ADDENDUM TO ICH E11: CLINICAL INVESTIGATION OF …

1 INTERNATIONAL COUNCIL FOR HARMONISATION OF TECHNICAL REQUIREMENTS FOR PHARMACEUTICALS FOR human USE ICH HARMONISED GUIDELINE ADDENDUM TO ICH E11: CLINICAL INVESTIGATION OF medicinal PRODUCTS IN THE PEDIATRIC POPULATION E11 (R1) Final version Adopted on 18 August 2017 This Guideline has been developed by the appropriate ICH Expert Working Group and has been subject to consultation by the regulatory parties, in accordance with the ICH Process. At Step 4 of the Process the final draft is recommended for adoption to the ICH regulatory bodies.

2 ICH E11(R1) Document History First Codification History Date New Codification November 2005 E11 Approval by the Steering Committee under Step 2 and release for public consultation. 7 October 1999 E11 E11 Approval by the Steering Committee under Step 4 and recommendation for adoption to the three ICH regulatory bodies. 19 July 2000 E11 Current Step 4 version of the E11(R1) Code History Date E11(R1) Endorsement by the ICH Assembly under Step 2 and release for public consultation. 12 October 2016 E11(R1) Adoption by the Regulatory Members of the ICH Assembly under Step 4 (document dated 20 July 2017).

3 18 August 2017 Legal notice: This document is protected by copyright and may be used, reproduced, incorporated into other works, adapted, modified, translated or distributed under a public license provided that ICH's copyright in the document is acknowledged at all times. In case of any adaption, modification or translation of the document, reasonable steps must be taken to clearly label, demarcate or otherwise identify that changes were made to or based on the original document. Any impression that the adaption, modification or translation of the original document is endorsed or sponsored by the ICH must be avoided.

4 The document is provided "as is" without warranty of any kind. In no event shall the ICH or the authors of the original document be liable for any claim, damages or other liability arising from the use of the document. The above-mentioned permissions do not apply to content supplied by third parties. Therefore, for documents where the copyright vests in a third party, permission for reproduction must be obtained from this copyright holder. i ICH HARMONISED GUIDELINE CLINICAL INVESTIGATION OF medicinal PRODUCTS IN THE PEDIATRIC POPULATION E11(R1) ICH Consensus Guideline TABLE OF CONTENTS.

5 Objectives of the Guidance ..3 Background ..3 Scope of the Guidance ..3 General Principles ..3 ..4 Issues When Initiating a Pediatric medicinal product Development Program ..4 Pediatric Formulations ..4 Timing of Studies ..5 medicinal Products for Diseases Predominantly or Exclusively Affecting Pediatric Patients .. 5 medicinal Products Intended to Treat Serious or Life-Threatening Diseases, Occurring in Both Adults and Pediatric Patients, for Which There Are Currently No or Limited Therapeutic Options .. 5 medicinal Products Intended to Treat Other Diseases and Conditions.

6 5 Types of Studies ..6 Pharmacokinetics .. 7 Efficacy .. 8 Safety .. 8 Postmarketing 8 Age Classification of Pediatric Patients ..8 Preterm Newborn Infants .. 9 Term newborn infants (0 to 27 days) .. 9 Infants and toddlers (28 days to 23 months) .. 10 Children (2 to 11 years) .. 10 Adolescents (12 to 16-18 years (dependent on region)) .. 10 Ethical Issues in Pediatric Studies ..11 Institutional Review Board/Independent Ethics Committee (IRB/IEC) .. 11 CLINICAL INVESTIGATION of medicinal Products in the Pediatric Population ii Recruitment.

7 11 Consent and Assent .. 11 Minimizing Risk .. 12 Minimizing Distress .. 12 TO ICH E11 .. 13 3 CLINICAL INVESTIGATION OF medicinal PRODUCTS IN THE PEDIATRIC POPULATION Objectives of the Guidance The number of medicinal products currently labeled for pediatric use is limited. It is the goal of this guidance 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.

8 Background Other ICH documents with relevant information impacting on pediatric studies include: E2: CLINICAL Safety Data Management E3: Structure and Content of CLINICAL Study Reports E4: Dose-Response Information to Support Drug Registration E5: Ethnic Factors in the Acceptability of Foreign CLINICAL Data E6: Good CLINICAL Practice: Consolidated Guideline E8: General Considerations for CLINICAL Trials E9: Statistical Principles for CLINICAL Trials E10: Choice of Control Group in CLINICAL Trials M3: Nonclinical Safety Studies for the Conduct of human CLINICAL Trials for Pharmaceuticals Q1: Stability Testing Q2: Validation of Analytical Procedures Q3: Impurity Testing Scope of the Guidance Specific CLINICAL study issues addressed include: (1) considerations when initiating a pediatric program for a medicinal product ; (2) timing of initiation of pediatric studies during medicinal product development.

9 (3) types of studies (pharmacokinetic, pharmacokinetic/pharmacodynamic (PK/PD), efficacy, safety); (4) age categories; and (5) ethics of pediatric CLINICAL INVESTIGATION . This guidance is not intended to be comprehensive; other ICH guidances, as well as documents from regional regulatory authorities and pediatric societies, provide additional detail. General Principles Pediatric patients should be given medicines that have been appropriately evaluated for their use. Safe and effective pharmacotherapy in pediatric patients requires the timely development of information on the proper use of medicinal products in pediatric patients of various ages and, often, the development of pediatric formulations of those products.

10 Advances in formulation chemistry and in pediatric study design will help facilitate the development of medicinal products for pediatric use. Drug development programs should usually include the pediatric patient population when a product is being developed for a disease or condition in adults and it is anticipated the product will be used in the pediatric population. Obtaining knowledge of the effects CLINICAL INVESTIGATION of medicinal Products in the Pediatric Population 4 of medicinal products in pediatric patients is an important goal.