Document ID: FDA-2018-N-0236-0028
Agency: fda
Document Type: Rule
Title: Medical Device De Novo Classification Process
Posted Date: 2021-10-05T04:00Z

[Federal Register Volume 86, Number 190 (Tuesday, October 5, 2021)]
[Rules and Regulations]
[Pages 54826-54851]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2021-21677]

=======================================================================
-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 860

[Docket No. FDA-2018-N-0236]
RIN 0910-AH53

Medical Device De Novo Classification Process

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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

SUMMARY: The Food and Drug Administration (FDA) is issuing a final rule 
to establish requirements for the medical device De Novo classification 
process under the Federal Food, Drug, and Cosmetic Act (FD&C Act). This 
final rule establishes procedures and criteria related to requests for 
De Novo classification (``De Novo request'') and provides a pathway to 
obtain marketing authorization as a class I or class II device and for 
certain combination products. These requirements are intended to ensure 
the most appropriate classification of devices consistent with the 
protection of the public health and the statutory scheme for device 
regulation. They are also intended to limit the unnecessary expenditure 
of FDA and industry resources that may occur if devices for which 
general controls or general and special controls provide a reasonable 
assurance of safety and effectiveness are subject to premarket 
approval. The final rule implements the De Novo classification process 
under the FD&C Act, as enacted by the Food and Drug Administration 
Modernization Act of 1997 (FDAMA) and modified by the Food and Drug 
Administration Safety and Innovation Act (FDASIA) and the 21st Century 
Cures Act (Cures Act).

DATES: This rule is effective January 3, 2022.

ADDRESSES: For access to the docket to read background documents or 
comments received, go to https://www.regulations.gov and insert the 
docket number found in brackets in the heading of this final rule into 
the ``Search'' box and follow the prompts, and/or go to the Dockets 
Management Staff, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852, 
240-402-7500.

FOR FURTHER INFORMATION CONTACT: Sergio de del Castillo, Center for 
Devices and Radiological Health, Food and Drug Administration, 10903 
New Hampshire Ave., Bldg. 66, Rm. 2431, Silver Spring, MD 20993, 301-
796-6419.

SUPPLEMENTARY INFORMATION:

Table of Contents

I. Executive Summary
    A. Purpose of the Final Rule
    B. Summary of the Major Provisions of the Final Rule
    C. Legal Authority
    D. Costs and Benefits
II. Table of Abbreviations/Commonly Used Acronyms in This Document
III. Background
    A. Need for the Regulation/History of This Rulemaking
    B. Summary of Comments to the Proposed Rule
    C. General Overview of Final Rule
IV. Legal Authority
V. Comments on the Proposed Rule and FDA Response
    A. Introduction
    B. Description of General Comments and FDA Response
    C. Comments and FDA Response on Use of Advisory Committees and 
Bundling Devices
    D. Comments and FDA Response on De Novo Request Information 
Disclosure
    E. Comments and FDA Response on Facility Inspections
    F. Comments and FDA Response on Definitions
    G. Comments and FDA Response on De Novo Request Format
    H. Comments and FDA Response on De Novo Request Content
    I. Comments and FDA Response on Criteria for Accepting a De Novo 
Request
    J. Comments and FDA Response on Criteria for Granting or 
Declining a De Novo Request
    K. Comments and FDA Response on Availability of the De Novo 
Classification Process for Combination Products
VI. Effective Date
VII. Economic Analysis of Impacts
VIII. Analysis of Environmental Impact
IX. Paperwork Reduction Act of 1995
X. Federalism
XI. Consultation and Coordination With Indian Tribal Governments
XII. References

I. Executive Summary

A. Purpose of the Final Rule

    This rule establishes new regulations implementing the medical 
device De Novo classification process under the FD&C Act, which 
provides a pathway for certain new types of devices to obtain marketing 
authorization as class I or class II devices, rather than remaining 
automatically designated as a class III device, which would require 
premarket approval under the postamendments device classification 
section of the FD&C Act.
    The De Novo classification process is intended to provide an 
efficient pathway to ensure the most appropriate classification of a 
device consistent with the protection of the public health and the 
statutory scheme for device regulation. When FDA classifies a device 
type as class I or II via the De Novo classification process, other 
manufacturers do not necessarily have to submit a De Novo request or 
premarket approval application (PMA) to legally market a device of the 
same type. Instead, manufacturers can use the less burdensome pathway 
of premarket notification (510(k)), when applicable, to legally market 
their device, because the device that was the subject of the original 
De Novo request can serve as a predicate device for a substantial 
equivalence determination.

B. Summary of the Major Provisions of the Final Rule

    This rule establishes procedures and criteria for the submission 
and withdrawal of a De Novo request. It also establishes procedures and 
criteria for FDA to accept, review, grant, and/or decline a De Novo 
request. While several comments object to sections or subsections of 
the proposed rule, almost all comments voice support for the objective 
of the proposed rule: To establish regulations implementing the De Novo 
classification process. The rule provides that:
     A person may submit a De Novo request after submitting a 
510(k) and receiving a not substantially equivalent (NSE) 
determination.
     A person may also submit a De Novo request without first 
submitting a 510(k), if the person determines that

[[Page 54827]]

there is no legally marketed device upon which to base a determination 
of substantial equivalence (SE).
     FDA will classify devices according to the classification 
criteria in the FD&C Act. FDA classifies devices into class I (general 
controls) if there is information showing that the general controls of 
the FD&C Act are sufficient to reasonably assure safety and 
effectiveness; into class II (special controls) if general controls, by 
themselves, are insufficient to provide reasonable assurance of safety 
and effectiveness, but there is sufficient information to establish 
special controls to provide such assurance; and into class III 
(premarket approval) if there is insufficient information to support 
classifying a device into class I or class II and the device is a life-
sustaining or life-supporting device or is for a use which is of 
substantial importance in preventing impairment of human health or 
presents a potential unreasonable risk of illness or injury.
     Devices will be classified by FDA by written order.
     A De Novo request includes administrative information, 
regulatory history, device description, classification summary 
information, benefits and risks of device use, and performance data to 
demonstrate reasonable assurance of safety and effectiveness.
     FDA may refuse to accept a De Novo request that is 
ineligible or that is not sufficiently complete to permit a substantive 
review.
     After a De Novo request is accepted, FDA will begin a 
substantive review of the De Novo request that may result in either FDA 
requesting additional information, issuing an order granting the 
request, or declining the De Novo request.
     FDA may decline a De Novo request if, among other things, 
the device is ineligible or insufficient information is provided to 
support De Novo classification.
    The rule also describes our practices for the conditions under 
which the confidentiality of a De Novo file is maintained.

C. Legal Authority

    This rule is being issued under the device definition provision of 
the FD&C Act, the combination products provision of the FD&C Act, the 
device classification section of the FD&C Act, the De Novo 
classification section of the FD&C Act, the general rulemaking section 
of the FD&C Act, and the inspection section of the FD&C Act.

D. Costs and Benefits

    The final rule clarifies the De Novo classification process for 
certain medical devices to obtain marketing authorization as class I or 
class II devices, rather than remaining automatically designated as 
class III devices under the FD&C Act. A more transparent De Novo 
classification process could improve the efficiency of obtaining 
marketing authorization for certain novel medical devices. The medical 
device industry will incur one-time costs to read and understand this 
rule. Over 10 years, the annualized cost estimates a 7 percent discount 
rate range from $0.01 million to $0.17 million, with a primary estimate 
of $0.09 million. The annualized costs over 10 years at a 3 percent 
discount rate range from $0.1 million to $0.15 million, with a primary 
estimate of $0.08 million.

II. Table of Abbreviations/Commonly Used Acronyms in This Document

----------------------------------------------------------------------------------------------------------------
       Abbreviation or acronym                                       What it means
----------------------------------------------------------------------------------------------------------------
510(k)..............................  Premarket Notification
CDRH................................  Center for Devices and Radiological Health
CFR.................................  Code of Federal Regulations
EUA.................................  Emergency Use Authorization
FDA.................................  Food and Drug Administration
FD&C Act............................  Federal Food, Drug, and Cosmetic Act
FDAMA...............................  Food and Drug Administration Modernization Act of 1997
FOIA................................  Freedom of Information Act
FR..................................  Federal Register
GLP.................................  Good Laboratory Practice
HDE.................................  Humanitarian Device Exemption
IDE.................................  Investigational Device Exemption
IC..................................  Information Collection
ICR.................................  Information Collection Request
NSE.................................  Not Substantially Equivalent
OMB.................................  Office of Management and Budget
PHI.................................  Protected Health Information
PMA.................................  Premarket Approval Application
PRA.................................  Paperwork Reduction Act of 1995
Pub. L..............................  Public Law
QSR.................................  Quality System Regulation
Ref.................................  Reference
RFD.................................  Requests for Designation under 21 CFR 3.7 (Sec.   3.7)
SE..................................  Substantially Equivalent
SSED................................  Summary of Safety and Effectiveness Data
U.S.C...............................  United States Code
----------------------------------------------------------------------------------------------------------------

III. Background

A. Need for the Regulation/History of This Rulemaking

    In the Federal Register on December 7, 2018 (83 FR 63127), FDA 
issued a proposed rule entitled ``Medical Device De Novo Classification 
Process'' and requested comments on the proposed rule by March 7, 2019. 
This rule establishes procedures and criteria for the submission and 
withdrawal of a De Novo request. It also establishes procedures and 
criteria for FDA to accept, review, grant, and/or decline a De Novo 
request.

B. Summary of Comments to the Proposed Rule

    FDA received comments on the proposed rule from several entities, 
including medical device associations; industry, medical and healthcare 
professional associations; public health

[[Page 54828]]

advocacy groups; law firms; and individuals. While several comments 
object to sections or subsections of the proposed rule, almost all 
comments voice support for the objective of the proposed rule: To 
establish regulations implementing the De Novo classification process. 
Comments raise concerns or request clarification regarding several 
issues, including:
     De Novo request information disclosure,
     facility inspections,
     devices that collect protected health information,
     training of FDA reviewers,
     the definitions,
     the De Novo request format,
     the De Novo request content,
     the criteria for accepting a De Novo request,
     the criteria for declining a De Novo request,
     the availability of the De Novo classification process for 
combination products, and
     the information needed to support FDA's determination to 
grant a De Novo classification request.

C. General Overview of Final Rule

    FDA considered all comments received on the proposed rule and made 
changes, primarily for clarity and accuracy and to reduce burden in 
meeting regulatory requirements. On its own initiative, FDA is 
renumbering the sections to make them easier for De Novo requesters and 
the public to research and use. On its own initiative, FDA is also 
making minor technical changes to make the regulatory history, 
withdrawal, nonclinical studies, and classification summary provisions 
clearer. FDA also changed the word ``guidance'' to ``guidelines'' in 
the definition of Class II at Sec.  860.3 (21 CFR 860.3) on its own 
initiative for consistency with the language used in section 
513(a)(1)(B) of the FD&C Act (21 U.S.C. 360c (a)(1)(B)) and with Sec.  
860.123 (21 CFR 860.123) in the final rule. Finally, on its own 
initiative, FDA is adding requests for information regarding the class 
in which a device has been classified or the requirements applicable to 
a device under the FD&C Act that are submitted in accordance with 
section 513(g) of the FD&C Act, to the regulatory history information 
required to be included in a De Novo request under proposed Sec.  
860.234(a)(3) (21 CFR 860.234(a)(3)) (see Sec.  860.220(a)(3) in the 
final rule). In the preamble of the proposed rule, FDA described 
section 513(g) requests for information as one of the submissions it 
was proposing to require requesters to identify as part of the 
regulatory history section of a De Novo request (see 83 FR 63127 at 
63132). However, a reference to section 513(g) of the FD&C Act was 
inadvertently omitted from the proposed regulatory text included in the 
proposed rule. The changes from the proposed rule include the following 
revisions, additions, and removals.
     Renumber the proposed De Novo section numbers as follows:

                      Table 1--Renumbered Sections
------------------------------------------------------------------------
                               Renumbered
    Proposed section No.      section No.           Section name
------------------------------------------------------------------------
860.201.....................      860.200  Purpose and applicability.
860.223.....................      860.210  De Novo request format.
860.234.....................      860.220  De Novo request content.
860.245.....................      860.230  Accepting a De Novo request.
860.256.....................      860.240  Procedures for review of a De
                                            Novo request.
860.267.....................      860.250  Withdrawal of a De Novo
                                            request.
860.289.....................      860.260  Granting or declining a De
                                            Novo request.
------------------------------------------------------------------------

     Revise the De Novo request confidentiality provision 
(Sec.  860.5(g)) to clarify that after an order granting a De Novo 
request is issued, data and information in the De Novo file that are 
not exempt from release under the Freedom of Information Act (FOIA) (5 
U.S.C. 552) are immediately available for public disclosure; and to 
replace certain references to ``De Novo request'' with ``De Novo 
file.''
     Revise the De Novo format requirements as follows:
    [cir] Remove the requirement to cite the volume number in the table 
of contents if the De Novo request consists of only one volume,
    [cir] remove the requirement to provide a fax number when 
submitting a De Novo request, and
    [cir] clarify that the De Novo request must be submitted as a 
single version in electronic format.
     Revise the De Novo content requirements as follows:
    [cir] Add section 513(g) requests for information to the regulatory 
history requirement in proposed Sec.  860.234(a)(3) (see Sec.  
860.220(a)(3)) and change the term ``use'' to ``device'' in the 
regulatory history requirement so the text more accurately refers to an 
application for ``humanitarian device exemption''.
    [cir] Revise the order of the proposed requirements for the content 
of a De Novo request in proposed Sec.  860.234(a)(9) through (11) (see 
Sec.  860.220(a)(9) through (11) in the final rule).
    [cir] Revise Sec.  860.220(a)(7) and (a)(9) (this final rule 
renumbers proposed Sec.  860.234(a)(7) as Sec.  860.220(a)(7)) to 
clarify that the information required is that known to or that 
reasonably should be known to the requester.
    [cir] Remove ``laboratory'' to clarify Sec.  860.220(a)(13)(i) and 
(a)(15)(i) (this final rule renumbers proposed Sec.  860.234(a)(13)(i) 
and (a)(15)(i) to Sec.  860.220(a)(13)(i) and (a)(15)(i)) requires a 
summary of each nonclinical study.
    [cir] Move the phrase, ``as appropriate,'' in Sec.  
860.220(a)(15)(i) to clarify that not all of the identified nonclinical 
studies may be applicable to the subject device.
    [cir] Revise Sec.  860.220(a)(15)(i) to clarify that a De Novo 
requester must include a protocol and complete test report for each 
nonclinical study.
    [cir] Revise Sec.  860.220(a)(15)(i) to clarify that a De Novo 
request must only include a statement regarding compliance with good 
laboratory practice (GLP) requirements in part 58 (21 CFR part 58) for 
nonclinical studies that are subject to part 58.
     Revise the provisions for withdrawal of a De Novo request 
to make minor technical changes.
     Revise the provisions for granting a De Novo request to 
specify that FDA will publish a notice of the classification order in 
the Federal Register within 30 days after granting the request.
     Revise the provisions for declining of a De Novo request 
to clarify that FDA will decline a De Novo request by written order and 
moves the grounds for which FDA may decline a De Novo request from 
Sec.  860.260(b) into Sec.  860.260(c).

IV. Legal Authority

    The FD&C Act establishes a comprehensive system for the regulation 
of medical devices intended for human use. Among the provisions that 
provide authority for this final rule are sections 201(h), 503(g), 
513(a) and (f), 701(a), and 704 of the FD&C Act (21 U.S.C. 321(h), 
353(g), 360c(a) and (f), 371(a), and 374). This final rule establishes 
regulations to implement the De Novo classification process created by 
section 207 of FDAMA (Pub. L. 105-115) and amended by section 607 of 
FDASIA (Pub. L. 112-144) and section 3101 of the Cures Act (Pub. L. 
114-255).

[[Page 54829]]

V. Comments on Proposed Rule and FDA Response

A. Introduction

    We received several sets of comments on the proposed rule by the 
close of the comment period, each containing one or more comments on 
one or more issues. We received comments from medical device 
associations, industry, medical and healthcare professional 
associations, public health advocacy groups, law firms, and 
individuals. We describe and respond to comments in sections V.B 
through V.K. We have numbered each comment to help distinguish between 
different comments. We have grouped similar comments together under the 
same number, and, in some cases, we have separated different issues 
discussed in the same comment and designated them as distinct comments 
for purposes of our responses. The number assigned to each comment or 
comment topic is purely for organizational purposes and does not 
signify the comment's value or importance or the order in which 
comments were received.

