Document ID: FDA-2018-D-3130-0008
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; Guidance for Industry and Food and Drug Administration Staff; Availability
Posted Date: 2019-08-30T04:00Z

[Federal Register Volume 84, Number 169 (Friday, August 30, 2019)]
[Notices]
[Pages 45771-45773]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-18802]

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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; 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 a final 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 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 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.

DATES: The announcement of the guidance is published in the Federal 
Register on August 30, 2019.

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-3130 for ``Consideration of Uncertainty in Making Benefit-
Risk Determinations in Medical Device Premarket Approvals, De Novo 
Classifications, and Humanitarian Device Exemptions; Guidance for 
Industry and Food and Drug Administration Staff; Availability.'' 
Received comments will be placed in the docket and, except for those 
submitted as ``Confidential Submissions,'' publicly viewable at

[[Page 45772]]

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 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 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 Policy, 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, Office of Policy, 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 1976 Medical Device Amendments (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, for any regulatory 
decision, 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 (EAP) 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, 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 guidance provides further information on how FDA considers 
uncertainty in benefit-risk determinations for PMAs, De Novo requests, 
and Humanitarian Device Exemption applications. FDA considered comments 
received on the draft guidance that appeared in the Federal Register of 
September 6, 2018 (83 FR 45247). FDA revised the guidance as 
appropriate in response to the comments.

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 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 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 or 
https://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/default.htm. 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'' may send an 
email request to CDRH-Guidance@fda.hhs.gov to receive an electronic 
copy of the document. Please use the document number 17039 to identify 
the guidance you are requesting.

[[Page 45773]]

IV. Paperwork Reduction Act of 1995

    This guidance refers to previously approved collections of 
information. 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 
the following FDA regulations and guidance have been approved by OMB as 
listed in the following table:

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                                                            OMB control
21 CFR part; guidance; or FDA form          Topic               No.
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814, subparts A through E.........  Premarket approval..       0910-0231
814, subpart H....................  Humanitarian Device        0910-0332
                                     Exemption.
``De Novo Classification Process    De Novo                    0910-0844
 (Evaluation of Automatic Class      classification
 III Designation)''.                 process.
``Requests for Feedback on Medical  Q-submissions.......       0910-0756
 Device Submissions: The Pre-
 Submission Program and Meetings
 with Food and Drug Administration
 Staff``.
801 and 809.......................  Medical Device             0910-0485
                                     Labeling
                                     Regulations.
822...............................  Postmarket                 0910-0449
                                     Surveillance of
                                     Medical Devices.
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    Dated: August 27, 2019.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2019-18802 Filed 8-29-19; 8:45 am]
BILLING CODE 4164-01-P