Contains Nonbinding Recommendations
Acceptance Review for De Novo 
Classification Requests
Guidance for Industry and
Food and Drug Administration Staff
Document issued on October 5, 2021.
Document originally issued on September 9, 2019.
For questions about this document regarding CDRH-regulated devices, contact the Division of 
Industry and Consumer Education (DICE) at 1-800-638-2041, 301-796-7100, or 
DICE@fda.hhs.gov.
For questions about this document regarding CBER-regulated devices, contact the Office of 
Communication, Outreach, and Development (OCOD) at 1-800-835-4709 or 240-402-8010, or 
by email at ocod@fda.hhs.gov.
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Devices and Radiological Health
Center for Biologics Evaluation and Research
OMB Control No. 0910-0844
Current expiration date available at https://www.reginfo.gov.
See additional PRA statement in Section VII of this guidance. Contains Nonbinding Recommendations
Preface
Public Comment
You may submit electronic comments and suggestions at any time for Agency consideration to 
https://www.regulations.gov.  Submit written comments to the Dockets Management Staff, Food 
and Drug Administration, 5630 Fishers Lane, Room 1061, (HFA-305), Rockville, MD 20852.  
Identify all comments with the docket number FDA-2017-D-6069. Comments may not be acted 
upon by the Agency until the document is next revised or updated.
Additional Copies
CDRH
Additional copies are available from the Internet. You may also send an e-mail request to 
CDRH-Guidance@fda.hhs.gov to receive a copy of the guidance. Please include the document 
number 16055 and complete title of the guidance in the request.
CBER
Additional copies are available from the Center for Biologics Evaluation and Research (CBER), 
Office of Communication, Outreach, and Development (OCOD), 10903 New Hampshire Ave., 
Bldg. 71, Room 3128, Silver Spring, MD 20993, or by calling 1-800-835-4709 or 240-402-8010, 
by email, ocod@fda.hhs.gov, or from the Internet at https://www.fda.gov/vaccines-blood-
biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances. Contains Nonbinding Recommendations
Table of Contents
I.  Introduction .......................................................................................................................... 1
II.  Scope .................................................................................................................................... 2
III.  De Novo Acceptance Review Policies and Procedures ....................................................... 2
A.  Acceptance Review Policies and Procedures .................................................................. 2
B.  FDA Review Clock .......................................................................................................... 5
C.  Notification of Acceptance Review Result ...................................................................... 5
IV.  Refuse to Accept Principles ................................................................................................. 6
V.  The Checklist  Preliminary Questions ................................................................................ 6
VI.  The Checklist  Acceptance Review .................................................................................... 9
A.  Elements of a Complete De Novo Request (RTA Items) ................................................ 9
B.  Applying the Checklist of RTA Items ............................................................................. 9
C.  Elements Marked as Not Applicable (N/A) ................................................................. 9
D.  Adequacy of Information ............................................................................................... 10
E.  Elements Marked No .................................................................................................. 10
F.  Combination Product Administrative Items .................................................................. 10
G.  De Novo Requesters of Combination Products That Do Not Contain as a Constituent 
Part an Approved Drug ............................................................................................................. 10
H.  De Novo Requesters of Combination Products That Contain as a Constituent Part an 
Approved Drug ......................................................................................................................... 11
I.  Is there an open or pending premarket submission or reclassification petition for the 
same device with the same indications for use? ....................................................................... 11
J.  De Novo Request is for a Single Device Type .............................................................. 12
K.  Prior Submission(s) Relevant to the De Novo Request Under Review ......................... 12
VII.  Paperwork Reduction Act of 1995 ..................................................................................... 13
Appendix A. Acceptance Checklist for De Novo Classification Requests .................................. 14 Contains Nonbinding Recommendations
Acceptance Review for De Novo 
Classification Requests
Guidance for Industry and
Food and Drug Administration Staff
This guidance represents the current thinking of the Food and Drug Administration (FDA or 
Agency) on this topic.  It does not establish any rights for any person and is not binding on 
FDA or the public.  You can use an alternative approach if it satisfies the requirements of the 
applicable statutes and regulations.  To discuss an alternative approach, contact the FDA staff 
or Office responsible for this guidance as listed on the title page. 
I.  Introduction
On October 5, 2021, FDA issued a final rule on the De Novo Classification Process.1 This final 
rule will add new regulations at 21 CFR Part 860, Subpart D--De Novo Classification that 
describe the procedures and criteria FDA will use in assessing whether a request for an 
evaluation of automatic class III designation (De Novo classification request or De Novo 
request) contains the information necessary to permit a substantive review.2 This guidance 
provides recommendations with further detail regarding the types of information FDA believes 
are necessary to conduct a substantive review for a De Novo request, as well as 
recommendations regarding the acceptance review process.
Focusing the Agencys review resources on complete De Novo requests will provide a more 
efficient approach to ensuring that safe and effective medical devices reach patients as quickly as 
possible. Moreover, with the enactment of the Medical Device User Fee Amendments of 2017 
(MDUFA IV),3 FDA agreed to performance goals based on the timeliness of reviews, as well as 
to issue guidance that includes a submission checklist to facilitate a more efficient and timely 
review process (see Section II.E. of the MDUFA IV Commitment Letter).4 Acceptance review is 
important in both encouraging incoming quality applications from De Novo requesters and 
allowing the Agency to appropriately concentrate resources on complete applications.
1 Medical Device De Novo Classification Process (86 FR 54826) 
2 21 CFR 860.230. For more information regarding the De Novo review process, please see the FDA guidance, De 
Novo Classification Process (Evaluation of Automatic Class III Designation), available at 
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/de-novo-classification-process-
evaluation-automatic-class-iii-designation. 
3 See Title II of the FDA Reauthorization Act of 2017 (Public Law 115-52).
4 https://www.fda.gov/media/102699/download 
1 Contains Nonbinding Recommendations
The contents of this document do not have the force and effect of law and are not meant to bind 
the public in any way, unless specifically incorporated into a contract. This document is intended 
only to provide clarity to the public regarding existing requirements under the law. FDA 
guidance documents, including this guidance, should be viewed only as recommendations, unless 
specific regulatory or statutory requirements are cited. The use of the word should in Agency 
guidance means that something is suggested or recommended, but not required.
II.  Scope
The information presented in this document is intended to provide De Novo requesters with 
additional transparency regarding the types of information FDA believes are necessary to 
conduct a substantive review for a De Novo request as part of the acceptance review process 
described in 21 CFR 860.230. To enhance consistency, the document provides FDA staff with a 
clear, consistent approach to making Accept or Refuse to Accept (RTA) decisions on De 
Novo requests.
The acceptance review requirements do not alter the process by which devices are classified in a 
