[Federal Register Volume 83, Number 235 (Friday, December 7, 2018)]
[Proposed Rules]
[Pages 63127-63146]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-26378]


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

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: Proposed rule.

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

SUMMARY: The Food and Drug Administration (FDA) proposes to establish 
requirements for the medical device De Novo classification process 
under the Federal Food, Drug, and Cosmetic Act (FD&C Act). The proposed 
requirements establish procedures and criteria related to requests for 
De Novo classification (``De Novo request''). 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, as well as 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 proposed rule, if finalized, would implement 
the De Novo classification process under the FD&C Act, as enacted by 
the Food and Drug Administration Modernization Act of 1997 and modified 
by the Food and Drug Administration Safety and Innovation Act and the 
21st Century Cures Act.

DATES: Submit either electronic or written comments on the proposed 
rule by March 7, 2019. Submit comments on information collection issues 
under the Paperwork Reduction Act of 1995 by January 7, 2019.

ADDRESSES: You may submit comments as follows. Please note that late, 
untimely filed comments will not be considered. Electronic comments 
must be submitted on or before March 7, 2019. The https://www.regulations.gov electronic filing system will accept comments until 
11:59 p.m. Eastern Time at the end of March 7, 2019. Comments received 
by mail/hand delivery/courier (for written/paper submissions) will be 
considered timely if they are postmarked or the delivery service 
acceptance receipt is on or before that date.

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to https://www.regulations.gov 
will be posted to the docket unchanged. Because your comment will be 
made public, you are solely responsible for ensuring that your comment 
does not include any confidential information that you or a third party 
may not wish to be posted, such as medical information, your or anyone 
else's Social Security number, or confidential business information, 
such as a manufacturing process. Please note that if you include your 
name, contact information, or other information that identifies you in 
the body of your comments, that information will be posted on https://www.regulations.gov.
     If you want to submit a comment with confidential 
information that you do not wish to be made available to the public, 
submit the comment as a written/paper submission and in the manner 
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand delivery/Courier (for written/paper 
submissions): Dockets Management Staff (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Dockets 
Management Staff, FDA will post your comment, as well as any 
attachments, except for information submitted, marked and identified, 
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No. 
FDA-2018-N-0236 for Medical Device De Novo Classification Process. 
Received comments, those filed in a timely manner (see ADDRESSES), will 
be placed in the docket and, except for those submitted as 
``Confidential Submissions,'' publicly viewable at https://www.regulations.gov or at the Dockets Management Staff between 9 a.m. 
and 4 p.m., Monday through Friday.
     Confidential Submissions--To submit a comment with 
confidential information that you do not wish to be made publicly 
available, submit your comments only as a written/paper submission. You 
should submit two copies total. One copy will include the information 
you claim to be confidential with a heading or cover note that states 
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will 
review this copy, including the claimed confidential information, in 
its consideration of comments. The second copy, which will have the 
claimed confidential information redacted/blacked out, will be 
available for public viewing and posted on https://www.regulations.gov. 
Submit both copies to the Dockets Management Staff. If you do not wish 
your name and contact information to be made publicly available, you 
can provide this information on the cover sheet and not in the body of 
your comments and you must identify this information as 
``confidential.'' Any information marked as ``confidential'' will not 
be disclosed except in accordance with 21 CFR 10.20 and other 
applicable disclosure law. For more information about FDA's posting of 
comments to public dockets, see 80 FR 56469, September 18, 2015, or 
access the information at: https://www.gpo.gov/fdsys/pkg/FR-2015-09-18/pdf/2015-23389.pdf.

[[Page 63128]]

    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in 
the heading of this document, into the ``Search'' box and follow the 
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852.
    Submit comments on information collection issues to the Office of 
Management and Budget (OMB) in the following ways:
     Fax to the Office of Information and Regulatory Affairs, 
OMB, Attn: FDA Desk Officer, Fax: 202-395-7285, or email to 
[email protected]. All comments should be identified with the 
title, ``Medical Device De Novo Classification Process.''

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. 1538, Silver Spring, MD 20993, 301-
796- 6419.

SUPPLEMENTARY INFORMATION:

Table of Contents

I. Executive Summary
    A. Purpose of the Proposed Rule
    B. Summary of the Major Provisions of the Proposed Rule
    C. Legal Authority
    D. Costs and Benefits
II. Table of Abbreviations/Commonly Used Acronyms in This Document
III. Background
IV. Statutory Framework and Authority
V. Proposed Rule
    A. Scope (Proposed Subpart D and Sec.  860.1)
    B. Definitions (Proposed Sec.  860.3)
    C. Confidentiality of Information and Data Related to a De Novo 
Request (Proposed Sec.  860.5)
    D. De Novo Classification--General (Proposed Sec.  860.201)
    E. De Novo Request Format (Proposed Sec.  860.223)
    F. De Novo Request Content (Proposed Sec.  860.234)
    G. Accepting a De Novo Request (Proposed Sec.  860.245)
    H. Procedures for Review of a De Novo Request (Proposed Sec.  
860.256)
    I. Withdrawal of a De Novo Request (Proposed Sec.  860.267)
    J. Granting or Declining a De Novo Request (Proposed Sec.  
860.289)
VI. Proposed Effective Date
VII. Economic Analysis of Impacts
VIII. Analysis of Environmental Impact
IX. Consultation and Coordination With Indian Tribal Governments
X. Paperwork Reduction Act of 1995
XI. Federalism
XII. References

I. Executive Summary

A. Purpose of the Proposed Rule

    This proposed rule implements the medical device De Novo 
classification process under the FD&C Act (section 513(f)(2) (21 U.S.C. 
360c(f)(2)), 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) (21 U.S.C. 
360c(f)(1)).
    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) in 
order to legally market a device of the same type. Instead, 
manufacturers can use the less burdensome pathway of premarket 
notification (section 510(k) of the FD&C Act (21 U.S.C. 360(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 Proposed Rule

    If this rule is finalized as proposed, it will establish procedures 
and criteria for the submission and withdrawal of a De Novo request. It 
would also establish procedures and criteria for FDA to accept, review, 
grant and/or decline a De Novo request. The proposed 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 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 is incomplete on its face.
     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 proposed rule also describes our practices for the conditions 
under which the confidentiality of a De Novo request is maintained.

C. Legal Authority

    FDA is issuing this rule under the De Novo classification section 
of the FD&C Act, the device classification section of the FD&C Act, and 
the general rulemaking section of the FD&C Act. (See section 513(f)(2), 
section 513(a)(1), and section 701(a) of the FD&C Act (21 U.S.C. 
371(a).)

D. Costs and Benefits

    The proposed rule would clarify and make more efficient 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 would improve the 
efficiency of obtaining marketing authorization for certain novel 
medical devices. Over 10 years, the annualized cost estimates

[[Page 63129]]

range from $0.0 million to $0.08 million with a 7 percent discount 
rate, and range from $0.0 million to $0.03 million with a 3 percent 
discount rate.

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

                                       Table 1--Abbreviations and Acronyms
----------------------------------------------------------------------------------------------------------------
       Abbreviation or acronym                                       What it means
----------------------------------------------------------------------------------------------------------------
510(k)..............................  Premarket Notification.
CFR.................................  Code of Federal Regulations.
EUA.................................  Emergency Use Authorization.
FDA.................................  Food and Drug Administration.
FD&C Act............................  Federal Food, Drug, and Cosmetic Act.
FR..................................  Federal Register.
GLP.................................  Good Laboratory Practice.
HDE.................................  Humanitarian Device Exemption.
IDE.................................  Investigational Device Exemption.
MDR.................................  Medical Device Reporting.
NSE.................................  Not Substantially Equivalent.
OMB.................................  Office of Management and Budget.
PMA.................................  Premarket Approval Application.
PRA.................................  Paperwork Reduction Act of 1995.
Pub. L..............................  Public Law.
Ref.................................  Reference.
RFD.................................  Requests for Designation under Sec.   3.7.
SE..................................  Substantially Equivalent.
U.S.C...............................  United States Code.
----------------------------------------------------------------------------------------------------------------

III. Background

    The De Novo classification process provides a 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. This pathway is intended to limit 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 a PMA due to a 
lack of a predicate.
    When FDA classifies a device type as class I or II via the De Novo 
classification pathway, other manufacturers do not have to submit a De 
Novo request or PMA in order to market the same device type, unless the 
device has a new intended use or technological characteristics that 
raise different questions of safety or effectiveness. Instead, 
manufacturers can use the less burdensome 510(k) pathway, when 
applicable, to market their device, because the device that was the 
subject of the original De Novo classification can serve as a predicate 
device.
    On October 30, 2017, FDA issued a final guidance (Ref. 1) to 
provide recommendations on the process for the submission and review of 
a De Novo request. The guidance provides recommendations for 
interactions with FDA related to the De Novo classification process, 
including what information to submit when seeking a path to market via 
the De Novo classification process. Nevertheless, some De Novo requests 
lack crucial data or other information rendering the requests 
incomplete and requiring additional reviews.
    To enhance regulatory clarity and predictability, FDA is also 
conducting this rulemaking. We believe it will, when finalized, provide 
a regulatory framework that sets clear standards, expectations and 
processes for De Novo classification. The statutory language on the 
content of De Novo requests is vague regarding what specific 
information is expected from the requester. With codified minimum 
content requirements, industry will be better able to anticipate what 
is necessary for successful De Novo classification, and FDA staff will 
have clear standards for the content and process for De Novo 
classification. This may also reduce the number of questions raised by 
FDA during the review of the De Novo request and may reduce the total 
review time needed to render a final decision. It is important to have 
enforceable content requirements for De Novo requests as well as 
additional clarity regarding FDA's review and ultimate decision on a De 
Novo request. A regulation will allow FDA to communicate minimum 
content requirements, which will thereby give FDA the ability to triage 
inadequate De Novo requests by refusing to accept such De Novo 
requests.

