Document ID: FDA-2018-D-3130-0001
Agency: fda
Document Type: Notice
Title: Consideration of Uncertainty in Making Benefit-Risk Determinations in Medical Device Premarket Approvals, De Novo Classifications, and Humanitarian Device Exemptions; Draft Guidance for Industry and Food and Drug Administration Staff; Availability
Posted Date: 2018-09-06T04:00Z

[Federal Register Volume 83, Number 173 (Thursday, September 6, 2018)]
[Notices]
[Pages 45247-45249]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-19249]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2018-D-3130]

Consideration of Uncertainty in Making Benefit-Risk 
Determinations in Medical Device Premarket Approvals, De Novo 
Classifications, and Humanitarian Device Exemptions; Draft Guidance for 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the availability of the draft guidance entitled ``Consideration of 
Uncertainty in Making Benefit-Risk Determinations in Medical Device 
Premarket Approvals, De Novo Classifications, and Humanitarian Device 
Exemptions.'' This guidance document describes FDA's current approach 
to considering uncertainty in making benefit-risk determinations to 
support certain FDA premarket decisions for medical devices--premarket 
approval applications (PMAs), De Novo requests, and humanitarian device 
exemption (HDE) applications. This guidance document elaborates on the 
consideration of uncertainty as part of our overarching approach to a 
benefit-risk based framework that is intended to assure greater 
predictability, consistency, and efficiency through the application of 
least burdensome principles. This draft guidance also provides examples 
of how the principles for considering uncertainty could be applied in 
the context of clinical evidence and circumstances where greater 
uncertainty could be appropriate in premarket decisions, balanced by 
postmarket controls--PMAs for Breakthrough Devices and PMAs for devices 
for small patient populations. This draft guidance is not final nor is 
it in effect at this time.

DATES: Submit either electronic or written comments on the draft 
guidance by December 5, 2018 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 
version of the guidance.

ADDRESSES: You may submit comments on any guidance 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-3130 for ``Consideration of Uncertainty in Making Benefit-
Risk Determinations in Medical Device Premarket Approvals, De Novo 
Classifications, and Humanitarian Device Exemptions; Draft 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 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

[[Page 45248]]

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)).
    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 draft guidance document entitled 
``Consideration of Uncertainty in Making Benefit-Risk Determinations in 
Medical Device Premarket Approvals, De Novo Classifications, and 
Humanitarian Device Exemptions'' 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. Send one self-addressed 
adhesive label to assist that office in processing your request.

FOR FURTHER INFORMATION CONTACT: Sonja Fulmer, Center for Devices and 
Radiological Health, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 66, Rm. 5451, Silver Spring, MD 20993-0002, 240-402-5979.

SUPPLEMENTARY INFORMATION:

I. Background

    The Medical Device Amendments of 1976 (Pub. L. 94-295) to the 
Federal Food, Drug, and Cosmetic Act (FD&C Act) established a risk-
based framework for the regulation of medical devices. The law 
established a three-tiered risk classification system based on the risk 
posed to patients should the device fail to perform as intended. Under 
this system, devices that pose greater risks to patients are subject to 
more regulatory controls and requirements. Generally, in premarket 
decision-making for devices, there exists some uncertainty around 
benefits and risks. The Agency generally provides marketing 
authorization for a device when it meets the applicable standards, 
including that its benefits outweigh its risks.
    In 2015, following pilots conducted over 4 years, FDA established 
the Expedited Access Pathway Program as a voluntary program for certain 
medical devices that address an unmet need in the treatment or 
diagnosis of life-threatening or irreversibly debilitating diseases or 
conditions. Under this program, an eligible device subject to a PMA 
could be approved with greater uncertainty about the product's benefits 
and risks, provided that, among other requirements, the data still 
support a reasonable assurance of safety and effectiveness, including 
that the probable benefits of the device outweigh its risks for a 
patient population with unmet medical needs. For devices subject to 
PMA, the Agency has the authority to impose, when warranted, postmarket 
requirements, including post-approval studies and postmarket 
surveillance, as a condition of approval, which could be used to 
address this greater uncertainty.\1\ In the Breakthrough Device 
provisions of the FD&C Act, as added by the 21st Century Cures Act 
(Cures Act) and amended by the FDA Reauthorization Act of 2017 (FDARA), 
Congress codified and expanded this program to include devices reviewed 
through a 510(k) notification.\2\
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    \1\ See sections 513(a)(3)(C), 515(c)(5)(C), 515(d)(1)(B)(ii), 
and 515B(e)(2)(C) of the FD&C Act (21 U.S.C. 360c(a)(3)(C), 
360e(c)(5)(C), 360e(d)(1)(B)(ii), and 360e-3(e)(2)(C)); 21 CFR 
814.82).
    \2\ See section 515B of the FD&C Act (21 U.S.C. 360e-3), as 
created by section 3051 of the Cures Act (Pub. L. 114-255) and 
amended by section 901 of FDARA (Pub. L. 115-52).
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    This draft guidance provides further information on how FDA 
considers uncertainty in benefit-risk determinations for PMAs, De Novo 
requests, and HDE applications.

II. Significance of Guidance

    This draft guidance is being issued consistent with FDA's good 
guidance practices regulation (21 CFR 10.115). The draft guidance, when 
finalized, will represent the current thinking of FDA on consideration 
of uncertainty in making benefit-risk determinations in medical device 
premarket approvals, De Novo classifications, and humanitarian device 
exemptions. 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.

III. Electronic Access

    Persons interested in obtaining a copy of the draft 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. This 
guidance document is also available at https://www.regulations.gov. 
Persons unable to download an electronic copy of ``Consideration of 
Uncertainty in Making Benefit-Risk Determinations in Medical Device 
Premarket Approvals, De Novo Classifications, and Humanitarian Device 
Exemptions; Draft 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 17039 to identify the guidance you are 
requesting.

IV. Paperwork Reduction Act of 1995

    This draft 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 part 801 have been approved under 
OMB control number 0910-0485; the collections of information for De 
Novo classification requests have been approved under OMB control 
number 0910-0844; the collections of information in 21 CFR part 814, 
subparts A through E, have been approved under OMB control number 0910-
0231; the collections of information in 21 CFR part 814, subpart H, 
have been approved under OMB control number 0910-0332; and the 
collections of information in 21 CFR

[[Page 45249]]

part 822 have been approved under OMB control number 0910-0449.

    Dated: August 30, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-19249 Filed 9-5-18; 8:45 am]
 BILLING CODE 4164-01-P