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Today’s Topic: De Novo Final Rule: Overview and Guidance Updates

December 14, 2021, 1-2 pm EST
De Novo Final Rule: 

Overview and Guidance Updates

Peter J. Yang, PhD

De Novo Policy Analyst and Program Lead

Division of Submission Support

Office of Regulatory Programs

Office of Product Evaluation and Quality

Center for Devices and Radiological Health

U.S. Food and Drug Administration
De Novo Final Rule: 

Overview and Guidance Updates

Peter J. Yang, PhD

De Novo Policy Analyst and Program Lead

Division of Submission Support

Office of Regulatory Programs

Office of Product Evaluation and Quality

Center for Devices and Radiological Health

U.S. Food and Drug Administration
Learning Objectives

• Describe the background and history of the De Novo Program

• Describe the new De Novo regulations and changes to the De 

Novo review process

• Describe what the updated De Novo guidances cover

• Identify the contents of the updated De Novo Refuse-to-Accept 

(RTA) checklist and what is required for acceptance of a De Novo 

request

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Keep in mind...

• Final rule, updated guidances, and RTA checklist are 

not for implementation until January 3, 2022.

• For any De Novo request received prior to January 3, 

2022, FDA will review under existing policies, including 

the current RTA guidance.

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What Is a De Novo Request?

• A type of premarket submission (marketing authorization)

• Intended for devices that are automatically classified into class 

III by virtue of not yet being classified

• Request to classify the device into class I or class II based on a 

determination of reasonable assurance of safety and 

effectiveness (RASE)

• If the De Novo request is granted:

– FDA creates a new classification regulation

– the new device type is now regulated through 510(k), if class II

– the De Novo device can serve as the first predicate device of its kind

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A De Novo Request is Not:

• A type of premarket notification [510(k)]

• A substantial equivalence (SE) determination

• A premarket approval application (PMA)

• A 513(g) Request for Information

7
Classification Process – Goals

• Determine if probable benefits outweigh probable risks

• Identify probable risks to health for the device/product

• Determine level of regulatory controls needed:

– general controls only = class I

– general controls + special controls = class II

Together, these provide reasonable assurance of 

safety and effectiveness.

8
History and Evolution

FDAMA (1997) Created De Novo pathway

FDASIA (2012) Added Direct De Novo option

21st Century Cures (2016) Added combination products (21 CFR 3.2(e))

FDARA (2017) Added user fees; resulted in new guidances

De Novo Final Rule Published October 5, 2021

De Novo RTA Final guidance issued September 2019

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User Fees

• Standard fee = 30% of PMA user 

fee

• Small business fee = 25% of 

standard fee

Performance Goals

• Based on 150 FDA days

– Different than statutory deadline of 

120 FDA days

• Based on % of De Novo requests 

reaching final decision (grant, 

decline, withdraw)

MDUFA IV User Fees and Performance 

Final 

Decision by 

Day 150

User Fee

Small 

Business 

Fee

FY 2018 50% $93,229 $23,307

FY 2019 55% $96,644 $24,161

FY 2020 60% $102,299 $25,575

FY 2021 65% $109,697 $27,424

FY 2022 70% $112,457 $28,114

MDUFA: Medical Device User Fee Amendments 10
De Novos Received In CDRH

19 22

46 42

59 54

99

56 61

69 63

0

20

40

60

80

100

120

FY

2011

FY

2012

FY

2013

FY

2014

FY

2015

FY

2016

FY

2017

FY

2018

FY

2019

FY

2020

FY

2021

De Novo Requests Received

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What we have (had)

• Statute – section 513(f)(2) of the 

Federal Food, Drug, and Cosmetic 

Act (FD&C Act)

• Guidances

– De Novo Program

– De Novo User Fees (MDUFA IV)

– De Novo Actions/Clock 

(MDUFA IV)

– De Novo RTA (MDUFA IV, 

guidance issued in 2019)

What we need(ed)

• Regulations

– De Novo program and review 

process implemented entirely 

through non-binding guidance

– Provides clarity in the review 

procedures for De Novo requests

– Provides regulatory framework 

for De Novo program, similar to 

510(k) and PMA regulations

12

De Novo Program Support
What’s in the De Novo Final Rule?

