The US Food and Drug Administration (FDA) adopted its version of the International Council for Harmonization’s (ICH) addendum on pediatric drug development, with a substantial amount of new information added to the policy principles initially set forth in 2000.
The agency’s guidance—released Tuesday and based on the August 2017 version of ICH’s E11(R1) Addendum: Clinical Investigation of Medicinal Products in the Pediatric Population—updates the 2000 version to reflect the current regulatory perspectives on the outlined topics, addressing new scientific and technical advances. The scope, however, remains unchanged and the previous policies still apply.
There are several new recommendations in the sections on ethical considerations, age subgroups and pediatric formulations. The recommended approaches in drug development are also more detailed, with new information on the use of existing knowledge, extrapolation, as well as modelling and simulation.
Under ethical considerations, a “fundamental principle” added “requires that children should not be enrolled in a clinical study unless necessary to achieve an important pediatric public health need,” while another relates to the importance of making study results public. The section also points to the need for reevaluating child assent
as a clinical study progresses, to recognize evolved maturity and competency.
FDA cautions against using chronological age to define subgroups in pediatric studies. “Physiological development and maturity of organs, pathophysiology of disease or condition, and the pharmacology of the investigational product are factors to be considered in determining the subgroups,” FDA said.
In addition, drug development research in “neonates” has become increasingly important, according to FDA as medical care advancements have improved survival rates among high-risk newborns. Early discussions with regulatory authorities are recommended to address the remaining challenges in pediatric drug development, including ethical and feasibility issues.
Pediatric formulations were separated into four categories—dosage and administration, excipients, palatability and acceptability, and neonates.
Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) implemented the addendum last December.
E11(R1) Addendum: Clinical Investigation of Medicinal Products in the Pediatric Population Guidance for Industry