De Novo request once accepted for substantive review; however, they do alter the start of the 
FDA review clock for purposes of MDUFA performance goals for De Novo requests that are not 
accepted for review. Further, FDAs decision to accept a De Novo request does not imply that 
the information provided in the De Novo request, including performance data, demonstrates that 
general controls, or general and special controls, are sufficient to provide reasonable assurance of 
the safety and effectiveness of your device or assure granting of the De Novo request.
As mentioned above, the purpose of this guidance is to explain the procedures and criteria FDA 
intends to use to make a threshold determination that the De Novo request contains the 
information necessary to permit a substantive review. This document includes an Acceptance 
Checklist (Appendix A. Acceptance Checklist for De Novo Classification Requests), as 
explained in further detail below.
The effective date of the final rule rule is 90 days after the publication of the rule in the Federal 
Register to provide additional time for requesters to make any changes necessary, for example, to 
their internal operating procedures and documents, in preparation for submission. For a De Novo 
request received by FDA before the effective date of the final rule,5 FDA staff should not use the 
revised checklist in this guidance when conducting acceptance reviews. Until the effective date 
of the final rule, FDA staff should use the version of this guidance issued September 9, 2019.
III.  De Novo Acceptance Review Policies and Procedures
A.  Acceptance Review Policies and Procedures
5 Please refer to the final rule (86 FR 54826) published on October 5, 2021 and available at 
https://www.federalregister.gov/d/2021-21677.
2 Contains Nonbinding Recommendations
FDA staff conduct acceptance reviews of De Novo requests based on objective criteria using the 
Acceptance Checklist (see Appendix A. Acceptance Checklist for De Novo Classification 
Requests) to ensure that the De Novo request contains the information necessary to permit a 
substantive review. The De Novo request regulations identify criteria that, if not met, may serve 
as the basis for FDA refusing to accept a De Novo request (21 CFR 860.230(c)(1)). For the De 
Novo request to be accepted, all items identified as elements of a complete De Novo request 
(RTA items) in the Acceptance Checklist should be present or a rationale should be provided 
for those elements determined by the requester to be not applicable. To aid in the acceptance 
review, it is recommended that requesters complete and submit Acceptance Checklists with their 
De Novo requests that identify the location of supporting information for each acceptance 
element.
The acceptance review occurs prior to the substantive review and should be conducted and 
completed within 15 calendar days of FDA receiving the De Novo request. An acceptance 
review will only begin for De Novo requests for which the applicable user fee has been paid and 
a valid eCopy has been received.6
The acceptance review will be conducted on original De Novo requests and responses to 
acceptance review communications but not supplements or amendments submitted in response to 
requests for additional information after a De Novo request has been accepted for a substantive 
review. FDA staff should assess whether the De Novo request should be accepted by first 
answering the preliminary questions below and then verifying that the De Novo request contains 
all the information identified as RTA items in the Acceptance Checklist.
The purpose of the acceptance review is to assess whether a De Novo request contains the 
information necessary for FDA to conduct a substantive review (see 21 CFR 860.230(a)). 
Therefore, the De Novo request generally should not be accepted and should receive an RTA 
designation if one or more of the items noted as RTA items in the Acceptance Checklist are not 
present and no explanation is provided for the omission(s). However, during the RTA review, 
FDA staff has discretion to determine whether missing checklist items are needed to ensure that 
the De Novo request contains the information necessary to permit a substantive review. FDA 
staff also has discretion to request missing checklist items interactively from requesters during 
the RTA review. Interaction during the RTA reviews is dependent on FDA staffs determination 
that outstanding issues are appropriate for interactive review and that adequate time is available 
for the requester to provide supporting information and for FDA staff to assess responses.
If FDA refuses to accept a De Novo request, FDA will notify the requester of the reasons for the 
refusal and identify the deficiencies in the De Novo request that prevent accepting (21 CFR 
860.230(c)(2)). If one or more items noted as RTA items on the Acceptance Checklist are not 
6 See sections 738(a)(2)(A)(xi) and 738(f)(1) of the FD&C Act, section 745A(b) of the FD&C Act, and the FDA 
guidance, eCopy Program for Medical Device Submissions, available at https://www.fda.gov/regulatory-
information/search-fda-guidance-documents/ecopy-program-medical-device-submissions. Additional information is 
also provided in the FDA guidance, FDA and Industry Actions on De Novo Classification Requests: Effect on 
FDA Review Clock and Goals, available at https://www.fda.gov/regulatory-information/search-fda-guidance-
documents/fda-and-industry-actions-de-novo-classification-requests-effect-fda-review-clock-and-goals.
3 Contains Nonbinding Recommendations
present and FDA staff conducting the acceptance review determine that the submission should be 
refused, FDA staff should obtain management concurrence and notify the designated De Novo 
contact person electronically7 that the De Novo request has not been accepted. FDA staff will 
also provide the requester with a copy of the completed checklist indicating which item(s) are the 
basis for the RTA designation.
The De Novo requester may respond to the RTA notification by providing the missing 
information identified in the Acceptance Checklist. When providing the missing information, the 
De Novo requester must submit this information to the respective Centers Document Control 
Center (DCC)8 to be included in the file under the originally assigned De Novo request reference 
number (21 CFR 860.210(a)(1) and 860.230(c)(3)). A new De Novo request and new user fee are 
not necessary, and it is not necessary to resend the entire De Novo request, unless FDA notes 
otherwise (e.g., because the De Novo request is missing the majority of the items on the 
checklist). It is sufficient to submit and address only the information requested in the RTA 
notification. If a complete response to the RTA notification is not received within 180 days of 
the date of RTA notification, FDA will consider the De Novo request to be withdrawn and the 
De Novo request will be closed in the system (21 CFR 860.250(a)(2)).
Upon receipt of newly submitted information in response to an RTA notification, FDA staff 
should conduct the acceptance review again, following the same procedure, within 15 calendar 
days of receipt of the new information. This acceptance review will assess whether the new 
information makes the De Novo request complete according to the checklist criteria for 
completeness. If the De Novo request is still found to be incomplete, FDA staff should notify the 
contact person and provide a copy of the new checklist indicating the missing item(s). 
When a De Novo request is accepted, FDA will notify the requester (21 CFR 860.230(a)). FDA 
staff should electronically notify the De Novo request contact person that the De Novo request 
has been accepted and begin a substantive review of the De Novo request. If FDA does not 
complete the acceptance review within the acceptance review period (i.e., within 15 calendar 
days of receipt), FDA will accept the De Novo request for review and will notify the requester 
(21 CFR 860.230(b)). In this situation, the De Novo requester should be electronically notified 
that the acceptance review was not completed and the De Novo request is under substantive 
review.9 FDA may request any information that may have resulted in an RTA designation during 
the substantive review. Once a De Novo request has been accepted, FDA may ask for relevant
7 For additional information about email communications with CBER, please see SOPP 8119: Use of Email for 
Regulatory Communications, available at https://www.fda.gov/media/108992/download.
8 For devices regulated by the CDRH, the information must be sent to the current address displayed on the website 
https://www.fda.gov/cdrhsubmissionaddress. For devices regulated by the CBER, the information must be sent to 
the current address displayed on the website https://www.fda.gov/about-fda/center-biologics-evaluation-and-