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What is the De Novo Final Rule?

• Adds new regulations to the Code of Federal 

Regulations (CFR) that govern the De Novo review 

process

• 21 CFR 860: Medical device classification procedures

• De Novo regulations placed at 21 CFR 860 Subpart D

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21 CFR 860 Subpart D Overview

• 21 CFR 860 Subpart D: 860.200 – 860.260

– 860.200: Purpose and applicability.

– 860.210: De Novo request format.

– 860.220: De Novo request content.

– 860.230: Accepting a De Novo request.

– 860.240: Procedures for review of a De Novo request.

– 860.250: Withdrawal of a De Novo request.

– 860.260: Granting or declining a De Novo request. 

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21 CFR 860.200 and 21 CFR 860.210

• 21 CFR 860.200: Purpose and applicability

– Explains the purpose of the De Novo classification process

– Distinguishes between post-Not Substantially Equivalent 

(NSE) and direct De Novos

• 21 CFR 860.210: De Novo request format

– Specifies electronic format 

– Specifies where to send the De Novo request

– Requires De Novo request to be submitted in English

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• Table of contents

• Administrative information

• Regulatory history

• Device name

• Indications for use

• Device description

• Alternative practices and procedures

• Classification summary

• Summary of risks and mitigations

• Proposed special controls

• Classification recommendation

• Standards

• Summary of studies

• Benefit and risk considerations

• Technical sections: 

– Non-clinical testing

– Software

– Clinical testing

• Other information

– Bibliography

– Other information reasonably known to 

the requester

– Other information to support reasonable 

assurance of safety and effectiveness

• Samples (if requested)

• Labeling

Blue text: De Novo classification-specific elements 17

21 CFR 860.220: 

De Novo request content.
• Codifies acceptance review process

– Aligns with current Refuse-to-Accept (RTA) guidance for De Novo 

requests and RTA policies for other programs

– Acceptance means the De Novo request contains the information 

necessary to permit a substantive review.

– FDA will perform an acceptance review within 15 days of receipt.

– If acceptance review not performed, the file is automatically 

accepted.

18

21 CFR 860.230: 

Accepting a De Novo request.
• Codifies acceptance review process

– Aligns with current Refuse-to-Accept (RTA) guidance for De Novo 

requests and RTA policies for other programs

– Acceptance means the De Novo request contains the information 

necessary to permit a substantive review.

– FDA will perform an acceptance review within 15 days of receipt.

– If acceptance review not performed, the file is automatically 

accepted.

19

21 CFR 860.230: 

Accepting a De Novo request.
21 CFR 860.230(c): 

Accepting a De Novo request.

• FDA may refuse to accept a De Novo if:

– Existing open or pending submission (510(k), PMA, etc.) or 

reclassification petition for the same device and indication

– De Novo request is incomplete or does not follow proper 

format

– De Novo request is for more than one type of device

– Requester has not responded (or provided a justification for 

not responding) to a previous deficiency

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• Review takes place in 120 days (statutory requirement, 

but 150 days per MDUFA IV)

• Outlines additional information request process

• Outlines inspection authority

– Data integrity 

– Quality System Regulation inspection for critical and/or novel 

manufacturing processes

21

21 CFR 860.240: 

Procedures for review of a De Novo request.
• De Novo requests are considered withdrawn when:

– Requester voluntarily withdraws De Novo request

– Requester does not respond to RTA decision within 180 days

– Requester does not respond to additional information 

request within 180 days

– Requester does not permit FDA to inspect facilities at a 

reasonable time and in a reasonable manner

22

21 CFR 860.250: 

Withdrawal of a De Novo request.
• Granting decisions

– Grant De Novo request unless there is a reason to decline

– Within 30 days of granting, a notice will be published in the Federal 

Register to update the CFR with the new regulation and special controls 

(if class II)