IV. Statutory Framework and Authority

    The FD&C Act establishes a comprehensive system for the regulation 
of medical devices intended for human use. The FD&C Act establishes 
three categories (classes) of medical devices based on the extent of 
the regulatory controls necessary and sufficient to provide reasonable 
assurance of safety and effectiveness of the device. The three 
categories of devices are class I (general controls), class II (special 
controls), and class III (premarket approval).
    FDA refers to devices that were not in commercial distribution 
before May 28, 1976, the enactment date of the Medical Device 
Amendments of 1976, as ``postamendments'' devices. Postamendments 
devices are classified into class III ``automatically'' or 
``statutorily.'' (Section 513(f)(1) of the FD&C Act.) These devices are 
automatically designated as class III devices and require premarket 
approval, unless: (1) FDA issues an order classifying the device into 
class I or II; (2) FDA reclassifies the device into class I or II; or 
(3) FDA issues an order finding the device to be SE to a predicate 
device that does not require premarket approval. Under this third 
option, FDA determines whether a postamendments device is SE to a 
previously cleared device (predicate device) by means of its 510(k) 
procedures (section 510(k) of the FD&C Act; 21 CFR part 807). Legally 
marketed devices that may serve as a predicate device include: A device 
that has been cleared through the 510(k) process, including a device 
that is not currently being marketed; a device that was legally 
marketed prior to May 28, 1976 (``preamendments device'') for which a 
PMA is not required; a device that has been reclassified from class III 
into class II or I; or a device that by

[[Page 63130]]

regulation is exempted from premarket notification (``510(k)-exempt 
device''). A device removed from the market at the initiative of the 
Commissioner of Foods and Drugs or that has been determined by judicial 
order to be misbranded or adulterated cannot serve as a predicate 
device (section 513(i)(2) of the FD&C Act and Sec.  807.100(b)(3)).
    In 1997, Congress enacted a new De Novo classification pathway. 
(Section 207 of the Food and Drug Administration Modernization Act of 
1997 (Pub. L. 105-115)). Congress included this new pathway to limit 
unnecessary expenditure of FDA and industry resources that may occur if 
devices for which general controls or general and special controls 
would provide a reasonable assurance of safety and effectiveness were, 
nevertheless, subject to premarket approval by operation of law because 
a predicate device could not be identified. In 2012, Congress 
streamlined the De Novo classification process by providing that FDA 
may classify certain medical devices under the De Novo classification 
process without first issuing a determination that such devices are NSE 
to legally marketed devices (Section 607 of the Food and Drug 
Administration Safety and Innovation Act (Pub. L. 112-144)). In 2016, 
the process was further modified so that a De Novo request need not be 
submitted within 30 days of receiving an NSE determination (Section 
3101 of the 21st Century Cures Act (Pub. L. 114-255)).
    A De Novo request may recommend to FDA whether the device should be 
class I or class II. The De Novo request should describe why general 
controls or general and special controls are adequate to provide 
reasonable assurance of safety and effectiveness of the device. For any 
class II recommendation, the De Novo request must also provide an 
initial draft of proposed special controls along with a description of 
how the special controls provide reasonable assurance of safety and 
effectiveness. In response to a De Novo request, FDA will classify the 
device by written order within 120 days. This classification is the 
initial classification of the device. After the issuance of an order 
classifying the device, FDA will publish a notice in the Federal 
Register announcing this classification.\1\
---------------------------------------------------------------------------

    \1\ The FD&C Act provides that a class I device is generally 
exempt from 510(k) requirements (section 510(l) of the FD&C Act (21 
U.S.C. 360(l))). FDA also may exempt a class II device from 510(k) 
requirements if FDA determines that 510(k) is not necessary to 
provide reasonable assurance of the safety and effectiveness of the 
device (section 510(m) of the FD&C Act (21 U.S.C. 360(m))). The 
process to exempt a class II device from 510(k) requirements is 
separate from FDA's consideration and granting of a De Novo request. 
For more information about procedures for class II device exemptions 
from premarket notification, see FDA's guidance ``Procedures for 
Class II Device Exemptions from Premarket Notification, Guidance for 
Industry and CDRH Staff'' (Ref. 2).
---------------------------------------------------------------------------

    FDA may decline a De Novo request when the device does not meet the 
statutory criteria for classification into class I or II. For De Novo 
requests that are not preceded by a 510(k) and an NSE determination, 
FDA may also decline to undertake the De Novo request if FDA identifies 
a legally marketed device that could provide a reasonable basis for 
review of substantial equivalence with the device, or when FDA 
determines that the device submitted is not of low to moderate risk or 
that general controls would be inadequate to control the risks and 
special controls to mitigate the risks cannot be established. A device 
that remains in class III shall be deemed adulterated and may not be 
distributed until approved in a PMA or exempted from such approval by 
an investigational device exemption (IDE).
    In addition, the general administrative provisions of the FD&C Act 
provide authority to issue regulations for the efficient enforcement of 
the FD&C Act (section 701(a) of the FD&C Act).

V. Proposed Rule

    FDA is proposing to amend its regulations to establish a new 
subpart to the medical device classification procedures regulations. 
The proposed rule, if finalized, would establish requirements for the 
medical device De Novo classification process.

A. Scope (Adding Proposed Subpart D to Part 860 and Modifying Sec.  
860.1)

    FDA proposes to add a new subpart to the medical device 
classification procedures regulations, subpart D (21 CFR part 860, 
subpart D). The new proposed subpart will describe the form and manner 
for submission of a De Novo request. It would also describe FDA's 
process for a review of a De Novo request, and the form and manner in 
which FDA would grant or decline a De Novo request. Lastly, it would 
also describe the form and manner for withdrawal of a De Novo request.
    The proposed rule would clarify and explain the regulatory 
framework and process for submitting a De Novo classification request. 
A De Novo request can be submitted after the submission of a premarket 
notification (510(k)) and a subsequent order declaring the device NSE 
to legally marketed devices. Under the proposed rule, a De Novo request 
may also be submitted without first submitting a 510(k) for that 
device, if the submitter determines that there is no legally marketed 
device upon which to base a determination of substantial equivalence.
    In response to a De Novo request, FDA would classify the device by 
written order. This classification would be the initial classification 
of the device (section 513(f)(1) of the FD&C Act). FDA would publish a 
notice in the Federal Register announcing the new classification and 
codifying it in the CFR.
    FDA proposes to amend its regulations to prescribe the content and 
format of a De Novo request. FDA also proposes to amend its regulations 
to include processes and criteria for FDA to accept, review, grant, and 
decline a De Novo request.
    The proposed regulation would define the scope of the medical 
device classification procedures (Sec.  860.1 (21 CFR 860.1)). It 
includes the criteria and procedures used by classification panels and 
the FDA Commissioner in the classification and reclassification of 
devices (sections 513, 514(b), (21 U.S.C. 360d(b)), 515(b) (21 U.S.C. 
360e(b)) and 520(l) (21 U.S.C. 360j(l)) of the FD&C Act). FDA proposes 
to update the scope to add ``advisory committees,'' to authorize such 
committees to provide panel recommendations as to the classification or 
reclassification of medical devices. (Sec.  860.1(b).)

B. Definitions (Proposed Sec.  860.3)

    FDA proposes to add five new definitions to the definitions section 
of the medical device classification procedures regulations (Sec.  
860.3). FDA also proposes to amend the definitions section to remove 
the paragraph designations and to list the definitions alphabetically. 
This proposed amendment would make adding any new definitions to this 
part easier in the future. Except for removing the paragraph 
designations, and deleting the definition for ``the act'' because we 
are replacing ``the act'' with ``Federal Food, Drug, and Cosmetic Act'' 
throughout part 860, FDA is not proposing in this rulemaking to change 
any of the definitions currently listed in the definitions section.
    FDA proposes to add the term, classification regulation, to the 
definitions section. FDA proposes to define classification regulation 
to mean a regulation that identifies the generic type of device and its 
class. The proposed definition explains that FDA's medical device 
classification regulations are in parts 862 through 892 of FDA's 
regulations (21 CFR parts 862-892).

[[Page 63131]]

    FDA proposes to add the term, De Novo request, to the definitions 
section. FDA proposes to define De Novo request to mean the information 
that is submitted as part of a request to FDA to issue an order to 
classify a device under the De Novo classification section of the FD&C 
Act (section 513(f)(2) of the FD&C Act). The proposed definition 
explains that information submitted as part of a De Novo request 
includes information incorporated into that request by reference.
    For convenience, we propose to add a definition of FDA. FDA 
proposes to define FDA as the Food and Drug Administration. This 
addition is intended to remove the need to further define this term in 
the proposed De Novo regulation, as well as in the other subparts of 
medical device classification procedures regulations (part 860).
    FDA proposes to add a definition of general controls. This proposed 
definition harmonizes with the definition in the FD&C Act and the 
definition of Class I currently listed in the definitions section of 
the medical device classification procedures regulations (section 
513(a)(1)(A) of the FD&C Act and Sec.  860.3). While the meaning of 
general controls has been provided in guidance, adding the definition 
to this regulation will provide another opportunity to explain which 
controls are included as general controls.
    FDA proposes to add a definition of special controls. This proposed 
definition harmonizes with the definition in section of the FD&C Act 
and the definition of Class II currently listed in the definitions 
section of the medical device classification procedures regulations, 
and is intended to clarify the regulatory significance of special 
controls as the controls necessary to provide reasonable assurance of 
safety and effectiveness for a type of device classified as class II 
(section 513(a)(1)(B) of the FD&C Act and Sec.  860.3). Special 
controls may include such things as performance standards, performance 
testing (e.g., biocompatibility testing, sterilization validation, 
clinical investigations), postmarket surveillance, patient registries, 
and development and dissemination of guidelines (including guidelines 
for the submission of clinical data in premarket notification 
submissions in accordance with premarket notification of the FD&C Act). 
While explanations of special controls have been provided in guidance, 
adding the definition to this regulation will provide another 
opportunity to clarify which controls are special controls.

