Leveraging Existing Clinical Data for Extrapolation to Pediatric Uses of Medical Devices; Guidance for Industry and Food and Drug Administration Staff; Availability, 40317-40319 [2016-14640]

Download as PDF Federal Register / Vol. 81, No. 119 / Tuesday, June 21, 2016 / Notices 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 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: https://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 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 Division of Dockets Management, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. FOR FURTHER INFORMATION CONTACT: Beverly Friedman, Office of Regulatory Policy, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 6250, Silver Spring, MD 20993, 301–796–3600. SUPPLEMENTARY INFORMATION: asabaliauskas on DSK3SPTVN1PROD with NOTICES I. Background The Drug Price Competition and Patent Term Restoration Act of 1984 (Pub. L. 98–417) and the Generic Animal Drug and Patent Term Restoration Act (Pub. L. 100–670) generally provide that a patent may be extended for a period of up to 5 years so long as the patented item (human drug product, animal drug product, medical device, food additive, or color additive) was subject to regulatory review by FDA before the item was marketed. Under these acts, a product’s regulatory review period forms the basis for determining the amount of extension an applicant may receive. A regulatory review period consists of two periods of time: A testing phase and an approval phase. For human drug products, the testing phase begins when the exemption to permit the clinical VerDate Sep<11>2014 18:37 Jun 20, 2016 Jkt 238001 investigations of the drug becomes effective and runs until the approval phase begins. The approval phase starts with the initial submission of an application to market the human drug product and continues until FDA grants permission to market the drug product. Although only a portion of a regulatory review period may count toward the actual amount of extension that the Director of USPTO may award (for example, half the testing phase must be subtracted as well as any time that may have occurred before the patent was issued), FDA’s determination of the length of a regulatory review period for a human drug product will include all of the testing phase and approval phase as specified in 35 U.S.C. 156(g)(1)(B). FDA has approved for marketing the human drug product XOFIGO (radium 223 dichloride). XOFIGO is indicated for treatment of patients with castrationresistant prostate cancer, symptomatic bone metastases and no known visceral metastatic disease. Subsequent to this approval, the USPTO received a patent term restoration application for XOFIGO (U.S. Patent No. 6,635,234) from Algeta ASA, and the USPTO requested FDA’s assistance in determining this patent’s eligibility for patent term restoration. In a letter dated March 19, 2015, FDA advised the USPTO that this human drug product had undergone a regulatory review period and that the approval of XOFIGO represented the first permitted commercial marketing or use of the product. Thereafter, the USPTO requested that FDA determine the product’s regulatory review period. II. Determination of Regulatory Review Period FDA has determined that the applicable regulatory review period for XOFIGO is 1,945 days. Of this time, 1,792 days occurred during the testing phase of the regulatory review period, while 153 days occurred during the approval phase. These periods of time were derived from the following dates: 1. The date an exemption under section 505(i) of the Federal Food, Drug, and Cosmetic Act (the FD&C Act) (21 U.S.C. 355(i)) became effective: January 19, 2008. Algeta ASA claims that February 21, 2008, is the date the investigational new drug application (IND) became effective. However, FDA records indicate that the IND effective date was January 19, 2008, which was 30 days after FDA receipt of the IND. 2. The date the application was initially submitted with respect to the human drug product under section 505(b) of the FD&C Act: December 14, 2012. FDA has verified the applicant’s claim that the new drug application PO 00000 Frm 00059 Fmt 4703 Sfmt 4703 40317 (NDA) for XOFIGO (NDA 203971) was initially submitted on December 14, 2012. 3. The date the application was approved: May 15, 2013. FDA has verified the applicant’s claim that NDA 203971 was approved on May 15, 2013. This determination of the regulatory review period establishes the maximum potential length of a patent extension. However, the USPTO applies several statutory limitations in its calculations of the actual period for patent extension. In its application for patent extension, this applicant seeks 1,032 days of patent term extension. III. Petitions Anyone with knowledge that any of the dates as published are incorrect may submit either electronic or written comments and ask for a redetermination (see DATES). Furthermore, any interested person may petition FDA for a determination regarding whether the applicant for extension acted with due diligence during the regulatory review period. To meet its burden, the petition must be timely (see DATES) and contain sufficient facts to merit an FDA investigation. (See H. Rept. 857, part 1, 98th Cong., 