[Federal Register Volume 86, Number 90 (Wednesday, May 12, 2021)]
[Notices]
[Pages 26056-26058]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2021-09964]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2018-D-4524]


S11 Nonclinical Safety Testing in Support of Development of 
Pediatric Pharmaceuticals; 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 final guidance for industry entitled ``S11 
Nonclinical Safety Testing in Support of Development of Pediatric 
Pharmaceuticals.'' The guidance was prepared under the auspices of the 
International Council for Harmonisation of Technical Requirements for 
Registration of Pharmaceuticals for Human Use (ICH), formerly the 
International Conference on Harmonisation of Technical Requirements for 
Registration of Pharmaceuticals for Human Use. The guidance recommends 
international standards for the nonclinical safety studies recommended 
to support the development of pediatric medicines. The guidance 
provides a weight of evidence approach to determine when nonclinical 
toxicity studies may be recommended in juvenile animals. If such 
studies are recommended, the guidance provides appropriate study 
designs. The guidance is intended to promote harmonization of 
recommendations for such studies and should facilitate the timely 
conduct of pediatric clinical trials and reduce the use of animals in 
accordance with the 3R (replace/reduce/refine) principles. Tissue 
engineered products, gene and cellular therapies, and vaccines are 
excluded from the scope of this guidance. The guidance replaces the 
draft guidance issued on February 1, 2019.

DATES: The announcement of the guidance is published in the Federal 
Register on May 12, 2021.

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-2018-D-4524 for ``S11 Nonclinical Safety Testing in Support of 
Development of Pediatric Pharmaceuticals.'' Received comments will be 
placed in the docket and, except for those 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, 240-402-7500.
     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

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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.govinfo.gov/content/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, 240-402-7500.
    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 (CBER), 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: Karen Davis Bruno, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 22, Rm. 6428, Silver Spring, MD 20993-0002, 301-
796-1199; 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: Jill Adleberg, Center for Drug Evaluation and 
Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 
51, Rm. 6364, Silver Spring, MD 20993-0002, 301-796-5259, 
[email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a guidance for industry 
entitled ``S11 Nonclinical Safety Testing in Support of Development of 
Pediatric Pharmaceuticals.'' The guidance was prepared under the 
auspices of ICH. ICH has the mission of achieving greater regulatory 
harmonization worldwide to ensure that safe, effective, high-quality 
medicines are developed, registered, and maintained in the most 
resource-efficient manner. By harmonizing the regulatory requirements 
in regions around the world, ICH guidelines have substantially reduced 
duplicative clinical studies, prevented unnecessary animal studies, 
standardized the reporting of important safety information, 
standardized marketing application submissions, and made many other 
improvements in the quality of global drug development and 
manufacturing and the products available to patients.
    The six Founding Members of the ICH are FDA; the Pharmaceutical 
Research and Manufacturers of America; the European Commission; the 
European Federation of Pharmaceutical Industries Associations; the 
Japanese Ministry of Health, Labour, and Welfare; and the Japanese 
Pharmaceutical Manufacturers Association. The Standing Members of the 
ICH Association include Health Canada and Swissmedic. Additionally, the 
Membership of ICH has expanded to include other regulatory authorities 
and industry associations from around the world (refer to https://www.ich.org/).
    ICH works by involving technical experts from both regulators and 
industry parties in detailed technical harmonization work and the 
application of a science-based approach to harmonization through a 
consensus-driven process that results in the development of ICH 
guidelines. The regulators around the world are committed to 
consistently adopting these consensus-based guidelines, realizing the 
benefits for patients and for industry.
    As a Founding Regulatory Member of ICH, FDA plays a major role in 
the development of each of the ICH guidelines, which FDA then adopts 
and issues as guidance for industry. FDA's guidance documents do not 
establish legally enforceable responsibilities. Instead, they describe 
the Agency's current thinking on a topic and should be viewed only as 
recommendations, unless specific regulatory or statutory requirements 
are cited. In the Federal Register of February 1, 2019 (84 FR 1161), 
FDA published a notice announcing the availability of a draft guidance 
entitled ``S11 Nonclinical Safety Testing in Support of Development of 
Pediatric Medicines.'' The notice gave interested persons an 
opportunity to submit comments by April 2, 2019. 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 April 2020.
    This guidance finalizes the draft guidance issued on February 1, 
2019. The guidance describes a weight of evidence approach to determine 
when nonclinical toxicity studies may be recommended in juvenile 
animals to support development of medicines to be used in pediatric 
patients. If such studies are recommended, the guidance also provides 
appropriate study designs. The guidance describes study designs as 
consisting of a core set of endpoints that can be supplemented by 
additional endpoints depending on the concerns identified in the weight 
of evidence approach. The guidance also provides guidance on potential 
approaches for the nonclinical support of drugs that will be developed 
only for use in pediatric patients or that will be first tested in 
pediatric patients. The guidance is intended to promote harmonization 
of recommendations for such studies and should facilitate the timely 
conduct of pediatric clinical trials and reduce the use of animals in 
accordance with the 3R (replace/reduce/refine) principles.
    The draft guidance was revised based on comments received. The 
revisions include refinement of the weight of evidence approach and in 
descriptions of the core and additional endpoints that can be 
incorporated into juvenile animal studies. The final guidance also 
includes a new section on data interpretation. The appendices on age-
dependent development of organ systems by species and preweaning litter 
allocation in the rodent were also updated. Additionally, the title of 
the guidance was updated from ``Nonclinical Safety Testing in Support 
of Development of Pediatric Medicines'' to ``Nonclinical Safety Testing 
in Support of Development of Pediatric Pharmaceuticals.''

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    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 ``S11 Nonclinical Safety Testing in Support 
of Development of Pediatric Pharmaceuticals.'' 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.

II. Paperwork Reduction Act of 1995

    While this guidance contains no collection of information, it does 
refer to previously approved FDA collections of information. Therefore, 
clearance by the Office of Management and Budget (OMB) under the 
Paperwork Reduction Act of 1995 (PRA) (44 U.S.C. 3501-3521) is not 
required for this guidance. The previously approved collections of 
information are subject to review by OMB under the PRA. The collections 
of information in 21 CFR part 312, pertaining to the submission of 
nonclinical and preclinical data, including a pediatric clinical 
development plan, have been approved under OMB control number 0910-
0014; the collections of information in 21 CFR part 58 pertaining to 
good laboratory practice for nonclinical laboratory studies have been 
approved under OMB control number 0910-0119; and the collections of 
information in FDA's guidance for industry on ``Expedited Programs for 
Serious Conditions--Drugs and Biologics'' has been approved under OMB 
control number 0910-0765.

III. Electronic Access

    Persons with access to the internet may obtain the guidance at 
https://www.regulations.gov, https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs, or https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances.

    Dated: May 6, 2021.
Lauren K. Roth,
Acting Principal Associate Commissioner for Policy.
[FR Doc. 2021-09964 Filed 5-11-21; 8:45 am]
BILLING CODE 4164-01-P