[Federal Register Volume 81, Number 119 (Tuesday, June 21, 2016)]
[Notices]
[Pages 40317-40319]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-14640]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2015-D-1376]


Leveraging Existing Clinical Data for Extrapolation to Pediatric 
Uses of Medical Devices; Guidance for Industry and Food and Drug 
Administration Staff; 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 the final guidance entitled ``Leveraging Existing

[[Page 40318]]

Clinical Data for Extrapolation to Pediatric Uses of Medical Devices; 
Guidance for Industry and Food and Drug Administration Staff.'' This 
guidance explains the circumstances in which it may be appropriate to 
extrapolate existing medical device data to support pediatric device 
indications in premarket approval applications (PMAs), humanitarian 
device exemptions (HDEs) and de novo requests. This guidance also 
describes FDA's approach for determining whether extrapolation may be 
appropriate and the factors that should be considered within a 
statistical model for extrapolation. Extrapolation may be appropriate 
when there are few differences in safety or effectiveness of the 
proposed device when used in adult as compared to the intended 
pediatric populations and the adult data are of high quality for 
borrowing.

DATES: Submit either electronic or written comments on this guidance at 
any time. General comments on Agency guidance documents are welcome at 
any time.

ADDRESSES: You may submit comments as follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to http://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 http://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): Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Division of 
Dockets Management, 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-2015-D-1376 for ``Leveraging Existing Clinical Data for 
Extrapolation to Pediatric Uses of Medical Devices; Guidance for 
Industry and Food and Drug Administration Staff.'' Received comments 
will be placed in the docket and, except for those submitted as 
``Confidential Submissions,'' publicly viewable at http://www.regulations.gov or at the Division of Dockets Management 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 http://www.regulations.gov. 
Submit both copies to the Division of Dockets Management. 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: http://www.fda.gov/regulatoryinformation/dockets/default.htm.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to http://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 Division of Dockets Management, 5630 Fishers 
Lane, Rm. 1061, Rockville, MD 20852.
    An electronic copy of the guidance document is available for 
download from the Internet. See the SUPPLEMENTARY INFORMATION section 
for information on electronic access to the guidance. Submit written 
requests for a single hard copy of the guidance document entitled 
``Leveraging Existing Clinical Data for Extrapolation to Pediatric Uses 
of Medical Devices; Guidance for Industry and Food and Drug 
Administration Staff'' to the Office of the Center Director, Guidance 
and Policy Development, Center for Devices and Radiological Health, 
Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 66, Rm. 
5431, 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 request.

FOR FURTHER INFORMATION CONTACT: Jacqueline Francis, Center for Devices 
and Radiological Health, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 66, Rm. G426, Silver Spring, MD 20993-0002, 301-
796-6405; 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, 240-402-7911.

SUPPLEMENTARY INFORMATION:

I. Background

    The objectives of this final guidance are: (1) To increase the 
availability of safe and effective pediatric devices by providing a 
roadmap for leveraging relevant existing clinical data for use in 
demonstrating a reasonable assurance of safety and effectiveness in 
PMAs and de novo requests, as well as for use in supporting approvals 
of HDEs; (2) to explain the circumstances in which it may be 
appropriate to leverage existing clinical data to support pediatric 
device indications and labeling; (3) to outline the approach FDA uses 
to determine whether extrapolation is appropriate, and, to what extent 
the data can be leveraged; and (4) to describe statistical methodology 
that can be used to leverage the data in a way that increases precision 
for pediatric inferences. This approach will potentially streamline the 
process for establishing a pediatric

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intended use claim, and enhance and encourage pediatric device 
development programs.
    This guidance does not change the regulatory threshold for valid 
scientific evidence. Instead, the document seeks to provide clarity and 
predictability for device sponsors and to ensure consistency within FDA 
regarding the specific criteria that should be considered when deciding 
whether leveraging existing clinical data to support pediatric claims 
is appropriate, and if so, to what extent. When considering 
extrapolation, sponsors are encouraged to engage FDA early in product 
development planning.
    For the purposes of this document, ``extrapolation'' refers to the 
leveraging process whereby an indication for use of a device in a new 
pediatric patient population can be supported by existing clinical data 
from a studied patient population. That is, when existing data are 
relevant to a pediatric indication and determined to be valid 
scientific evidence, it may be scientifically appropriate to attempt to 
extrapolate such data to a pediatric use in support of demonstrating a 
reasonable assurance of effectiveness or probable benefit and, 
occasionally, safety.
    FDA published in the Federal Register of May 6, 2015 (80 FR 26061), 
the document entitled ``Leveraging Existing Clinical Data for 
Extrapolation to Pediatric Uses of Medical Devices; Guidance for 
Industry and Food and Drug Administration Staff'' and the comment 
period closed on August 4, 2015. FDA has considered all of the comments 
received in finalizing this guidance. The comments from the docket 
sought further clarification of the scope of the document, the extent 
of extrapolation that may be feasible across various pediatric 
subpopulations, and the concept of ``borrowing strength'' from existing 
adult data. Accordingly, this guidance document has been updated to 
include de novo requests within the scope and to provide additional 
explanation on the concepts of extrapolation of data across pediatric 
subpopulations and ``borrowing strength.''
    This guidance should be used in conjunction with other device-
specific guidances to help ensure that medical devices intended for use 
in pediatric population provide reasonable assurance of safety and 
effectiveness.

II. Significance of Guidance

    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 the extrapolation of data for pediatric uses 
of medical devices. 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.

III. Electronic Access

    Persons interested in obtaining a copy of the guidance may do so by 
downloading an electronic copy from the Internet. A search capability 
for all Center for Devices and Radiological Health guidance documents 
is available at http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/default.htm. Guidance 
documents are also available at http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/default.htm or http://www.regulations.gov. Persons unable to download 
an electronic copy of ``Leveraging Existing Clinical Data for 
Extrapolation to Pediatric Uses of Medical Devices; Guidance for 
Industry and Food and Drug Administration Staff'' may send an email 
request to [email protected] to receive an electronic copy of 
the document. Please use the document number 1827 to identify the 
guidance you are requesting.

IV. Paperwork Reduction Act of 1995

    This guidance refers to previously approved collections of 
information found in FDA regulations. These collections of information 
are subject to review by the Office of Management and Budget (OMB) 
under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520). The 
collections of information in 21 CFR parts 801 and 809 have been 
approved under OMB control number 0910-0485 (medical device labeling); 
the collections of information in 21 CFR part 812 have been approved 
under OMB control number 0910-0078 (investigational device exemptions); 
the collections of information in 21 CFR part 814 have been approved 
under OMB control number 0910-0231 (subparts A through E, premarket 
approval).

V. References

    The following references are on display in the Division of Dockets 
Management (see ADDRESSES) and are available for viewing by interested 
persons between 9 a.m. and 4 p.m., Monday through Friday; they are also 
available electronically at http://www.regulations.gov. FDA has 
verified the Web site addresses, as of the date this document publishes 
in the Federal Register, but Web sites are subject to change over time.

1. FDA guidance entitled ``Premarket Assessment of Pediatric Medical 
Devices,'' March 24, 2014, available at http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm089740.htm.

    Dated: June 16, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016-14640 Filed 6-20-16; 8:45 am]
 BILLING CODE 4164-01-P