C. Confidentiality of Information and Data Related to a De Novo Request 
(Proposed Sec.  860.5)

    The proposed additions to confidentiality of information and data 
section of the medical device classification procedures regulations 
address the public disclosure of data and information submitted as part 
of a De Novo request (Sec.  860.5). FDA is proposing that the public 
disclosure of data and information in a De Novo request be governed by 
the confidentiality sections of the regulations (Sec.  860.5 and part 
20 (21 CFR part 20)).
    The proposed De Novo request confidentiality section discusses 
which De Novo request information is covered (Sec.  860.5(g)(1)). FDA 
proposes that information covered includes all information submitted or 
incorporated by reference in the De Novo request, any De Novo 
supplement, or any other submission relevant to the administrative file 
(as defined in 21 CFR 10.3(a)).
    The proposed De Novo request confidentiality section discusses when 
FDA may disclose the existence of a De Novo request (Sec.  
860.5(g)(2)). FDA is proposing that the existence of a De Novo request 
may not be disclosed before it issues an order granting the De Novo 
request. FDA is further proposing that when a De Novo requester itself 
has disclosed the existence of the De Novo request publicly, then FDA 
may also publicly disclose the existence of a De Novo request before 
issuing an order granting the De Novo request.
    The proposed De Novo request confidentiality section discusses when 
FDA may publicly disclose data or information contained in a De Novo 
request before FDA issues an order granting the De Novo request (Sec.  
860.5(g)(3)). The data or information contained in the De Novo request 
will not be disclosed unless the De Novo requestor has publicly 
disclosed or acknowledged the information.
    The proposed De Novo request confidentiality section proposes that 
FDA may immediately disclose any safety and effectiveness information 
and any other information not exempt from release under the trade 
secret and confidential commercial information section of the 
regulations after FDA issues the order granting the De Novo request 
(Sec.  860.5(g)(4) and Sec.  20.61).

D. De Novo Classification--General (Proposed Sec.  860.201)

    The proposed section provides the purpose of the new subpart and 
the devices to which the subpart is applicable (Sec.  860.201). In this 
proposed rule, FDA would add a new subpart to the medical device 
classification procedures regulations (part 860, subpart D). The new 
proposed subpart contains the procedures and criteria for the De Novo 
classification process (section 513(f)(2) of the FD&C Act).
    The proposed purpose section states that the purpose of the new 
subpart is to establish an efficient and thorough process to facilitate 
the classification into class I or II for devices for which there are 
no legally marketed devices on which to base a review of substantial 
equivalence and which meet the requirements for class I or class II as 
described in (Sec.  860.201(a), and section 513(a)(1) of the FD&C Act 
and Sec.  860.3).
    The proposed purpose section would identify the devices for which a 
De Novo request may be submitted (Sec.  860.201(b)). Under the proposed 
purpose section, a De Novo request may be submitted after receiving a 
NSE determination in response to a 510(k) (Sec.  860.201(b)(1)). We 
note that devices that have been found to be NSE for lack of a 
predicate, new intended use, or different technological characteristics 
that raise different questions of safety and effectiveness will 
generally be eligible for the De Novo classification process. We 
further note that a De Novo request for more than one device type would 
not be eligible for the De Novo classification process as part of the 
same request.
    Under the proposed purpose section, a De Novo request may also be 
submitted if a person, without first submitting a 510(k) and receiving 
an NSE determination, determines that there is no legally marketed 
device upon which to base a SE determination (Sec.  860.201(b)(2)).
    The De Novo classification process is a pathway to market for 
devices for which there are no legally marketed devices on which to 
base a review of SE and which meet the requirements for class I or 
class II (as described in section 513(a)(1) of the FD&C Act and 21 CFR 
860.3). Under the De Novo classification section of the FD&C Act, if 
FDA identifies a legally marketed device that could provide a 
reasonable basis for review of SE, FDA may decline to undertake a De 
Novo request (section 513(f)(2)(A)(iv) of the FD&C Act). A device that 
could provide a reasonable basis for review of SE with another device 
is known as a predicate device. Thus, devices that have been found to 
be NSE solely due to inadequate performance data to demonstrate SE will 
generally be ineligible for the De Novo classification process because 
a predicate device that could provide a

[[Page 63132]]

reasonable basis for review of SE exists. (The substantial equivalence 
section of the FD&C Act provides the criteria for FDA to determine SE 
(section 513(i) of the FD&C Act).)

E. De Novo Request Format (Proposed Sec.  860.223)

    FDA proposes a submission process and format for a De Novo request 
in this section (Sec.  860.223). FDA proposes in the format section 
that De Novo requests for a device be submitted to the FDA Center that 
has the lead in regulating that device (Sec.  860.223(a)(1)). FDA 
proposes that De Novo requests related to devices regulated by the 
Center for Devices for Radiological Health (CDRH) be submitted to CDRH 
and that those De Novo requests related to devices regulated by the 
Center for Biologics Evaluation and Research (CBER) be submitted to 
CBER. FDA provides the appropriate CBER and CDRH addresses as part of 
the proposed rule.
    FDA also proposes in the format section that the De Novo request be 
signed by the requester or its authorized representative (Sec.  
860.223(a)(2)).
    FDA is proposing further format requirements for the De Novo 
request (Sec. Sec.  860.223(a)(3) and (4)). These proposed requirements 
are intended to assist in the efficiency of FDA's processing and review 
of the De Novo request. FDA is proposing in the format requirements 
that a cover page designate the De Novo request as a ``De Novo 
Request'' (Sec.  860.223(a)(3)). FDA is proposing that the entire 
content of the submission be in English or translated into English 
(Sec.  860.223(a)(4)). FDA proposes this requirement because FDA does 
not have the resources to assure the accurate and timely English 
translation of documents written in a non-English language to 
facilitate the document's use in FDA's review. Please note FDA's 
``eCopy Program for Medical Device Submissions'' guidance (Ref. 3), is 
applicable to De Novo requests.

F. De Novo Request Content (Proposed Sec.  860.234)

    FDA proposes requirements for the content of a De Novo request 
(Sec.  860.234). This proposed section would establish the types of 
information that must be included in each De Novo request. To 
adequately support a request for De Novo classification, FDA proposes 
that the De Novo request include the following information, unless the 
De Novo requester provides a justification for each particular 
omission.
    FDA proposes the De Novo request must include a table of contents 
that identifies the volume and page number for each item listed (Sec.  
860.234(a)(1)). A table of contents assists FDA in locating information 
included in the De Novo request, including during the review of the De 
Novo request.
    To assist FDA in contacting the De Novo requester during review of 
a De Novo request, FDA is proposing that the De Novo request include 
the appropriate contact information of the De Novo requester (Sec.  
860.234(a)(2)). During its review of a De Novo request, FDA may need to 
contact the De Novo requester for various reasons, including to ask 
questions. Contact information would assist in quick and efficient 
contact of the appropriate person. FDA is proposing to require that the 
De Novo request include the name, address, phone, fax, and email 
address of the De Novo requester.
    FDA is also proposing to require that a De Novo request include the 
establishment registration number of the owner or operator submitting 
the De Novo request, if applicable (Sec.  860.234(a)(2)). FDA would use 
this information should FDA determine an onsite inspection is 
necessary.
    FDA is proposing that a De Novo request include a statement 
regarding the regulatory history of the device, including if there have 
been prior submissions to FDA on the device (Sec.  860.234(a)(3)). If 
there has been a prior submission, FDA proposes to require that a De 
Novo request identify on the prior submission, including any 510(k)s 
and related NSE decisions, IDEs, requests for designation (RFD) under 
Sec.  3.7 (21 CFR 3.7), Pre-Submission, PMAs, Humanitarian Device 
Exemptions (HDEs), Emergency Use Authorizations (EUAs), section 513(g) 
requests for information, and previously withdrawn or declined De Novo 
requests (Sec.  860.234(a)(3)). The identification of the prior 
submission would also be required to identify any feedback or 
deficiencies communicated to the requester during the Agency's review 
of the prior submission and how the feedback or deficiencies are 
addressed in the De Novo request, where applicable. This proposed 
requirement is useful for FDA in communicating with a firm or when 
determining whether there is an existing active submission for the same 
device. This information may also assist FDA in determining if feedback 
provided during a related submission noted above, including any 
deficiencies communicated to the requester, was addressed in a previous 
De Novo request. FDA also uses this regulatory history information when 
determining whether a potential predicate device exists or whether a 
more appropriate pathway to marketing exists for the device.
    FDA is proposing that the De Novo request include the name of the 
device (Sec.  860.234(a)(4)). The name of the device would include any 
generic, proprietary, and trade names. These names help FDA identify 
the device.
    FDA is proposing that the De Novo request include the device's 
indications for use, including whether the device would be prescription 
or over the counter (Sec.  860.234(a)(5)). As part of the indications 
for use, the De Novo request must describe the disease or condition the 
device would diagnose, treat, prevent, cure or mitigate, or how the 
device would affect the structure or function of the body, including a 
description of the patient population for which the device is intended. 
The indications would include all the labeled patient uses of the 
device. FDA uses this information to assess whether all of the risks 
associated with the device are identified, whether the indications for 
use are consistent with the labeling, and to determine whether the 
device is of a type that has already been classified. For more 
information about indications for use, see FDA's guidance ``The 510(k) 
Program: Evaluating Substantial Equivalence in Premarket Notifications 
[510(k)], Guidance for Industry and CDRH Staff'' (Ref. 1).
    FDA is proposing that the De Novo request include a device 
description (Sec.  860.234(a)(6)). Proposed Sec.  860.234(a)(6)(i) 
requires the submission of a complete description of the device. This 
may include a narrative description of the device pictorial 
representations, device specifications, and engineering drawings, where 
applicable.
    FDA is proposing that the device description include a description 
of each of the functional components or ingredients of the device, if 
the device consists of more than one physical component or ingredient 
(Sec.  860.234(a)(6)(ii)).
    FDA is proposing that the device description include a description 
of the properties of the device relevant to diagnosing, treating, 
preventing, curing, or mitigating the disease or condition, and/or the 
effect of the device on the structure or function of the body (Sec.  
860.234(a)(6)(iii)). This description is intended to assist in FDA's 
assessment of the benefits and risks of the device type.
    FDA is proposing that the De Novo request include a complete 
description of the operational principles of the device (Sec.  
860.234(a)(6)(iv)). This would include the mode of operation through

