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E11 Clinical Investigation of Medicinal Products in the Pediatric Population

FinalCenter for Drug Evaluation and Research Center for Biologics Evaluation and Research12/15/2000
Good Clinical PracticeStudy Design

Description

The number of medicinal products currently labeled for pediatric use is limited. This guidance is intended to encourage and facilitate timely pediatric medicinal product development internationally. The guidance provides an outline of critical issues in pediatric drug development and approaches to the safe, efficient, and ethical study of medicinal products in the pediatric population.

Key Topics

Terms and concepts identified from this document

Scope & Applicability

Product Classes

2
Medicinal Products

Subject of stability testing guidance

Medicinal Product

Includes pharmaceuticals, biologics, vaccines, cell or gene therapy products

Stakeholders

10
Regulatory Authorities

Early discussion is recommended regarding safety dataset size.; Entities with whom the adequacy of RWD and extrapolation plans should be discussed.; early discussion useful when proposed endpoints differ; Entities that should agree upon success criteria in advance.

Investigator

Responsible for qualifications, training, and trial conduct; Individual responsible for trial conduct and data governance at a site.; May delegate tasks but retains overall responsibility; Person responsible for the conduct of the clinical trial at a trial site; Responsible for trial conduct and participant safety; Responsible for trial conduct, data integrity, and investigational product management.; Individual responsible for trial conduct at a site and informing the institution.; maintaining

IEC

Independent Ethics Committee listed in eCTD documentation

IRB

Institutional Review Board providing study approvals

Legal guardian

Involved in the recruitment process; Person responsible for providing consent for pediatric participants

Health Professionals

Shared responsibility for pediatric drug development

Institutional Review Boards

Bodies responsible for evaluating trial risks and benefits for pregnant participants.; IRBs experienced in this population may advise on compensation.

Independent Ethics Committees

Review and define maximum blood volume for studies

Institutional Review Board

Governs top dose in clinical studies

Independent Ethics Committee

Responsible for submission and communication oversight; Safeguard the rights, safety and well-being of trial participants; Reviewing trial conduct and records

Regulatory Context

Document Types

4
Pediatric Formulations

Documentation and development of dosage forms for children

Assent Form

Written form signed by pediatric participants of appropriate intellectual maturity

Informed Consent

Process by which a subject voluntarily confirms his or her willingness to participate in a particular trial; Integral feature of the ethical conduct of a trial

Marketing Application

Submissions standardized by ICH guidelines

Attributes

3
Gestational age

Factor related to neurodevelopmental vulnerability

Tanner stages

Used to assess pubertal development

Serious or Life-Threatening Disease

Factor suggesting urgent initiation of pediatric studies

Technical Details

Substances

3
Surfactant

Therapy for respiratory distress syndrome

Topical Anesthesia

Used to minimize discomfort during IV catheter placement

Benzyl Alcohol

Fatal Benzyl Alcohol Poisoning in Neonatal Intensive Care Units

Testing Methods

7
Pharmacokinetic

PK data used for dose selection

Pharmacodynamic

PD data used for dose selection

Pharmacokinetic Studies

AI used to reduce the number of animal-based PK studies.

Pharmacodynamic Endpoints

Used to confirm effectiveness when blood levels are unclear

Repeated Dose Toxicity Studies

Nonclinical safety data

Population pharmacokinetics

M&S method included in MIDD; Model coding scripts for base and final models

Sparse sampling

Practical approach for obtaining pharmacokinetic data in neonatal studies due to blood volume limits.

Processes

3
Pediatric Formulation Development

Development of drug forms suitable for pediatric use

Venipuncture

Procedure for blood sampling that should be minimized to reduce distress

Postmarketing surveillance

Evaluation of human data after drug approval

Clinical Concepts

10
Pediatric Population

Frequently underrepresented in trials.

Adverse Events

Reporting adverse events when engaging with patients.; changes may be related to benefits, tolerability, and/or unintended effects

Necrotizing enterocolitis

Condition unique to neonates

Respiratory distress syndrome of the newborn

Unique neonatal disease state

Respiratory Distress Syndrome

Disease predominantly affecting preterm infants

Preterm newborn infants

Sub-population within the neonatal period definition

Term newborn infants

Pediatric age category from 0 to 27 days

Infants and toddlers

Pediatric age category from 28 days to 23 months

Children

Subject population requiring additional safeguards in research

Adolescents

Pediatric population that may be included in adult clinical trials.; inclusion in adult clinical trials recommended when disease is similar

Identified Hazards

Hazards

2
Developmental Toxicology

Basis for considering juvenile animal studies

Preclinical Toxicity

Known toxicity risks that investigators must be aware of

Standards & References

Specifications

1
Milligram/Kilogram Body Weight

Basis for dosing recommendations

ICH References (10)

ICH E11

Clinical Investigation of Medicinal Products in the Pediatric Population.

ICH E2

Referenced for basic considerations in safety data collection.

ICH E3

document remedial actions in the clinical trial report; Structure and Content of Clinical Study Reports standards.

ICH E4

Dose-Response Information to Support Drug Registration

ICH E5

Ethnic Factors in the Accessibility of Foreign Clinical Data.

ICH E6

Referenced for safety data collection and adverse event reporting plans.

ICH E8

General Considerations for Clinical Studies

ICH E9

Statistical Principles for Clinical Trials; Discourages deterministic procedures due to high risk of bias; Notes that the use of Bayesian methods in clinical trials may be considered.

ICH E10

Choice of Control Group in Clinical Trials.

ICH M3

Nonclinical Safety Studies for the Conduct of Human Clinical Trials

Related MFDS Guidelines

Korean regulatory guidelines covering similar topics

See Also (8)

E11 Clinical Investigation of Medicinal Products in the Pediatric Population | Guideline Explorer | BioRegHub