nervous system (CNS), respiratory system, skeletal muscle, immune response, and endocrine functions.
As a first-class pharmaceutical company around the world, Creative Biolabs has gained a great reputation for successfully accomplishing many challenging projects regarding supplemental safety pharmacology on various tissue or organ systems. In addition to dedicated devices and advanced platforms, our pharmacologists have abundant in vitro and in vivo expertise to support a comprehensive approach for low-risking compounds across organ system facilitating effective decision-making in early pre-clinical development. If you’re interested in our safety pharmacology services, please contact us for more information.
References
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