Pediatric Developmental Safety Assessment: New Approach Methods

Credit: FDA + Triangle CERSI

‘This meeting comes at a critical time for pediatric drug development. An accumulation of knowledge from pediatric drug development programs over the past 25 years provides information that should be used to improve the efficient development of safe and effective new drugs for children. At the same time, the reliance on juvenile animal testing for all pediatric preclinical assessments has run into both the realization of the limitations to this assessment plus the need to develop new approach methods (NAMs) to animal testing as expressed by the U.S. FDA and multiple federal agencies (see FDA-NIH Workshop on Reducing Animal Testing).

‘In addition, the recent ICH E11A Guidance on Pediatric Extrapolation has indicated that, under some conditions, safety can be extrapolated from the adult population to the pediatric patient population. Since developmental drug toxicity is not evaluable in the adult population, additional methods must be identified that can answer the critical developmental safety questions raised in the ICH E11A guidance.

‘Therefore, the goal of this workshop is to discuss new approach methods that can address pediatric developmental safety during drug development.’

Agenda (in Eastern Standard Time):

• 8:00am — Welcome and Introduction
• 8:15am — Pediatric Developmental Safety, Extrapolating Drug Safety, and the Road Ahead for Pediatric Safety Assessments
• 8:35am — Pediatric Developmental Genotype-Tissue Expression Program, National Human Genome Research Institute, NIH
• 8:55am — FDA Experience with Secondary Targets for New Drugs
• 9:15am — Making Secondary Targets a Routine Part of Drug Development
• 9:35am — Developing a Panel of Secondary Targets for Pediatric Developmental Safety
• 9:55am — Break
• 10:15am — Industry Experience with Juvenile Animal Studies
• 10:35am — Microphysiological Systems In Vitro Systems to Complement Pediatric Developmental Efficacy and Safety Assessment
• 10:55am — In vitro and In Silico Tools for Safety Assessment for the Postnatal Period
• 11:15am — Topics 1 and 2 Panel Discussion and Questions
• 12:00pm — Break
• 12:45pm — Building a QSP Tool for Pediatric Safety Analysis: DILIsym
• 1:05pm — Adapting a secondary pharmacology-based tool to flag-up offtarget interactions of particular concern in pediatric patients
• 1:25pm — Resources Available for Analysis of Prior Information for Pediatric Developmental Safety
• 1:45pm — Use of Modeling and Simulation in Safety Assessments
• 2:05pm — Multiomics-informed Modeling of Drug Disposition and Safety in

Pediatric Patients

• 2:25pm — How can we answer the Pediatric Developmental Safety

Questions in ICH E11A Using These Techniques?

• 2:45pm — Topics 3 and 4 Panel Discussion and Questions
• 3:45pm — Wrap Up

Workshop Summary:

‘The U.S. Food and Drug Administration (FDA) in collaboration with the Triangle Center of Excellence in Regulatory Science and Innovation (Triangle CERSI) will host a one-day virtual public workshop entitled “Pediatric Developmental Safety Assessment and New Approach Methodologies” on December 5, 2025. This workshop comes at a critical time for pediatric drug development. An accumulation of knowledge from pediatric drug development programs over the past 25 years provides information that should be used about new drugs intended for pediatric use going forward. At the same time, the reliance on juvenile animal testing for all pediatric preclinical assessments has run into both the realization of the limitations to this assessment plus the need to develop new approach methodologies (NAMs) to animal testing expressed by the US FDA and multiple federal agencies.

‘These NAMs are being further developed, and all of this new and prior information in this pediatric/maternal knowledge base can be quickly assessed by new approaches including artificial intelligence. This information can also be modeled in a quantitative fashion using quantitative systems pharmacology and quantitative structure activity relationships to provide a realistic basis for identification and incorporation into a panel of secondary targets. This panel of pediatric developmental secondary targets could then be included in the normal screening process that takes place in drug development.’

Workshop Objectives: ‘To understand the current programs in federal agencies related to new approach methodologies and pediatric developmental biology; To discuss the identification and utilization of secondary targets in a pediatric developmental safety assessment; To review the use of juvenile animal studies and in vitro tools to assess pediatric developmental safety assessment; and To explore the use of model-informed drug development techniques such as quantitative systems pharmacology and the use of artificial intelligence and machine learning in pediatric developmental safety assessment.’