B. Description of General Comments and FDA Response

    Several comments made general remarks supporting the proposed rule 
without focusing on a particular proposed provision. Almost all 
comments supported the objective of the proposed rule: To establish 
regulations implementing the De Novo classification process. Several 
comments also requested that FDA make changes without focusing on a 
particular provision of the proposed rule. In the following paragraphs, 
we discuss and respond to such general comments.
    (Comment 1) A commenter states that FDA should retain patient 
safety as its number one priority and integrate cybersecurity into the 
De Novo request process, and that science should support any decisions.
    (Response 1) FDA agrees with this comment. As part of the 
cybersecurity review for premarket submissions for devices that contain 
software (including firmware) or programmable logic as well as software 
that is a medical device, FDA recommends that medical device 
manufacturers assess the impact of threats and vulnerabilities on 
device functionality and end users/patients as part of the 
cybersecurity review (Ref. 1).
    (Comment 2) A commenter requests FDA to adopt an abbreviated 
procedure and a reduced user fee for De Novo requests when the 
requester believes that its device meets the criteria for 
classification in class I under section 513(a)(1)(A)(ii) of the FD&C 
Act, because the commenter believes that it would help provide more 
timely access to low-risk devices and conserve valuable FDA premarket 
review resources without compromising public health protection.
    (Response 2) We do not agree that the procedure proposed by the 
commenter would be more efficient than the procedures described in 
FDA's proposed rule. The De Novo classification process provides a 
pathway for certain devices to obtain marketing authorization as class 
I or class II devices, rather than remaining automatically designated 
as class III under section 513(f)(1) of the FD&C Act. FDA makes the 
determination that a device is class I or class II under section 
513(f)(2) of the FD&C Act using the criteria in section 513(a) of the 
FD&C Act. The process proposed by the commenter would require an 
abbreviated submission with only some of the information FDA proposed 
to require in a De Novo request when the requester believes that its 
device meets the criteria for classification as a class I device. The 
proposed process would also add a step to the Agency's review process 
for such devices by requiring FDA to determine within 15 days of 
receiving the request either that the device meets the criteria for 
classification into class I or that additional information is required 
to make the classification determination.
    The FD&C Act provides 120 days for review of a De Novo request, 
regardless of the ultimate classification determination. In FDA's 
experience, 15 days is not a workable timeframe for the Agency to 
complete a substantive review of a submission for a new device type to 
determine that the device meets the criteria for classification into 
class I. Further, the commenter's suggested abbreviated initial 
submission omits information that is important for FDA's classification 
determinations, such as information on probable risks to health 
associated with use of the device. Therefore, under the commenter's 
proposed process, FDA would usually, if not always, need to require 
additional information within 15 days. In Sec.  860.220(a) of this 
final rule, FDA has identified the required contents of a De Novo 
request taking into account the Agency's experience with the types of 
information needed to make a determination on a De Novo request. If a 
requester believes that some of the required information is not 
applicable to its device, the requester may submit a justification for 
omitting that information pursuant to Sec.  860.220(c).
    We also note that the proposed process does not appear to provide 
for any FDA action other than requesting additional information or 
classifying the device. Section 513(f)(2) of the FD&C Act provides for 
FDA to decline a De Novo request.
    With respect to the user fees applicable to a De Novo request, the 
Medical Device User Fee Amendments of 2017 amended the FD&C Act to 
authorize FDA to collect user fees for certain premarket submissions 
received on or after October 1, 2017, including De Novo requests (see 
section 738 of the FD&C Act (21 U.S.C. 379j)). The fees are set by 
statute (section 738(a)(2)(A)(xi) of the FD&C Act) and therefore any 
changes to such fees are outside the scope of this rulemaking.
    (Comment 3) A commenter concerned about the design of a remote 
monitoring system containing software states that as part of the De 
Novo request, a manufacturer should provide information on whether the 
device collects protected health information (PHI). The same commenter 
requests that the Health and Human Services' Office for Civil Rights 
should complete a review prior to the De Novo request being granted by 
FDA. A commenter states that a PHI pre-approval plan should be reviewed 
with the impact and patient experience included in the overall De Novo 
request grant.
    (Response 3) Standards for the use and disclosure of protected 
health information by certain entities are set forth in regulations 
implementing the Health Insurance Portability and Accountability Act of 
1996 (HIPAA) (Pub. L. 101-191), which are outside the scope of this 
rulemaking. To demonstrate a reasonable assurance of safety and 
effectiveness for software devices, documentation related to the 
requirements of the quality system regulation (QSR) (21 CFR part 820) 
is often a necessary part of the premarket submission. See also 
``Guidance for the Content of Premarket Submissions for Software 
Contained in Medical Devices'' (Ref. 2). As part of QSR design 
controls, a manufacturer must ``establish and maintain procedures for 
validating the device design,'' which ``shall include software 
validation and risk analysis, where appropriate.'' (Sec.  820.30(g)). 
As part of the software validation and risk analysis required by Sec.  
820.30(g), software device manufacturers may need to establish a 
cybersecurity vulnerability and management approach, where appropriate. 
Such cybersecurity design controls help to ensure device security, 
including protection of health information.

[[Page 54830]]

    (Comment 4) A comment recommends FDA provide additional training 
for FDA reviewers on De Novo classification to assist FDA reviewers in 
more thoroughly understanding the devices and how to review De Novo 
requests with the broader view of assessing the nature of the devices 
and their value to the patient.
    (Response 4) FDA currently provides training to FDA staff on the De 
Novo classification process. With the publication of this final rule, 
FDA intends to update its current training to be reflective of the 
requirements of the final rule. FDA also understands that patient input 
can be an important consideration during FDA's review of a De Novo 
request, as reflected in our guidance for industry and FDA Staff, 
``Factors to Consider When Making Benefit-Risk Determinations in 
Medical Device Premarket Approval and De Novo Classifications'' (Ref. 
3) and ``Patient Preference Information--Voluntary Submission, Review 
in Premarket Approval Applications, Humanitarian Device Exemption 
Applications, and De Novo Requests, and Inclusion in Decision Summaries 
and Device Labeling'' (Ref. 4).
    (Comment 5) A commenter proposes that unless required by the FD&C 
Act or the device is of high public health importance, FDA defer the 
identification of special controls for devices being granted De Novo 
classification until after the De Novo request is granted and FDA can 
make a general assessment of all class II devices. The same commenter 
also requests that FDA prioritize the identification of special 
controls for all class II devices.
    (Response 5) Because special controls are necessary to assure the 
safety and effectiveness of class II devices, FDA does not agree with 
the commenter's proposal. FDA believes it is important to identify the 
appropriate special controls for class II devices at the time FDA 
grants the De Novo request. The granting of the De Novo request does 
several things: It allows the device to be marketed immediately, 
creates a classification regulation for devices of the type, and 
permits the device to serve as a predicate device (section 513(f)(2)(B) 
of the FD&C Act) (Ref. 5). Because these consequences flow from the 
grant of a De Novo request, and because special controls are necessary 
to reasonably assure the safety and effectiveness of a class II device, 
FDA will continue to identify special controls at the time that it 
grants a De Novo classification request.
    The request that FDA prioritize the identification of special 
controls for all class II devices is outside the scope of this 
rulemaking.
    (Comment 6) A comment recommends that medical device applicants be 
encouraged to perform and/or review studies that address the effect of 
the device on patient function, because the commenter states that, for 
all populations, the ability to function at work, at home, and with 
family is an important outcome.
    (Response 6) Where relevant to the intended use of a device, FDA 
currently would take patient function into account in evaluating the 
safety and effectiveness of the device. As part of its initiative for 
patients to engage with FDA, FDA has incorporated patient perspectives 
into the total product life cycle, including in the premarket 
evaluation of devices (Refs. 4 and 6).
    (Comment 7) A comment objects to the placement of all the De Novo 
request regulatory requirements in part 860 and suggests that the 
Center for Devices and Radiological Health (CDRH) separate requirements 
for the information needed to classify a device type from requirements 
for the information needed to authorize a specific low to moderate risk 
device for marketing by placing the latter in a separate regulation for 
``Premarket Approval of Novel Class I and II Medical Devices.''
    (Response 7) FDA disagrees with this comment. The De Novo 
classification provisions will be housed in part 860 of the CFR with 
the other device classification subparts. We recognize that, because 
the De Novo classification process includes a pathway to obtain 
marketing authorization for a specific device, placement of the De Novo 
classification regulations may not be as straightforward as the other 
classification regulations. FDA believes that part 860 is the most 
appropriate fit.
    (Comment 8) A comment asserts that some devices, especially 
implantable devices, are inappropriately classified as class II instead 
of class III because these devices are ``potentially life-saving or 
life-threatening.'' The comment further indicates that the De Novo 
pathway should not replace the PMA pathway for implanted devices that 
are not eligible for 510(k) clearance and recommends that FDA document 
whether the increase in De Novo grants over the past few years 
indicates a movement from 510(k) clearance of devices to De Novo or 
from PMA review to the less stringent De Novo pathway before finalizing 
the proposed rule.
    (Response 8) Altering the statutory standards for device 
classification and marketing authorization is outside the scope of this 
rulemaking. FDA classifies devices according to the statutory criteria 
set forth in section 513(a)(1) of the FD&C Act. Therefore, if FDA 
determines that general and special controls are sufficient to provide 
a reasonable assurance of safety and effectiveness for a potentially 
life-supporting device, FDA must classify that device into class II 
(see section 513(a)(1)(B) of the FD&C Act). Congress added section 
513(f)(2) of the FD&C Act as part of FDAMA to limit unnecessary 
expenditure of FDA and industry resources that could occur if devices 
for which general controls or general and special controls provide a 
reasonable assurance of safety and effectiveness were subject to 
premarket approval under section 515 of the FD&C Act (21 U.S.C. 360e). 
As enacted by FDAMA, to submit a De Novo request, a device first had to 
be found NSE to legally marketed predicate devices through a 510(k). 
Section 513(f)(2) of the FD&C Act was modified by section 607 of 
FDASIA, which created an alternative mechanism for submitting a De Novo 
request that does not require that a device be reviewed first under a 
510(k) and found NSE prior to submission of a De Novo request. If a 
person believes their device is appropriate for classification into 
class I or class II and determines, based on currently available 
information, there is no legally marketed predicate device, they may 
submit a De Novo request without a preceding 510(k) and NSE.
    (Comment 9) A comment objects to making De Novo devices immediately 
available as a predicate device because the commenter suggests that it 
puts patient safety at risk and does not reward innovation. The 
commenter proposes a ``safe harbor'' of several years where the De Novo 
device cannot be used as a predicate.
    (Response 9) FDA disagrees with this comment. Section 513(f)(2) of 
the FD&C Act provides that any device classified through the De Novo 
pathway ``shall be a predicate device for determining substantial 
equivalence'' and does not impose a waiting period for such devices to 
be used as predicates.

C. Comments and FDA Response on Use of Advisory Committees and Bundling 
Devices

    (Comment 10) A comment requests FDA to revise Sec.  860.1 to limit 
the use of advisory committees to cases of high-risk, life-supporting, 
or life-sustaining devices, or to classification panels because the 
commenter states that referring a De Novo request to an advisory 
committee should be unusual, as the devices that are the subject of 
such requests generally present low to moderate risk.

[[Page 54831]]

    (Response 10) We disagree with this proposed revision. This comment 
is directed specifically to the De Novo classification process, and 
Sec.  860.1 applies to both premarket and postmarket classifications 
and reclassifications. In addition, we do not agree that the only time 
we should seek advice from an advisory committee is in cases of high-
risk, life-supporting, or life-sustaining devices, or in a 
classification panel; FDA may refer a matter to an advisory committee 
because it chooses to do so at its own discretion (see our guidance 
``Procedures for Meetings of the Medical Devices Advisory Committee'' 
(Ref. 7).) For example, the Agency may present a matter before an 
advisory committee if the matter is of significant public interest or 
there is additional or special expertise provided by the panel that 
could assist FDA in its decision making.
    (Comment 11) A comment asks FDA to revise the De Novo ``Purpose and 
applicability'' provision (the final rule renumbers the proposed Sec.  
860.201(b) as Sec.  860.200(b)) to clarify that a De Novo request may 
also be submitted for a group of related devices because a commenter 
states that, in some cases, more than one related device should be 
submitted for De Novo classification.
    (Response 11) FDA disagrees with this comment. Generally, it is not 
appropriate to bundle multiple devices in a single De Novo request. For 
example, FDA would not grant a De Novo request that would require FDA 
to create more than one classification regulation. If an applicant 
feels that they have a situation where it makes logical sense to bundle 
multiple devices into one De Novo request, it would be advisable to 
discuss proactively with FDA in advance of submission of the De Novo 
request.

D. Comments and FDA Response on De Novo Request Information Disclosure

    (Comment 12) A comment requests that FDA revise the De Novo file 
confidentiality provision in Sec.  860.5(g) so that it follows the 
approach for PMAs concerning confidentiality because the commenter 
asserts requesters are entitled to maintain confidentiality for 
information submitted to FDA through the De Novo process even if some 
information relating to the De Novo request has been disclosed 
publicly. Another comment requests that FDA revise the provision 
regarding disclosure of the existence of a De Novo request before an 
order granting the request is issued to clarify that such disclosure is 
governed by the trade secrets and confidential commercial information 
provisions in Sec.  20.61 (21 CFR 20.61). A different comment questions 
why CDRH could not disclose the existence of a De Novo request and the 
date of its acceptance for review or the date it was refused.
    (Response 12) FDA is making minor revisions to refer to the ``De 
Novo file'' instead of the ``De Novo request'' in four places in Sec.  
860.5(g) for consistency with the language used in Sec.  860.5(g)(1) 
and to align with similar language used in 21 CFR 814.9 regarding 
confidentiality of information in a PMA file. FDA otherwise disagrees 
with the comments requesting revision of the proposed De Novo request 
confidentiality requirements. The provisions in Sec.  860.5(g)(2) and 
(3) provide that, before an order granting the De Novo request is 
issued, FDA may not publicly disclose the existence of or data and 
information contained in a De Novo file, unless such information has 
already been publicly disclosed or acknowledged by the De Novo 
requester. Therefore, if a requester publicly acknowledges only the 
date and existence of a De Novo request submission, that acknowledgment 
would not, by itself, make underlying data and information in the De 
Novo file publicly available for disclosure under Sec.  860.5(g). 
Further, the requester cannot have confidentiality concerns about 
information it has already publicly disclosed. This approach is 
concordant with FDA's general public information regulations at Sec.  
20.61 and Sec.  20.81 (21 CFR 20.81). Under Sec.  20.61, information 
submitted to FDA that qualifies as trade secret or confidential 
commercial information is generally exempt from public disclosure, but 
Sec.  20.81 provides that records otherwise exempt from disclosure are 
available for public disclosure to the extent that they ``contain data 
or information that have previously been disclosed in a lawful manner 
to any member of the public, other than an employee or consultant or 
pursuant to other commercial arrangements with appropriate safeguards 
for secrecy.''
    Regarding why FDA will not disclose the existence of a De Novo 
request that has not been publicly disclosed or acknowledged, 
disclosing the existence of the De Novo request would disclose the 
requester's intent to market the device. Consistent with FDA's approach 
in other premarket programs, we generally consider an applicant's 
intent to market a device to be confidential commercial information 
where the applicant has kept that intent confidential. This approach is 
supported by the Supreme Court's recent decision in Food Mktg. Inst. v. 
Argus Leader Media, 139 S. Ct. 2356, 2363 (2019).
    (Comment 13) Some comments requested more clarity on how and when 
data and information may be disclosed by FDA, and some comments 
suggested that the data and information disclosed after FDA issues an 
order granting a De Novo request should only be available following a 
FOIA request. A commenter also recommended changes to clarify that the 
requester would have an opportunity to review and redact trade secret 
information before the release of any data and information in the De 
Novo request. Another commenter recommended that CDRH draft and post on 
its website a summary of the information submitted to support FDA's 
classification determination and require De Novo requesters to prepare 
summaries of data and information submitted to support the safety and 
effectiveness of the specific device that could be posted in FDA's De 
Novo database to align with public disclosure of 510(k) and PMA 
summaries.
    (Response 13) As discussed in response to the previous comment, 
prior to sending an order granting the De Novo request to the De Novo 
requester, FDA will not disclose the data or information contained in 
the De Novo file, unless the De Novo requester has publicly disclosed 
or acknowledged such information (Sec.  860.5(g)(3)). To provide more 
clarity and to help ensure that information exempt from release is 
appropriately protected, we are revising Sec.  860.5(g)(4) to make 
clear that after FDA sends an order granting the De Novo request to the 
De Novo requester, FDA may immediately disclose any safety and 
effectiveness information and any other information in the De Novo file 
that is not exempt from release under FOIA.
    FDA disagrees with the comments requesting FDA to limit the release 
of data and information contained in a granted De Novo request to 
situations in which the Agency has received a FOIA request for that 
information. FDA proactively discloses information of interest to the 
public on a regular basis. For example, granting a De Novo request 
allows marketing of the particular device that is the subject of the 
request, creates a classification regulation for devices of this type, 
and permits the device to serve as a predicate device (section 
513(f)(2) of the FD&C Act; Ref. 5). FDA believes that information 
regarding granted De Novo requests and summaries of safety and 
effectiveness information that formed the basis of FDA's granting 
decisions should be publicly posted without waiting to receive a FOIA 
request for that

[[Page 54832]]

information. With respect to affording requesters an opportunity to 
review and redact records that may contain trade secret information 
before they are disclosed, FDA will follow its existing pre-disclosure 
notification requirements in Sec.  20.61.
    Since 2010, FDA has posted on its website classification orders and 
redacted decision summary documents for devices classified through the 
De Novo classification process. This approach is analogous to our 
current approach for other marketing authorization pathways: summaries 
of safety and effectiveness information that formed the basis of FDA's 
decisions are posted on FDA's website for PMA approvals, available at 
https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMA/pma.cfm; and 
for 510(k) clearances, 510(k) summaries are available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMN/pmn.cfm. We believe 
the comment suggesting that FDA require a De Novo requester to prepare 
a summary of safety and effectiveness information for public posting to 
align with PMA and 510(k) procedures confuses the requirement for a PMA 
to include a summary that allows the reader to gain a general 
understanding of the data and information in the application (Sec.  
814.20 (21 CFR 814.20(b)(3))) with the publicly posted detailed summary 
of safety and effectiveness data (SSED) on which an approval or denial 
decision is based for a PMA. Although some PMA applicants may submit 
draft SSEDs, the final SSEDs posted online are FDA documents. The De 
Novo decision summary is intended to present an objective and balanced 
summary of the scientific evidence that served as the basis for the 
decision to grant a De Novo request. Because the Agency already 
prepares such documents and determines what information supports its 
decision to grant the De Novo request, FDA is not revising the final 
rule to require requesters to prepare a similar summary, as this 
commenter requests. We believe the information that the commenter 
indicates would be of interest to healthcare providers and patients is 
already made publicly available through FDA's current approach.