research-cber/regulatory-submissions-electronic-and-paper.
9 In the case of a government closure during the 15-day acceptance review period, the review period may be 
extended by a comparable number of business days that the FDA buildings are closed. If the submitter receives an 
automated notice that the acceptance review was not completed because the screening period has exceeded 15 days, 
FDA may send a correction notice to the De Novo requester.
4 Contains Nonbinding Recommendations
information during the substantive review that may have been unintentionally overlooked during 
the acceptance review.
B.  FDA Review Clock
The FDA review clock start date is the DCC receipt date of the most recent De Novo request or 
additional information that resulted in an acceptance designation for the De Novo request (21 
CFR 860.230(b) and 21 CFR 860.230(c)(3)). As stated above, an acceptance review will only 
begin for De Novo requests for which the applicable user fee has been paid and a valid eCopy 
has been received. Thus, the FDA review clock does not start when a De Novo request is placed 
on eCopy or User Fee hold or is designated RTA.
De Novo requests and additional information submitted in response to an RTA designation are 
received by the respective Centers DCC. If the De Novo request is accepted for substantive 
review on the first acceptance review, the FDA review clock start date is the DCC receipt date of 
the De Novo request. However, if the De Novo request is designated RTA, the FDA review 
clock start date will be the DCC receipt date of the De Novo request including the additional 
information that results in an acceptance designation (even if FDA later requests information that 
should have been requested during acceptance review). In the event the acceptance review was 
not completed within 15 calendar days, the De Novo request will be considered to be under 
substantive review, and the FDA review clock start date will be the DCC receipt date of the most 
recently received information that was the subject of the acceptance review for the De Novo 
request. Once the De Novo request is under substantive review, the calendar days used to 
conduct the acceptance review (i.e., up to 15 days) are included within the calendar days to reach 
a final decision for the De Novo request.
C.  Notification of Acceptance Review Result
The De Novo requester should receive an electronic notification of the acceptance review result 
within 15 calendar days of DCC receipt (i.e., that the De Novo request has been accepted for 
substantive review, that the De Novo request is not accepted for review (RTA), or that the De 
Novo request is now under substantive review because the acceptance review was not 
completed). This notification will also serve to identify the FDA lead reviewer10 assigned to the 
De Novo request. The notification of either the acceptance or RTA designation will be made 
only with supervisory concurrence of the lead reviewers acceptance review determination. The 
notification of acceptance or RTA designation may occur on any day prior to the 15th calendar 
day of DCC receipt. However, in the event the acceptance review was not completed within 15 
calendar days, a notification that an RTA review was not completed will be sent on the 16th day. 
The notification will be sent only to the designated contact person identified in the De Novo 
request. In the case of an RTA designation, the notification should be accompanied by the 
completed Acceptance Checklist indicating the missing elements that resulted in the RTA 
designation. The completed checklists are considered part of the De Novo requests 
administrative file and are not posted publicly when FDA makes the RTA designation. 
10 In the case of De Novo requests submitted to CBER, whenever the term lead reviewer is used in this guidance, 
the equivalent CBER contact person is the regulatory project manager (RPM).
5 Contains Nonbinding Recommendations
Therefore, it is imperative that the De Novo request identify complete contact information, 
including the email address to which the notification should be sent as required under 21 CFR 
860.220(a)(2).11
IV.  Refuse to Accept Principles
In order to use this guidance appropriately, FDA staff should review the following basic 
principles regarding FDAs review policies and procedures.
Acceptance should not be based on a substantive review of the information provided in the 
De Novo request.
It is important to make the distinction between the acceptance review and the substantive review. 
The acceptance review is conducted to make a threshold determination of whether the De Novo 
request contains information necessary, as identified in 21 CFR 860.220, 21 CFR 860.230, and 
the Acceptance Checklist, to permit a substantive review. In assessing whether a De Novo 
request should be accepted, submitted information is not evaluated for adequacy to support 
granting the De Novo request. The Acceptance Checklist is a tool to ensure that the De Novo 
request contains the necessary information to conduct a substantive review (i.e., FDA should not 
refuse to accept a De Novo request if information is present but inadequate to support granting 
the De Novo request). The evaluation of the quality of the content occurs within the substantive 
review once the De Novo request has been accepted.
FDA staff should determine whether the requester provided a justification for any 
alternative approach.
The De Novo requester may provide a rationale for why any criteria in the checklist are not 
applicable to the device. It is FDAs expectation that each item in the Acceptance Checklist will 
be addressed either by including the requested information or providing a rationale for why it is 
not applicable or why there is a deviation.
FDA will not consider a given criterion in the checklist to be present if the De Novo request 
fails to include either the information identified or a rationale for omission or deviation. If a 
justification to omit certain information or for taking an alternative approach is provided, FDA 
will consider the adequacy of that justification or alternative approach during substantive review 
of the De Novo request. See Section VI below for examples and further explanation.
V.  The Checklist  Preliminary Questions
Within 15 calendar days of receipt of the De Novo request, FDA staff should answer the 
preliminary questions below, which are included on the first page of the Acceptance Checklist. 
The preliminary questions are intended to be answered by the lead reviewer as an initial 
11 CBER will accommodate the use of faxes; submitters may also wish to provide a fax number.
6 Contains Nonbinding Recommendations
screening of the De Novo request. Depending upon the answers to these preliminary questions, 
the remainder of the acceptance review may or may not be necessary.
If the responses to the preliminary questions and subsequent consultation with the Center 
personnel identified below indicate that the De Novo acceptance review should not continue12
the CDRH lead reviewer or the CBER regulatory project manager (RPM) should promptly:
 inform the De Novo review team (including consulting reviewers); and
 notify the requester using proper administrative procedures.
The preliminary questions are:
1.  Is the product a device (per section 201(h) of the FD&C Act) or a combination product 
(per 21 CFR 3.2(e)) with a device constituent part subject to review in a De Novo 
request?
If the product does not appear to meet the definition of a device under section 201(h) of the 
FD&C Act, or does not appear to be a combination product with a device constituent part, then 
the De Novo lead reviewer should consult with the CDRH Product Jurisdiction Officer or the 
CBER Product Jurisdiction Officer to determine the appropriate action and inform management. 
If FDA staff determines that the product does not appear to be a device or a combination product 
with a device constituent part, the De Novo review team should stop the review and notify the 
requester.
2.  Is the De Novo request with the appropriate Center?
If the De Novo request is for a single-entity device and appears to be subject to review in a 
Center different from the one to which it was submitted, or if it is for a combination product with 
a device constituent part and it appears that a Center different from the one to which it was 
submitted has the lead, the De Novo request lead reviewer should consult with the CDRH 
Product Jurisdiction Officer or the CBER Product Jurisdiction Officer to determine the 
appropriate action and inform management. If the De Novo request is submitted to CDRH and 
CDRH staff determines that the De Novo request is not subject to CDRH review, or the De Novo 
