Bridging studies in support of oral pediatric formulation development

Area of Science:

• Pharmaceutical Sciences
• Pediatric Drug Development
• Clinical Pharmacology

Background:

• Pediatric drug formulations require specific development to ensure treatment compliance and safe dosing.
• Adult formulations are often unsuitable for pediatric use, necessitating dedicated pediatric formulations for studies and market.
• Early-stage development may utilize preliminary "enabling" formulations before optimizing for market.

Purpose of the Study:

• To outline the strategic considerations for developing and validating pediatric drug formulations.
• To emphasize the importance of bridging studies, such as relative bioavailability (RBA), for formulation transitions.
• To highlight the critical timing for introducing final pediatric formulations to avoid regulatory delays.

Main Methods:

• Utilizing supportive clinical studies, including relative bioavailability (RBA) studies, to link adult/enabling formulations to final pediatric versions.
• Establishing bioequivalence (BE) when late changes to pediatric formulations occur.
• Considering in vitro approaches for formulation bridging in specific scenarios like minor changes or new strengths.

Main Results:

• RBA studies are typically conducted in adult healthy volunteers to assess formulation performance.
• Potential age and disease-related interplays with formulation effects must be considered in RBA studies.
• Late formulation changes necessitate robust bioequivalence demonstration to ensure regulatory approval.

Conclusions:

• The final pediatric formulation should be introduced early in the development program, ideally by the pivotal study stage.
• Failure to demonstrate bioequivalence can significantly delay drug approval.
• In vitro methods may support formulation bridging under defined circumstances, including BCS class biowaivers.