E. Comments and FDA Response on Facility Inspections

    (Comment 14) A comment supported facility inspection prior to 
granting or declining a De Novo request because the commenter states 
that it is essential for safety in the case of novel medical devices. 
Several comments wanted to delete either all of subsection Sec.  
860.240(c) (this final rule renumbers proposed Sec.  860.256(c) as 
Sec.  860.240(c)) or paragraph Sec.  860.240(c)(2) (this final rule 
renumbers proposed Sec.  860.256(c)(2) as Sec.  860.240(c)(2)) or 
revise subsection Sec.  860.240(c) because the commenters state these 
provisions are unduly burdensome or that FDA lacks statutory authority 
to require facility inspections to assess implementation of the QSR 
(part 820).
    (Response 14) Several comments objected to proposed Sec.  
860.256(c) (this final rule renumbers proposed Sec.  860.256(c) as 
Sec.  860.240(c)), which relates to the inspection of relevant 
facilities prior to granting or declining a De Novo request and argued 
that the FD&C Act does not give FDA this inspection authority. FDA 
disagrees with the comments, and, as described below, is finalizing the 
provision with clarifying changes. The inspection would be done only in 
the two circumstances specified in the regulation. Based on past 
experience, inspections in these circumstances should arise with a 
small percentage of De Novo requests.
1. Clinical and Nonclinical Data
    As explained in the proposed rule preamble, an inspection prior to 
its De Novo decision is used to help FDA determine whether clinical or 
nonclinical data were collected in a manner that ensures the data 
accurately represents the risks and benefits of the device, in 
accordance with section 513(a)(1)(C) of the FD&C Act. FDA has been 
conducting such inspections when data integrity and quality concerns 
arise during its review of a De Novo request, and information from 
these inspections has been critically important to the Agency's De Novo 
determination. For example, based on review of the clinical data 
provided in the De Novo request, FDA may determine that the results of 
a clinical investigation are clinically or physiologically improbable. 
An inspection may be conducted to verify the integrity of the data.
    In another example, FDA may receive a whistleblower complaint 
alleging misconduct at one or more clinical investigational sites, and 
the results from the clinical investigation are used to support a De 
Novo request. Our assessment of the subject device is dependent on the 
veracity of the complaint. FDA inspections of one or more 
investigational sites to assess the veracity of the complaint would 
help determine whether evidence submitted in support of the De Novo 
request (e.g., data from a particular site) needs to be excluded from 
FDA's consideration.
2. Quality System Regulation and Current Good Manufacturing Practices
    For certain devices with critical and/or novel manufacturing 
processes that may impact the safety and effectiveness of the device, 
FDA also believes that an inspection may be necessary for FDA to 
determine whether general controls, including the QSR (part 820) for 
devices and current good manufacturing practices (21 CFR part 4, 
subpart A) for combination products, are adequate to provide a 
reasonable assurance of safety and effectiveness of the device, or 
whether special controls to mitigate risks must be developed. Such 
inspections are not for the purpose of reviewing for compliance with 
the QSR. Rather, the purpose of such an inspection is to gather 
information on critical and/or novel manufacturing processes, the 
methods and procedures used, and such additional information as may be 
necessary to assess the safety and effectiveness of a drug or biologic 
constituent part of a combination product. Such information will help 
classify the device type by providing an understanding of critical and/
or novel manufacturing processes to determine if the device type is of 
low to moderate risk, to determine if general controls and special 
controls can effectively mitigate the probable risks to health, and to 
determine if the product specifications can reasonably be met. In some 
circumstances, this information can only be obtained by an inspection--
and not any other means, such as through review of standard operating 
procedures--because it requires a detailed understanding of how 
manufacturers, in practice, carry out complex and/or safety critical 
processes, methods, or procedures. In these situations, the information 
obtained from an inspection would be necessary for FDA to make a De 
Novo determination.
    For example, FDA may receive a De Novo request for a permanent 
implant with a coating that contains the same active ingredient that is 
in a new drug application (NDA) approved drug product. The combination 
product is intended to reduce the risk of surgical site infections. The 
safety and effectiveness of the combination product is linked to the 
ability of the manufacturer to ensure consistent levels of drug coating 
and drug release batch-to-batch. Probable risks associated with 
inconsistent coating or inconsistent drug release may include local/
systemic toxicity, reproductive/genotoxicity, antibiotic resistance, 
and infection. An inspection would help assess the sampling methodology 
and laboratory

[[Page 54833]]

controls used by the manufacturer to ensure consistent levels of drug 
coating and drug release batch-to-batch. Such information would be 
critical to FDA in its De Novo determination because assessment of the 
sampling methodology and laboratory controls at the manufacturing 
facility would aid in FDA's determination that the product has 
consistent levels of drug coating and drug release batch-to-batch. This 
information would enable FDA to determine whether the proposed special 
controls are sufficient to reasonably assure safety and effectiveness 
or if additional controls are needed.
    In another example, FDA may receive a De Novo request for a device 
that is provided sterile using a novel sterilization method for which 
there is little or no published information and limited or no history 
of FDA evaluation of sterilization development and/or validation data. 
Probable risks associated with inadequate sterilization may include 
risk of infection or contamination. An inspection of the facility where 
the device is sterilized would be critical to determining if special 
controls regarding sterilization validation are sufficient to mitigate 
the device's probable risks, verify that the novel sterilization method 
can feasibly be carried out, and determine if additional controls are 
needed to mitigate the risks associated with inadequate sterilization 
to reasonably assure the device's safety.
    One commenter objected to inspections used to assess whether QSRs 
are adequate to ensure that critical and/or novel manufacturing 
processes that may impact the safety and effectiveness of the device 
are controlled on the grounds that such inspections require either a 
warrant or specific statutory authorization under the Constitution. 
Section 704(a)(1) of the FD&C Act grants FDA authority to enter and 
inspect ``any factory, warehouse, or establishment in which food, 
drugs, or devices are manufactured, processed, packed, or held for the 
introduction into interstate commerce or after such introduction.'' 21 
U.S.C. 374. In addition, FDA intends to undertake inspections only in 
limited circumstances when the inspection is to help determine whether 
to grant a De Novo request from a firm and determine whether the 
proposed special controls are sufficient to reasonably assure safety 
and effectiveness or if additional controls are needed under section 
513(f)(2) of the FD&C Act.

F. Comments and FDA Response on Definitions

    (Comment 15) A comment proposed several changes to the 
``Supplemental data sheet'' definition because not all implanted 
devices are class III, and another comment recommended changes to Form 
FDA 3429 (General Device Classification Questionnaire).
    (Response 15) These comments are moot because, in a separate 
rulemaking (see 83 FR 64443 at 64454 through 64456, December 17, 2018, 
effective March 18, 2019), the definitions for the terms ``Supplemental 
data sheet'' and ``Classification questionnaire'' were removed from 
Sec.  860.3 and the prior requirements to provide Form FDA 3427 
(Supplemental Data Sheet) and Form FDA 3429 (General Device 
Classification Questionnaire) were removed from Sec. Sec.  860.84 and 
860.123.
    (Comment 16) A comment requests that FDA keep the individual 
paragraph designations in the definitions section (Sec.  860.3) because 
the commenter states it is helpful to industry to be able to cite a 
specific term by paragraph designation.
    (Response 16) FDA disagrees with this comment. FDA believes it 
would be easier for industry to locate definitions listed 
alphabetically. FDA has taken a similar approach in its labeling and 
unique device identification regulations (see 21 CFR 801.3 and 830.3). 
FDA further believes that it is not difficult to cite to alphabetical 
definitions within Sec.  860.3.

G. Comments and FDA Response on De Novo Request Format

    (Comment 17) A comment asks FDA to revise the proposed De Novo 
request format requirements to clarify that the application can be a 
single version in electronic format, conforming it to FDA's proposed 
rule, ``Medical Device Submissions: Amending Premarket Regulations That 
Require Multiple Copies and Specify Paper Copies To Be Allowed in 
Electronic Format'' (83 FR 46444, September 13, 2018).
    (Response 17) FDA agrees that a De Novo request may be submitted as 
a single version in electronic format, which is currently eCopy and, in 
the future, may be a different electronic format. De Novo requests 
currently must be submitted as a single eCopy, in accordance with 
section 745A(b)(1) of the FD&C Act (21 U.S.C. 379k-1(b)(1)) and FDA's 
guidance, ``eCopy Program for Medical Device Submissions,'' issued 
April 27, 2020 (Ref. 8). Section 745A(b)(3) of the FD&C Act requires 
the presubmission and submission types enumerated in section 745A(b)(1) 
(including De Novo requests), any supplements to such presubmissions or 
submissions for devices, and any appeals of action taken with respect 
to such presubmissions or submissions, including devices under the 
Public Health Service Act, to be submitted solely in electronic format 
as specified by FDA in guidance. Once FDA issues guidance under section 
745A(b)(3) of the FD&C Act, the Agency can require De Novo request 
submissions in electronic formats other than eCopy. We are revising 
paragraph Sec.  860.210(a) (this final rule renumbers proposed Sec.  
860.223(a) as Sec.  860.210(a)) to require submission of a De Novo 
request as a single version in electronic format).
    (Comment 18) A commenter states it is overly prescriptive to 
require a specific format for a De Novo request.
    (Response 18) We do not agree that the format FDA is requiring is 
overly prescriptive. Section 860.210 (this final rule renumbers 
proposed Sec.  860.223 as Sec.  860.210), the format section, requires 
that the De Novo request be signed by the requester or an authorized 
representative, be designated as a ``De Novo request,'' and be written 
or translated into English. FDA believes it is easier for FDA reviewers 
to find required information if the De Novo request information is 
provided in a specific format, thereby facilitating more efficient 
review and processing of the request.
    (Comment 19) Because a De Novo request may contain only one volume, 
a comment asks FDA to revise the De Novo request format paragraph to 
qualify that the table of contents of a De Novo request reference a 
volume number only if the De Novo request contains more than one 
volume.
    (Response 19) FDA agrees that it is unnecessary to cite the volume 
if the De Novo request does not contain more than one volume. We are 
revising paragraph Sec.  860.220(a)(1) (this final rule renumbers 
proposed Sec.  860.234(a)(1) as Sec.  860.220(a)(1)) accordingly.

H. Comments and FDA Response on De Novo Request Content

    (Comment 20) Some comments request FDA to revise the ``Device 
description'' provision at Sec.  860.220(a)(6)(ii) ((this final rule 
renumbers proposed Sec.  860.234(a)(6)(ii) as Sec.  860.220(a)(6)(ii)) 
because the commenters state some of the terminology is more typically 
used to describe drugs than devices. The commenters suggest that 
``component'' is more applicable to devices than ``ingredient,'' and 
that some components may not be ``functional'' but may still be 
important to a De Novo

[[Page 54834]]

classification decision. A commenter states the term ``principal 
components'' is appropriate because it signals that the submitter 
should identify the device's primary components but need not identify 
every component. Another commenter similarly suggests the term ``major 
components'' would be appropriate.
    (Response 20) FDA disagrees that ingredient is an atypical term for 
a device. For example, in vitro diagnostic device labels generally are 
required to include the quantity, proportion, or concentration of each 
reactive ingredient for a reagent (21 CFR 809.10(a)(3)).
    In addition, FDA does not agree with requiring only a device's 
principal or major components to be described in a De Novo request. FDA 
is requesting identification of all functional components or 
ingredients that comprise the subject device or combination product so 
that FDA has sufficient understanding of the device to evaluate whether 
general controls or general and special controls are sufficient to 
provide reasonable assurance of safety and effectiveness. We would 
consider any component of the device relating to how the device 
operates be a functional component. It was not our intent to limit the 
identification of the components or ingredients of the device or 
combination product. To that end, we disagree with the commenters' 
proposed edits to require identification of only major or principal 
components.
    (Comment 21) Comments on the summary of studies (this final rule 
renumbers proposed Sec.  860.234(a)(13)(ii) as Sec.  
860.220(a)(13)(ii)), the technical sections (this final rule renumbers 
proposed Sec.  860.234(a)(15)(i) and (iii) as Sec.  860.220(a)(15)(i) 
and (iii)), and the bibliography (this final rule renumbers proposed 
Sec.  860.234(a)(16)(i) as Sec.  860.220(a)(16)(i)) that are part of 
the required content of a De Novo request ask that FDA limit the 
required information to that ``necessary to determine the 
classification of the device.'' The commenter states that it is 
necessary to clarify that data unrelated to classification of the 
device (e.g., for other indications) do not need to be submitted and 
that the focus of the application is to determine the classification of 
the device.
    (Response 21) FDA does not agree with these comments and does not 
believe the requested clarifications are necessary. Under the FD&C Act, 
FDA determines the classification of a device that is the subject of a 
De Novo request (section 513(f)(2) of the FD&C Act). The requirements 
for the content of a De Novo request reflect the information that, in 
FDA's experience, generally is necessary to determine if general or 
general and special controls are sufficient to provide a reasonable 
assurance of safety and effectiveness of the device that is the subject 
of the De Novo request. To the extent the requester believes that 
certain required content for a De Novo request is not applicable to its 
device, the requester has the option under Sec.  860.220(c) (this final 
rule renumbers proposed Sec.  860.234(c) to Sec.  860.220(c)) to omit 
that information and submit a statement that specifies the omitted 
information and justifies the omission. FDA will notify the requester 
if it does not accept the justification.
    Further, Sec.  860.220(a)(15) (this final rule renumbers proposed 
Sec.  860.234(a)(15) as Sec.  860.220(a)(15)) already specifies that 
the required technical sections must include data and information ``in 
sufficient detail to permit FDA to determine whether to grant or 
decline the De Novo request.'' Therefore, we believe it is already 
clear the information required in the technical sections under Sec.  
860.220(a)(15)(i) and (iii) (the final rule renumbers proposed Sec.  
860.234(a)(15)(i) and (iii) as Sec.  860.220(a)(15)(i) and (iii)) and 
the related summary of studies under Sec.  860.220(a)(13) (the final 
rule renumbers proposed Sec.  860.234(a)(13) as Sec.  860.220(a)(13)) 
is information focused on FDA's classification determination. In 
addition, the bibliography of published reports required under Sec.  
860.220(a)(16)(i) (the final rule renumbers proposed Sec.  
860.234(a)(16)(i) as Sec.  860.220(a)(16)(i)) is limited to reports 
``that concern the safety or effectiveness of the device.'' Published 
reports concerning the safety or effectiveness of the device that is 
the subject of the De Novo request would be useful to FDA's evaluation 
of the request.
    (Comment 22) Some comments object that FDA's proposed requirements 
for the data and information submitted in a De Novo request are overly 
broad or potentially confusing. One commenter supports requirements for 
a thorough review of existing data but requests that the requirement to 
submit '' `all' available data . . . should be clarified to indicate 
that which is reasonably attainable by'' the De Novo requester. Other 
commenters request that FDA change the phrase ``known or reasonably 
known'' in certain provisions of Sec.  860.220(a) (this final rule 
renumbers proposed Sec.  860.234(a) to Sec.  860.220(a)) to ``known or 
reasonably available to'' the requester. These commenters indicate that 
the ``known or reasonably known'' standard does not clarify to whom the 
required information is known or reasonably known. A commenter also 
indicates that the proposed language could lead FDA reviewers to decide 
a De Novo requester is ``hiding something'' if the submission lacks 
information known to the reviewer but not the requester. Another 
commenter states that use of the term ``reasonably available'' instead 
would ``impl[y] that the sponsor must engage in reasonable effort to 
obtain the relevant information.''
    (Response 22) FDA did not include provisions in the proposed rule 
using the phrase ``all available data'' as one comment suggests, but we 
believe limiting all of the required information for a De Novo request 
to that ``reasonably attainable by'' the requester is inappropriate. In 
some cases, for example, a requester may know of studies or reports 
concerning the safety or effectiveness of the device but be unable to 
obtain them for some reason (e.g., the requester must pay to gain 
access to a registry containing the relevant data). In these cases, it 
is still useful to provide to FDA the information about such studies or 
reports that is known or reasonably should be known to the requester, 
even if complete information about or copies of such studies or reports 
is unavailable to the requester. For example, FDA may have a greater 
ability to access a publication with more complete information.
    In response to these comments, FDA is revising Sec.  860.220(a)(7) 
and (9) (this final rule renumbers proposed Sec.  860.234(a)(7) as 
Sec.  860.220(a)(7) and renumbers Sec.  860.234(a)(11) as Sec.  
860.220(a)(9)) to clarify that the information required is that known 
to or that reasonably should be known to the requester. The intent of 
requiring a De Novo request to include information that is known or 
reasonably known to the requester is to ensure that the requester 
engages in a reasonable effort to provide relevant information and does 
not omit information important to FDA's determination to grant or 
decline the De Novo request because of a failure to conduct reasonable 
searches for such information. As explained in the proposed rule, for 
example, the summary of known or reasonably known probable risks to 
health associated with the use of the device required in the De Novo 
request under Sec.  860.220(a)(9) ``should be based on the best 
available information at the time of submission of the De Novo 
request.'' (83 FR 63127 at 63133) These requirements help ensure that 
FDA's evaluation of a

[[Page 54835]]

De Novo request is based on complete and quality information and 
minimize review staff's need to request additional information. We 
believe the term ``should reasonably be known'' appropriately captures 
the intent of these requirements.
    (Comment 23) A comment requests that FDA provide more flexibility 
in the standard for valid scientific evidence for De Novo devices as a 
way to address lower risk devices, rather than requiring only less-
detailed summary information for some components of a complete De Novo 
request.
    (Response 23) FDA disagrees with the comment. As in other device 
classification processes, FDA relies upon valid scientific evidence in 
determining the safety and effectiveness of a device that is the 
subject of a De Novo request (Sec.  860.260(e) (this final rule 
renumbers proposed Sec.  860.289(d) as Sec.  860.260(e)). This is 
unchanged by the requirement to provide summaries of certain 
information as part of a De Novo request. In addition, the required 
content of a De Novo request must include, in addition to such 
summaries, technical sections containing nonclinical study results, 
software information and testing, and clinical investigation results 
with sufficient detail to allow FDA to make a determination on the De 
Novo request.
    Regarding the commenter's request for ``flexibility'' in the 
standard for valid scientific evidence, FDA does not believe any change 
is necessary. FDA's regulatory definition of valid scientific evidence 
already makes clear that ``[t]he evidence required may vary according 
to the characteristics of the device, its conditions of use, the 
existence and adequacy of warnings and other restrictions, and the 
extent of experience with its use'' (Sec.  860.7(c)(2)). FDA has also 
issued guidance explaining its approach to making benefit-risk 
determinations in the context of De Novo requests, which is a flexible, 
patient-centric approach tailored to the type and intended use of the 
device. See our guidances ``Factors to Consider When Making Benefit-
Risk Determinations in Medical Device Premarket Approval and De Novo 
Classifications'' (Ref. 3) and ``Consideration of Uncertainty in Making 
Benefit-Risk Determinations in Medical Device Premarket Approvals, De 
Novo Classifications, and Humanitarian Device Exemptions'' (Ref. 9).
    (Comment 24) A commenter states FDA should focus on device design 
to improve device safety. The same commenter asserts that all premarket 
applications (PMA, 510(k), and De Novo requests) should include a 
design and development plan, design input, output, design reviews, 
verification, validation, transfer, and all design changes.
    (Response 24) FDA agrees that device design is important to device 
safety. Manufacturers are already required under part 820 (QSR) to 
focus on device design (Sec.  820.30, Design controls). Additionally, 
FDA may require additional verification or validation information for 
specific design features or inspect relevant facilities, where 
appropriate (Sec.  860.240, this final rule renumbers proposed Sec.  
860.256 as Sec.  860.240).
    (Comment 25) Because a commenter notes that ``manufacturer'' is 
used elsewhere in the proposed rule and because some commenters state 
that many companies no longer use Fax machines, the comments request 
that FDA revise the ``Administrative information'' provision of the De 
Novo request content section to add a reference to ``manufacturer,'' in 
addition to owners and operators, and to remove the reference to Fax 
machines from Sec.  860.220(a)(2) (this final rule renumbers proposed 
Sec.  860.234(a)(2) as Sec.  860.220(a)(2)).
    (Response 25) FDA agrees to remove the reference to Fax machines 
and is revising paragraph Sec.  860.220(a)(2) (this final rule 
renumbers proposed Sec.  860.234(a)(2) as Sec.  860.220(a)(2)) 
accordingly. However, we do not agree that it is necessary to add a 
reference to ``manufacturer'' in this provision. In the final rule, 
Sec.  860.220(a)(2) requires that the De Novo request include the 
establishment registration number of the owner or operator submitting 
the De Novo request, if applicable, because certain ``owners or 
operators,'' as defined in 21 CFR 807.3(f), are the entities required 
to register and submit listing information under 21 CFR part 807. Use 
of the terms ``owner'' and ``operator'' in Sec.  860.220(a)(2) does not 
mean that a device manufacturer is unable to submit a De Novo request. 
The registration and listing requirements apply to owners or operators 
of establishments who are ``engaged in the manufacture, preparation, 
propagation, compounding, assembly, or processing of a device intended 
for human use,'' unless they are exempt under 510(g) of the FD&C Act or 
FDA regulations (see 21 CFR 807.20).
    (Comment 26) A comment requests FDA revise the indications for use 
paragraph (Sec.  860.220(a)(5), this final rule renumbers the proposed 
Sec.  860.234(a)(5) as Sec.  860.220(a)(5)) in the De Novo request 
content section to include references to intended use and the meaning 
of that term for the purpose of determining substantial equivalence 
because intended use will be relevant to 510(k) submissions made after 
FDA grants a De Novo request. The commenter also suggests the revisions 
would align more closely with the PMA requirements in Sec.  
814.20(b)(3).
    (Response 26) FDA does not agree with this comment and believes 
that the indications for use requirement is aligned with Sec.  
814.20(b)(3)(i) and the definitions in Appendix D of FDA's guidance, 
``The 510(k) Program: Evaluating Substantial Equivalence in Premarket 
Notifications [510(k)]'' (Ref. 10).
    (Comment 27) A few commenters state it is unnecessary and places a 
potentially unrealistic burden on the De Novo requester to provide a 
``complete'' device description; the comments request FDA require a 
``device description.''
    (Response 27) FDA disagrees with these comments and is retaining 
the word ``complete'' in Sec.  860.220(a)(6) (this final rule renumbers 
the proposed Sec.  860.234(a)(6) as Sec.  860.220(a)(6)). The word 
``complete'' is appropriate in this context and not overly burdensome. 
FDA does not expect an excessively detailed description of the device, 
but there must be sufficient detail to describe the aspects of the 
device that could affect safety or effectiveness. A complete device 
description is necessary for FDA to classify a device.
    (Comment 28) Comments on the requirement to describe alternative 
practices (Sec.  860.220(a)(7), this final rule renumbers proposed 
Sec.  860.234(a)(7) as Sec.  860.220(a)(7)) either support the 
requirement as facilitating classification and improving transparency, 
or request revisions to reduce the burden of describing known or 
reasonably known alternative practices and procedures. The comments 
suggest revising the provision to instead ask for a summary related to 
the standard of care for a disease or condition for which the device is 
indicated as it bears on the device's proposed classification or 
assessment of probable benefits and risks.
    (Response 28) FDA disagrees with the comments to limit the 
description of alternative practices. We do not believe this 
requirement requires extensive unnecessary efforts, as some of the 
commenters suggest. As explained in the proposed rule, this requirement 
is intended to capture alternative biologic, device, or drug practices 
or procedures. An understanding of available alternative practices or 
procedures that are used to diagnose, treat, prevent, cure, or mitigate 
the disease or condition for which the device is