[[Page 63133]]

which a device achieves its intended use. This information would be 
used during FDA's review of the De Novo request to help determine 
whether the device is of a type that has been previously classified.
    FDA is proposing that the device description include FDA assigned 
reference numbers (e.g., 510(k) number, classification regulation 
number) for any legally marketed devices (including accessories) that 
are intended to be used with the device (Sec.  860.234(a)(6)(v)).
    FDA proposes that the De Novo request include a description of 
known or reasonably known existing alternative practices or procedures 
for 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 (Sec.  860.234(a)(6)(v)). 
This information is intended to capture available alternative biologic, 
device, or drug practices or procedures during FDA's assessment of the 
benefits and risks of the device and device type.
    FDA proposes a classification summary requirement for a De Novo 
request for a device that has not previously been the subject of a 
premarket notification under section 510(k) of the FD&C Act (Sec.  
860.234(a)(8)(i)). This information would be intended to assist FDA to 
establish that the De Novo classification process is appropriate for 
the device or if a legally marketed device of the same type exists. For 
such devices, FDA proposes that the De Novo request include a complete 
description of the searches used to establish that no legally marketed 
device of the same type exists (Sec.  860.234(a)(8)(i)(A)). Further, 
for such devices, FDA proposes that the De Novo request include a list 
of potentially similar devices to the subject device, including any 
classification regulations, PMAs, HDEs, 510(k)s, EUAs, or product codes 
applicable to the other devices, and a rationale explaining how the 
subject device is different from these devices (Sec.  
860.234(a)(8)(i)(B) and (C)). FDA intends to use this information in 
assessing the appropriate classification of the device.
    FDA proposes a classification summary requirement for a De Novo 
request for a device that has been the subject of a premarket 
notification under section 510(k) of the FD&C Act (Sec.  
860.234(a)(8)(ii)). For such devices, FDA proposes that the submitter 
include the relevant 510(k) number(s) to assist FDA in locating the 
previously submitted information. Further, for such devices, FDA 
proposes that the submitter include a summary of the search performed 
to confirm that no legally marketed device of the same type exists 
since the date FDA issued the NSE determination letter. This 
requirement would assist FDA in establishing that no legally marketed 
device of the same type exists.
    In accordance with the De Novo classification section in the FD&C 
Act, FDA proposes that the De Novo request must recommend class I or II 
classification (section 513(f)(2)(A)(v) of the FD&C Act and Sec.  
860.234(a)(9)). FDA proposes that this classification recommendation 
include a description of why the De Novo requester believes general 
controls or general and special controls are adequate to provide 
reasonable assurance of safety and effectiveness. If the submitter 
recommends that the device be classified as class II, FDA proposes that 
the recommendation must include a draft proposal for applicable special 
controls, and a description of how those special controls provide 
reasonable assurance of safety and effectiveness of the device (Sec.  
860.234(a)(10)).
    FDA proposes that the De Novo request include a summary of known or 
reasonably known probable risks to health associated with the use of 
the device and any proposed mitigations for each probable risk (Sec.  
860.234(a)(11)). FDA would use this information to assess the different 
types of harmful events that may potentially result from use of the 
device and when determining if the harmful events can be mitigated 
sufficiently. A summary of probable risks to health should be based on 
the best available information at the time of submission of the De Novo 
request. A summary of any proposed mitigation should identify whether 
the mitigation is a general control or a special control and provide 
details about each control. A summary of any proposed mitigation that 
involves specific performance testing or labeling must include 
references to the applicable section or pages in the De Novo request 
that support the proposed testing or labeling.
    FDA proposes that the De Novo request include reference to any 
published standard relevant to the safety or effectiveness of the 
device and that are known or should reasonably be known to the 
requester (Sec.  860.234(a)(12)). The proposed standards section would 
require that the De Novo request provide adequate information to 
demonstrate how the device meets, or justify any deviation from, 
performance standards (Sec.  860.234(a)(12)(i)). These published 
standards include both voluntary consensus standards recognized under 
the recognition of standards section of the FD&C Act and any voluntary 
consensus standard not yet recognized by FDA but cited in the De Novo 
request (section 514(c) of the FD&C Act (21 U.S.C. 360d(c)). This 
explanation would specify what applicable voluntary consensus standards 
or parts of standard(s) the device does not meet and explain any 
deviations.
    FDA proposes that the De Novo request summarize each study used to 
support the De Novo request (Sec.  860.234(a)(13)). This proposed 
requirement is intended to ensure the quality and integrity of data 
obtained from these studies. This proposed requirement would apply to 
nonclinical laboratory studies and clinical investigations involving 
human subjects. For nonclinical laboratory studies and clinical 
investigations involving human subjects, the summary would be required 
to include a description of the following: The study objective, the 
experimental design, any data collection and analysis, and any 
positive, negative, or inconclusive study results. For nonclinical 
laboratory studies, FDA proposes to require a summary of each study 
(Sec.  860.234(a)(13)(i)). For a clinical investigation involving human 
subjects, FDA proposes to require that a discussion of subject 
selection and exclusion criteria, investigation population, 
investigation period, safety and effectiveness data, adverse reactions 
and complications, patient discontinuation, patient complaints, device 
failures (including unexpected software events if applicable) and 
replacements, results of statistical analyses of the clinical 
investigation, contraindications and precautions for use of the device, 
and other information from the clinical investigation as appropriate 
(any investigation conducted under an IDE must be identified as such) 
must be included (Sec.  860.234(a)(13)(ii)). FDA proposes these 
requirements to assure that a study's data and reported results are 
credible and accurate and to ensure consistency in FDA clinical data 
requirements. FDA would use the summary of investigations in assessing 
safety and effectiveness of the device.
    FDA proposes that the De Novo request include a discussion of 
benefit and risk considerations (Sec.  860.234(a)(14)). The proposed 
benefit and risk consideration section would require a discussion 
demonstrating that the data and information in the De Novo request 
constitute valid scientific evidence (Sec.  860.234(a)(14)(i)). Valid 
scientific evidence is evidence from well-controlled investigations, 
partially controlled investigations, investigations and objective 
trials without matched

[[Page 63134]]

controls, well-documented case histories conducted by qualified 
experts, and reports of significant human experience with a marketed 
device, from which it can fairly and responsibly be concluded by 
qualified experts that there is reasonable assurance of the safety and 
effectiveness of a device under its conditions of use (Sec.  
860.7(c)(2)). The proposed benefit and risk considerations section 
would expressly require that, pursuant to the determination of safety 
and effectiveness section of the regulations, a discussion be included 
demonstrating that, 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 (i.e., a 
discussion demonstrating the safety and effectiveness of the device) 
when the device is used according to its labeling (Sec.  
860.234(a)(14)(ii) and Sec.  860.7). Factors to consider in discussing 
benefits and risks are discussed in the guidance FDA issued on August 
24, 2016, entitled, ``Factors to Consider When Making Benefit-Risk 
Determinations in Medical Device Premarket Approval and De Novo 
Classifications, Guidance for Industry and CDRH Staff'' (Ref. 6).
    FDA proposes that a De Novo request must include technical sections 
that contain data and information in sufficient detail to permit FDA to 
reach a decision on whether to grant or decline the De Novo request (in 
Sec.  860.234(a)(15)). This proposed section would require the 
inclusion of a section containing the nonclinical laboratory studies of 
the device (Sec.  860.234(a)(15)(i)). A nonclinical laboratory study is 
an in vivo or in vitro experiment in which a test article is studied 
prospectively in a test system under laboratory conditions to determine 
its safety (21 CFR 58.3(d)). The nonclinical laboratory studies' 
section would include information on microbiology, toxicology, 
immunology, biocompatibility (see FDA's guidance ``Use of International 
Standard ISO-10993, ``Biological evaluation of medical devices--Part 1: 
Evaluation and testing within a risk management process'' (Ref. 7)), 
stress, wear, shelf life, electrical safety, electromagnetic 
compatibility, and other laboratory or animal tests results,\2\ as 
appropriate (Sec.  860.234(a)(15)(i)). The information for the proposed 
technical sections would be required to include a statement that each 
study was conducted in compliance with the Good Laboratory Practice 
(GLP) for nonclinical laboratory studies (Sec.  860.234(a)(15)(i) and 
part 58). If the study is not compliant with GLP, the proposed 
technical section would require that the De Novo requester provide a 
brief statement explaining the reason for noncompliance with GLP. 
(Sec.  860.234(a)(15)(i)). The brief statement would assist FDA in 
determining whether the non-compliance may relate to potential bias or 
credibility of the study.
---------------------------------------------------------------------------

    \2\ FDA supports the principles of the ``3Rs,'' to reduce, 
refine, and replace animal use in testing. We encourage sponsors to 
consult with us if 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.
---------------------------------------------------------------------------

