81 FR 40317 - Leveraging Existing Clinical Data for Extrapolation to Pediatric Uses of Medical Devices; Guidance for Industry and Food and Drug Administration Staff; Availability
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration Federal Register Volume 81, Issue 119 (June 21, 2016)
Food and Drug Administration
Federal Register Volume 81, Issue 119 (June 21, 2016)
| Page Range | 40317-40319 | |
| FR Document | 2016-14640 |
[Federal Register Volume 81, Number 119 (Tuesday, June 21, 2016)] [Notices] [Pages 40317-40319] From the Federal Register Online [www.thefederalregister.org] [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: 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 [[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 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
![Federal Register / Vol. 81, No. 119 / Tuesday, June 21, 2016 / Notices 40317
CONFIDENTIAL INFORMATION.’’ The investigations of the drug becomes (NDA) for XOFIGO (NDA 203971) was
Agency will review this copy, including effective and runs until the approval initially submitted on December 14,
the claimed confidential information, in phase begins. The approval phase starts 2012.
its consideration of comments. The with the initial submission of an 3. The date the application was
second copy, which will have the application to market the human drug approved: May 15, 2013. FDA has
claimed confidential information product and continues until FDA grants verified the applicant’s claim that NDA
redacted/blacked out, will be available permission to market the drug product. 203971 was approved on May 15, 2013.
for public viewing and posted on http:// Although only a portion of a regulatory This determination of the regulatory
www.regulations.gov. Submit both review period may count toward the review period establishes the maximum
copies to the Division of Dockets actual amount of extension that the potential length of a patent extension.
Management. If you do not wish your Director of USPTO may award (for However, the USPTO applies several
name and contact information to be example, half the testing phase must be statutory limitations in its calculations
made publicly available, you can subtracted as well as any time that may of the actual period for patent extension.
provide this information on the cover have occurred before the patent was In its application for patent extension,
sheet and not in the body of your issued), FDA’s determination of the this applicant seeks 1,032 days of patent
comments and you must identify this length of a regulatory review period for term extension.
information as ‘‘confidential.’’ Any a human drug product will include all III. Petitions
information marked as ‘‘confidential’’ of the testing phase and approval phase
will not be disclosed except in as specified in 35 U.S.C. 156(g)(1)(B). Anyone with knowledge that any of
accordance with 21 CFR 10.20 and other FDA has approved for marketing the the dates as published are incorrect may
applicable disclosure law. For more human drug product XOFIGO (radium submit either electronic or written
information about FDA’s posting of 223 dichloride). XOFIGO is indicated comments and ask for a redetermination
comments to public dockets, see 80 FR for treatment of patients with castration- (see DATES). Furthermore, any interested
56469, September 18, 2015, or access resistant prostate cancer, symptomatic person may petition FDA for a
the information at: http://www.fda.gov/ bone metastases and no known visceral determination regarding whether the
regulatoryinformation/dockets/ metastatic disease. Subsequent to this applicant for extension acted with due
default.htm. approval, the USPTO received a patent diligence during the regulatory review
Docket: For access to the docket to term restoration application for XOFIGO period. To meet its burden, the petition
read background documents or the (U.S. Patent No. 6,635,234) from Algeta must be timely (see DATES) and contain
electronic and written/paper comments ASA, and the USPTO requested FDA’s sufficient facts to merit an FDA
received, go to http:// assistance in determining this patent’s investigation. (See H. Rept. 857, part 1,
www.regulations.gov and insert the eligibility for patent term restoration. In 98th Cong., 2d sess., pp. 41–42, 1984.)
docket number, found in brackets in the a letter dated March 19, 2015, FDA Petitions should be in the format
heading of this document, into the advised the USPTO that this human specified in 21 CFR 10.30.
drug product had undergone a Submit petitions electronically to
‘‘Search’’ box and follow the prompts
regulatory review period and that the http://www.regulations.gov at Docket
and/or go to the Division of Dockets
approval of XOFIGO represented the No. FDA–2013–S–0610. Submit written
Management, 5630 Fishers Lane, Rm.
first permitted commercial marketing or petitions (two copies are required) to the
1061, Rockville, MD 20852.
use of the product. Thereafter, the Division of Dockets Management (HFA–
FOR FURTHER INFORMATION CONTACT: 305), Food and Drug Administration,
USPTO requested that FDA determine
Beverly Friedman, Office of Regulatory the product’s regulatory review period. 5630 Fishers Lane, Rm. 1061, Rockville,
Policy, Food and Drug Administration, MD 20852.