[[Page 54836]]

intended or that similarly affect the structure or function of the body 
is one of the factors FDA considers in its benefit-risk assessments to 
determine the appropriate classification for a device. For example, for 
a device indicated to treat a rare condition for which there are no 
alternative treatments, FDA may accept greater uncertainty in the 
evidence regarding the device's probable benefits and probable risks. 
Furthermore, FDA does not agree with the assumption that a standard of 
care exists for all diseases or conditions for which a device is 
intended.
    (Comment 29) Comments request that FDA rearrange the order of the 
provisions in proposed Sec.  860.234(a)(9) through (11) (this final 
rule renumbers proposed Sec.  860.234(a)(9) as Sec.  860.220(a)(11) and 
this final rule renumbers proposed Sec.  860.234(a)(11) as Sec.  
860.220(a)(9)). Commenters suggest that the risks and mitigations form 
the basis for the classification recommendation and accordingly request 
that the Summary of risks and mitigations provision (proposed Sec.  
860.234(a)(11) precede the Classification recommendation provision 
(proposed Sec.  860.234(a)(9)). Commenters further suggest that the 
Proposed special controls provision (proposed Sec.  860.234(a)(10)) 
should immediately follow the Summary of risks and mitigations 
provision to demonstrate whether specific mitigations are general and/
or special controls.
    (Response 29) The order in proposed Sec.  860.234(a)(9) through 
(11) follows the order in which section 513(f)(2)(A)(v) of the FD&C Act 
discusses corresponding items. However, we believe the commenters' 
proposed changes make sense. Accordingly, we are revising the order of 
the paragraphs as follows:
     Sec.  860.220(a)(9) Summary of risks and mitigations;
     Sec.  860.220(a)(10) Proposed special controls; and
     Sec.  860.220(a)(11) Classification recommendation.
    (Comment 30) A comment supports the requirement for a summary of 
known or reasonably known probable risks, while another comment 
suggests that the De Novo request include both a summary and a 
discussion of the probable risks and mitigations identified through a 
formal risk analysis.
    (Response 30) FDA agrees with the comment supporting the 
requirement for a De Novo request to include a summary of known or 
reasonably known probable risks, but FDA believes that requiring both a 
summary and a discussion of these probable risks and proposed 
mitigations is unnecessary. The De Novo request will be required to 
summarize probable risks to health associated with use of the device 
that are known or should reasonably be known to the requester and the 
proposed mitigations. For each mitigation measure that involves 
specific performance testing or labeling, the request must reference 
the associated section or pages of the supporting information, such as 
supporting protocols and/or testing data. FDA believes such information 
is sufficient to assist the Agency in identifying the probable risks to 
health and in evaluating the proposed risk mitigation measures to 
determine whether general controls or general and special controls can 
provide reasonable assurance of safety and effectiveness. Furthermore, 
FDA requires a related discussion demonstrating that the probable 
benefit to health outweighs the probable risks of the De Novo device in 
Sec.  860.220(a)(14) (this final rule renumbers the proposed Sec.  
860.234(a)(14) as Sec.  860.220(a)(14)).
    (Comment 31) A comment requests that FDA revise the standards 
paragraph to clarify that De Novo requesters are not required to 
declare conformity to standards referenced in the De Novo request.
    (Response 31) The standards paragraph at Sec.  860.220(a)(12) (this 
final rule renumbers the proposed Sec.  860.234(a)(12) as Sec.  
860.220(a)(12)) does not require that De Novo requesters submit a 
declaration of conformity to the referenced standard, so the requested 
clarification is not necessary. See our guidance, ``Appropriate Use of 
Voluntary Consensus Standards in Premarket Submissions for Medical 
Devices'' (Ref. 11) for additional information on how to use consensus 
standards in premarket submissions, including information for those 
choosing to rely on a consensus standard in a declaration of conformity 
to meet a premarket submission requirement.
    (Comment 32) A commenter states that the bibliography of all 
published reports concerning the safety or effectiveness of the device 
not submitted under the technical sections of the De Novo request 
(Sec.  860.220(a)(16)(i), this final rule renumbers proposed Sec.  
860.234(a)(16)(i) as Sec.  860.220(a)(16)(i)) and the identification, 
discussion, and analysis of any other data, information, or report 
relevant to an evaluation of the safety and effectiveness of the device 
(Sec.  860.220(a)(16)(ii), this final rule renumbers proposed Sec.  
860.234(a)(16)(ii) as Sec.  860.220(a)(16)(ii)) should be provided to 
FDA for consideration.
    (Response 32) FDA agrees with the comment and believes that 
providing a bibliography of all published reports concerning the safety 
or effectiveness of the device not submitted under the technical 
sections of the De Novo request, as required by Sec.  
860.220(a)(16)(i), and the information on other data, information, or 
reports relevant to an evaluation of the safety and effectiveness of 
the device required under Sec.  860.220(a)(16)(ii) will be useful to 
FDA's assessment of safety and effectiveness.
    (Comment 33) A comment opposed authorizing implanted medical 
devices for marketing through the De Novo pathway without long-term 
controlled clinical trials because the commenter states patients 
deserve long-term safety and effectiveness data. A comment further 
recommends FDA require information about changes to the research 
protocol and statistical methodology in the summary of studies 
submitted in the De Novo request because the commenter states the 
information is important for evaluating the quality of the study.
    (Response 33) FDA disagrees that long-term controlled clinical 
trials must be required across all implanted medical devices. In 
reviewing a De Novo classification request, studies other than long-
term controlled clinical trials may also constitute valid scientific 
evidence that FDA can rely upon in making a benefit-risk determination 
for an implanted device, as discussed in our guidance ``Factors to 
Consider When Making Benefit-Risk Determinations in Medical Device 
Premarket Approval and De Novo Classifications'' (Ref. 3). ``Valid 
scientific evidence'' is defined in section 513(a)(3) of the FD&C Act 
and Sec.  860.7(c)(2). Valid scientific evidence, as discussed in Sec.  
860.7(c)(2), includes ``partially controlled studies, studies and 
objective trials without matched controls, well-documented case 
histories conducted by qualified experts, and reports of significant 
human experience with a marketed device.'' FDA does not believe long-
term, controlled clinical studies are necessary to demonstrate that 
general controls or general and special controls will provide a 
reasonable assurance of safety and effectiveness for all implantable 
devices reviewed through the De Novo pathway. For example, some devices 
are intended to be implanted for a relatively short period of time 
(e.g., 30 days) and then removed from the body; longer term clinical 
data therefore may not be needed to assess

[[Page 54837]]

the safety and effectiveness of these devices when used as intended.
    Requiring these studies for all implantable devices is also 
inconsistent with FDA's least burdensome approach to medical device 
regulation, which is intended to eliminate unnecessary burdens that may 
delay the marketing of beneficial new products, while maintaining the 
statutory requirements for marketing authorization. As discussed in 
FDA's guidance, ``The Least Burdensome Provisions: Concept and 
Principles'' (Ref. 12), FDA typically follows a stepwise analytical 
process when requesting additional information to make a decision on a 
marketing submission to ensure the information requested reflects the 
least burdensome approach. FDA typically requests clinical data when 
analytical or nonclinical bench performance testing data, or 
nonclinical animal \1\ and/or biocompatibility studies are 
insufficient, or available scientific methods are not acceptable, e.g., 
the scientific methods are deemed unacceptable because they are not 
clinically validated or are not supported by a valid scientific 
rationale.
---------------------------------------------------------------------------

    \1\ FDA supports the principles of the ``3Rs,'' to reduce, 
refine, and replace animal use in testing when feasible. We 
encourage sponsors to consult with us if it they wish to use a non-
animal testing method they believe is suitable, adequate, validated, 
and feasible. We will consider if such an alternative method could 
be assessed for equivalency to an animal test method.
---------------------------------------------------------------------------

    We do not believe any changes are necessary to address the 
comment's request that FDA require information about changes to the 
research protocol and statistical methodology. In addition to the 
summary of studies required under Sec.  860.220(a)(13) (this final rule 
renumbers proposed Sec.  860.234(a)(13) as Sec.  860.220(a)(13)), the 
technical sections of the De Novo request must include, among other 
things, protocols, investigation design, results of statistical 
analyses, and any other appropriate information, for each clinical 
investigation used to support the De Novo request (Sec.  
860.220(a)(15), this final rule renumbers proposed Sec.  860.234(a)(15) 
as Sec.  860.220(a)(15)). Therefore, the required contents of the 
technical section would already capture information regarding 
significant changes made to the protocol or to the statistical 
methodology that would be important for evaluating the results of the 
study.
    (Comment 34) A few comments propose revisions to the human subject 
study summaries provision at Sec.  860.220(a)(13)(ii) (this final rule 
renumbers proposed Sec.  860.234(a)(13)(ii) as Sec.  
860.220(a)(13)(ii)) to require that this section of the De Novo request 
include a summary of ``any clinical data'' known by or reasonably 
available to the requester submitted in the De Novo request instead of 
a summary of ``each clinical investigation'' submitted in the De Novo 
request. The commenters suggest that the language in the proposed rule 
appeared to assume that the requester's only source of clinical data 
would be clinical investigations that the requester initiated and note 
that there may be other sources of clinical data, such as studies 
described in literature or conducted by others, or in marketing data 
from other countries. They also recommend limiting the information 
about such clinical data required in the summary to that ``known or 
reasonably available'' to the requester because it would clarify that 
when complete data are not available, they are not required.
    (Response 34) FDA agrees that sources of clinical data other than 
clinical investigations initiated by the requester may be available to 
the requester; however, we do not agree that the proposed requirement 
for the De Novo request to include a summary of studies limits the 
types of clinical data that may be submitted in a De Novo request. 
Under Sec.  860.220(a)(13), (this final rule renumbers proposed Sec.  
860.234(a)(13) as Sec.  860.220(a)(13)), the De Novo request must 
include an abstract of any information or report described in the De 
Novo request under Sec.  860.220(a)(16)(ii) (this final rule renumbers 
proposed Sec.  860.234(a)(16)(ii) as Sec.  860.220(a)(16)(ii)) and a 
summary of the results of technical data submitted under Sec.  
860.220(a)(15) (this final rule renumbers proposed Sec.  860.234(a)(15) 
as Sec.  860.220(a)(15)). The information required under Sec.  
860.220(a)(16)(ii) includes ``information derived from investigations 
other than those in the request and from commercial marketing 
experience.'' Therefore, clinical data derived from other sources, such 
as marketing experience in other countries, are among the types of data 
that would be summarized under Sec.  860.220(a)(13). The particular 
paragraph of Sec.  860.220(a)(13) that the commenters suggest revising 
sets forth additional information that summaries must discuss for those 
clinical investigations involving human subjects that are submitted in 
the De Novo request.
    FDA also disagrees that it is necessary to limit the information 
required under Sec.  860.220(a)(13)(ii) (this final rule renumbers 
proposed Sec.  860.234(a)(13)(ii) as Sec.  860.220(a)(13)(ii)) to that 
known or reasonably available to the requester. The requester should be 
able to provide the information required under Sec.  860.220(a)(13)(ii) 
for clinical investigations submitted in the technical sections in 
support of the De Novo request. To the extent certain elements required 
for the summary of such clinical investigations are not included in the 
De Novo request because they are not reasonably available to the 
requester, the requester should address why they are not available. 
Therefore, we are not revising Sec.  860.220(a)(13)(ii) in response to 
these comments.
    (Comment 35) A comment requests FDA to qualify the requirement for 
a De Novo request to provide a discussion demonstrating that the data 
and information in the request constitute valid scientific evidence, 
with the phrase, ``if applicable,'' because a De Novo request for a 
low-risk device may present de minimis valid scientific evidence.
    (Response 35) FDA disagrees with this comment. As part of the De 
Novo classification process, FDA must determine that the device is of 
low to moderate risk (21 U.S.C. 360c(f)(2)(A)(iv)). FDA relies upon 
valid scientific evidence in determining the safety and effectiveness 
of a device for purposes of classification, as explained in our 
response to Comment 23. Therefore, adding the phrase ``if applicable'' 
as the commenter suggests would not be appropriate.
    As discussed in FDA's guidance, ``Factors to Consider When Making 
Benefit-Risk Determinations Medical Device Premarket Approval and De 
Novo Classifications'' (Ref. 3), FDA assesses the benefits and risks of 
a device that is the subject of a De Novo request to determine if 
general or general and special controls are sufficient to provide 
reasonable assurance of safety and effectiveness (see Sec.  860.7(d)(1) 
and (e)(1)). While low-risk devices may not need to show as substantial 
a benefit to patients to have a favorable benefit-risk profile, FDA's 
classification determination must still be based on valid scientific 
evidence.
    (Comment 36) A comment requests FDA to clarify that, where 
relevant, requirements for data and information in the technical 
sections in Sec.  860.220(a)(15) (this final rule renumbers proposed 
Sec.  860.234(a)(15) as Sec.  860.220(a)(15)) may be satisfied by 
cross-referencing data and information submitted in satisfaction of the 
summary of studies provision (Sec.  860.220(a)(13), this final rule 
renumbers proposed Sec.  860.234(a)(13) as Sec.  860.220(a)(13)) to 
avoid requiring a requester to repeat information provided earlier in 
the De Novo request. A comment also requests that FDA remove the list 
of specific items that must be