– Device can be used as a predicate for future 510(k)s, when necessary

• Decline decisions 

– Sent by written order to the requester

– Include all outstanding deficiencies

• Specifies that final decisions are always based on the 

classification criteria explained in 21 CFR 860.7

23

21 CFR 860.260: 

Granting or declining a De Novo request.
Ineligibility

• Not a device or combination product

• Device type has already been approved in existing PMAs

• Device type is already classified into class I, class II, or class III 

(including unclassified devices)

General

• Device does not meet criteria in section 513(a)(1) of the FD&C Act for 

classification into class I or II

• False statement of material fact or a material omission

• Labeling does not comply with 21 CFR 801 or 809 (in vitro diagnostics)

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Reasons for Declining per 21 CFR 860.260(c):
Reasons for Declining per 21 CFR 860.260(c):

Data

• Inspection results in determination that general or general & special controls would not provide 

reasonable assurance of safety and effectiveness (RASE)

• Nonclinical study was not performed according to 21 CFR 58 and the practices used in conducting the 

study do not support the validity of the study

• Clinical study was not performed in accordance with 21 CFR 50, 21 CFR 56, or 21 CFR 812.28(a) (good 

clinical practices) such that subject rights or safety were not adequately protected or the supporting 

data was found to be otherwise unreliable

• A clinical or nonclinical study was either (i) not completed per the study protocol or (ii) deficiencies 

related to the study have not been adequately addressed

• After a De Novo request has been accepted for review, the requester makes significant unsolicited 

changes to the device’s (i) indications for use or (ii) technological characteristics

25
De Novo Final Rule: Other Updates

• Minor editorial changes to 21 CFR 860

– scope, definitions

• Addition of confidentiality provisions for De Novo 

requests

– De Novo files are not available for public disclosure 

(including their existence) until De Novo request is granted

26
De Novo Regulation Distinctives

• Specifies submission content requirements

• Codifies acceptance review process

• Adds specific inspection authority

• Outlines specific reasons for declining a De Novo, 

including reasons related to eligibility, inspections, and 

non-clinical and clinical data deficiencies

27
De Novo Guidance Updates

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Updated De Novo Guidances

• De Novo Program: De Novo Classification Process 

(Evaluation of Automatic Class III Designation)

• De Novo User Fees: User Fees and Refunds for De Novo 

Classification Requests 

• De Novo Actions/Clock: FDA and Industry Actions on De 

Novo Classification Requests: Effect on FDA Review Clock 

and Goals

• De Novo RTA: Acceptance Review for De Novo Classification 

Requests

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Summary of Changes

• Guidances updated to reflect changes for consistency with 

the final rule.

• De Novo final rule largely reflects the existing process as 

implemented through guidance. Therefore, changes to the 

guidances are generally not substantive.

• Minor updates to guidances to reflect the final rule include:

– Adding references to 21 CFR 860 

– An updated acceptance checklist based on 21 CFR 860

30
De Novo Program Guidance

• Purpose: Provide overview of De Novo classification 

pathway and FDA review process

• Explains when De Novo classification is and is not 

appropriate (eligibility)

• Emphasizes the importance of early interaction with the 

Agency (Pre-Submission)

• Outlines the De Novo request review process

• Explains what happens when De Novo is granted

31
De Novo User Fees Guidance

• Purpose: Provide overview of user fee policy for De 

Novo requests

• Explains when and how to pay a user fee for a De Novo 

request

• Explains circumstances under which FDA will or will not 

refund a user fee

• Adding minor clarifications in refunds policy

32
De Novo Actions/Clock Guidance

• Purpose: Describe actions that FDA and industry may take 

on De Novo requests, and how those actions affect the 

FDA review clock

• Describes FDA actions (grant, decline, request information)

– Enumeration of each reason why a De Novo may be declined, 

referencing 21 CFR 860.260(c)

• Describes industry actions (submitting or withdrawing De 

Novo requests, or submitting additional information)

• Describes De Novo performance goals for MDUFA IV

33
De Novo RTA Guidance

• Purpose: Ensure De Novo request is acceptable for 

substantive review

• Facilitates efficient and timely review

• Similar to RTA policies for 510(k) and PMA

– Intend to complete RTA review within 15 calendar days of 

receiving De Novo

– De Novo is considered accepted if RTA review is not completed 

within 15 calendar days

• Fulfills MDUFA IV commitment (“submission checklist”)