10903 New Hampshire Ave., Bldg. 51, II. Determination of Regulatory Review
Rm. 6250, Silver Spring, MD 20993, Period Dated: June 15, 2016.
301–796–3600. Leslie Kux,
FDA has determined that the
Associate Commissioner for Policy.
SUPPLEMENTARY INFORMATION: applicable regulatory review period for
XOFIGO is 1,945 days. Of this time, [FR Doc. 2016–14551 Filed 6–20–16; 8:45 am]
I. Background
1,792 days occurred during the testing BILLING CODE 4164–01–P
The Drug Price Competition and phase of the regulatory review period,
Patent Term Restoration Act of 1984 while 153 days occurred during the
(Pub. L. 98–417) and the Generic approval phase. These periods of time DEPARTMENT OF HEALTH AND
Animal Drug and Patent Term were derived from the following dates: HUMAN SERVICES
Restoration Act (Pub. L. 100–670) 1. The date an exemption under Food and Drug Administration
generally provide that a patent may be section 505(i) of the Federal Food, Drug,
extended for a period of up to 5 years and Cosmetic Act (the FD&C Act) (21 [Docket No. FDA–2015–D–1376]
so long as the patented item (human U.S.C. 355(i)) became effective: January
drug product, animal drug product, 19, 2008. Algeta ASA claims that Leveraging Existing Clinical Data for
medical device, food additive, or color February 21, 2008, is the date the Extrapolation to Pediatric Uses of
additive) was subject to regulatory investigational new drug application Medical Devices; Guidance for
review by FDA before the item was (IND) became effective. However, FDA Industry and Food and Drug
marketed. Under these acts, a product’s records indicate that the IND effective Administration Staff; Availability
asabaliauskas on DSK3SPTVN1PROD with NOTICES
regulatory review period forms the basis date was January 19, 2008, which was AGENCY: Food and Drug Administration,
for determining the amount of extension 30 days after FDA receipt of the IND. HHS.
an applicant may receive. 2. The date the application was ACTION: Notice of availability.
A regulatory review period consists of initially submitted with respect to the
two periods of time: A testing phase and human drug product under section SUMMARY: The Food and Drug
an approval phase. For human drug 505(b) of the FD&C Act: December 14, Administration (FDA or Agency) is
products, the testing phase begins when 2012. FDA has verified the applicant’s announcing the availability of the final
the exemption to permit the clinical claim that the new drug application guidance entitled ‘‘Leveraging Existing
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![Federal Register / Vol. 81, No. 119 / Tuesday, June 21, 2016 / Notices 40319
intended use claim, and enhance and data for pediatric uses of medical Register, but Web sites are subject to
encourage pediatric device development devices. It does not establish any rights change over time.
programs. for any person and is not binding on 1. FDA guidance entitled ‘‘Premarket
This guidance does not change the FDA or the public. You can use an Assessment of Pediatric Medical
regulatory threshold for valid scientific alternative approach if it satisfies the Devices,’’ March 24, 2014, available at
evidence. Instead, the document seeks requirements of the applicable statutes http://www.fda.gov/MedicalDevices/
to provide clarity and predictability for and regulations. DeviceRegulationandGuidance/
device sponsors and to ensure GuidanceDocuments/ucm089740.htm.
consistency within FDA regarding the III. Electronic Access
Dated: June 16, 2016.
specific criteria that should be Persons interested in obtaining a copy Leslie Kux,
considered when deciding whether of the guidance may do so by Associate Commissioner for Policy.
leveraging existing clinical data to downloading an electronic copy from [FR Doc. 2016–14640 Filed 6–20–16; 8:45 am]
support pediatric claims is appropriate, the Internet. A search capability for all
and if so, to what extent. When BILLING CODE 4164–01–P
Center for Devices and Radiological
considering extrapolation, sponsors are Health guidance documents is available
encouraged to engage FDA early in at http://www.fda.gov/MedicalDevices/
product development planning. DEPARTMENT OF HEALTH AND
DeviceRegulationandGuidance/ HUMAN SERVICES
For the purposes of this document, GuidanceDocuments/default.htm.
