[Federal Register Volume 83, Number 70 (Wednesday, April 11, 2018)]
[Notices]
[Pages 15581-15583]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-07375]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2016-D-3848]


E11(R1) Addendum: Clinical Investigation of Medicinal Products in 
the Pediatric Population; International Council for Harmonisation; 
Guidance for Industry; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
the availability of a guidance for industry entitled ``E11(R1) 
Addendum: Clinical Investigation of Medicinal Products in the Pediatric 
Population'' (E11(R1) addendum or addendum). The guidance was prepared 
under the auspices of the International Council for Harmonisation 
(ICH), formerly the International Conference on Harmonisation. The 
guidance is an addendum to the guidance published in 2000 entitled 
``E11 Clinical Investigation of Medicinal Products in the Pediatric 
Population'' (ICH E11 (2000)), and provides updates to the original 
guidance. This addendum does not alter the scope of the original 
guidance, which outlines an approach to the safe, efficient, and 
ethical study of medicinal products in the pediatric population. This 
addendum complements and provides clarification and current regulatory 
perspective on topics in pediatric drug development. The guidance is 
intended to provide high-level guidance on the implementation of 
important approaches in pediatric drug development. This harmonized 
addendum will help to define the current recommendations and reduce the 
likelihood that substantial differences will exist among regions for 
the acceptance of data generated in pediatric global drug development 
programs and ensure timely access to medicines for children.

DATES: The announcement of the guidance is published in the Federal 
Register on April 11, 2018.

ADDRESSES: You may submit either electronic or written comments on 
Agency guidances at any time as follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to https://www.regulations.gov 
will be posted to the docket unchanged. Because your comment will be 
made public, you are solely responsible for ensuring that your comment 
does not include any confidential information that you or a third party 
may not wish to be posted, such as medical information, your or anyone 
else's Social Security number, or confidential business information, 
such as a manufacturing process. Please note that if you include your 
name, contact information, or other information that identifies you in 
the body of your comments, that information will be posted on https://www.regulations.gov.
     If you want to submit a comment with confidential 
information that you do not wish to be made available to the public, 
submit the comment as a written/paper submission and in the manner 
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand delivery/Courier (for written/paper 
submissions): Dockets Management Staff (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Dockets 
Management Staff, FDA will post your comment, as well as any 
attachments, except for information submitted, marked and identified, 
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No. 
FDA-2016-D-3848 for ``E11(R1) Addendum: Clinical Investigation of 
Medicinal Products in the Pediatric Population.'' Received comments 
will be placed in the docket and, except for those

[[Page 15582]]

submitted as ``Confidential Submissions,'' publicly viewable at https://www.regulations.gov or at the Dockets Management Staff between 9 a.m. 
and 4 p.m., Monday through Friday.
     Confidential Submissions--To submit a comment with 
confidential information that you do not wish to be made publicly 
available, submit your comments only as a written/paper submission. You 
should submit two copies total. One copy will include the information 
you claim to be confidential with a heading or cover note that states 
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will 
review this copy, including the claimed confidential information, in 
its consideration of comments. The second copy, which will have the 
claimed confidential information redacted/blacked out, will be 
available for public viewing and posted on https://www.regulations.gov. 
Submit both copies to the Dockets Management Staff. If you do not wish 
your name and contact information to be made publicly available, you 
can provide this information on the cover sheet and not in the body of 
your comments and you must identify this information as 
``confidential.''
    Any information marked as ``confidential'' will not be disclosed 
except in accordance with 21 CFR 10.20 and other applicable disclosure 
law. For more information about FDA's posting of comments to public 
dockets, see 80 FR 56469, September 18, 2015, or access the information 
at: https://www.gpo.gov/fdsys/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in 
the heading of this document, into the ``Search'' box and follow the 
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852.
    You may submit comments on any guidance at any time (see 21 CFR 
10.115(g)(5)).
    Submit written requests for single copies of this guidance to the 
Division of Drug Information, Center for Drug Evaluation and Research, 
Food and Drug Administration, 10001 New Hampshire Ave., Hillandale 
Building, 4th Floor, Silver Spring, MD 20993-0002, or the Office of 
Communication, Outreach and Development, Center for Biologics 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 71, Rm. 3128, Silver Spring, MD 20993-0002. Send 
one self-addressed adhesive label to assist that office in processing 
your requests. The guidance may also be obtained by mail by calling 
CBER at 1-800-835-4709 or 240-402-8010. See the SUPPLEMENTARY 
INFORMATION section for electronic access to the guidance document.