34
Background

• Current RTA checklist is split into 

two:

– Appendix A – Acceptance Checklist 

(required)

– Appendix B – Recommended 

Checklist (not required)

• New RTA checklist requires all 

content described in 21 CFR 

860.220 and essentially combines 

both Required and Recommended 

checklists, so all elements are now 

Required 

Changes

• Current RTA checklist includes 

items such as:

– Intended use

– Device description

– Proposed special controls (if 

proposing class II)

• New RTA checklist adds items such 

as:

– Prior submissions

– Classification summary (eligibility 

analysis)

– Device labeling

Specific Changes – RTA Guidance

35
Keep in mind...

• Final rule, updated guidances, and RTA checklist are 

not for implementation until January 3, 2022.

• For any file received prior to January 3, 2022, FDA will 

review under existing policies.

• Both current and updated RTA guidances are published 

on FDA’s website so you can prepare for the change.

36
What’s Ahead

• Electronic Submission Template And Resource (eSTAR)

– Official De Novo eSTAR anticipated to be available to use 

after January 3, 2022

– eSTAR will reflect items required by the updated RTA 

checklist

– See the voluntary eSTAR Program webpage

37
De Novo Resources

• De Novo Final Rule in the Federal Register

• De Novo Classification Requests (includes guidance 

links at the bottom of the webpage)

• Other resources

– De Novo Transparency Web Page

– De Novo Searchable Database

38
Resources

De Novo Final Rule www.federalregister.gov/documents/2021/10/05/2021-21677/medical-device-de-novoclassification-process

De Novo Classification Requests www.fda.gov/medical-devices/premarket-submissions/de-novo-classification-request

De Novo Classification Process (Evaluation of Automatic 

Class III Designation) (“De Novo Program Guidance”)

www.fda.gov/regulatory-information/search-fda-guidance-documents/de-novo-classificationprocess-evaluation-automatic-class-iii-designation

User Fees and Refunds for De Novo Classification Requests 

(“De Novo User Fees”)

www.fda.gov/regulatory-information/search-fda-guidance-documents/user-fees-and-refundsde-novo-classification-requests

FDA and Industry Actions on De Novo Classification 

Requests: Effect on FDA Review Clock and Goals (“De Novo 

Actions/Clock”)

www.fda.gov/regulatory-information/search-fda-guidance-documents/fda-and-industryactions-de-novo-classification-requests-effect-fda-review-clock-and-goals

Acceptance Review for De Novo Classification Requests 

(“De Novo RTA Guidance”, both current and new)

www.fda.gov/regulatory-information/search-fda-guidance-documents/acceptance-review-denovo-classification-requests

Voluntary eSTAR Program www.fda.gov/medical-devices/premarket-notification-510k/voluntary-estar-program

CDRH Transparency – De Novo Summaries www.fda.gov/about-fda/cdrh-transparency/evaluation-automatic-class-iii-designation-de-novosummaries

De Novo Searchable Database www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMN/denovo.cfm 39
Peter J. Yang

De Novo Program Lead

FDA/CDRH/OPEQ/Office of Regulatory Programs

Peter.Yang@fda.hhs.gov

40
Summary

• The De Novo review process has evolved since its creation in 1997.

• The De Novo regulations codify the processes for De Novo request 

review, which largely reflect current review practices.

• The De Novo program guidance documents have been updated to 

reflect the final rule, including a new RTA checklist that essentially 

combines the Recommended and Required checklists from the 

current RTA guidance.

• The De Novo final rule and associated guidances are for 

implementation on January 3, 2022.

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Let’s Take Your Questions

• To Ask a Question:

1. Please “Raise Your Hand”

2. Moderator will Announce Your Name to Invite You to Ask Your Question

3. Unmute yourself when called

• When Asking a Question:

• Ask 1 question only

• Keep question short

• No questions about specific submissions or data-specific

• After Question is Answered:

• Please mute yourself again

• If you have more questions - raise your hand again

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