request is submitted to CBER and CBER staff determines that the De Novo request is not subject 
to CBER review, the De Novo request review team should stop the review and notify the 
requester.
12 FDA will not process a De Novo request unless it meets the following requirements: (a) the submission must be 
sent with the user fee required by section 738 of FD&C Act and (b) a valid eCopy is provided. See sections 
738(a)(2)(A)(xi) and 738(f)(1) of the FD&C Act, section 745A(b) of the FD&C Act, and the FDA guidance, eCopy 
Program for Medical Device Submissions, available at https://www.fda.gov/regulatory-information/search-fda-
guidance-documents/ecopy-program-medical-device-submissions. Because any De Novo request not meeting these 
two requirements will not be processed by the CDRH DCC or the CBER RPM, these requirements are not included 
in the checklist.
7 Contains Nonbinding Recommendations
3.  If a Request for Designation (RFD) was submitted for the device or combination 
product with a device constituent part and assigned to your Center, identify the RFD # 
and confirm the following:
 Is the device or combination product the same (e.g., design, formulation) as that 
presented in the RFD submission?
 Are the indications for use for the device or combination product identified in the 
De Novo request the same as those identified in the RFD submission?
An RFD determination is specific to the device or combination product and indications for use 
for the device or combination product described in the RFD submission. If the device or 
combination product has been modified or the indications for use have been modified since the 
RFD, the RFD determination may no longer be applicable and jurisdiction may need to be 
reevaluated by the Office of Combination Products (OCP). The De Novo lead reviewer should 
consult with the CDRH Product Jurisdiction Officer or the CBER Product Jurisdiction Officer to 
determine the appropriate action and inform management.
4.  Is the De Novo request for a combination product that contains as a constituent part a 
drug that has the same active moiety as an approved drug with exclusivity as described 
in section 503(g)(5)(C)(ii)-(v) of the FD&C Act?
If the De Novo request is for a combination product and contains as a constituent a drug that has 
the same active moiety as an approved drug with exclusivity as described in section 
503(g)(5)(C)(ii)-(v) of the FD&C Act, the lead reviewer should contact the CDRH Product 
Jurisdiction Officer or CBER Product Jurisdiction Officer to determine the appropriate action 
and inform management.
5.  Is this device type eligible on its face for De Novo classification?
FDA staff should determine whether the subject device is a device type for which De Novo 
classification is known to be an inappropriate regulatory approach. If the device does not appear 
to be eligible for De Novo classification (e.g., a predicate device exists, an existing classification 
regulation exists for the same device type, or an approved PMA(s) exists for the same device 
type), FDA staff should make this determination during the acceptance review. This question is 
not intended to identify De Novo requests for which a substantive review is required in order to 
determine if De Novo classification is an inappropriate approach (e.g., FDA staff need to 
conduct a substantive review of information in the request to research and analyze De Novo 
eligibility or to determine if special controls can mitigate the identified risks to health). If FDA 
determines the device is ineligible during the acceptance review, FDA considers this to be a basis 
for refusing to accept the submission (see section 513(f)(2) of the FD&C Act, 21 CFR 860.200, 
21 CFR 860.230(c)(1)(ii), and 83 FR 63128). 
We do not anticipate that De Novo requests for the same device type from different requesters 
will frequently be under review concurrently. If a De Novo request for the same device from a 
different requester is currently under review at the time another De Novo request for the same 
device type is submitted to the Agency, this fact alone would not result in a Refuse to Accept 
8 Contains Nonbinding Recommendations
decision. Please see De Novo Classification Process (Evaluation of Automatic Class III 
Designation)13 for additional information regarding this situation.
6.  Is the requester subject to the Application Integrity Policy (AIP)?14
The lead reviewer should refer to the AIP list.15 If the requester is on the list, the reviewer should 
consult the CDRH OPEQ: Office of Product Evaluation and Quality/OCEA: Office of Clinical 
Evidence and Analysis/DCEA1: Division of Clinical Science and Quality or CBER Office of 
Compliance and Biologics Quality/Division of Inspections and Surveillance/Bioresearch 
Monitoring Branch (OCBQ/DIS/BMB) to determine the appropriate action. 
VI.  The Checklist  Acceptance Review
A.  Elements of a Complete De Novo Request (RTA Items)
The objective criteria in the Acceptance Checklist outline those elements that are essential to 
FDAs substantive review of the De Novo request and classification of the subject device under 
section 513(a)(1) of the FD&C Act, 513(f)(2) of the FD&C Act, and 21 CFR Part 860, Subpart D 
or required under other statutory provisions or regulations.
B.  Applying the Checklist of RTA Items
Using the Acceptance Checklist, within 15 calendar days of receipt of the De Novo request, FDA 
staff should answer each question for the elements identified as RTA items. For those items that 
have an option of yes, no, or not applicable (N/A) as an answer, the item should receive an 
answer of yes or N/A for the De Novo request to be accepted for substantive review. For any 
element that offers more than one option to be accepted for substantive review, FDA staff should 
indicate whether the De Novo request has addressed one of the options for acceptance. 
C.  Elements Marked as Not Applicable (N/A)
The Acceptance Checklist is intended to contain elements necessary for FDAs substantive 
review of the wide range of medical devices that are appropriate for De Novo classification. All 
such criteria may not be pertinent to a particular device. FDA staff should select N/A for those 
elements that do not apply to the subject device. For example, the requirements for financial 
certification and disclosure statements (21 CFR 860.220(a)(15)(iii)(E)) only apply to De Novo 
13 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/de-novo-classification-process-
evaluation-automatic-class-iii-designation 
14 When data in a pending submission have been called into question by certain wrongful acts (fraud, untrue 
statements of material facts, bribery, or illegal gratuities), FDA intends to defer substantive scientific review of such 
data until completion of a validity assessment and questions regarding reliability of the data are resolved. (See FDA 
Guide 7150.09 Compliance Policy Guide, Chapter 50  General Policy  Subject: Fraud, Untrue Statements of 
Material Facts, Bribery, and Illegal Gratuities, 56 FR 46191.)
15 https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/application-integrity-
policy/application-integrity-policy-list 
9 Contains Nonbinding Recommendations
requests with clinical data. If the De Novo request contains no clinical data, FDA staff should 
select N/A.
D.  Adequacy of Information
In order to make the checklist criteria objective, for each RTA item, FDA should consider only 
the presence or omission of the element or a rationale for the omission of the element or use of 
an alternative approach during acceptance review. It is likely that FDA staff will encounter 
scenarios where information is provided but is incomplete or inadequate. In such instances, FDA 
staff should answer the question for the respective item as yes but may communicate the 
inadequacy or request additional information during the substantive review. For example, the 
requester may have provided  information for performance testing; however, during the 
acceptance review, the reviewer may note that the results of a particular test may not be 
sufficient to determine if the test adequately mitigates a risk to health, and additional justification 
would be needed. The performance testing criterion would be marked yes in the checklist, and 
the full assessment of the results and communication to the requester that additional justification 
is needed should occur during the substantive review.
E.  Elements Marked No
For any acceptance criterion designated as no, FDA intends to provide an explanation to 
describe the missing element(s), if needed. This explanation is particularly important for a 
criterion in which it may not be immediately apparent to the requester what necessary 
information, specifically, is not present. FDA staff should include a list or statement of the 
