Pediatric Developmental Safety Assessment: New Approach Methods

‘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