    FDA proposes that, for all devices incorporating software, the De 
Novo request include a section containing all relevant information 
regarding software information and testing, including, but not limited 
to, appropriate device hazard analysis, hardware, and system 
information (Sec.  860.234(a)(15)(ii)). FDA recommends consulting FDA's 
``Guidance for the Content of Premarket Submissions for Software 
Contained in Medical Devices'' (Ref. 8).
    FDA proposes that a section be included in a De Novo request that 
contains the results of any clinical investigation of the device 
involving human subjects (Sec.  860.234(a)(15)(iii)). This information 
is intended to assist FDA in its assessment of the quality and 
integrity of data obtained from these investigations. The following 
elements would be included in this section of the request, pursuant to 
the proposed rule:
     Discussion of clinical protocols in sufficient detail for 
FDA to assess the strengths and limitations of the investigation, which 
generally include a discussion of the objectives, design, methodology, 
and organization of the clinical investigation.
     The number of investigators and the number of subjects per 
investigator.
     Discussion of any subject selection and exclusion 
criteria, and the investigation population, to assist FDA in assessing 
whether the selection of clinical investigation subjects reflects the 
intended target population for the device. Selection and exclusion 
criteria typically include standards that investigation participants 
must meet or characteristics they must have, such as age, gender, type 
and stage of a disease, previous treatment history, and other medical 
conditions that may impact selection or exclusion criteria. To the 
extent a device has disparate safety or effectiveness outcomes or 
benefits in different demographic groups, differences in the race, 
ethnicity, age, gender, and sex of a subject population can affect the 
applicability of the investigation to the intended population. For more 
information, see FDA guidance documents ``Collection of Race and 
Ethnicity Data in Clinical Trials'' (Ref. 4) and ``Evaluation and 
Reporting of Age-, Race-, and Ethnicity-Specific Data in Medical Device 
Clinical Studies (Ref. 5).
     An investigation period description to assist FDA in 
assessing whether the clinical investigation period is applicable to 
the target population. The investigation period also would assist FDA 
in evaluating whether the clinical investigation supports the 
effectiveness of the device as labeled.
     Any safety and effectiveness data to assist FDA in 
assessing whether the clinical investigation supports that a reasonable 
assurance of safety and effectiveness exists. FDA would assess 
reasonable assurance of safety and effectiveness by evaluating the 
valid scientific evidence submitted to support the De Novo request. FDA 
would review the data to assess whether the data supports the claims 
made in the indications for use and demonstrates that the probable 
benefits of the device outweigh the probable risks. For more 
information, see FDA's guidance ``Factors to Consider When Making 
Benefit-Risk Determinations in Medical Device Premarket Approval and De 
Novo Classifications'' (Ref. 6).
     Discussion of data on any adverse reactions to the use of 
the device (e.g., any unfavorable response that caused or has potential 
to cause an injury) or complications related to the use of the device. 
An adverse reaction may occur as part of the effect of the device or 
may occur unpredictably. Frequency data and severity data are 
particularly useful in safety and effectiveness determinations. FDA 
would review the rates of complications in clinical investigations in 
assessing the safety and effectiveness of the device. The applicability 
of the adverse event information depends on the existing safety 
information and whether the population or use presents a new or serious 
safety issue.
     Discussion of data on any subject discontinuation that 
occurred in an investigation including the reasons for the 
discontinuation and the extent of the discontinuation of the subject. 
FDA would need all discontinuation data in order to determine the 
safety and effectiveness of the device. Whether the subject decides to 
discontinue participation in the clinical investigation, or is 
discontinued by the investigator because the subject no longer 
qualifies under the protocol, the data collected up to withdrawal of 
the subject are required for clinical investigation data to be 
complete.

[[Page 63135]]

Without such a control, i.e., if a subject or an investigator were able 
to decide whether to include a subject's data, depending on whether a 
subject discontinues participation in the trial, the potential for bias 
could impact the credibility of the data.
     Discussion of any identified trends after analyzing any 
subject complaints that occurred. In analyzing trends, factors such as 
location, user application, as well as repeat component or device 
events may apply. Trends in complaints may point to possible risks 
posed by the device. FDA would review such trend analyses in assessing 
the safety and effectiveness of the device.
     Discussion of any device failures and replacements. In 
analyzing failures, factors such as location, user application, and 
repeat component failures may apply. FDA would review such analyses in 
assessing the safety and effectiveness of the device.
     Discussion of any tabulations of data from all individual 
subject reporting forms and copies of such forms for each subject who 
died during a clinical investigation or who did not complete the 
investigation. Complete information for all subjects who died during 
the investigation would assist in assessing safety problems as well as 
to ensure that the investigation evaluation is as unbiased as possible.
     Statistical analysis of the results from each clinical 
investigation. The statistical analysis should specify and discuss all 
effects. FDA would review such analyses in assessing the safety and 
effectiveness of the device.
     Any contraindication, precaution, warning, or other 
limiting statement relevant to the use of the device (e.g., a statement 
providing that the device is limited to prescription use only). This 
includes information regarding any special care to be exercised by a 
practitioner or patient for the safe and effective use of the device. 
This section should describe situations in which the device should not 
be used because the risk of use exceeds the benefit.
     Other appropriate information from the clinical 
investigation. For example, this section should identify any 
investigation conducted under an IDE.
    For clinical investigations conducted in the United States, FDA 
proposes that the technical sections of the De Novo request would 
include a number of statements indicating compliance (or, if the 
investigation is noncompliant, a brief statement of the reason for the 
noncompliance) with the following FDA requirements with respect to each 
investigation conducted (Sec.  860.234(a)(15)(iii)(A)-(B)): (1) The 
institutional review board regulations (21 CFR part 56), or 
alternatively, a statement that the investigation was not subject to 
the regulations under Sec.  56.104 or Sec.  56.105; (2) the informed 
consent regulations (21 CFR part 50); and (3) the applicable IDE 
regulations concerning sponsors of clinical investigations and clinical 
investigators (21 CFR part 812). Proposed Sec.  860.234(a)(15)(iii)(A)-
(B) would also remind requesters that failure or inability to comply 
with the requirements does not justify failure to provide information 
on a relevant clinical investigation.
    For clinical investigations conducted outside the United States 
that are intended to support a De Novo request, the requirements under 
21 CFR 812.28 relating to Good Clinical Practice (GCP) would apply when 
they become effective on February 21, 2019 (83 FR 7366). Consistent 
with the new provisions for 510(k)s and PMAs that were promulgated as 
part of the GCP rulemaking (83 FR 7366, 7385 & 7387), FDA proposes to 
include a provision (Sec.  860.234(a)(15)(iii)(C)) stating that, for 
clinical investigations conducted outside the United States that are 
intended to support a De Novo request, the requirements under Sec.  
812.28 would apply. If any such investigation was not conducted in 
accordance with GCP, FDA proposes that the De Novo request would be 
required to include either a waiver request in accordance with Sec.  
812.28(c) or a brief statement of the reason for not conducting the 
investigation in accordance with GCP, as well as 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. Proposed Sec.  860.234(a)(15)(iii)(C) would also 
remind requesters that failure or inability to comply with the 
requirements does not justify failure to provide information on a 
relevant clinical investigation.
    For clinical investigations conducted in the United States and 
outside the United States, FDA proposes to require the De Novo request 
include the following elements (Sec.  860.234(a)(15)(iii)(D)-(E)): (1) 
A statement that each investigation has been completed in accordance 
with the protocol or a summary of any deviations from the protocol; and 
(2) a financial certification or disclosure statement (21 CFR part 54). 
This information would assist FDA in its assessment of the quality and 
integrity of data obtained from these investigations, as well as to 
evaluate any uncertainty in the data as part of the benefit-risk 
assessment.
    FDA further proposes that, if a De Novo request relies primarily on 
data from a single investigator at one investigation site, the De Novo 
request must include a justification showing why these data and other 
information are sufficient to demonstrate the safety and effectiveness 
of the device and to ensure that the results from a site are applicable 
to the intended population (Sec.  860.234(a)(15)(iii)(F)). This 
information would assist FDA in verifying that data from a single 
investigation site are representative of the safety and effectiveness 
of the device when used in the intended population.
    FDA further proposes to require that a De Novo request include a 
discussion of the clinical significance of the results, pursuant to the 
determination of safety and effectiveness (Sec.  860.234(a)(15)(iii)(G) 
and Sec.  860.7(e)).
    FDA proposes to require that a De Novo request include a 
bibliography of all published reports not submitted under the technical 
sections in (Sec. Sec.  860.234(a)(16)(i) and 860.234(a)(15)). These 
reports are in addition to, and not the same as, the data and 
information on any laboratory studies and any clinical investigations 
conducted by the requester. FDA proposes to require that the De Novo 
request include any other identification, discussion, and analysis of 
any other data, information, or report relevant to the safety and 
effectiveness of the device (Sec.  860.234(a)(16)(ii)). Under the 
proposed other information section, such information may be from 
foreign or domestic sources, and includes information obtained from 
investigations other than those in the De Novo request and from 
commercial marketing experience, if applicable (Sec.  
860.234(a)(16)(ii)). FDA proposes that the De Novo request would be 
required to include copies of such reports or information, if requested 
by FDA (Sec.  860.234(a)(16)(iii)). Only those reports or information 
in the possession of the De Novo requester or reasonably obtainable by 
the De Novo requester would be required to be provided when requested.
    FDA proposes that, if requested by FDA, the De Novo request would 
be required to include one or more samples of the device and its 
components, as requested (Sec.  860.234(a)(17)). If submitting samples 
of the device is impractical, the De Novo requester would be required 
to name the location where FDA may examine or test one or more of the 
devices.
    FDA proposes to require that the De Novo request include any 
proposed labels, labeling, and advertisements for the device (Sec.  
860.234(a)(18)). The

[[Page 63136]]

proposed labeling and advertisements would have to be sufficient to 
describe the device and its intended use, and provide adequate 
directions for its use. Photographs or engineering drawings would be 
required, where applicable.
    FDA proposes that the De Novo request must include other 
information that is necessary for FDA to determine whether general 
controls or general and special controls provide a reasonable assurance 
of safety and effectiveness of the device (Sec.  860.234(a)(19)). 
Examples would include marketing experience outside the United States, 
medical device reporting (MDR) data (if the device is legally marketed 
in the United States for a different intended use, and such data may be 
relevant to an evaluation of safety of the device), and patient 
preference information (e.g., testimonials from patients who were 
treated with or used the subject device). Patient preference 
information that may be used by FDA staff in decision making related to 
De Novo requests is discussed in the guidance FDA issued on August 24, 
2016, entitled, ``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, Guidance for Industry, Food and Drug 
Administration Staff, and Other Stakeholders'' (Ref. 9).
    FDA proposes that pertinent information in FDA files specifically 
referred to by a De Novo requester may be included in a De Novo request 
by reference (Sec.  860.234(b)). This would include information that is 
specifically referred to and incorporated by reference from any of the 
De Novo requester's submissions or submissions of someone other than 
the De Novo requester. The De Novo requester would be required to 
include the written authorization to reference the information by the 
person who submitted that information.
    FDA proposes to require that the De Novo request include a 
statement for any omission of any information required by the De Novo 
content regulation if the requester believes the information is not 
applicable to the device that is the subject of the De Novo request (in 
Sec. Sec.  860.234(c) and 860.234(a)). The statement would have to be 
in a separate section of the De Novo request and listed in the table of 
contents. FDA would require the statement for any omission to specify 
the information omitted, and include a justification for the omission. 
FDA would notify the De Novo requester if the justification for the 
omission is not accepted.
    FDA proposes to require the De Novo requester to update its 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 safety or effectiveness of 
the device as such information becomes available (Sec.  860.234(d)).