additional information that is necessary to meet the acceptance criteria. This list or statement can 
be communicated in the comment section on the checklist beside each specific criterion.
F.  Combination Product Administrative Items
The 21st Century Cures Act, which amended section 503(g) of the FD&C Act, requires 
requesters seeking action on a combination product to identify the product as such (section 
503(g)(8)(C)(v) of the FD&C Act). Additionally, per the amended section 503(g)(5), requests for 
device-led, device-drug combination products must include the patent certification or statement 
as described in section 505(b)(2) and provide notice as described in section 505(b)(3) if the 
combination product contains as a constituent part an approved drug(see section 503(g)(5)(A) of 
the FD&C Act). De Novo requesters of products that are not combination products, as defined in 
21 CFR 3.2(e), should mark N/A and omit this section pertaining to combination products. 
G.  De Novo Requesters of Combination Products That Do 
Not Contain as a Constituent Part an Approved Drug
If the combination products do not include as a constituent part an approved drug as defined in 
section 503(g)(5)(B), requesters of device-led, device-drug combination products should mark 
N/A for element B.8.b.
10 Contains Nonbinding Recommendations
H.  De Novo Requesters of Combination Products That 
Contain as a Constituent Part an Approved Drug
De Novo requesters of combination products containing as a constituent part an approved drug 
should address question B.8 by including patent information. For each relevant patent, the 
requester should include certification to one of the following certifications:
i.  That such patent information has not been filed (section 505(b)(2)(A)(i)).
ii.  That such patent has expired (section 505(b)(2)(A)(ii)).
iii.  The date on which the patent will expire (section 505(b)(2)(A)(iii)).
iv.  That such patent is invalid or will not be infringed by the manufacture, use, or sale of 
the drug constituent part for which this submission is made (section 
505(b)(2)(A)(iv)). 
However, for a method of use patent which does not claim a use for which the requester is 
seeking approval, the requester should include a statement per section 505(b)(2)(B) that the 
method of use patent does not claim such a use.
Requesters including a certification under paragraph (iv) (section 505(b)(2)(A)(iv)) should also 
certify that they will provide notice to the owner of the patent(s) and the holder of the approved 
application that lists the patent(s) that is/are being challenged. The process for giving notice is 
provided in section 505(b)(3) of the FD&C Act. De Novo requesters should submit to FDA 
documentation of the date of receipt of notice by the holder of the approved application and the 
owner of the patent(s).
I.  Is there an open or pending premarket submission or 
reclassification petition for the same device with the same 
indications for use?
If the De Novo requester has an open or pending premarket submission (510(k), PMA, HDE),16
or reclassification petition for the same device with the same indications for use, the De Novo 
request should receive an RTA designation (21 CFR 860.230(c)(1)(i)), and the review team 
should work with the De Novo requester to clarify the appropriate regulatory pathway and 
premarket submission type. The review team should also consult management and other Center 
resources to determine which premarket review pathway applies to the device and the 
appropriate processes for addressing the situation. FDA staff should also consult management 
and other Center resources if a 510(k), PMA, HDE,or reclassification petition has been submitted 
for the same device type by different applicants.
16 FDA does not intend to refuse a De Novo request on the basis that there are open or pending Investigational 
Device Exemptions (IDEs) or Q-Submissions for the device.
11 Contains Nonbinding Recommendations
J.  De Novo Request is for a Single Device Type
It may be appropriate for FDA to review multiple devices in a single marketing submission 
under certain circumstances.17 For example, it may be appropriate for multiple sizes of a device 
to be reviewed together in a De Novo request and classified together as the same type of device 
under a single regulation. However, if a De Novo requester is instead proposing that multiple 
device types be classified under a single De Novo request (e.g., a submission for a device with 
multiple proposed indications or technologies that each have different benefit-risk considerations 
and supporting datasets would likely constitute more than one device type), the De Novo request 
should receive an RTA designation (see 21 CFR 860.230(c)(1)(iv)) and the review team should 
work with the De Novo requester to clarify which device type should be the subject of the De 
Novo request. This helps ensure efficient use of FDA resources by confining the scientific and 
regulatory issues in a submission to a single classification decision so that FDA can render a 
timely decision and assess user fees appropriately.
K.  Prior Submission(s) Relevant to the De Novo Request 
Under Review
For certain De Novo requests, the requester may have previously provided other submissions for 
the same device for which FDA provided feedback related to the data or information needed to 
support De Novo classification (e.g., a Pre-Submission request, Investigational Device 
Exemption (IDE), prior Not Substantially Equivalent (NSE) determination, or prior 510(k) or De 
Novo that was deleted or withdrawn). These prior submissions must be identified in the De Novo 
request or the request must include a statement that there have been no prior submissions (21 
CFR 860.220(a)(3)). In some cases, the requester may also have received a prior decline order 
for the same device, or FDA may have identified deficiencies in another previous submission for 
the same device that is the subject of the De Novo request. If the requester has not responded to, 
or has failed to provide a rationale for not responding to, such deficiencies, FDA may refuse to 
accept the De Novo request  (21 CFR 860.230(c)(1)(v)), and the Acceptance Checklist includes a 
corresponding criterion. FDA suggests designating a separate section of the De Novo request that 
identifies any prior submission(s) by number, includes a copy of or cross-reference to prior FDA 
feedback (e.g., letter or meeting minutes), and states how or where in the De Novo request this 
prior feedback was addressed, including feedback related to any prior related De Novo requests. 
Note that the adequacy of how the feedback was addressed should be assessed during the 
substantive review.
To address the requirement under 21 CFR 860.220(a)(3) regarding the existence of prior 
submissions and the corresponding checklist criterion, FDA recommends that requesters provide 
this information in Section F of the CDRH Premarket Review Submission Cover Sheet,
17 See also FDAs guidance entitled Bundling Multiple Devices or Multiple Indications in a Single Submission, 
available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/bundling-multiple-devices-
or-multiple-indications-single-submission.
12 Contains Nonbinding Recommendations
indicating the submission is a De Novo request.18 Requesters should list prior submissions in 
Section F of this form or state that there were no prior submissions to address this criterion. 
Please be advised that leaving this section of the form blank will not be considered a statement 
that there were no prior submissions. This information may also be included in the cover letter 
(i.e., either as a statement that there were no prior submissions for the device, or a listing of the 
number(s) of the prior submission(s)).
VII. Paperwork Reduction Act of 1995 
This guidance 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). 
The time required to complete this information collection is estimated to be 182 hours. This 
includes the time to review instructions, search existing data sources, gather the data needed, and 
complete and review the information collection. Send comments regarding this burden estimate 
or suggestions for reducing this burden to: 
Department of Health and Human Services 
Food and Drug Administration 
Office of Chief Information Officer 
Paperwork Reduction Act (PRA) Staff 
PRAStaff@fda.hhs.gov 
An agency may not conduct or sponsor, and a person is not required to respond to, a 
collection of information unless it displays a currently valid OMB control number.  
The OMB control number for this information collection is 0910-0844 (To find the 
current expiration date, search for this OMB control number available at 
https://www.reginfo.gov).
18 Form FDA 3514, available at https://www.fda.gov/media/72421/download.
13 Contains Nonbinding Recommendations 
 