[[Page 54838]]

included in the summary of each clinical investigation under Sec.  
860.220(a)(13)(ii) (this final rule renumbers proposed Sec.  
860.234(a)(13)(ii) as Sec.  860.220(a)(13)(ii)) because the commenter 
asserts it is unnecessarily restrictive and repetitive to require this 
information in the summary when the same information is also required 
in the technical sections of the De Novo request under Sec.  
860.220(a)(15)(iii) (this final rule renumbers proposed Sec.  
860.234(a)(15)(iii) as Sec.  860.220(a)(15)(iii)).
    (Response 36) FDA does not agree with this comment. The summary of 
technical data required under Sec.  860.220(a)(13) is intended to be 
analogous to an executive summary of each study used to support the De 
Novo request and would typically include less information than that 
submitted in the technical sections. The information required in the 
technical sections (Sec.  860.220(a)(15)) is the more detailed and 
complete information regarding each study. While it may be appropriate 
to cross reference the information from the summary section (Sec.  
860.220(a)(13)), FDA does not believe cross referencing the information 
in the summary required under Sec.  860.220(a)(13) would be sufficient 
to provide all of the required technical information to support 
marketing authorization. Because the summary information required for 
clinical investigations submitted in the De Novo request may include 
information other than the specific items listed in Sec.  
860.220(a)(13)(ii) and because it is intended to be a higher level 
summary of the data in the technical sections, we do not believe the 
required summary is unnecessarily restrictive or repetitive.
    (Comment 37) A few comments ask FDA to revise the nonclinical 
testing paragraph (Sec.  860.220(a)(15)(i), this final rule renumbers 
proposed (Sec.  860.234(a)(15)(i) as (Sec.  860.220(a)(15)(i)) by 
moving the ``as appropriate'' qualifier forward in the sentence.
    (Response 37) FDA agrees that moving the words ``as appropriate'' 
forward in the sentence would clarify the requirement. We are revising 
paragraph Sec.  860.220(a)(15)(i) accordingly.
    (Comment 38) A few comments ask FDA to revise the requirements for 
a summary of studies and the technical sections in a De Novo request to 
clarify that a statement regarding compliance with part 58 is only 
necessary for studies that are required to comply with part 58 because 
the commenters state that many nonclinical studies are outside the 
scope of part 58 if they do not involve the use of animals or other 
test systems.
    (Response 38) FDA agrees that some nonclinical studies that may be 
submitted to support a De Novo request, such as certain electromagnetic 
compatibility testing, are not subject to part 58. In response to these 
comments, FDA is revising Sec.  860.220(a)(15)(i) (this final rule 
renumbers proposed Sec.  860.234(a)(15)(i) as Sec.  860.220(a)(15)(i)) 
to clarify that a statement of compliance with part 58 (or a brief 
statement of the reason for noncompliance) is required only for 
nonclinical studies subject to part 58.
    (Comment 39) A comment asks FDA to revise the requirements for 
submitting results of clinical investigations involving human subjects 
(Sec.  860.220(a)(15)(iii), this final rule renumbers proposed Sec.  
860.234(a)(15)(iii) as Sec.  860.220(a)(15)(iii)) to clarify that 
clinical investigations are not required in all cases to support the De 
Novo classification decision. Comments also requested revisions to this 
provision to clarify that some clinical investigations submitted in the 
De Novo request may be ongoing (e.g., clinical investigations that are 
ongoing but for which all subjects have reached the primary endpoint). 
These comments also ask FDA to revise the proposed regulatory text to 
refer to ``records'' instead of copies of individual subject report 
forms because the commenters assert that many clinical investigations 
are carried out with validated electronic data capture systems and 
individual human subject forms are not used.
    (Response 39) FDA agrees that clinical evidence may not always be 
required in a De Novo request to support a determination that general 
controls or general and special controls provide a reasonable assurance 
of safety and effectiveness of the device and device type. However, we 
believe no clarification is needed regarding whether a clinical 
investigation involving human subjects is required because that 
determination will be specific to the De Novo request. If the requester 
believes that information regarding clinical investigations required 
under Sec.  860.220(a)(15)(iii) (this final rule renumbers proposed 
Sec.  860.234(a)(15)(iii) as Sec.  860.220(a)(15)(iii)), or other 
information required under Sec.  860.220(a)(15)(i) (this final rule 
renumbers proposed Sec.  860.234(a)(15)(i) as Sec.  860.220(a)(15)(i)), 
is not applicable to its device, then the requester may include a 
justification for omitting that information from the De Novo request in 
accordance with Sec.  860.220(c) (this final rule renumbers proposed 
Sec.  860.234(c) as Sec.  860.220(c)). If De Novo requesters have 
questions about the process for submission and review of a De Novo 
request for their device, we recommend that they consult FDA's 
guidance, ``De Novo Classification Process (Evaluation of Automatic 
Class III Designation)'' (Ref. 5) and request a meeting with FDA 
through the Q-submission program. Meetings between the requester and 
FDA allow for an open discussion and exchange of technical, scientific, 
and regulatory information that can help build a common understanding 
of FDA's initial expectations regarding clinical studies and 
nonclinical studies related to the De Novo request (Ref. 13).
    FDA recognizes that some De Novo requests include results from 
clinical investigations that remain ongoing, such as a study that has a 
pre-specified interim analysis of safety or effectiveness data. 
However, FDA believes the regulatory text in Sec.  860.220(a)(15)(iii) 
would already permit inclusion of such results and does not believe a 
revision to the regulatory text is necessary.
    We also recognize that some comments raise a concern that 
individual subject forms are not used in many clinical investigations. 
While the commenters do not object to providing individual subject 
information for those subjects who died during a clinical investigation 
or who did not complete the investigation, the commenters suggest that 
the term ``records'' would better reflect electronic source data 
instead of the term ``copies of such forms.'' We agree with the 
comments that data capture and collection methods used in clinical 
investigations have evolved over time. FDA has published guidance, 
``Use of Electronic Health Record Data in Clinical Investigations,'' 
addressing data capture in clinical investigations that do not use 
paper case report forms (Ref. 14). FDA interprets the term ``individual 
subject form,'' as used in this rule, to include the different 
electronic or paper formats used to capture individual subject data. 
Therefore, we do not believe that using the term ``record'' is 
necessary.
    (Comment 40) A comment asks FDA to require that the technical 
sections of a De Novo request include a protocol and a report for all 
clinical investigations and laboratory studies to make the requirements 
for the technical sections more consistent and less confusing.
    (Response 40) We agree that additional clarity regarding technical 
sections requirements for nonclinical studies would be helpful. 
Protocols and complete test reports generally are necessary to provide 
sufficient detail

[[Page 54839]]

regarding the results of a nonclinical study to permit FDA to determine 
whether to grant or decline the De Novo request. However, we are 
revising Sec.  860.220(a)(15)(i) (this final rule renumbers proposed 
Sec.  860.234(a)(15)(i) as Sec.  860.220(a)(15)(i)) to state expressly 
that these materials must be provided for each nonclinical study 
submitted in the technical sections of the request. FDA's guidance, 
``Recommended Content and Format of Non-Clinical Bench Performance 
Testing Information in Premarket Submissions'' (Ref. 15) discusses the 
information that should typically be included in test protocols and 
complete test reports for nonclinical bench performance testing 
provided in a premarket submission. We note that in cases where a 
requester is appropriately declaring conformity with a voluntary 
consensus standard that FDA has recognized pursuant to section 514(c) 
of the FD&C Act (21 U.S.C. 360d(c)) to meet applicable requirements, it 
may not be necessary to submit complete test reports with respect to 
those requirements. In these cases, the requester may submit a 
statement of omission for this information in the De Novo request in 
accordance with Sec.  860.220(c). However, consistent with section 
514(c)(3)(B) of the FD&C Act, FDA may request, at any time, the data or 
information relied on by a person to make a declaration of conformity 
with respect to a recognized standard. See FDA's guidance ``Appropriate 
Use of Voluntary Consensus Standards in Premarket Submissions for 
Medical Devices'' (Ref. 11) for more information regarding use of 
declarations of conformity in premarket submissions.
    FDA disagrees with modifying Sec.  860.220(a)(15)(iii) to 
specifically require submission of a clinical investigation report. 
This provision already describes the supporting information required 
regarding the results of each clinical investigation, and in our 
experience, there can be significant variability in the types of 
information included in ``reports'' prepared for clinical 
investigations. If some or all of the information required under Sec.  
860.220(a)(15)(iii) is included in a separate clinical investigation 
report, the requester may include the report in its De Novo request to 
satisfy those requirements.
    (Comment 41) A comment asks FDA to revise the ``other information'' 
provision (Sec.  860.220(a)(16), this final rule renumbers proposed 
Sec.  860.234(a)(16) as Sec.  860.220(a)(16)) to limit the information 
required in the bibliography of all published reports not submitted 
under the technical sections of the De Novo request (Sec.  
860.220(a)(15), this final rule renumbers proposed Sec.  860.234(a)(15) 
as Sec.  860.220(a)(15)) to those ``necessary to support the safety or 
effectiveness of the device'' because the commenter asserts such 
reports should be limited to those needed to establish the device's 
proposed classification, its probable risk, and its probable benefit.
    (Response 41) We do not agree with limiting the bibliography 
required under Sec.  860.220(a)(16) to that information necessary to 
support the device's safety or effectiveness. Paragraph Sec.  
860.220(a)(16)(i) (this final rule renumbers proposed Sec.  
860.234(a)(16)(i) as Sec.  860.220(a)(16)(i)) requires that the 
requester submit a bibliography of all adverse or supportive published 
reports, other than those submitted in greater detail in the technical 
sections of the De Novo request, that are known to or should reasonably 
be known to the requester and that concern the safety and effectiveness 
of the device. The commenter's proposed revision would eliminate the 
requirement to include adverse published reports that may call into 
question the safety or effectiveness of the device at issue. However, 
such adverse reports may be important to FDA's assessment of the 
probable benefits and risks of the device and affect the Agency's 
classification determination.
    (Comment 42) A comment supports the requirement to provide a sample 
of the device, if requested by FDA (Sec.  860.220(a)(17), this final 
rule renumbers proposed Sec.  860.234(a)(17) as Sec.  860.220(a)(17)) 
because it improves transparency. Other comments request that FDA 
eliminate the language indicating that the Agency may ``test'' one or 
more of the devices because FDA has traditionally relied on testing by 
the manufacturer. Another commenter indicated that while providing 
samples may be appropriate for a high-risk device likely to be reviewed 
in a PMA, it is unclear that samples are necessary for devices reviewed 
through the De Novo pathway.
    (Response 42) FDA disagrees with the comments that suggest limiting 
the sample requirement and agrees with the comment that the request for 
samples improves transparency. In many cases, FDA relies on 
descriptions of a device and testing performed by manufacturers to 
evaluate safety and effectiveness. However, there are some situations 
in which FDA would request a sample of a device reviewed through the De 
Novo pathway because FDA needs to see or test the device to understand 
the device and determine if general or general and special controls are 
sufficient to reasonably assure safety and effectiveness of the device 
and device type. Examples of the situations where a device sample may 
be requested by FDA for examination or testing include devices intended 
for use by a lay person that previously have been marketed for use by a 
physician or other experienced healthcare professional, and devices 
with novel, complex designs that are difficult to assess solely through 
written description and/or engineering drawings.
    (Comment 43) A comment supports the proposed requirement that a De 
Novo request include ``[l]abels, labeling, and advertisements 
sufficient to describe the device, its intended use, and the directions 
for its use'' (Sec.  860.220(a)(18), this final rule renumbers proposed 
Sec.  860.234(a)(18) as Sec.  860.220(a)(18)) because this requirement 
improves transparency. Other commenters propose limiting the 
requirement to not include advertisements because the commenters state 
advertisements are outside the scope of a class I and class II device 
review.
    (Response 43) FDA agrees that the requirement to submit labels, 
labeling, and advertisements improves transparency. FDA disagrees that 
review of advertisements is outside the scope of De Novo request 
review. Under the proposed provision, only labels, labeling, and 
advertisements ``sufficient to describe the device, its intended use, 
and the directions for its use'' are required, and such information is 
necessary to determine the device's intended use and its safety and 
effectiveness for the purposes of classification. See, e.g., Sec.  
860.7(b)(2).
    (Comment 44) A comment supports the requirement for a requester to 
provide a list of any required information that is omitted from the De 
Novo request and a justification for any omission because the commenter 
states it would ensure completeness of the applicant's research and 
pre-application evaluations.
    (Response 44) FDA agrees that it is beneficial for the requester to 
provide a statement identifying and justifying the omission of any 
information required under Sec.  860.220(a) (this final rule renumbers 
proposed Sec.  860.234(a) as Sec.  860.220(a)) and is finalizing the 
requirement to provide such a statement in Sec.  860.220(c) (this final 
rule renumbers proposed Sec.  860.234(c) as Sec.  860.220(c)). However, 
we wish to clarify that the omissions statement is not required to be 
in the format of a list, as the comment suggests.
    (Comment 45) A comment requests FDA to revise the requirements for 
incorporation of information in FDA files by reference (Sec.  
860.220(b), this final

[[Page 54840]]

rule renumbers proposed Sec.  860.234(b) as Sec.  860.220(b)) to permit 
the requester to file a general authorization allowing another person 
to submit additional pertinent information. According to the commenter, 
this would allow De Novo requesters to avoid the need for case-by-case 
authorization.
    (Response 45) FDA disagrees with this comment and believes the 
commenter misunderstands the circumstances in which FDA requires an 
authorization. The provision in Sec.  860.220(b) addresses situations 
in which a De Novo request references information in FDA's files that 
was submitted by someone other than the requester. For FDA to consider 
that information as part of the De Novo request, we require a written 
authorization from the person originally submitting that information to 
FDA that authorizes the use of the information in the De Novo request. 
Because the authorizer determines the scope of the authorization, it 
can be as broad or as limited as the authorizer wants the authorization 
to be. The comment seems to suggest that the requester should be able 
to provide authorization for the De Novo request to reference 
information in FDA's files submitted by others, but the submitters of 
the data are the ones in a position to authorize references to it.
    (Comment 46) A few comments request FDA to revise the requirement 
to update a pending De Novo request with new information from ongoing 
or completed studies that may reasonably affect an evaluation of the 
safety and effectiveness of the device as it becomes available (Sec.  
860.220(d), this final rule renumbers proposed Sec.  860.234(d) as 
Sec.  860.220(d)) because the commenters assert FDA should allow time 
for data aggregation and assessment. The comments suggest that FDA 
should require such information as agreed upon with the De Novo 
requester or as specified in a protocol.
    (Response 46) FDA disagrees with these comments. The comments 
assume incorrectly that for each ongoing or completed nonclinical and/
or clinical study, there exists a protocol that has timeframes for 
reporting new safety and effectiveness information to FDA or an 
agreement specifying when new safety and effectiveness information must 
be submitted to update a pending De Novo request. FDA is also concerned 
that specifying a set time period for updating the De Novo request 
would be problematic because the importance of the data required to be 
reported may vary. For example, FDA would be particularly interested in 
receiving quickly information that concerns the death of a human 
subject. Updating a De Novo request in accordance with pre-set periods 
in a protocol or agreement could also result in FDA making a decision 
on a De Novo request without key, available safety and effectiveness 
information. For example, an unplanned review of the safety data could 
have implications on the statistical validity of a study.

I. Comments and FDA Response on Criteria for Accepting a De Novo 
Request

    (Comment 47) A comment states the requirements in Sec.  860.230 
(this final rule renumbers proposed Sec.  860.245 as Sec.  860.230)) 
should be moved to FDA's guidance, ``Acceptance Review for De Novo 
Classification Requests'' (FDA draft guidance published October 30, 
2017). Another comment recommends finalizing FDA's guidance, 
``Acceptance Review for De Novo Classification Requests,'' concurrently 
with finalizing the rule.
    (Response 47) FDA disagrees with this comment because FDA's 
requirements are based on its statutes and regulations. FDA guidance 
provides non-binding recommendations. Regulations are necessary because 
they allow the Agency to enforce the requirements therein. For this 
reason, we decline to remove the accepting a De Novo request 
requirements, including those in Sec.  860.230, from this regulation.
    FDA's ``Acceptance Review for De Novo Classification Requests'' 
guidance was finalized on September 9, 2019 (84 FR 47310) (Ref. 16), so 
the comment requesting concurrent publication is moot.
    (Comment 48) A comment requests FDA to clarify that references to 
``15 days'' signify calendar days because it will enhance De Novo 
requester planning.
    (Response 48) FDA declines to clarify in the codified but confirms 
that it interprets ``15 days'' to mean ``15 calendar days.'' This 
interpretation is consistent with FDA's final guidance entitled, 
``Acceptance Review for De Novo Classification Requests'' (Ref. 16), 
which explains that the 15 days are calendar days. It is also 
consistent with our interpretation of ``days'' as used in analogous 
regulations for PMAs and 510(k)s.

J. Comments and FDA Response on Granting or Declining a De Novo Request

    (Comment 49) A comment objects to developing a new lexicon for De 
Novo requests (i.e., grant or decline) and asks FDA to use the term 
``approval'' because the commenter asserts that CDRH approves both ``De 
Novo devices'' and ``PMA devices'' for marketing based on a 
determination that they are safe and effective for their intended use.
    (Response 49) We disagree with this comment. The term ``decline'' 
is language from section 513(f)(2) of the FD&C Act, and FDA believes 
the term ``grant'' is appropriate, given that section 513(f)(2) of the 
FD&C Act addresses a ``request for classification.'' In addition, FDA 
does not make identical determinations when approving a PMA or granting 
a De Novo request. The statutory standards for approval of a PMA 
include a showing of reasonable assurance that the device is safe and 
effective (see section 515(d) of the FD&C Act). FDA will grant a De 
Novo request and classify the device as either class I or class II when 
the request demonstrates that general controls or general and special 
controls are adequate to provide reasonable assurance of safety and 
effectiveness (see section 513(a) and (f)(2) of the FD&C Act).
    (Comment 50) To be consistent with section 513(f)(2)(C) of the FD&C 
Act, a few comments requested that FDA revise the provision regarding 
publication in the Federal Register of the notice announcing the 
classification of the device to state that the publication will occur 
within 30 days of granting the request.
    (Response 50) FDA agrees to revise Sec.  860.260(a)(2) (this final 
rule renumbers proposed Sec.  860.289(a)(2) as Sec.  860.260(a)(2)) to 
reflect the statutory timeframe for publishing a notice in the Federal 
Register announcing the classification of a device under section 
513(f)(2)(C) of the FD&C Act. We are revising Sec.  860.260(a)(2) 
accordingly to add the phrase ``within 30 days after the issuance of an 
order granting the De Novo request.'' We note that the classification 
of a device, including any special controls, is effective on the date 
the order letter is issued granting the De Novo request. Once the De 
Novo request is granted, the device may serve as a predicate device to 
which another device can claim substantial equivalence. FDA places 
copies of such orders on its website.
    (Comment 51) A comment on the proposed provisions for declining a 
De Novo request notes that stating FDA ``may issue written notice'' 
declining a request suggests there is an alternative to issuing a 
written notice and asks FDA to describe the alternative.
    (Response 51) FDA intended to outline the grounds for which FDA may 
decline a De Novo request in proposed Sec.  860.289(b) (this final rule 
renumbers proposed Sec.  860.289(b) as Sec.  860.260(c) and moves the 
grounds for which FDA may decline a De Novo request into

[[Page 54841]]