G. Accepting a De Novo Request (Proposed Sec.  860.245)

    The proposed section provides proposed criteria for FDA's 
acceptance of a De Novo request (Sec.  860.245). The purpose of the 
criteria for FDA's acceptance for review of the De Novo request would 
be to enable FDA to make a threshold determination whether the De Novo 
request contains the information necessary to permit a substantive 
review. FDA proposes that, after a De Novo request is received by FDA, 
FDA would notify the requester whether the submission has been accepted 
for review (Sec.  860.245(a)). FDA proposes that, if FDA does not find 
any reason to refuse to accept the De Novo request, or FDA fails to 
complete the acceptance review within 15 days, FDA would accept the De 
Novo request and notify the De Novo requester (Sec.  860.245(b)). For 
an accepted De Novo request, FDA proposes that the date of acceptance 
would be the date FDA received the De Novo request or the date FDA 
received additional information that results in acceptance of the De 
Novo request.
    FDA proposes that, if a De Novo request contains one or more of the 
listed deficiencies, FDA would be able to refuse to accept the De Novo 
request (Sec.  860.245(c)). The deficiencies are as follows:
     The requester has a pending premarket submission, 
including a 510(k), HDE, EUA, PMA, or reclassification petition for the 
same device.
     The De Novo request does not contain either: (1) Each of 
the items required under the De Novo classification section of the FD&C 
Act or this part or (2) a justification for any omission of the items 
(section 513(f)(2) of the FD&C Act).
     The De Novo request is not in the required format set out 
in proposed Sec.  860.223.
     The De Novo request is for more than one device type. A 
device type is 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.
     The requester has either not provided a complete response 
(e.g., for each FDA additional information request, the requester has 
not provided a supplement or amendment to their De Novo request 
containing all information requested by FDA) to deficiencies identified 
by FDA in previous submissions for the same device, including those 
submissions described in the regulatory history, or the requester has 
failed to provide a rationale for not responding to those deficiencies 
as set out in proposed Sec.  860.234(a)(3).
    The proposed section on acceptance of a De Novo request provides 
that FDA would notify the De Novo requester of the reasons for refusal 
if FDA refuses to accept a De Novo request (Sec.  860.245(c)(2)). The 
notice would include the De Novo request reference number and will 
identify the deficiencies in the De Novo request. FDA proposes that, if 
FDA refuses to accept a De Novo request, the requester would be 
permitted to submit the additional information necessary to comply with 
the requirements of the De Novo classification section of the FD&C Act 
and applicable regulations, including the provisions of this part 
(Sec.  860.245(c)(3) and section 513(f)(2) of the FD&C Act). If FDA 
subsequently accepts the De Novo request, the acceptance date for the 
De Novo request would be the date FDA received the additional 
information.

H. Procedures for Review of a De Novo Request (Proposed Sec.  860.256)

    FDA proposes that FDA would substantively review and grant or 
decline a De Novo request within 120 days after the De Novo request is 
received or additional information is received that results in 
acceptance of the De Novo request (Sec.  860.256(a)). The 120 days 
would begin on the day FDA receives the most recent De Novo request or 
additional information that results in acceptance of the De Novo 
request (Sec.  860.245).
    FDA proposes that a De Novo requester would be permitted to 
supplement or amend a pending De Novo request to revise existing 
information or provide additional information (Sec.  860.256(b)). Under 
the proposed rule, FDA may request this information, or a De Novo 
requester may submit this information on its own initiative. These 
responses to the FDA requests for additional information regarding a De 
Novo request under

[[Page 63137]]

review are referred to as amendments or supplements. If the requested 
information is not received within the timeframe specified in FDA's 
request for information, or the information is incomplete, the De Novo 
request would be placed on hold until the information is received. If 
additional information is submitted at the De Novo requester's own 
initiative, the reason for the additional information and the reference 
number for the original De Novo request should be included. Additional 
information may be used by FDA, or an advisory committee if 
appropriate, during review of the De Novo request.
    FDA proposes that FDA would be able to inspect relevant facilities 
prior to granting or declining a De Novo request (Sec.  860.256(c)). 
Such an inspection is intended to assist FDA in determining whether a 
reasonable assurance of safety and effectiveness can be provided by 
general or general and special controls. FDA proposes to inspect to 
help determine that clinical or nonclinical data were collected in a 
manner that ensures the data accurately represents the risks and 
benefits of the device, and to help determine that that FDA's Quality 
System Regulation (QSR), in addition to other general and any special 
controls, are adequate to ensure that critical and/or novel 
manufacturing processes that may impact the safety and effectiveness of 
the device are controlled (21 CFR part 820). Inspection would allow FDA 
to verify the documentation and implementation of a facility's QSR.

I. Withdrawal of a De Novo Request (Proposed Sec.  860.267)

    The proposed section on withdrawal of a De Novo request specifies 
when FDA would notify a requester that FDA considers the De Novo 
request withdrawn (Sec.  860.267). Once a De Novo request has been 
withdrawn, the requester would be required to submit a new De Novo 
request to restart the De Novo review process.
    The proposed section on withdrawal of a De Novo request provides 
when FDA would consider a De Novo request to have been withdrawn (Sec.  
860.267(a)). Under the proposed section, if the De Novo requester fails 
to provide a complete response to a request for additional information 
within 180 days, FDA would consider the De Novo request withdrawn 
(Sec.  860.267(a)(1)). Under the proposed section, if the De Novo 
requester fails to provide a complete response to any deficiencies 
identified by FDA within 180 days of the date FDA notifies the 
requester of such deficiencies, FDA would also consider the De Novo 
request withdrawn (Sec.  860.267(a)(2)). In addition, under the 
proposed section, if the De Novo requester does not permit an 
authorized FDA employee an opportunity to inspect the facilities and to 
have access to copy and verify records pertinent to the De Novo 
request, FDA would consider the De Novo request withdrawn (section 
Sec.  860.267(a)(3)). Finally, under the proposed section, if the De 
Novo requester submits a written notice to FDA that the De Novo request 
has been withdrawn, FDA would also consider the De Novo request 
withdrawn (Sec.  860.267(a)(4)).
    Under the proposed section, if FDA considers a De Novo request 
withdrawn, FDA would notify the De Novo requester (Sec.  860.267(b)). 
The written notice would include the De Novo request reference number 
and the date FDA considered the De Novo request withdrawn.

J. Granting or Declining a De Novo Request (Proposed Sec.  860.289)

    FDA proposes the processes and criteria for granting and declining 
a De Novo request (Sec.  860.289). Pursuant to the De Novo 
classification section of the FD&C Act, a De Novo request will be 
granted by administrative order (section 513(f)(2)(B)(i) of the FD&C 
Act). The order will classify the device into class I or class II, and 
include any special controls, if applicable. Prior to the issuance of 
the administrative order, FDA will review the De Novo request under the 
criteria set forth in the classification section of the FD&C Act, 
determine the appropriate class of the device, and issue an order to 
the requester in the form of a letter that classifies the device 
(section 513(a)(1) of the FD&C Act). The proposed section on granting 
or declining a De Novo request provides that FDA would grant a De Novo 
request if none of the reasons listed in the section for denying a De 
Novo request applies (Sec. Sec.  860.289(a)(1) and 860.289(b)). Under 
the proposed section, and as required by the De Novo classification 
section of the FD&C Act, FDA would subsequently publish a notice in the 
Federal Register announcing the classification order (Sec.  
860.289(a)(2) and section 513(f)(2)(C) of the FD&C Act). This 
announcement would codify the classification of the device and 
establish the device type.
    FDA proposes that it would decline a De Novo request by issuing a 
written order to the requester (Sec.  860.289(b)). If the De Novo 
request is declined, the device would remain in class III and may not 
be legally marketed unless and until it has been approved in a PMA, 
cleared in a 510(k), or a new De Novo request has been granted.
    FDA proposes the following grounds for declining a De Novo request 
(Sec.  860.289(b)):
     The device does not meet the criteria under the 
classification section of the FD&C Act and the definitions section of 
the medical device classification procedures regulations for 
classification into class I or II (section 513(a)(1) of the FD&C Act 
and Sec.  860.3).
     The De Novo request contains a false statement of material 
fact, or there is a material omission. FDA may rescind a De Novo 
request containing a false statement of material fact or a material 
omission.
     The proposed labeling for the device does not meet the 
requirements in the labeling part and the in vitro diagnostic products 
for human use part, as applicable (part 801 (21 CFR part 801) and part 
809 (21 CFR part 809)).
     The product does not meet the definition of a device at 
section 201(h) in the FD&C Act (21 U.S.C. 321(h)) and is not a 
combination product as defined at Sec.  3.2(e)) (21 CFR 3.2(e)). 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)-(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, new drug application, or biologics license 
application). We welcome comment on this issue.
     The device is of a type which has already been approved in 
existing applications for PMAs submitted under the premarket approval 
of medical devices (21 CFR part 814).
     The device type has already been classified into class I, 
class II, or class III.
     An inspection of a relevant facility under the procedures 
for review of a De Novo request section results in a determination that 
general or general and special controls would not provide a reasonable 
assurance of safety and effectiveness (Sec.  860.256(c)).
     A nonclinical laboratory study that is described in the De 
Novo request, and that is essential to show the device there is a 
reasonable assurance of safety was not conducted in compliance with the 
GLP requirements and no reason for the noncompliance is provided or, if 
a reason for noncompliance with the GLP