‘‘extrapolation’’ refers to the leveraging Guidance documents are also available Food and Drug Administration
process whereby an indication for use of at http://www.fda.gov/BiologicsBlood
a device in a new pediatric patient Vaccines/GuidanceCompliance
[Docket No. FDA–2012–N–0977]
population can be supported by existing RegulatoryInformation/default.htm or
clinical data from a studied patient Agency Information Collection
http://www.regulations.gov. Persons Activities; Submission for Office of
population. That is, when existing data unable to download an electronic copy
are relevant to a pediatric indication Management and Budget Review;
of ‘‘Leveraging Existing Clinical Data for Comment Request; Regulations
and determined to be valid scientific
Extrapolation to Pediatric Uses of Restricting the Sale and Distribution of
evidence, it may be scientifically
Medical Devices; Guidance for Industry Cigarettes and Smokeless Tobacco To
appropriate to attempt to extrapolate
and Food and Drug Administration Protect Children and Adolescents
such data to a pediatric use in support
Staff’’ may send an email request to
of demonstrating a reasonable assurance AGENCY: Food and Drug Administration,
CDRH-Guidance@fda.hhs.gov to receive
of effectiveness or probable benefit and, HHS.
an electronic copy of the document.
occasionally, safety.
FDA published in the Federal Please use the document number 1827 ACTION: Notice of availability.
Register of May 6, 2015 (80 FR 26061), to identify the guidance you are
requesting. SUMMARY: The Food and Drug
the document entitled ‘‘Leveraging Administration (FDA) is announcing
Existing Clinical Data for Extrapolation IV. Paperwork Reduction Act of 1995 that a proposed collection of
to Pediatric Uses of Medical Devices; information has been submitted to the
Guidance for Industry and Food and This guidance refers to previously
approved collections of information Office of Management and Budget
Drug Administration Staff’’ and the (OMB) for review and clearance under
comment period closed on August 4, found in FDA regulations. These
collections of information are subject to the Paperwork Reduction Act of 1995.
2015. FDA has considered all of the
review by the Office of Management and DATES: Fax written comments on the
comments received in finalizing this
guidance. The comments from the Budget (OMB) under the Paperwork collection of information by July 21,
docket sought further clarification of the Reduction Act of 1995 (44 U.S.C. 3501– 2016.
scope of the document, the extent of 3520). The collections of information in ADDRESSES: To ensure that comments on
extrapolation that may be feasible across 21 CFR parts 801 and 809 have been the information collection are received,
various pediatric subpopulations, and approved under OMB control number OMB recommends that written
the concept of ‘‘borrowing strength’’ 0910–0485 (medical device labeling); comments be faxed to the Office of
from existing adult data. Accordingly, the collections of information in 21 CFR Information and Regulatory Affairs,
this guidance document has been part 812 have been approved under OMB, Attn: FDA Desk Officer, FAX:
updated to include de novo requests OMB control number 0910–0078 202–395–7285, or emailed to oira_
within the scope and to provide (investigational device exemptions); the submission@omb.eop.gov. All
additional explanation on the concepts collections of information in 21 CFR comments should be identified with the
of extrapolation of data across pediatric part 814 have been approved under OMB control number 0910–0312. Also
subpopulations and ‘‘borrowing OMB control number 0910–0231 include the FDA docket number found
strength.’’ (subparts A through E, premarket in brackets in the heading of this
This guidance should be used in approval). document.
conjunction with other device-specific V. References FOR FURTHER INFORMATION CONTACT: FDA
guidances to help ensure that medical PRA Staff, Office of Operations, Food
devices intended for use in pediatric The following references are on
display in the Division of Dockets and Drug Administration, 8455
asabaliauskas on DSK3SPTVN1PROD with NOTICES
population provide reasonable Colesville Rd., COLE–14526, Silver
assurance of safety and effectiveness. Management (see ADDRESSES) and are
available for viewing by interested Spring, MD 20993–0002, PRAStaff@
II. Significance of Guidance persons between 9 a.m. and 4 p.m., fda.hhs.gov.
This guidance is being issued Monday through Friday; they are also SUPPLEMENTARY INFORMATION: In
consistent with FDA’s good guidance available electronically at http:// compliance with 44 U.S.C. 3507, FDA
practices regulation (21 CFR 10.115). www.regulations.gov. FDA has verified has submitted the following proposed
The guidance represents the current the Web site addresses, as of the date collection of information to OMB for
thinking of FDA on the extrapolation of this document publishes in the Federal review and clearance.
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Document Created: 2016-06-21 01:30:37
Document Modified: 2016-06-21 01:30:37
| Category | Regulatory Information | |
| Collection | Federal Register | |
| sudoc Class | AE 2.7: GS 4.107: AE 2.106: | |
| Publisher | Office of the Federal Register, National Archives and Records Administration | |
| Section | Notices | |
| Action | Notice of availability. | |
| Dates | Submit either electronic or written comments on this guidance at any time. General comments on Agency guidance documents are welcome at any time. | |
| 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. | |
| FR Citation | 81 FR 40317 |
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