Sec.  860.260(c)). FDA explained in the preamble to the proposed rule 
that it was proposing to ``decline a De Novo request by issuing a 
written order to the requester'' (83 FR 63127 at 63137). However, FDA 
is revising paragraph Sec.  860.260(b) and (c) accordingly to clarify 
this point.
    (Comment 52) A comment asks FDA to delete the entire paragraph 
Sec.  860.260(c) (this final rule renumbers proposed Sec.  860.289(b) 
as Sec.  860.260(c) and moves the grounds for which FDA may decline a 
De Novo request into Sec.  860.260(c)) on declining a De Novo request 
because the commenter states the paragraph exceeds the appropriate 
bases for denial of a De Novo request, which the commenter identifies 
as the device is inappropriate for classification into class I or class 
II, or there is a legally marketed predicate device.
    (Response 52) FDA disagrees with this comment. Section 860.260(c)) 
(this final rule renumbers proposed Sec.  860.289(b) as Sec.  
860.260(b) and moves the grounds for which FDA may decline a De Novo 
request into Sec.  860.260(c)) explains FDA's interpretation and 
implementation of the statutory grounds for declining a De Novo 
request, which does not rely upon only section 513(f)(2)(A)(iv) of the 
FD&C Act. For example, if a product is not a device within the meaning 
of section 201(h) of the FD&C Act or a combination product as defined 
at Sec.  3.2(e) (21 CFR 3.2(e)), then FDA may decline to grant the De 
Novo request.
    As noted in the proposed rule (83 FR 63127 at 63137), FDA generally 
intends to decline a De Novo request for a combination product that 
does not have a device primary mode of action--(see Sec.  3.2(m)). 
However, a De Novo request may be appropriate, for example, for the 
device constituent part of such a combination product if the 
constituent parts of the combination product are to be distributed 
separately (see Sec.  3.2(e)(3) through (4)), and the other constituent 
part (drug or biological product) of the combination product is to be 
marketed under its own, separate application (i.e., abbreviated new 
drug application, NDA, or biologics license application).
    (Comment 53) A few comments request that FDA delete the entire 
paragraph on declining a De Novo request because the device labeling 
does not comply with parts 801 and 809 (21 CFR parts 801 and 809) 
because the commenters state it is outside the scope of the De Novo 
classification process to deny classification based on the device's 
labeling.
    (Response 53) FDA disagrees with these comments. Parts 801 and 809 
are general controls, and whether the device complies with general 
controls is necessary to determine whether it is of low to moderate 
risk for the purposes of classification. FDA may decline a De Novo 
request if it determines that the device submitted is not of low to 
moderate risk, or that general controls would be inadequate to control 
the risk and special controls to mitigate the risks cannot be 
developed. Whether the device's labeling complies with the requirements 
in parts 801 and 809 is necessary to determine which regulatory 
controls are appropriate for the new device type class. The device's 
labeling compliance with parts 801 and 809 is also necessary to 
determine the device's safety and effectiveness for the purposes of 
classification.
    (Comment 54) A comment requests FDA to revise the basis for 
declining a De Novo request set forth in Sec.  860.260(c)(8) (this 
final rule renumbers proposed Sec.  860.289(b)(8) as Sec.  
860.260(c)(8)) to specify that a request may only be declined when 
certain nonclinical studies within the scope of part 58 are not 
conducted in compliance with those regulations. The commenter asserts 
that many nonclinical studies are outside the scope of part 58.
    (Response 54) FDA agrees that a De Novo request may include 
nonclinical studies that are not subject to part 58, as we explained in 
Response 38. FDA would not decline a De Novo request on the basis that 
a nonclinical study failed to comply with part 58, if that study did 
not fall within the scope of studies that are subject to part 58. 
However, FDA is revising Sec.  860.260(c)(8) to make this clearer.
    (Comment 55) A comment requests that FDA revise the paragraph on 
declining a De Novo request (Sec.  860.260(c)(10)(i), this final rule 
renumbers proposed Sec.  860.289(b)(10)(i) as Sec.  860.260(c)(10)(i)) 
because the commenter states that failure to follow a protocol is not, 
per se, a reason to decline a De Novo request.
    (Response 55) FDA disagrees with the commenter's suggestion to 
revise the provision on declining a De Novo request so that it does not 
include failure to follow a protocol. The failure to follow a protocol 
may cause the resulting data to be incomplete, invalid, or otherwise 
unreliable, and may be a sufficient reason to decline a De Novo 
request. Protocols typically discuss the objectives, design, 
methodology, and organization of a clinical or nonclinical study. 
Significant deviations from a study protocol may lead to a study that, 
as conducted, does not produce valid scientific evidence. 
Alternatively, data from a study that was terminated early may not 
provide sufficient information to support a reasonable assurance of 
safety or effectiveness.
    (Comment 56) A comment objects to the placement of the paragraph on 
determining safety and effectiveness as one of the last paragraphs in 
subpart D because the commenter states FDA should do both a 
classification determination and a determination of the device's safety 
and effectiveness.
    (Response 56) FDA does not agree with the comment's premise that 
the location of the paragraph in subpart D is an indication of the 
paragraph's importance. The FD&C Act provides that the De Novo process 
is both a classification and a marketing authorization grant for the 
particular device (section 513(f)(2) of the FD&C Act). The 
classification determination and ``determination of safety and 
effectiveness'' are necessary to make a determination regarding the 
device which is the subject of the De Novo request.

K. Comments and FDA Response on Availability of the De Novo 
Classification Process for Combination Products

    (Comment 57) A comment requests that FDA clarify that for the 
summary of risk and mitigations and the risk-benefit discussion 
required to be submitted in the De Novo request, the summary and the 
risk-benefit discussion should describe the incremental risk and 
benefits posed by a combination product because the commenter states 
the content requirements should reflect that the De Novo classification 
process is available for combination products.
    (Response 57) FDA believes that inclusion of this language is 
unnecessary as we consider section 503(g)(3) of the FD&C Act to be 
clear regarding its applicability to combination products that include 
an approved constituent part as defined in section 503(g)(3) of the 
FD&C Act. In addition, the statute is clear that these considerations 
apply to such combination products submitted under sections 515, 
510(k), and 513(f)(2) of the FD&C Act. We do not believe inclusion of 
this language is necessary to provide further clarity beyond what is 
stated in the statute. Combination products have distinct premarket 
review and approvability considerations arising from combining a drug, 
device, and/or biological product, which retain their regulatory 
identities when they become constituent parts of combination products. 
Combination products are also a separate legal category of medical 
products, distinct from biological products, devices, and drugs. 
General principles of premarket review and

[[Page 54842]]

regulation for combination products include application of a risk-based 
approach and coordination among Centers for their review and 
regulation. Review of combination products in a De Novo classification 
request would consider safety and effectiveness questions relating to 
the combination product as a whole, each constituent part, interactions 
between them, and user/patient interaction with the product.
    (Comment 58) A comment asks FDA to clarify that while a De Novo 
request may be appropriate for the device constituent part of a 
combination product where the constituent parts of the combination 
product are distributed separately (e.g., Sec.  3.2(e)(3) through (4)), 
and the non-device (drug or biologic) constituent part is to be 
marketed under its own, separate application, the non-device 
constituent part must be appropriately labeled for use with the device 
constituent part (i.e., approved at doses, concentrations, routes of 
administration, indications, and adequate instructions for use). The 
commenter notes that if the non-device constituent part is not 
appropriately labeled for use with the device constituent part, then 
FDA would cause the non-device constituent party to be adulterated or 
misbranded.
    (Response 58) FDA does not agree that clarification is necessary. 
Per Sec.  3.2(e), the labeling of the constituent parts of such 
``cross-labeled'' combination products specify use only with the other 
approved individually specified constituent part(s), which are required 
to achieve the intended use, indication, or effect. The labeling for 
the combination product is comprised of the labeling for each 
constituent part.
    (Comment 59) A comment requests that FDA consider ``co-packaged'' 
combination products (per Sec.  3.2(e)(2)) that have a device primary 
mode of action as eligible for the De Novo classification process.
    (Response 59) Regarding inclusion of co-packaged combination 
products as defined in Sec.  3.2(e)(2) that have a device primary mode 
of action, FDA does not believe further clarification is warranted in 
the codified because Sec.  860.260 (this final rule renumbers proposed 
Sec.  860.289 as Sec.  860.260) explains that we are using the 
definition of combination products in Sec.  3.2(e)(1) through (4). Co-
packaged combination products as defined in Sec.  3.2(e)(2) that have a 
device primary mode of action are part of this definition and eligible 
for the De Novo classification process.

VI. Effective Date

    This final rule will become effective 90 days after the date of 
publication in the Federal Register.

VII. Economic Analysis of Impacts

    We have examined the impacts of the final rule under Executive 
Order 12866, Executive Order 13563, the Regulatory Flexibility Act (5 
U.S.C. 601-612), and the Unfunded Mandates Reform Act of 1995 (Pub. L. 
104-4). Executive Orders 12866 and 13563 direct us to assess all costs 
and benefits of available regulatory alternatives and, when regulation 
is necessary, to select regulatory approaches that maximize net 
benefits (including potential economic, environmental, public health 
and safety, and other advantages; distributive impacts; and equity). We 
believe that this final rule is a significant regulatory action as 
defined by Executive Order 12866.
    The Regulatory Flexibility Act requires us to analyze regulatory 
options that would minimize any significant impact of a rule on small 
entities. Because small entities affected by this final rule would 
incur very low one-time costs to read and understand the rule, we 
certify that the final rule will not have a significant economic impact 
on a substantial number of small entities.
    The Unfunded Mandates Reform Act of 1995 (section 202(a)) requires 
us to prepare a written statement, which includes an assessment of 
anticipated costs and benefits, before issuing ``any rule that includes 
any Federal mandate that may result in the expenditure by State, local, 
and tribal governments, in the aggregate, or by the private sector, of 
$100,000,000 or more (adjusted annually for inflation) in any one 
year.'' The current threshold after adjustment for inflation is $158 
million, using the most current (2020) Implicit Price Deflator for the 
Gross Domestic Product. This final rule would not result in an 
expenditure in any year that meets or exceeds this amount.
    The final rule will clarify the De Novo classification process for 
certain medical devices to obtain marketing authorization as class I or 
class II devices, rather than remaining automatically designated as 
class III devices under the FD&C Act. In addition, the final rule will 
clarify and create a more efficient De Novo classification process by 
specifying: (1) What medical devices are eligible for the De Novo 
classification process; (2) what information manufacturers must provide 
in De Novo requests; and (3) how to organize this information. By 
clarifying and making the process more efficient, the final rule could 
reduce the time and costs associated with reviewing De Novo requests. 
Moreover, the final rule will allow us to refuse to accept 
inappropriate and deficient De Novo requests and require us to protect 
the confidentiality of certain data and information submitted with a 
request until we issue an order granting the request.
    Industry will incur costs to read and understand this final rule. 
We estimate that the annualized costs over 10 years would range from 
$0.01 million to $0.17 million at a 7 percent discount rate, with a 
primary estimate of $0.09 million. We estimate that the annualized 
costs over 10 years at a 3 percent discount rate would range from $0.01 
million to $0.15 million, with a primary estimate of $0.08 million.

                                    Table 2--Summary of Benefits, Costs and Distributional Effects of the Final Rule
                                                                      [$ millions]
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                   Units
                                                                                   ------------------------------------
                   Category                       Primary       Low        High                  Discount     Period                  Notes
                                                 estimate    estimate    estimate      Year        rate       covered
                                                                                      dollars    (percent)    (years)
--------------------------------------------------------------------------------------------------------------------------------------------------------
Benefits:
    Annualized................................  ..........  ..........  ..........        2019           7          10
    Monetized $millions/year..................  ..........  ..........  ..........        2019           3          10
    Annualized Quantified.....................  ..........  ..........  ..........        2019           7          10  ................................
                                                                                          2019           3          10

[[Page 54843]]

 
    Qualitative...............................  ..........  ..........  ..........  ..........  ..........  ..........  Clarification of the De Novo
                                                                                                                         process for requesters.
                                                                                                                         Potentially fewer incomplete
                                                                                                                         submissions and faster
                                                                                                                         introduction of medical
                                                                                                                         devices.
--------------------------------------------------------------------------------------------------------------------------------------------------------
Costs:
    Annualized Monetized $millions/year.......       $0.09       $0.01       $0.17        2019           7          10  ................................
                                                      0.08        0.01        0.15        2019           3          10
    Annualized Quantified.....................  ..........  ..........  ..........        2019           7          10  ................................
                                                                                          2019           3          10
    Qualitative.
--------------------------------------------------------------------------------------------------------------------------------------------------------
Transfers:
    Federal Annualized Monetized $millions/     ..........  ..........  ..........        2019           7          10  ................................
     year.                                      ..........  ..........  ..........        2019           3          10
                                               ---------------------------------------------------------------------------------------------------------
                                                From:
                                                To:                                 ..........
                                               ---------------------------------------------------------------------------------------------------------
    Other Annualized Monetized $millions/year.  ..........  ..........  ..........        2019           7          10  ................................
                                                ..........  ..........  ..........        2019           3          10
                                               ---------------------------------------------------------------------------------------------------------
                                                From:
                                                To:                                 ..........
--------------------------------------------------------------------------------------------------------------------------------------------------------
Effects:
    State, Local or Tribal Government: None.
    Small Business: A small one-time administrative burden of up to $300 per year on each affected small entity.
    Wages: None.
    Growth: None.
--------------------------------------------------------------------------------------------------------------------------------------------------------

    We have developed a comprehensive Economic Analysis of Impacts that 
assesses the impacts of the final rule. The full analysis of economic 
impacts is available in the docket for this final rule (Ref. 20) and at 
https://www.fda.gov/about-fda/reports/economic-impact-analyses-fda-regulations.

VIII. Analysis of Environmental Impact

    We have determined under 21 CFR 25.34(b) and (f) that this action 
is of a type that does not individually or cumulatively have a 
significant effect on the human environment. Therefore, neither an 
environmental assessment nor an environmental impact statement is 
required.

IX. Paperwork Reduction Act of 1995

    This final rule contains information collection provisions that are 
subject to review by the Office of Management and Budget (OMB) under 
the Paperwork Reduction Act of 1995 (PRA) (44 U.S.C. 3501-3521). The 
title, description, and respondent description of the information 
collection provisions are shown in the following paragraphs with an 
estimate of the annual reporting burden. Included in the estimate is 
the time for reviewing instructions, searching existing data sources, 
gathering and maintaining the data needed, and completing and reviewing 
each collection of information.
    Title: Medical Device De Novo Classification Process (OMB Control 
Number 0910-0844)--Revision.
    Description: This final rule implements the medical device De Novo 
classification process under section 513(f)(2) of the FD&C Act, which 
provides a pathway for certain new types of devices to obtain marketing 
authorization as class I or class II devices, rather than remaining 
automatically designated as a class III device, which would require 
premarket approval under the postamendments device classification 
section of the FD&C Act (section 513(f)(1)).
    On October 30, 2017, FDA issued a final guidance (De Novo Program 
guidance) (Ref. 5) to provide recommendations on the process for the 
submission and review of a De Novo request. The information collections 
associated with the guidance are approved under OMB control number 
0910-0844. We provide below a revised burden estimate for the De Novo 
classification process as described in this final rule.
    Section 860.200 (this final rule renumbers proposed Sec.  860.201 
as Sec.  860.200) explains the purpose of the De Novo Classification 
regulations and provides the applicability of a De Novo request 
submission. Sections 860.210 and 860.220 (this final rule renumbers 
proposed Sec.  860.223 and Sec.  860.234 as Sec.  860.210 and Sec.  
860.220) describe the format and content, respectively, of a De Novo 
request. Section 860.230 (this final rule renumbers proposed Sec.  
860.245 as Sec.  860.230) describes the conditions under which FDA may 
refuse to accept a De Novo request. Section 860.240(b) (this final rule 
renumbers proposed Sec.  860.256(b) as Sec.  860.240(b)) provides for 
supplemental, amendatory, or additional information for a pending De 
Novo request. Section 860.250(a)(4) (this final rule renumbers proposed 
Sec.  860.267(a)(4) as Sec.  860.250(a)(4)) provides that a requester 
may submit a written notice to FDA that the De Novo request has been 
withdrawn.
    Description of Respondents: Respondents to the information 
collection are medical device manufacturers seeking to market medical 
device products that have been automatically designated as class III 
under section 513(f)(1) of the FD&C Act.

[[Page 54844]]

                                                     Table 3--Estimated Annual Reporting Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                               Total
                                         Number of       Number of     Total annual                                                       operating  and
      Activity; 21 CFR section          respondents   responses  per     responses       Average burden  per response       Total hours     maintenance
                                                         respondent                                                                            costs
--------------------------------------------------------------------------------------------------------------------------------------------------------
De Novo request--860.200, 860.210,                68               1              68  182...............................          12,376             $88
 860.220, 860.230, 860.240(b).
Written notice of withdrawal--                     5               1               5  0.17 (10 minutes).................               1               7
 860.250(a)(4).
                                     -------------------------------------------------------------------------------------------------------------------
    Total...........................  ..............  ..............  ..............  ..................................          12,377              95
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ Numbers have been rounded.

    The information collection request (ICR) previously approved for 
the De Novo classification process (OMB control number 0910-0844), 
includes separate information collections (ICs) for De Novo requests 
submitted under section 513(f)(2)(i) of the FD&C Act (estimated 100-
hour burden per response) and those submitted under section 
513(f)(2)(ii) (estimated 180-hour burden per response), with burden 
estimates further separated by those sent to CDRH and those sent to the 
Center for Biologics Evaluation and Research.
    For administrative efficiency, in this ICR revision, we are 
consolidating the separate ICs for requests submitted under section 
513(f)(2)(i) or (ii) of the FD&C Act into a single IC for all De Novo 
requests submitted to FDA. Therefore, this final rule simply provides a 
burden estimate for all De Novo requests without distinguishing between 
those submitted under 513(f)(2)(i) or (ii) of the FD&C Act. This 
estimate includes estimated burdens associated with the initial request 
(purpose and applicability in Sec.  860.200), format and content (Sec.  
860.210 and Sec.  860.220), supplements and amendments (Sec.  
860.240(b)), and time to ensure that all the format and content 
requirements are met before submission (Sec.  860.230). Based on our 
recent experience with the De Novo Program, FDA estimates that the 
average burden per response for a De Novo request is 182 hours. 
Additionally, we adjusted the estimated number of respondents based on 
updated data.
    The estimated burden for Sec.  860.230 includes 2 hours per 
response for manufacturers to review their De Novo request for 
compliance with the acceptance criteria listed in Sec.  860.230 to 
determine if it is complete and to complete the checklists recommended 
in the guidance ``Acceptance Review for De Novo Classification 
Requests'' (Ref.16). The information collections contained in the 
guidance, including 2 hours for review of the De Novo request for 
completeness and the checklists, were approved by OMB since publication 
of the proposed rule.
    We estimate that the average burden per response for written notice 
of withdrawal of a De Novo request, as described in Sec.  
860.250(a)(4), is 10 minutes (0.17 hours). The burden table in the 
proposed rule erroneously listed 10 hours, rather than 10 minutes, for 
the average burden per response. We have corrected the error. The 
average burden per response is based on estimates by FDA administrative 
and technical staff who are familiar with the requirements for 
submission of a De Novo request (and related materials), have consulted 
and advised manufacturers on submissions, and have reviewed the 
documentation submitted. We expect that we will receive approximately 
five notices of withdrawal per year. There is no change to the 
currently approved burden estimate for withdrawal of a De Novo request.
    These adjustments resulted in a 1,647-hour increase to the 
previously approved total burden estimate.
    We received several comments related to the proposed rule. 
Descriptions of the comments on the proposed rule and FDA's responses 
are provided in section V of this final rule. Comments and responses 
related to the provisions that underlie the information collection are 
described in the following sections: section V.B, regarding general 
comments; section V.D, De Novo request information disclosure; section 
V.F, regarding definitions; section V.G, regarding De Novo request 
format; section V.H, regarding De Novo request content; section V.I, 
regarding criteria for accepting a De Novo request; section V.J, 
regarding criteria for granting or declining a De Novo request; and 
section V.K, regarding availability of the De Novo classification 
process for combination products. We have not made changes to the 
estimated burden as a result of the comments.
    The estimate of the annual reporting burden provided in the 
proposed rule included printing and shipping for the complete paper 
submission and eCopy. Under Sec.  860.210 of the final rule, each De 
Novo request must be provided as a single version in electronic format. 
Therefore, we have adjusted the operating and maintenance cost in the 
final rule to include the cost of the eCopy and shipping of the eCopy.
    The cost per eCopy (CDs, DVDs, and flash drives) ranges from $0.25 
to $2.50 per eCopy. All forms of eCopy media cost roughly $0.22 to 
ship. We estimate the average cost per eCopy, plus shipping, for a De 
Novo request or a request for withdrawal to be $1.30 per submission.
    The annual cost estimate for De Novo requests is $88 (68 
submissions x $1.30) (rounded). The annual cost estimate for requests 
for withdrawal is $7 (5 requests x $1.30) (rounded). Therefore, we 
estimate the total annual operating and maintenance costs of this 
information collection to be $95. This is a decrease of $7,188 to the 
currently approved total annual operating and maintenance cost 
estimate.
    This final rule also refers to previously approved collections of 
information. These collections of information are subject to review by 
OMB under the PRA. The collections of information in the guidance 
entitled ``De Novo Classification Process (Evaluation of Automatic 
Class III Designation)'' (Ref. 5) have been approved under OMB control 
number 0910-0844; the collections of information in the guidance 
entitled ``Requests for Feedback and Meetings for Medical Device 
Submissions: The Q-Submission Program--Guidance for Industry and Food 
and Drug Administration Staff'' (Ref. 13) have been approved under OMB 
control number 0910-0756; the collections of information in the 
guidances entitled ``Guidance for Industry and Food and Drug 
Administration Staff--User Fees