[[Page 63138]]

requirements is provided, the practices used in the study do not 
support the validity of the study (part 58).
     A clinical investigation described in the De Novo request 
involving human subjects that is subject to the institutional review 
board regulations in part 56, the informed consent regulations in part 
50, or GCP described in Sec.  812.28(a), 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 are 
otherwise unreliable.
     A clinical or nonclinical study necessary to demonstrate 
that general or general and special controls provide a reasonable 
assurance of safety and effectiveness has either not been completed 
according to the study protocol, or deficiencies about such a study 
identified in a request for additional information under the procedures 
for review of a De Novo request section have not been adequately 
addressed (Sec.  860.256(b)(1)).
     After the De Novo request has been accepted for review 
under the accepting a De Novo request section, the De Novo requester 
makes significant changes not solicited by FDA to either the device's 
indications for use or to the device's technological characteristics 
(Sec.  860.245(b)).
    FDA proposes that FDA would issue an order declining a De Novo 
request that would inform the De Novo requester of the grounds for 
declining the request (Sec.  860.289(c)).
    As noted in the list above, one of the grounds for declining a De 
Novo request is that the device is of a type which has already been 
approved in a PMA submitted under the premarket approval of medical 
devices (21 CFR part 814). With respect to such devices (section 
513(f)(1) of the FD&C Act), the postamendments devices reclassification 
section of the FD&C Act (section 513(f)(3) of the FD&C Act), and not 
the De Novo classification section of the FD&C Act (section 513(f)(2) 
of the FD&C Act), is the appropriate pathway for reclassification of 
such devices. The classification section of the FD&C Act on 
classification and/or reclassification of postamendments devices 
(section 513(f)(2) and (3) of the FD&C Act), especially the unique 
provision (section 513(f)(3) of the FD&C Act) that supports 
reclassification of a group of devices, support the view that FD&C 
Act's provisions on reclassification of postamendments devices (section 
513(f)(3) of the FD&C Act), rather than its De Novo classification 
section (section 513(f)(2) of the FD&C Act), is to be used for 
reclassification of device types already approved in a PMA.\2\
---------------------------------------------------------------------------

    \3\ This interpretation is also consistent with FDA's historical 
use of the De Novo sections and the legislative history of the FD&C 
Act provisions on postabendments device relclassification.
---------------------------------------------------------------------------

    If a De Novo request is declined because a device was classified 
into class III under the classification section or the classification 
change section of the FD&C Act (section 513(d) or (e) of the FD&C Act), 
and there is evidence to support classification into class I or class 
II, a person, or FDA on its own initiative, may seek reclassification 
of the class III device under the classification change section of the 
FD&C Act (section 513(e) of the FD&C Act).
    FDA proposes that FDA would determine the safety and effectiveness 
of the device using the criteria specified in the determination of 
safety and effectiveness section of the regulations (Sec. Sec.  
860.289(d) and 860.7). Under the proposed rule, FDA would be permitted 
to use information other than that submitted by the De Novo requester 
in making such determinations, e.g., published literature.

VI. Proposed Effective Date

    FDA proposes that this rule would go into effect 90 days after 
publication of a final rule.

VII. Economic Analysis of Impacts

    We have examined the impacts of the proposed rule under Executive 
Order 12866, Executive Order 13563, Executive Order 13771, 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). Executive Order 13771 
requires that the costs associated with significant new regulations 
``shall, to the extent permitted by law, be offset by the elimination 
of existing costs associated with at least two prior regulations.'' We 
believe that this proposed 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 rule would incur very 
small one-time costs to read and understand the rule, we propose to 
certify that the proposed 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 proposing ``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 $150 million, using the most current (2017) Implicit 
Price Deflator for the Gross Domestic Product. This proposed rule would 
not result in an expenditure in any year that meets or exceeds this 
amount.
    The proposed rule, if finalized, would 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; 
(3) how to organize these data. By clarifying and making more efficient 
these requirements, we expect the proposed rule, if finalized, would 
reduce the time and costs associated with reviewing De Novo requests, 
and generate net benefits in the form of cost savings. Moreover, the 
proposed rule, if finalized, would 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. Table 2 
summarizes our estimate of the annualized costs and the annualized 
benefits of the proposed rule over 10 years.

[[Page 63139]]



                                   Table 2--Summary of Benefits, Costs and Distributional Effects of the Proposed Rule
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                            Units
                                                                                      ------------------------------------------------
               Category                    Primary      Low estimate    High estimate                                      Period            Notes
                                          estimate                                      Year dollars    Discount rate      covered
                                                                                                          (percent)        (years)
--------------------------------------------------------------------------------------------------------------------------------------------------------
Benefits:
    Annualized.......................  ..............  ..............  ..............            2016               7              10  .................
    Monetized $millions/year.........  ..............  ..............  ..............            2016               3              10  .................
    Annualized.......................  ..............  ..............  ..............            2016               7              10  .................
    Quantified.......................  ..............  ..............  ..............            2016               3              10  .................
    Qualitative
Costs:
    Annualized.......................           $0.04            $0.0           $0.08            2016               7              10  .................
    Monetized $millions/year.........           $0.02            $0.0           $0.03            2016               3              10  .................
    Annualized.......................  ..............  ..............  ..............            2016               7              10  .................
    Quantified.......................  ..............  ..............  ..............            2016               3              10  .................
    Qualitative
Transfers:
    Federal..........................  ..............  ..............  ..............            2016               7              10  .................
    Annualized.......................  ..............  ..............  ..............            2016               3              10  .................
--------------------------------------------------------------------------------------------------------------------------------------------------------
    Monetized $millions/year.........  From:
                                       To:                                             ..............
--------------------------------------------------------------------------------------------------------------------------------------------------------
    Other............................  ..............  ..............  ..............            2016               7              10  .................
    Annualized.......................  ..............  ..............  ..............            2016               3              10  .................
--------------------------------------------------------------------------------------------------------------------------------------------------------
    Monetized $millions/year.........  From:
                                       To:                                             ..............
--------------------------------------------------------------------------------------------------------------------------------------------------------
Effects:
    State, Local or Tribal
     Government: None.
    Small Business: None.
    Wages: None.
    Growth: None.
--------------------------------------------------------------------------------------------------------------------------------------------------------

    In line with Executive Order 13771, in Table 3 we estimate present 
and annualized values of the costs and cost-savings over an infinite 
time horizon.

                                                      Table 3--Executive Order 13771 Summary Table
                                                [In $ million 2016 dollars over an infinite time horizon]
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                            Lower bound                     Upper bound     Lower bound                     Upper bound
                                                               (7%)        Primary (7%)        (7%)            (3%)        Primary (3%)        (3%)
--------------------------------------------------------------------------------------------------------------------------------------------------------
Present Value of Costs..................................            $0.0            $0.6            $1.1            $0.0            $0.6            $1.1
Present Value of Cost-Savings...........................             0.0             0.0             0.0             0.0             0.0             0.0
Present Value of Net Costs \1\..........................             0.0             0.6             1.1             0.0             0.6             1.1
Annualized Costs........................................             0.0             0.0             0.0             0.0             0.0             0.0
Annualized Cost-Savings.................................             0.0             0.0             0.0             0.0             0.0             0.0
Annualized Net Costs \1\................................             0.0             0.0             0.0             0.0             0.0             0.0
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ We calculate net costs as costs minus cost savings.

    We have developed a comprehensive Preliminary Economic Analysis of 
Impacts that assesses the impacts of the proposed rule. The full 
preliminary analysis of economic impacts is available in the docket for 
this proposed rule (Ref. 10) and at https://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/EconomicAnalyses/default.htm.

VIII. Analysis of Environmental Impact

    We have determined that, under 21 CFR 25.34(b) and (f), this 
proposed 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. Consultation and Coordination With Indian Tribal Governments

    We have analyzed this proposed rule in accordance with the 
principles set forth in Executive Order 13175. We have tentatively 
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. The Agency solicits comments from tribal 
officials on any potential impact on Indian Tribes from this proposed 
action.

X. Paperwork Reduction Act of 1995

    This proposed 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 (44 U.S.C. 3501-3520). A 
description of these provisions is given in the

[[Page 63140]]

Description section of this document 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.
    FDA invites comments on these topics: (1) Whether the proposed 
collection of information is necessary for the proper performance of 
FDA's functions, including whether the information will have practical 
utility; (2) the accuracy of FDA's estimate of the burden of the 
proposed collection of information, including the validity of the 
methodology and assumptions used; (3) ways to enhance the quality, 
utility, and clarity of the information to be collected; and (4) ways 
to minimize the burden of the collection of information on respondents, 
including through the use of automated collection techniques, when 
appropriate, and other forms of information technology.
    Title: Medical Device De Novo Classification Process (OMB Control 
Number 0910-0844)--Revision.
    Description: This proposed 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. 1) 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 proposed rule.
    Proposed 860.201 explains the purpose of the proposed De Novo 
Classification regulations and provides the applicability of a De Novo 
request submission. Proposed 860.223 and 860.234 describe the format 
and content, respectively, of a De Novo request. Proposed 860.245 
describes the conditions under which FDA may refuse to accept a De Novo 
request. Proposed 860.256(b) provides for supplemental, amendatory, or 
additional information for a pending De Novo request. Proposed 
860.267(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 classified into class III under section 
513(f)(2) of the FD&C Act.