Appendix A. Acceptance Checklist for De Novo 
Classification Requests 
(To be completed within 15 days of DCC receipt) 
The following information is not intended to serve as a comprehensive review. 
FDA recommends that the requester include this completed checklist as part of the De 
Novo request. 
De Novo #: DEN______  Date Received by DCC:  
Lead Reviewer: 
Center:      Office:              Division: 
Note: If an element is left blank on the checklist, it does not mean the checklist is 
incomplete; it means the reviewer did not assess the element during the RTA review and 
that the element will be assessed during substantive review. 
Preliminary Questions 
Answers in the shaded blocks indicate consultation with a Center advisor is needed. 
(Boxes checked in this section represent FDAs preliminary assessment of these  Yes  No  N/A 
questions at the time of administrative review.) 
1.  Is the product a device (per section 201(h) of the FD&C Act) or a combination       
product (per 21 CFR 3.2(e)) with a device constituent part subject to review in a De 
Novo request? 
 
If it appears not to be a device (per section 201(h) of the FD&C Act) or such a 
combination product, or you are unsure, consult with the CDRH Product Jurisdiction 
Officer or the CBER Product Jurisdiction Officer to determine the appropriate action, 
and inform management. Provide a summary of the Product Jurisdiction Officers 
determination. If the product does not appear to be a device or such a combination 
product, mark No. 
Comments: 
2.  Is the De Novo request with the appropriate Center?       
 