2d sess., pp. 41–42, 1984.) Petitions should be in the format specified in 21 CFR 10.30. Submit petitions electronically to https://www.regulations.gov at Docket No. FDA–2013–S–0610. Submit written petitions (two copies are required) to the Division of Dockets Management (HFA– 305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. Dated: June 15, 2016. Leslie Kux, Associate Commissioner for Policy. [FR Doc. 2016–14551 Filed 6–20–16; 8:45 am] BILLING CODE 4164–01–P 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. The Food and Drug Administration (FDA or Agency) is announcing the availability of the final guidance entitled ‘‘Leveraging Existing SUMMARY: E:\FR\FM\21JNN1.SGM 21JNN1 40318 Federal Register / Vol. 81, No. 119 / Tuesday, June 21, 2016 / Notices 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: asabaliauskas on DSK3SPTVN1PROD with NOTICES 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): Division of VerDate Sep<11>2014 18:37 Jun 20, 2016 Jkt 238001 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 https://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 https:// 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: https://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 https:// www.regulations.gov and insert the docket number, found in brackets in the heading of this document, into the PO 00000 Frm 00060 Fmt 4703 Sfmt 4703 ‘‘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 E:\FR\FM\21JNN1.SGM 21JNN1 asabaliauskas on DSK3SPTVN1PROD with NOTICES Federal Register / Vol. 81, No. 119 / Tuesday, June 21, 2016 / Notices 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 VerDate Sep<11>2014 18:37 Jun 20, 2016 Jkt 238001 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 https://www.fda.gov/MedicalDevices/ DeviceRegulationandGuidance/ GuidanceDocuments/default.htm. Guidance documents are also available at https://www.fda.gov/BiologicsBlood Vaccines/GuidanceCompliance RegulatoryInformation/default.htm or https://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 CDRH-Guidance@fda.hhs.gov 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 Frm 00061 Fmt 4703 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 https://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 DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA–2012–N–0977] Agency Information Collection Activities; Submission for Office of Management and Budget Review; Comment Request; Regulations Restricting the Sale and Distribution of Cigarettes and Smokeless Tobacco To Protect Children and Adolescents AGENCY: Food and Drug Administration, HHS. ACTION: Notice of availability. The Food and Drug Administration (FDA) is announcing that a proposed collection of information has been submitted to the Office of Management and Budget (OMB) for review and clearance under the Paperwork Reduction Act of 1995. DATES: Fax written comments on the collection of information by July 21, 2016. SUMMARY: To ensure that comments on the information collection are received, OMB recommends that written comments be faxed to the Office of Information and Regulatory Affairs, OMB, Attn: FDA Desk Officer, FAX: 202–395–7285, or emailed to oira_ submission@omb.eop.gov. All comments should be identified with the OMB control number 0910–0312. Also include the FDA docket number found in brackets in the heading of this document. ADDRESSES: FDA PRA Staff, Office of Operations, Food and Drug Administration, 8455 Colesville Rd., COLE–14526, Silver Spring, MD 20993–0002, PRAStaff@ fda.hhs.gov. FOR FURTHER INFORMATION CONTACT: 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 https:// www.regulations.gov. FDA has verified the Web site addresses, as of the date this document publishes in the Federal PO 00000 40319 Sfmt 4703 In compliance with 44 U.S.C. 3507, FDA has submitted the following proposed collection of information to OMB for review and clearance. SUPPLEMENTARY INFORMATION: E:\FR\FM\21JNN1.SGM 21JNN1

Agencies

[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]


-----------------------------------------------------------------------

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.

-----------------------------------------------------------------------

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: 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): 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 https://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 https://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: https://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 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 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

[[Page 40319]]

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 https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/default.htm. Guidance 
documents are also available at https://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/default.htm or https://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 CDRH-Guidance@fda.hhs.gov 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 https://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 https://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
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