[[Page 54845]]

for 513(g) Requests for Information'' (Ref. 17) and ``FDA and Industry 
Procedures for Section 513(g) Requests for Information under the 
Federal Food, Drug, and Cosmetic Act--Guidance for Industry and Food 
and Drug Administration Staff'' (Ref. 18) have been approved under OMB 
control number 0910-0705; and the collections of information in the 
guidance entitled ``Emergency Use Authorization of Medical Products and 
Related Authorities'' (Ref. 19) have been approved under OMB control 
number 0910-0595. The collections of information in Title 21 of the 
Code of Federal Regulations (CFR) are approved under the following OMB 
control numbers: part 3 under 0910-0523; parts 50 and 56 under 0910-
0130; part 54 under 0910-0396; part 58 under 0910-0119; parts 801 and 
809 under 0910-0485; part 807, subpart E, under 0910-0120; part 812 
under 0910-0078; part 814, subparts A through E under 0910-0231; part 
814, subpart H under 0910-0332; part 820 under 0910-0073; part 860, 
subpart C under 0910-0138.
    The information collection provisions in this final rule have been 
submitted to OMB for review as required by section 3507(d) of the 
Paperwork Reduction Act of 1995.
    Before the effective date of this final rule, FDA will publish a 
notice in the Federal Register announcing OMB's decision to approve, 
modify, or disapprove the information collection provisions in this 
final rule. An Agency may not conduct or sponsor, and a person is not 
required to respond to, a collection of information unless it displays 
a currently valid OMB control number.

X. Federalism

    We have analyzed this final rule in accordance with the principles 
set forth in Executive Order 13132. We have determined that the rule 
does not contain policies that have substantial direct effects on the 
States, on the relationship between the National Government and the 
States, or on the distribution of power and responsibilities among the 
various levels of government. Accordingly, we conclude that the rule 
does not contain policies that have federalism implications as defined 
in the Executive order and, consequently, a federalism summary impact 
statement is not required.

XI. Consultation and Coordination With Indian Tribal Governments

    We have analyzed this rule in accordance with the principles set 
forth in Executive Order 13175. We have determined that the rule does 
not contain policies that would have a substantial direct effect on one 
or more Indian Tribes, on the relationship between the Federal 
Government and Indian Tribes, or on the distribution of power and 
responsibilities between the Federal Government and Indian Tribes. 
Accordingly, we conclude that the rule does not contain policies that 
have tribal implications as defined in the Executive Order and, 
consequently, a tribal summary impact statement is not required.

XII. References

    The following references are on display in the Dockets Management 
Staff (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 website addresses, as of the date this document publishes 
in the Federal Register, but websites are subject to change over time.

1. FDA, ``Content of Premarket Submissions for Management of 
Cybersecurity in Medical Devices,'' available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/content-premarket-submissions-management-cybersecurity-medical-devices.
2. FDA, ``Guidance for the Content of Premarket Submissions for 
Software Contained in Medical Devices,'' available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/guidance-content-premarket-submissions-software-contained-medical-devices.
3. FDA, ``Factors to Consider When Making Benefit-Risk 
Determinations in Medical Device Premarket Approval and De Novo 
Classifications,'' available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/factors-consider-when-making-benefit-risk-determinations-medical-device-premarket-approval-and-de.
4. FDA, ``Patient Preference Information--Voluntary Submission, 
Review in Premarket Approval Applications, Humanitarian Device 
Exemption Applications, and De Novo Requests, and Inclusion in 
Decision Summaries and Device Labeling,'' available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/patient-preference-information-voluntary-submission-review-premarket-approval-applications.
5. FDA, ``De Novo Classification Process (Evaluation of Automatic 
Class III Designation),'' available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/de-novo-classification-process-evaluation-automatic-class-iii-designation.
6. FDA, CDRH Patient Engagement web page, available at https://www.fda.gov/about-fda/about-center-devices-and-radiological-health/cdrh-patient-engagement.
7. FDA, ``Procedures for Meetings of the Medical Devices Advisory 
Committee,'' available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/procedures-meetings-medical-devices-advisory-committee.
8. FDA, ``eCopy Program for Medical Device Submissions,'' available 
at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/ecopy-program-medical-device-submissions.
9. FDA, ``Consideration of Uncertainty in Making Benefit-Risk 
Determinations in Medical Device Premarket Approvals, De Novo 
Classifications, and Humanitarian Device Exemptions,'' available at 
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/consideration-uncertainty-making-benefit-risk-determinations-medical-device-premarket-approvals-de.
10. FDA, ``The 510(k) Program: Evaluating Substantial Equivalence in 
Premarket Notifications [510(k)],'' available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/510k-program-evaluating-substantial-equivalence-premarket-notifications-510k.
11. FDA, ``Appropriate Use of Voluntary Consensus Standards in 
Premarket Submissions for Medical Devices,'' available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/appropriate-use-voluntary-consensus-standards-premarket-submissions-medical-devices.
12. FDA, ``The Least Burdensome Provisions: Concept and 
Principles,'' available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/least-burdensome-provisions-concept-and-principles.
13. FDA, ``Requests for Feedback and Meetings for Medical Device 
Submissions: The Q-Submission Program,'' available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/requests-feedback-and-meetings-medical-device-submissions-q-submission-program.
14. FDA, ``Use of Electronic Health Record Data in Clinical 
Investigations,'' available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/use-electronic-health-record-data-clinical-investigations-guidance-industry.
15. FDA, ``Recommended Content and Format of Non-Clinical Bench 
Performance Testing Information in Premarket Submissions,'' 
available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/recommended-content-and-format-non-clinical-bench-performance-testing-information-premarket.
16. FDA, ``Acceptance Review for De Novo Classification Requests,'' 
available at https://www.fda.gov/regulatory-information/search-fda-
guidance-

[[Page 54846]]

documents/acceptance-review-de-novo-classification-requests.
17. FDA's guidance ``Guidance for Industry and Food and Drug 
Administration Staff--User Fees for 513(g) Requests for 
Information,'' available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/user-fees-513g-requests-information.
18. FDA's guidance ``FDA and Industry Procedures for Section 513(g) 
Requests for Information under the Federal Food, Drug, and Cosmetic 
Act,'' available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/fda-and-industry-procedures-section-513g-requests-information-under-federal-food-drug-and-cosmetic.
19. ``Emergency Use Authorization of Medical Products and Related 
Authorities,'' available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/emergency-use-authorization-medical-products-and-related-authorities.
20. FDA's full analysis of economic impacts is available in the 
Docket No. FDA-2018-N-0236 for this rule and at https://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/EconomicAnalyses/default.htm.

List of Subjects in 21 CFR Part 860

    Administrative practice and procedure, Medical devices.

    Therefore, under the Federal Food, Drug, and Cosmetic Act, and 
under authority delegated to the Commissioner of Food and Drugs, 21 CFR 
part 860 is amended as follows:

PART 860--MEDICAL DEVICE CLASSIFICATION PROCEDURES

0
1. The authority citation for part 860 is revised to read as follows:

    Authority: 21 U.S.C. 321(h), 353(g), 360c, 360d, 360e, 360i, 
360j, 371, 374.

0
2. In part 860, remove all references to ``the act'' and add in their 
place ``the Federal Food, Drug, and Cosmetic Act''.

0
3. Amend Sec.  860.1 by revising paragraph (b) to read as follows:

Sec.  860.1  Scope.

* * * * *
    (b) This part prescribes the criteria and procedures to be used by 
advisory committees, including classification panels, where applicable, 
in making their recommendations, and by the Commissioner in making the 
Commissioner's determinations regarding the class of regulatory control 
(class I, class II, or class III) appropriate for particular devices. 
Supplementing the general Food and Drug Administration procedures 
governing advisory committees (part 14 of this chapter), this part also 
provides procedures for manufacturers, importers, and other interested 
persons to participate in proceedings to classify and reclassify 
devices. This part also describes the type of data required for 
determination of the safety and effectiveness of a device, and the 
circumstances under which information submitted to advisory committees, 
including classification panels, or to the Commissioner in connection 
with classification and reclassification proceedings, will be available 
to the public.

0
4. Revise Sec.  860.3 to read as follows:

Sec.  860.3  Definitions.

    For the purposes of this part:
    Class means one of the three categories of regulatory control for 
medical devices, defined as follows:
    Class I means the class of devices that are subject only to the 
general controls authorized by or under sections 501 (adulteration), 
502 (misbranding), 510 (registration), 516 (banned devices), 518 
(notification and other remedies), 519 (records and reports), and 520 
(general provisions) of the Federal Food, Drug, and Cosmetic Act. A 
device is in class I if:
    (1) General controls are sufficient to provide reasonable assurance 
of the safety and effectiveness of the device, or
    (2) There is insufficient information from which to determine that 
general controls are sufficient to provide reasonable assurance of the 
safety and effectiveness of the device or to establish special controls 
to provide such assurance, but the device is not life-supporting or 
life-sustaining, or for a use which is of substantial importance in 
preventing impairment of human health, and which does not present a 
potential unreasonable risk of illness or injury.
    Class II means the class of devices that is or eventually will be 
subject to special controls. A device is in class II if general 
controls alone are insufficient to provide reasonable assurance of its 
safety and effectiveness and there is sufficient information to 
establish special controls, including the promulgation of performance 
standards, postmarket surveillance, patient registries, development and 
dissemination of guidelines (including guidelines for the submission of 
clinical data in premarket notification submissions in accordance with 
section 510(k) of the Federal Food, Drug, and Cosmetic Act), 
recommendations, and other appropriate actions as the Commissioner 
deems necessary to provide such assurance. For a device that is 
purported or represented to be for use in supporting or sustaining 
human life, the Commissioner shall examine and identify the special 
controls, if any, which are necessary to provide adequate assurance of 
safety and effectiveness, and describe how such controls provide such 
assurance.
    Class III means the class of devices for which premarket approval 
is or will be required in accordance with section 515 of the Federal 
Food, Drug, and Cosmetic Act. A device is in class III if insufficient 
information exists to determine that general controls are sufficient to 
provide reasonable assurance of its safety and effectiveness, or that 
application of special controls described in the definition of ``Class 
II'' in this section in addition to general controls, would provide 
such assurance, and if, in addition, the device is life-supporting or 
life-sustaining, or for a use which is of substantial importance in 
preventing impairment of human health, or if the device presents a 
potential unreasonable risk of illness or injury.
    Classification panel means one of the several advisory committees 
established by the Commissioner under section 513 of the Federal Food, 
Drug, and Cosmetic Act and part 14 of this chapter for the purpose of 
making recommendations to the Commissioner on the classification and 
reclassification of devices and for other purposes prescribed by the 
Federal Food, Drug, and Cosmetic Act or by the Commissioner.
    Classification regulation means a section under parts 862 through 
892 of this chapter that contains the identification (general 
description and intended use) and classification (class I, II or III) 
of a single device type or more than one related device type(s).
    Commissioner means the Commissioner of Food and Drugs, Food and 
Drug Administration, United States Department of Health and Human 
Services, or the Commissioner's designee.
    De Novo request means any submission under section 513(f)(2) of the 
Federal Food, Drug, and Cosmetic Act for a medical device, requesting 
classification into class I or class II, including all information 
submitted with or incorporated by reference therein.
    FDA means the Food and Drug Administration.
    General controls mean the controls authorized by or under sections 
501 (adulteration), 502 (misbranding), 510 (registration, listing, and 
premarket notification), 516 (banned devices), 518 (notification and 
other remedies), 519 (records, reports, and unique device 
identification), and 520 (general provisions) of the Federal Food, 
Drug, and Cosmetic Act.

[[Page 54847]]

    Generic type of device means a grouping of devices that do not 
differ significantly in purpose, design, materials, energy source, 
function, or any other feature related to safety and effectiveness, and 
for which similar regulatory controls are sufficient to provide 
reasonable assurance of safety and effectiveness.
    Implant means a device that is placed into a surgically or 
naturally formed cavity of the human body. A device is regarded as an 
implant for the purpose of this part only if it is intended to remain 
implanted continuously for a period of 30 days or more, unless the 
Commissioner determines otherwise to protect human health.
    Life-supporting or life-sustaining device means a device that is 
essential to, or that yields information that is essential to, the 
restoration or continuation of a bodily function important to the 
continuation of human life.
    Petition means a submission seeking reclassification of a device in 
accordance with Sec.  860.123.
    Special controls mean the controls necessary to provide reasonable 
assurance of safety and effectiveness for a generic type of device that 
is class II. Special controls include performance standards, 
performance testing, postmarket surveillance, patient registries, 
development and dissemination of guidelines (including guidelines for 
the submission of clinical data in premarket notification submissions 
in accordance with section 510(k) of the Federal Food, Drug, and 
Cosmetic Act), recommendations, and other appropriate actions, as the 
Commissioner deems necessary to provide such assurance.

0
5. Amend Sec.  860.5 by adding paragraph (g) to read as follows:

Sec.  860.5   Confidentiality and use of data and information submitted 
in connection with classification and reclassification.

* * * * *
    (g) Confidentiality of data and information in a De Novo file is as 
follows:
    (1) A ``De Novo file'' includes all data and information from the 
requester submitted with or incorporated by reference in the De Novo 
request, any De Novo supplement, or any other related submission 
relevant to the administrative file, as defined in Sec.  10.3(a) of 
this chapter. Any record in the De Novo file will be available for 
public disclosure in accordance with the provisions of this section and 
part 20 of this chapter.
    (2) The existence of a De Novo file may not be disclosed by FDA 
before an order granting the De Novo request is issued unless it 
previously has been publicly disclosed or acknowledged by the De Novo 
requester.
    (3) Before an order granting the De Novo request is issued, data or 
information contained in the De Novo file is not available for public 
disclosure, except to the extent the existence of the De Novo file is 
disclosable under paragraph (g)(2) of this section and such data or 
information has been publicly disclosed or acknowledged by the De Novo 
requester.
    (4) After FDA issues an order granting a De Novo request, the data 
and information in the De Novo file that are not exempt from release 
under the Freedom of Information Act, 5 U.S.C. 552, are immediately 
available for public disclosure.

0
6. Add subpart D, consisting of Sec. Sec.  860.200 through 860.260, to 
read as follows:
Subpart D--De Novo Classification
Sec.
860.200 Purpose and applicability.
860.210 De Novo request format.
860.220 De Novo request content.
860.230 Accepting a De Novo request.
860.240 Procedures for review of a De Novo request.
860.250 Withdrawal of a De Novo request.
860.260 Granting or declining a De Novo request.

Subpart D--De Novo Classification

Sec.  860.200  Purpose and applicability.

    (a) The purpose of this part is to establish an efficient, 
transparent, and thorough process to facilitate De Novo classification 
into class I or class II for devices for which there is no legally 
marketed device on which to base a review of substantial equivalence 
and which meet the definition of class I or class II as described in 
section 513(a)(1) of the Federal Food, Drug, and Cosmetic Act and Sec.  
860.3.
    (b) De Novo requests can be submitted for a single device type:
    (1) After receiving a not substantially equivalent determination in 
response to a premarket notification (510(k)), or
    (2) If a person determines there is no legally marketed device upon 
which to base a determination of substantial equivalence.

Sec.  860.210  De Novo request format.

    (a) Each De Novo request or information related to a De Novo 
request pursuant to this part must be formatted in accordance with this 
section. Each De Novo request must be provided as a single version in 
electronic format. These materials must:
    (1)(i) For devices regulated by the Center for Devices and 
Radiological Health, be sent to the current address displayed on the 
website https://www.fda.gov/cdrhsubmissionaddress.
    (ii) For devices regulated by the Center for Biologics Evaluation 
and Research, be sent to the current address displayed on the website 
https://www.fda.gov/about-fda/center-biologics-evaluation-and-research-cber/regulatory-submissions-electronic-and-paper.
    (2) Be signed by the requester or an authorized representative.
    (3) Be designated ``De Novo Request'' in the cover letter.
    (4) Have all content used to support the request written in, or 
translated into, English.

Sec.  860.220  De Novo request content.