If the product is a device or a combination product with a device constituent part, is it 
subject to review by the Center in which the De Novo request was received? If you 
believe the De Novo request is not with the appropriate Center, or you are unsure, 
consult with the CDRH Product Jurisdiction Officer or the CBER Product Jurisdiction 
Officer to determine the appropriate action and inform your management. Provide a 
summary of the Product Jurisdiction Officers determination. If the De Novo request 
should not be reviewed by your Center, mark No. 
Comments: 
14  Contains Nonbinding Recommendations 
 
Preliminary Questions 
Answers in the shaded blocks indicate consultation with a Center advisor is needed. 
(Boxes checked in this section represent FDAs preliminary assessment of these  Yes  No  N/A 
questions at the time of administrative review.) 
3.  If a Request for Designation (RFD) was submitted for the device or combination       
product with a device constituent part and assigned to your Center, identify the 
RFD # and confirm the following: 
a.  Is the device or combination product the same (e.g., design, formulation) as that 
presented in the RFD submission? 
b.  Are the indications for use for the device or combination product identified in 
the De Novo request the same as those identified in the RFD submission? 
 
If you believe the product or the indications presented in the De Novo request have 
changed from the RFD, or you are unsure, consult with the CDRH Product Jurisdiction 
Officer or the CBER Product Jurisdiction Officer to determine the appropriate action and 
inform your management. Provide summary of Product Jurisdiction Officers 
determination. If the answer to either question above is no, mark No. If there was no 
RFD, mark N/A. 
Comments: 
4.  Is the De Novo request for a combination product that contains as a constituent       
part drug that has the same active moiety as an approved drug with exclusivity as 
described in section 503(g)(5)(C)(ii)-(v) of the FD&C Act? 
 
