Secondary Pharmacology Targets for Pediatric Developmental Safety Assessment of New Drugs: Clinical Pharmacology Considerations

Drug safety in pediatric patients has always been a concern. Major tragedies with drugs in pediatric patients created an environment of caution, but the experience with pediatric legislation and drug development over the past 20 years has eased the cautionary approach to pediatric drug safety. The advent of new methods of safety testing, driven by the movement away from animal use in research, provides new opportunities to screen for and prevent adverse developmental effects of drugs on pediatric patients. One approach that can be explored for use in pediatric developmental safety testing is secondary pharmacology, or screening for off-target drug effects. Secondary pharmacology, which is an established screening mechanism described in ICH S7A, could provide the opportunity to answer important off-target questions. Examples of 12 specific secondary pharmacology targets related to adverse effects on pediatric development are provided. Clinical pharmacology plays a critical role in the interpretation of secondary pharmacology through quantitative studies necessary to validate positive findings and through the final assessment of the risk:benefit associated with these findings. In conclusion, secondary pharmacology screening has the potential to reduce animal testing while addressing two critical objectives: screening drugs for off-target effects and providing information on off-target effects relevant to pediatric developmental safety.