FOR FURTHER INFORMATION CONTACT: Regarding the guidance: Lynne Yao, 
Center for Drug Evaluation and Research, Food and Drug Administration, 
10903 New Hampshire Avenue, Bldg. 22, Rm. 6406, Silver Spring, MD 
20993-0002, 301-796-2141; or Stephen Ripley, Center for Biologics 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 71, Rm. 7301, Silver Spring, MD 20993-0002, 240-
402-7911. Regarding the ICH: Amanda Roache, Center for Drug Evaluation 
and Research, Food and Drug Administration, 10903 New Hampshire Ave., 
Bldg. 51, Rm. 1176, Silver Spring, MD 20993-0002, 301-796-4548.

SUPPLEMENTARY INFORMATION:

I. Background

    In recent years, regulatory authorities and industry associations 
from around the world have participated in many important initiatives 
to promote international harmonization of regulatory requirements under 
the ICH. FDA has participated in several ICH meetings designed to 
enhance harmonization, and FDA is committed to seeking scientifically-
based harmonized technical procedures for pharmaceutical development. 
One of the goals of harmonization is to identify and reduce differences 
in technical requirements for drug development among regulatory 
agencies.
    The ICH was established to provide an opportunity for harmonization 
initiatives to be developed with input from both regulatory and 
industry representatives. FDA also seeks input from consumer 
representatives and others. The ICH is concerned with harmonization of 
technical requirements for the registration of pharmaceutical products 
for human use among regulators around the world. The six founding 
members of the ICH are the European Commission; the European Federation 
of Pharmaceutical Industries Associations; FDA; the Japanese Ministry 
of Health, Labour, and Welfare; the Japanese Pharmaceutical 
Manufacturers Association; and the Pharmaceutical Research and 
Manufacturers of America. The Standing Members of the ICH Association 
include Health Canada and Swissmedic. Any party eligible as a Member in 
accordance with the ICH Articles of Association can apply for 
membership in writing to the ICH Secretariat. The ICH Secretariat, 
which coordinates the preparation of documentation, operates as an 
international nonprofit organization, and is funded by the Members of 
the ICH Association.
    The ICH Assembly is the overarching body of the Association and 
includes representatives from each of the ICH members and observers. 
The Assembly is responsible for the endorsement of draft guidelines and 
adoption of final guidelines. FDA publishes ICH guidelines as FDA 
guidances.
    In the Federal Register of November 22, 2016 (81 FR 83847), FDA 
published a notice announcing the availability of a draft guidance 
entitled ``E11(R1) Addendum: Clinical Investigation of Medicinal 
Products in the Pediatric Population.'' The notice gave interested 
persons an opportunity to submit comments by February 21, 2017.
    After consideration of the comments received and revisions to the 
guideline, a final draft of the guideline was submitted to the ICH 
Assembly and endorsed by the regulatory agencies in August 2017.
    The E11(R1) addendum provides guidance on pediatric drug 
development and is intended to complement and provide clarification and 
current regulatory perspectives on topics in pediatric drug development 
that were originally presented in ICH E11 (2000). The addendum does not 
alter the scope of the original guidance, which outlines an approach to 
the safe, efficient, and ethical study of medicinal products in the 
pediatric population. In the addendum, section II (2) (ETHICAL 
CONSIDERATIONS), section IV (4) (AGE CLASSIFICATION AND PEDIATRIC 
SUBGROUPS, INCLUDING NEONATES), and section VII (7) (PEDIATRIC 
FORMULATIONS), supplement the content in ICH E11 (2000). Section III 
(3) (COMMONALITY OF SCIENTIFIC APPROACH FOR PEDIATRIC DRUG DEVELOPMENT 
PROGRAMS) addresses issues to aid scientific discussions at various 
stages of pediatric drug development in different regions. Section V 
(5) (APPROACHES TO OPTIMIZE PEDIATRIC DRUG DEVELOPMENT) includes 
enhancement to the topic of Extrapolation, and introduces Modeling and 
Simulation. Section VI (6) (PRACTICALITIES IN THE DESIGN AND EXECUTION 
OF PEDIATRIC CLINICAL TRIALS) includes discussion of feasibility, 
outcome assessments, and long-term clinical aspects, including

[[Page 15583]]

safety. These sections describe essential considerations intended to 
provide high-level guidance on the implementation of these approaches 
in pediatric drug development and have been revised based on comments 
received from global stakeholders.
    This guidance is being issued consistent with FDA's good guidance 
practices regulation (21 CFR 10.115). The guidance represents the 
current thinking of FDA on ``E11(R1) Addendum: Clinical Investigation 
of Medicinal Products in the Pediatric Population.'' It does not 
establish any rights for any person and is not binding on FDA or the 
public. You can use an alternative approach if it satisfies the 
requirements of the applicable statutes and regulations. This guidance 
is not subject to Executive Order 12866.

II. Electronic Access

    Persons with access to the internet may obtain the guidance at 
https://www.regulations.gov, https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, or 
https://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm.

    Dated: April 4, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-07375 Filed 4-10-18; 8:45 am]
BILLING CODE 4164-01-P