                                                       Table 1--Estimated Annual Reporting Burden
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                               Total
                                                             Number of       Number of     Total annual   Average burden                   operating and
                Activity; 21 CFR section                    respondents    responses per     responses     per response     Total hours     maintenance
                                                                            respondent                                                         costs
--------------------------------------------------------------------------------------------------------------------------------------------------------
De Novo request--proposed 860.201, 860.223, 860.234,                  60               1              60             182          10,920          $7,278
 860.245, 860.256(b)....................................
Written notice of withdrawal--proposed 860.267(a)(4)....               5               1               5              10              50               5
                                                         -----------------------------------------------------------------------------------------------
    Total...............................................  ..............  ..............  ..............  ..............          10,970           7,283
--------------------------------------------------------------------------------------------------------------------------------------------------------

    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. This includes information collection associated with the 
proposed provisions described in 860.201, 860.223, 860.234, 860.245, 
and 860.256(b). Because the provisions under proposed 860.245 are not 
included in the information collection burden estimates associated with 
the De Novo Program guidance, we have included an additional 2 hours 
per response in the average burden per response for manufacturers to 
review their De Novo request for compliance with the acceptance 
criteria listed in proposed 860.245. Based on updated program data and 
trends, we expect to receive approximately 60 De Novo requests per 
year. This estimate is a 3,640-hour increase from the burden estimate 
approved for the De Novo Program guidance.
    We estimate that the average burden per response for written notice 
of withdrawal of a De Novo request, as described in proposed 
860.267(a)(4), is 10 minutes. 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 requests for withdrawal per year. There is 
no change to the currently approved burden estimate for this 
information collection.
    The operating and maintenance cost for a De Novo submission 
includes the cost of printing, shipping, and the eCopy. We estimate the 
cost burden for a De Novo submission to be $121.30 ($90 printing + $30 
shipping + $1.30 eCopy). The annual cost estimate for De Novo 
submissions is $7,278 (60 submissions x $121.30). We estimate the cost 
for a request for withdrawal to be $1 (rounded) ($0.09 printing 1 page 
+ $0.03 shipping + $1.30 eCopy). The annual cost estimate for requests 
for withdrawal is $5.
    To ensure that comments on information collection are received, OMB 
recommends that written comments be faxed to the Office of Information 
and Regulatory Affairs, OMB (see ADDRESSES). All comments should be 
identified with the title of the information collection.
    In compliance with the Paperwork Reduction Act of 1995 (44 U.S.C. 
3407(d)), the Agency has submitted the information collection 
provisions of this proposed rule to OMB for review. These requirements 
will not be effective until FDA obtains OMB approval. FDA will publish 
a notice concerning OMB approval of these requirements in the Federal 
Register.
    This proposed rule also refers to previously approved collections 
of information. These collections of information are subject to review 
by the Office of Management and Budget (OMB) under the Paperwork 
Reduction Act of 1995 (44 U.S.C. 3501-3520). The collections of 
information in the

[[Page 63141]]

guidance document entitled ``De Novo Classification Process (Evaluation 
of Automatic Class III Designation)'' have been approved under OMB 
control number 0910-0844; the collections of information in the 
guidance document entitled ``Requests for Feedback on Medical Device 
Submissions: The Pre-Submission Program and Meetings with Food and Drug 
Administration Staff'' have been approved under OMB control number 
0910-0756; the collections of information in the guidance documents 
entitled ``Guidance for Industry and Food and Drug Administration 
Staff--User Fees for 513(g) Requests for Information'' 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'' have been approved under OMB 
control number 0910-0705; and the collections of information in the 
guidance document entitled ``Emergency Use Authorization of Medical 
Products and Related Authorities'' 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-
0755; 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.

XI. Federalism

    We have analyzed this proposed rule in accordance with the 
principles set forth in Executive Order 13132. We have determined that 
the proposed 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.

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's guidance ``De Novo Classification Process (Evaluation of 
Automatic Class III Designation)'' available at https://www.fda.gov/ucm/groups/fdagov-public/@fdagov-meddev-gen/documents/document/ucm080197.pdf.
2. FDA's guidance ``Procedures for Class II Device Exemptions from 
Premarket Notification, Guidance for Industry and CDRH Staff''' 
available at https://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM080199.pdf.
3. FDA's guidance ``eCopy Program for Medical Device Submissions'' 
available at https://www.fda.gov/ucm/groups/fdagov-public/@fdagov-meddev-gen/documents/document/ucm313794.pdf.
4. FDA's guidance ``Collection of Race and Ethnicity Data in 
Clinical Trials,'' available at https://www.fda.gov/downloads/regulatoryinformation/guidances/ucm126396.pdf.
5. FDA's guidance ``Evaluation and Reporting of Age-, Race-, and 
Ethnicity-Specific Data in Medical Device Clinical Studies,'' 
available at https://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM507278.pdf.
6. FDA's guidance ``Factors to Consider When Making Benefit-Risk 
Determinations in Medical Device Premarket Approval and De Novo 
Classifications, Guidance for Industry and CDRH Staff,'' available 
at (https://www.fda.gov/ucm/groups/fdagov-public/@fdagov-meddev-gen/documents/document/ucm517504.pdf.
7. FDA's guidance ``Use of International Standard ISO-10993, 
``Biological evaluation of medical devices--Part 1: Evaluation and 
testing within a risk management process,'') available at https://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm348890.pdf.
8. FDA's guidance ``Guidance for the Content of Premarket 
Submissions for Software Contained in Medical Devices,'' available 
at https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm089543.htm.
9. FDA's guidance ``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, Guidance for Industry, 
Food and Drug Administration Staff, and Other Stakeholders'' 
available at https://www.fda.gov/ucm/groups/fdagov-public/@fdagov-meddev-gen/documents/document/ucm446680.pdf.
10. FDA's full preliminary analysis of economic impacts is available 
in the Docket No. FDA-2018-N-0236 for this proposed 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, we propose 
that 21 CFR part 860 be 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), 360c, 360d, 360e, 360i, 360j, 371, 
374.

0
2. 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 FDA 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 kind 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
3. 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

[[Page 63142]]

(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 of 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 promulgation of performance 
standards, postmarket surveillance, patient registries, development and 
dissemination of guidance documents (including guidance on 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 questionnaire means a specific series of questions 
prepared by the Commissioner for use as guidelines by classification 
panels preparing recommendations to the Commissioner regarding 
classification and by petitioners submitting petitions for 
reclassification. The questions relate to the safety and effectiveness 
characteristics of a device and the answers are designed to help the 
Commissioner determine the proper classification of the device.
    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.
    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 in order 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.
    Supplemental data sheet means information compiled by a 
classification panel or submitted in a petition for reclassification, 
including:
    (1) A summary of the reasons for the recommendation (or petition);
    (2) A summary of the data upon which the recommendation (or 
petition) is based;
    (3) An identification of the risks to health (if any) presented by 
the device;
    (4) To the extent practicable in the case of a class II or class 
III device, a recommendation for the assignment of a priority for the 
application of the requirements of performance standards or premarket 
approval;
    (5) In the case of a class I device, a recommendation whether the 
device should be exempted from any of the requirements of registration, 
recordkeeping and reporting, or good manufacturing practice 
requirements of the quality system regulation;
    (6) In the case of an implant or a life-supporting or life-
sustaining device for which classification in class III is not 
recommended, a statement of the reasons for not recommending that the 
device be classified in class III;
    (7) Identification of any needed restrictions on the use of the 
device, e.g., whether the device requires special labeling, should be 
banned, or should be used only upon authorization of a

[[Page 63143]]

practitioner licensed by law to administer or use such device; and
    (8) Any known existing standards applicable to the device, device 
components, or device materials.
0
4. 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 request 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 request is not available for 
public disclosure, except to the extent the existence of the De Novo 
request is disclosable under paragraph (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 request that are not exempt from release 
under Sec.  20.61 of this chapter are immediately available for public 
disclosure.
0
5. Add subpart D, consisting of Sec. Sec.  860.201 through 860.289, to 
read as follows:
Subpart D--De Novo Classification
Sec.
860.201 Purpose and applicability.
860.223 De Novo request format.
860.234 De Novo request content.
860.245 Accepting a De Novo request.
860.256 Procedures for review of a De Novo request.
860.267 Withdrawal of a De Novo request.
860.289 Granting or declining a De Novo request.

Subpart D--De Novo Classification


Sec.  860.201   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.  860.223   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:
    (1)(i) For devices regulated by the Center for Devices and 
Radiological Health, be sent to the current mailing 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 mailing address displayed on the 
website https://www.fda.gov/BiologicsBloodVaccines/default.htm.
    (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.  860.234   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 and page number for each item.
    (2) Administrative information. The name, address, phone, fax, 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 use 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, 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 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 known or 
reasonably known existing alternative practices or procedures 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.
    (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, humanitarian use 
devices

[[Page 63144]]

(HUDs), 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, HUDs, 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) 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.
    (10) Proposed special controls. If the classification 
recommendation from paragraph (a)(9) 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) Summary of risks and mitigations. A summary of known or 
reasonably known probable risks to health associated with use of the 
device and the proposed mitigations, including general controls and, if 
the classification recommendation from paragraph (a)(9) 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.
    (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 laboratory 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 laboratory 
studies of the device, including microbiological, toxicological, 
immunological, biocompatibility, stress, wear, shelf life, electrical 
safety, electromagnetic compatibility, and other laboratory or animal 
tests, as appropriate. Information on nonclinical laboratory studies 
must include a statement that each such study was conducted in 
compliance with part 58 of this chapter, or, if the study was not 
conducted in compliance with such regulations, 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, 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

[[Page 63145]]

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 its 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.  860.245   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 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.  
860.223;
    (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.  860.234(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.  860.256   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.  860.245. 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.  860.245, 
FDA will review the De Novo request and send the requester an order 
granting the De Novo request under Sec.  860.289(a)

[[Page 63146]]

or an order declining the De Novo request under 860.289(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.  860.267   Withdrawal of a De Novo request.

    (a) FDA will consider 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.  860.256(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.  860.245(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.  860.256(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 FDA considers a De Novo request to be 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.  860.289   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 (b) of this section for 
declining the De Novo request applies.
    (2) If FDA grants a De Novo request, FDA will subsequently publish 
in the Federal Register a notice of the classification order, including 
any special controls.
    (b) FDA may issue written notice to the requester declining 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.  860.256(c) 
results in a determination that general or general and special controls 
would not provide reasonable assurance of safety and effectiveness;
    (8) A nonclinical laboratory study 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 the good laboratory 
practice regulations in 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 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.  860.256(b)(1) have 
not been adequately addressed; or
    (11) After a De Novo request is accepted for review under Sec.  
860.245(b), the requester makes significant unsolicited changes to the 
device's:
    (i) Indications for use; or
    (ii) Technological characteristics.
    (c) 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.
    (d) 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.
0
6. In part 860, remove all references to ``the act'' and add in their 
place ``the Federal Food, Drug, and Cosmetic Act''.

    Dated: November 27, 2018.
Scott Gottlieb,
Commissioner of Food and Drugs.
[FR Doc. 2018-26378 Filed 12-4-18; 8:45 am]
BILLING CODE 4164-01-P