    (a) Unless the requester justifies an omission in accordance with 
paragraph (c) of this section, a De Novo request must include:
    (1) Table of contents. A table of contents that specifies the 
volume (if the De Novo request contains more than one volume) and page 
number for each item.
    (2) Administrative information. The name, address, phone, and email 
address of the requester and U.S. representative, if applicable. The 
establishment registration number, if applicable, of the owner or 
operator submitting the De Novo request.
    (3) Regulatory history. Identify any prior submissions to FDA for 
the device, including, but not limited to, any premarket notifications 
(510(k)s) submitted under part 807 of this chapter; applications for 
premarket approval (PMAs) submitted under part 814 of this chapter; 
applications for humanitarian device exemption (HDE) submitted under 
part 814 of this chapter; applications for investigational device 
exemption (IDEs) submitted under part 812 of this chapter; requests for 
designation (RFD) under Sec.  3.7 of this chapter; requests for 
information under section 513(g) of the Federal Food, Drug, and 
Cosmetic Act; applications for emergency use authorization (EUA) under 
section 564 of the Federal Food, Drug, and Cosmetic Act; pre-
submissions, or previously submitted De Novo requests; or state that 
there have been no prior submissions.
    (4) Device name. The generic name of the device as well as any 
proprietary name or trade name.
    (5) Indications for use. A general description of the disease or 
condition the device is intended to diagnose, treat, prevent, cure or 
mitigate, or affect the structure or function of the body, including a 
description of the patient

[[Page 54848]]

population for which the device is intended. The indications for use 
include all the labeled patient uses of the device, including if it is 
prescription or over-the-counter.
    (6) Device description. A complete description of:
    (i) The device, including, where applicable, pictorial 
representations, device specifications, and engineering drawings;
    (ii) Each of the functional components or ingredients of the 
device, if the device consists of more than one physical component or 
ingredient;
    (iii) The properties of the device relevant to the diagnosis, 
treatment, prevention, cure, or mitigation of a disease or condition 
and/or the effect of the device on the structure or function of the 
body;
    (iv) The principles of operation of the device; and
    (v) The relevant FDA assigned reference number(s) for any medical 
devices (such as accessories or components) that are intended to be 
used with the device and that are already legally marketed.
    (7) Alternative practices and procedures. A description of existing 
alternative practices or procedures that are used in diagnosing, 
treating, preventing, curing, or mitigating the disease or condition 
for which the device is intended or which similarly affect the 
structure or function of the body and that are known or should 
reasonably be known to the requester.
    (8) Classification summary. (i) For devices not the subject of a 
previous submission under section 510(k) of the Federal Food, Drug, and 
Cosmetic Act, a complete description of:
    (A) The searches used to establish that no legally marketed device 
of the same type exists.
    (B) A list of classification regulations, PMAs, HDEs, premarket 
notifications (510(k)s), EUAs, and/or product codes regarding devices 
that are potentially similar to the subject device.
    (C) A rationale explaining how the device that is the subject of 
the De Novo request is different from the devices covered by the 
classification regulations, PMAs, HDEs, 510(k)s, EUAs, and/or product 
codes identified in paragraph (a)(8)(i)(B) of this section.
    (ii) For devices which were the subject of a previous submission 
under section 510(k) of the Federal Food, Drug, and Cosmetic Act that 
were determined not substantially equivalent (NSE), the relevant 510(k) 
number, along with a summary of the search performed to confirm the 
device has not been classified or reclassified since the date the NSE 
order was issued by FDA pursuant to Sec.  807.100(a) of this chapter.
    (9) Summary of risks and mitigations. A summary of probable risks 
to health associated with use of the device that are known or should 
reasonably be known to the requester and the proposed mitigations, 
including general controls and, if the classification recommendation 
from paragraph (a)(11) of this section is class II, special controls 
for each risk. For each mitigation measure that involves specific 
performance testing or labeling, the De Novo request must provide a 
reference to the associated section or pages for the supporting 
information in the De Novo request.
    (10) Proposed special controls. If the classification 
recommendation from paragraph (a)(11) of this section is class II, then 
the summary must include an initial draft proposal for applicable 
special controls and a description of how those special controls 
provide reasonable assurance of safety and effectiveness.
    (11) Classification recommendation. The recommended class (I or II) 
must be identified and must be supported by a description of why 
general controls, or general and special controls, are adequate to 
provide reasonable assurance of safety and effectiveness.
    (12) Standards. Reference to any published voluntary consensus 
standards that are relevant to any aspect of the safety or 
effectiveness of the device and that are known or should reasonably be 
known to the requester. Such standards include voluntary consensus 
standards whether recognized or not yet recognized under section 514(c) 
of the Federal Food, Drug, and Cosmetic Act. Provide adequate 
information to demonstrate how the device meets, or justify any 
deviation from, the referenced standard.
    (13) Summary of studies. An abstract of any information or report 
described in the De Novo request under paragraph (a)(16)(ii) of this 
section and a summary of the results of technical data submitted under 
paragraph (a)(15) of this section. Each such study summary must include 
a description of the objective of the study, a description of the 
experimental design of the study, a brief description of how the data 
were collected and analyzed, and a brief description of the results, 
whether positive, negative, or inconclusive. This section must also 
include the following:
    (i) A summary of each nonclinical study submitted in the De Novo 
request;
    (ii) A summary of each clinical investigation involving human 
subjects submitted in the De Novo request, including a discussion of 
investigation design, subject selection and exclusion criteria, 
investigation population, investigation period, safety and 
effectiveness data, adverse reactions and complications, subject 
discontinuation, subject complaints, device failures (including 
unexpected software events, if applicable) and replacements, results of 
statistical analyses of the clinical investigations, contraindications 
and precautions for use of the device, and other information from the 
clinical investigations as appropriate. Any investigation conducted 
under an investigational device exemption (IDE) under part 812 of this 
chapter must be identified as such.
    (14) Benefit and risk considerations. A discussion demonstrating 
that:
    (i) The data and information in the De Novo request constitute 
valid scientific evidence within the meaning of Sec.  860.7(c) and
    (ii) Pursuant to Sec.  860.7, when subject to general controls, or 
general and special controls, the probable benefit to health from use 
of the device outweighs any probable injury or illness from such use.
    (15) Technical sections. The following technical sections, which 
must contain data and information in sufficient detail to permit FDA to 
determine whether to grant or decline the De Novo request:
    (i) A section containing the results of the nonclinical studies of 
the device, including, as appropriate, microbiological, toxicological, 
immunological, biocompatibility, stress, wear, shelf life, electrical 
safety, electromagnetic compatibility, and other laboratory or animal 
tests. Information on nonclinical studies must include protocols and 
complete test reports for each study. For those nonclinical studies 
subject to part 58 of this chapter, this section must include a 
statement that each such study was conducted in compliance with such 
regulations, or, if the study was not conducted in compliance with part 
58 of this chapter, a brief statement of the reason for the 
noncompliance.
    (ii) For all devices that incorporate software, a section 
containing all relevant software information and testing, including, 
but not limited to, appropriate device hazard analysis, hardware, and 
system information.
    (iii) A section containing results of each clinical investigation 
of the device involving human subjects, including clinical protocols, 
number of investigators and subjects per investigator, investigation 
design, subject selection and exclusion criteria, investigation 
population, investigation period, safety and effectiveness data, 
adverse reactions and complications,

[[Page 54849]]

subject discontinuation, subject complaints, device failures (including 
unexpected software events if applicable) and replacements, tabulations 
of data from all individual subject report forms and copies of such 
forms for each subject who died during a clinical investigation or who 
did not complete the investigation, results of statistical analyses of 
the results of the clinical investigations, contraindications, 
warnings, precautions, and other limiting statements relevant to the 
use of the device type, and any other appropriate information from the 
clinical investigations. Any investigation conducted under an IDE under 
part 812 of this chapter must be identified as such. Information on 
clinical investigations involving human subjects must include the 
following:
    (A) For clinical investigations conducted in the United States, a 
statement with respect to each investigation that it either was 
conducted in compliance with the institutional review board regulations 
in part 56 of this chapter, or was not subject to the regulations under 
Sec.  56.104 or Sec.  56.105 of this chapter, and that it was conducted 
in compliance with the informed consent regulations in part 50 of this 
chapter; or if the investigation was not conducted in compliance with 
those regulations, a brief statement of the reason for the 
noncompliance. Failure or inability to comply with these requirements 
does not justify failure to provide information on a relevant clinical 
investigation.
    (B) For clinical investigations conducted in the United States, a 
statement that each investigation was conducted in compliance with part 
812 of this chapter concerning sponsors of clinical investigations and 
clinical investigators, or if the investigation was not conducted in 
compliance with those regulations, a brief statement of the reason for 
the noncompliance. Failure or inability to comply with these 
requirements does not justify failure to provide information on a 
relevant clinical investigation.
    (C) For clinical investigations conducted outside the United States 
that are intended to support the De Novo request, the requirements 
under Sec.  812.28 of this chapter apply. If any such investigation was 
not conducted in accordance with good clinical practice (GCP) as 
described in Sec.  812.28(a) of this chapter, include either a waiver 
request in accordance with Sec.  812.28(c) of this chapter or a brief 
statement of the reason for not conducting the investigation in 
accordance with GCP and a description of steps taken to ensure that the 
data and results are credible and accurate and that the rights, safety, 
and well-being of subjects have been adequately protected. Failure or 
inability to comply with these requirements does not justify failure to 
provide information on a relevant clinical investigation.
    (D) A statement that each investigation has been completed per the 
protocol or a summary of any protocol deviations.
    (E) A financial certification or disclosure statement or both as 
required by part 54 of this chapter.
    (F) For a De Novo request that relies primarily on data from a 
single investigator at one investigation site, a justification showing 
that these data and other information are sufficient to reasonably 
demonstrate the safety and effectiveness of the device when subject to 
general controls or general and special controls, and to ensure that 
the results from a site are applicable to the intended population.
    (G) A discussion of how the investigation data represent clinically 
significant results, pursuant to Sec.  860.7(e).
    (16) Other information. (i) A bibliography of all published reports 
not submitted under paragraph (a)(15) of this section, whether adverse 
or supportive, known to or that should reasonably be known to the 
requester and that concern the safety or effectiveness of the device.
    (ii) An identification, discussion, and analysis of any other data, 
information, or report relevant to an evaluation of the safety and 
effectiveness of the device known to or that should reasonably be known 
to the requester from any source, foreign or domestic, including 
information derived from investigations other than those in the request 
and from commercial marketing experience.
    (iii) Copies of such published reports or unpublished information 
in the possession of or reasonably obtainable by the requester, if 
requested by FDA.
    (17) Samples. If requested by FDA, one or more samples of the 
device and its components. If it is impractical to submit a requested 
sample of the device, the requester must name the location at which FDA 
may examine and test one or more of the devices.
    (18) Labeling and advertisements. Labels, labeling, and 
advertisements sufficient to describe the device, its intended use, and 
the directions for its use. Where applicable, photographs or 
engineering drawings must be supplied.
    (19) Other information. Such other information as is necessary to 
determine whether general controls or general and special controls 
provide reasonable assurance of safety and effectiveness of the device.
    (b) Pertinent information in FDA files specifically referred to by 
a requester may be incorporated into a De Novo request by reference. 
Information submitted to FDA by a person other than the requester will 
not be considered part of a De Novo request unless such reference is 
authorized in writing by the person who submitted the information.
    (c) If the requester believes that certain information required 
under paragraph (a) of this section to be in a De Novo request is not 
applicable to the device that is the subject of the De Novo request, 
and omits any such information from the De Novo request, the requester 
must submit a statement that specifies the omitted information and 
justifies the omission. The statement must be submitted as a separate 
section in the De Novo request and listed in the table of contents. If 
the justification for the omission is not accepted by FDA, FDA will so 
notify the requester.
    (d) The requester must update the pending De Novo request with new 
safety and effectiveness information learned about the device from 
ongoing or completed studies and investigations that may reasonably 
affect an evaluation of the safety or effectiveness of the device as 
such information becomes available.

Sec.  860.230  Accepting a De Novo request.

    (a) The acceptance of a De Novo request means that FDA has made a 
threshold determination that the De Novo request contains the 
information necessary to permit a substantive review. Within 15 days 
after a De Novo request is received by FDA, FDA will notify the 
requester whether the De Novo request has been accepted.
    (b) If FDA does not find that any of the reasons in paragraph 
(c)(1) of this section for refusing to accept the De Novo request apply 
or FDA fails to complete the acceptance review within 15 days, FDA will 
accept the De Novo request for review and will notify the requester. 
The notice will include the De Novo request reference number and the 
date FDA accepted the De Novo request. The date of acceptance is the 
date that an accepted De Novo request was received by FDA.
    (c)(1) FDA may refuse to accept a De Novo request if any of the 
following applies:
    (i) The requester has an open or pending premarket submission or 
reclassification petition for the device;
    (ii) The De Novo request is incomplete because it does not on its 
face contain all the information required

[[Page 54850]]

under section 513(f)(2) of the Federal Food, Drug, and Cosmetic Act or 
does not contain each of the items required under this part, or a 
justification for omission of any item;
    (iii) The De Novo request is not formatted as required under Sec.  
860.210;
    (iv) The De Novo request is for multiple devices and those devices 
are of more than one type; or
    (v) The requester has not responded to, or has failed to provide a 
rationale for not responding to, deficiencies identified by FDA in 
previous submissions for the same device, including those submissions 
described in Sec.  860.220(a)(3).
    (2) If FDA refuses to accept a De Novo request, FDA will notify the 
requester of the reasons for the refusal. The notice will identify the 
deficiencies in the De Novo request that prevent accepting and will 
include the De Novo request reference number.
    (3) If FDA refuses to accept a De Novo request, the requester may 
submit the additional information necessary to comply with the 
requirements of section 513(f)(2) of the Federal Food, Drug, and 
Cosmetic Act and this part. The additional information must include the 
De Novo request reference number of the original submission. If the De 
Novo request is subsequently accepted, the date of acceptance is the 
date FDA receives the additional information.

Sec.  860.240  Procedures for review of a De Novo request.

    (a) FDA will begin substantive review of a De Novo request after 
the De Novo request is accepted under Sec.  860.230. Within 120 days 
after receipt of a De Novo request or receipt of additional information 
that results in the De Novo request being accepted under Sec.  860.230, 
FDA will review the De Novo request and send the requester an order 
granting the De Novo request under Sec.  860.260(a) or an order 
declining the De Novo request under 860.260(b).
    (b) A requester may supplement or amend a pending De Novo request 
to revise existing information or provide additional information.
    (1) FDA may require additional information regarding the device 
that is necessary for FDA to complete the review of the De Novo 
request.
    (2) Additional information submitted to FDA must include the 
reference number assigned to the original De Novo request and, if 
submitted on the requester's own initiative, the reason for submitting 
the additional information.
    (c) Prior to granting or declining a De Novo request, FDA may 
inspect relevant facilities to help determine:
    (1) That clinical or nonclinical data were collected in a manner 
that ensures that the data accurately represents the benefits and risks 
of the device; or
    (2) That implementation of Quality System Regulation (part 820 of 
this chapter) requirements, in addition to other general controls and 
any specified special controls, provide adequate assurance that 
critical and/or novel manufacturing processes produce devices that meet 
specifications necessary to ensure reasonable assurance of safety and 
effectiveness.

Sec.  860.250  Withdrawal of a De Novo request.

    (a) FDA considers a De Novo request to have been withdrawn if:
    (1) The requester fails to provide a complete response to a request 
for additional information pursuant to Sec.  860.240(b)(1) within 180 
days after the date FDA issues such request;
    (2) The requester fails to provide a complete response to the 
deficiencies identified by FDA pursuant to Sec.  860.230(c)(2) within 
180 days of the date notification was issued by FDA;
    (3) The requester does not permit an authorized FDA employee an 
opportunity to inspect the facilities, pursuant to Sec.  860.240(c), at 
a reasonable time and in a reasonable manner, and to have access to 
copy and verify all records pertinent to the De Novo request; or
    (4) The requester submits a written notice to FDA that the De Novo 
request has been withdrawn.
    (b) If a De Novo request is withdrawn, the Agency will notify the 
requester. The notice will include the De Novo request reference number 
and the date FDA considered the De Novo request withdrawn.

Sec.  860.260  Granting or declining a De Novo request.

    (a)(1) FDA will issue to the requester an order granting a De Novo 
request if none of the reasons in paragraph (c) of this section for 
declining the De Novo request applies.
    (2) If FDA grants a De Novo request, within 30 days after the 
issuance of an order granting the De Novo request, FDA will publish in 
the Federal Register a notice of the classification order, including 
any special controls.
    (b) If FDA declines a De Novo request, FDA will issue a written 
order to the requester.
    (c) FDA may decline a De Novo request if the requester fails to 
follow the requirements of this part or if, upon the basis of the 
information submitted in the De Novo request or any other information 
before FDA, FDA determines:
    (1) The device does not meet the criteria under section 513(a)(1) 
of the Federal Food, Drug, and Cosmetic Act and Sec.  860.3 for 
classification into class I or II;
    (2) The De Novo request contains a false statement of material fact 
or there is a material omission;
    (3) The device's labeling does not comply with the requirements in 
parts 801 and 809 of this chapter, as applicable;
    (4) The product described in the De Novo request does not meet the 
definition of a device under section 201(h) of the Federal Food, Drug, 
and Cosmetic Act and is not a combination product as defined at Sec.  
3.2(e) of this chapter;
    (5) The device is of a type which has already been approved in 
existing applications for premarket approval (PMAs) submitted under 
part 814 of this chapter;
    (6) The device is of a type that has already been classified into 
class I, class II, or class III;
    (7) An inspection of a relevant facility under Sec.  860.240(c) 
results in a determination that general or general and special controls 
would not provide reasonable assurance of safety and effectiveness;
    (8) A nonclinical study subject to part 58 of this chapter that is 
described in the De Novo request, and that is essential to show there 
is reasonable assurance of safety, was not conducted in compliance with 
part 58 of this chapter and no reason for the noncompliance is provided 
or, if a reason is provided, the practices used in conducting the study 
do not support the validity of the study;
    (9) A clinical investigation described in the De Novo request 
involving human subjects that is subject to the institutional review 
board regulations in part 56 of this chapter, informed consent 
regulations in part 50 of this chapter, or GCP described in Sec.  
812.28(a) of this chapter, was not conducted in compliance with those 
regulations such that the rights or safety of human subjects were not 
adequately protected or the supporting data were determined to be 
otherwise unreliable;
    (10) A clinical or nonclinical study necessary to demonstrate that 
general controls or general and special controls provide reasonable 
assurance of safety and effectiveness:
    (i) Has not been completed per the study protocol, or
    (ii) Deficiencies related to the investigation and identified in 
any request for additional information under Sec.  860.240(b)(1) have 
not been adequately addressed; or

[[Page 54851]]

    (11) After a De Novo request is accepted for review under Sec.  
860.230(b), the requester makes significant unsolicited changes to the 
device's:
    (i) Indications for use; or
    (ii) Technological characteristics.
    (d) An order declining a De Novo request will inform the requester 
of the deficiencies in the De Novo request, including each applicable 
ground for declining the De Novo request.
    (e) FDA will use the criteria specified in Sec.  860.7 to determine 
the safety and effectiveness of a device in deciding whether to grant 
or decline a De Novo request. FDA may use information other than that 
submitted by the requester in making such determination.

    Dated: September 30, 2021.
Janet Woodcock,
Acting Commissioner of Food and Drugs.
[FR Doc. 2021-21677 Filed 10-4-21; 8:45 am]
BILLING CODE 4164-01-P