If Yes, then contact the CDRH Product Jurisdiction Officer or CBER Product 
Jurisdiction Officer, provide a summary of the discussion with them, and indicate their 
recommendation/action. 
Comments: 
5.  Is the device is eligible on its face for De Novo classification?       
If substantive review is required to determine whether the device is eligible for De Novo 
classification (e.g., research to determine whether a predicate device exists, an existing 
classification regulation exists for the same device type, or an approved PMA(s) exists 
for the same device type), this item can be left blank. If the device type is not eligible 
for De Novo classification, mark No. 
Comments: 
6.  Is the requester subject to the Application Integrity Policy (AIP)?       
 
If yes, consult with the CDRH Office of Product Evaluation and Quality/Office of 
Clinical Evidence and Analysis/Division of Clinical Science and Quality 
(OPEQ/OCEA/DCEA1) or CBER Office of Compliance and Biologics Quality/Division 
of Inspections and Surveillance/Bioresearch Monitoring Branch (OCBQ/DIS/BMB) to 
determine the appropriate action. Check the AIP list at https://www.fda.gov/inspections-
compliance-enforcement-and-criminal-investigations/application-integrity-
policy/application-integrity-policy-list. 
15  Contains Nonbinding Recommendations 
 
  If the answer to 1 or 2 appears to be No, then stop review of the De Novo request and 
contact the CDRH Product Jurisdiction Officer or CBER Product Jurisdiction Officer. 
  If the answer to 3a or 3b appears to be No, then stop the review and contact the CDRH 
Product Jurisdiction Officer or CBER Product Jurisdiction Officer. 
  If the answer to 4 is Yes, then contact the CDRH Product Jurisdiction Officer or CBER 
Product Jurisdiction Officer, provide a summary of the discussion with them, and indicate 
their recommendation/action. 
  If the answer to 5 is No, then stop review of the De Novo request and discuss with 
CDRH/OPEQ/ORP/DRP1 or CBER Device Regulatory Operations. This may be considered 
a basis for a refusal to accept the submission. 
  If the answer to 6 is Yes, then contact CDRH/OPEQ/OCEA/DCEA1 or 
CBER/OCBQ/DIS/BMB, provide a summary of the discussion with DCEA1 or BMB Staff, 
and indicate their recommendation/action. 
Elements of a Complete De Novo Request 
(Section 513(f)(2) of the FD&C Act and 21 CFR Part 860, Subpart D, unless otherwise indicated) 
  Any No answer can result in a Refuse to Accept decision; however, FDA staff has discretion to 
determine whether missing items are needed to ensure that the request is administratively complete to allow 
the request to be accepted or to request missing checklist items interactively from requesters during the 
RTA review. 
  Each element on the checklist should be addressed within the request. The requester may provide a rationale 
for omission for any criteria that are deemed not applicable. If a rationale is provided, the criterion is 
considered present (Yes). An assessment of the rationale will be considered during the review of the 
request. 
 
Elements of a Complete De Novo Request 
Check Yes if item is present, N/A if it is not needed, and No if it is not 
included but needed. 
 
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identify the page numbers where requested information is located. Use the 
comments section for an element if additional space is needed to identify the 
location of supporting information. 
A.  Organizational Elements 
1.  De Novo request contains a Table of Contents.         
 
Each section should be labeled (e.g., headings or tabs designating Device 
Description section, Classification Information and Supporting Data, etc.). 
16  Contains Nonbinding Recommendations 
 
Elements of a Complete De Novo Request 
Check Yes if item is present, N/A if it is not needed, and No if it is not 
included but needed. 
 
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identify the page numbers where requested information is located. Use the 
comments section for an element if additional space is needed to identify the 
location of supporting information. 
2.  All pages of the De Novo request are numbered.         
 
All pages should be numbered in such a manner that information can be 
referenced by page number. This may be done either by consecutively 
numbering the entire De Novo request, or numbering the pages within a 
section (e.g., 12-1, 12-2...). 
Comments: 
B.  Administrative Information 
1.  All content used to support the De Novo request is written in English         
(including translations of test reports, literature articles, etc.) 
Comments: 
2.  De Novo request includes the name, address, phone, and email address of         
the requester and U.S. representative, if applicable, as well as the 
establishment registration number, if applicable, of the owner or operator 
submitting the De Novo request. 
Comments: 
3.  De Novo request identifies the generic name of the device as well as any         
proprietary name or trade name.  
 
FDA recommends use of the CDRH Premarket Review Submission Cover 
Sheet (Form FDA 3514) and indicating that the submission is a De Novo 
request. 
Comments: 
4.  De Novo request contains a description of the devices indications for use,         
with prescription (Rx) and/or over-the-counter (OTC) use designated. 
Comments: 
5.  There are no open or pending premarket submissions, including a pending         
510(k), PMA, HDE, or reclassification petition submissions for the same 
device with the same indications for use. 
 
If the De Novo request is the only submission under review for this device, 
mark Yes. If there are other pending submissions, mark No and 
consult management and the appropriate CDRH or CBER staff to 
determine the appropriate action. 
Comments: 
17  Contains Nonbinding Recommendations 
 
Elements of a Complete De Novo Request 
Check Yes if item is present, N/A if it is not needed, and No if it is not 
included but needed. 
 
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identify the page numbers where requested information is located. Use the 
comments section for an element if additional space is needed to identify the 
location of supporting information. 
6.  The De Novo request is for a single device type.         
 
Multiple devices may be submitted for review in a De Novo request (e.g., 
multiple sizes of the same device). If multiple device types are proposed to 
be classified in a single De Novo request, mark No. 
Comments: 
7.  The De Novo request identifies prior submissions for the same device         
included in the current De Novo request (e.g., prior De Novo decline order; 
prior deleted or withdrawn 510(k) or De Novo request; prior 510(k) that 
received not substantially equivalent [NSE] determination; or prior Q-
Submission, IDE, PMA, etc.). 
 
OR 
 
The De Novo request states that there were no prior submissions for the 
subject device. 
 
Prior submissions (or statement of no prior submissions) for this device 
should be included in Section F of the CDRH Premarket Review 
Submission Cover Sheet (Form FDA 3514). This information may also be 
included in the Cover Letter (i.e., as a statement that there were no prior 
submissions for the device, or a listing of the number(s) of the prior 
submission(s)). 
a.  If there were prior submissions for the same device, the requester has         
responded to deficiencies identified by FDA in prior submissions, or 
has provided a rationale for not responding to those deficiencies. 
 
It is recommended that the De Novo request include a separate section 
with the prior submission number(s), a copy of the FDA feedback (e.g., 
letter, meeting minutes), and a statement of how or where in the 
submission this prior feedback was addressed.  
 
Select N/A if the requester states there were no prior submissions. 
Comments: 
18  Contains Nonbinding Recommendations 
 
Elements of a Complete De Novo Request 
Check Yes if item is present, N/A if it is not needed, and No if it is not 
included but needed. 
 
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identify the page numbers where requested information is located. Use the 
comments section for an element if additional space is needed to identify the 
location of supporting information. 
8.  Combination Product Provisions  Per 503(g) of the FD&C Act. Select         
N/A if the product is not a combination product. 21 CFR 3.2(e). The 
remaining criteria in this section will be omitted from the checklist if 
"N/A" is selected. If you are unsure if the product is a combination product, 
consult with the CDRH Product Jurisdiction Officer or CBER Product 
Jurisdiction Officer. 
a.  Request identifies the product as a combination product         
b.  The combination product contains as a constituent part an approved         
drug as defined in section 503(g)(5)(B) of the FD&C Act. Select N/A 
if the combination product does not contain as a constituent part an 
approved drug. Please also select N/A if a right of reference for use 
for the drug constituent part(s) is included with the request. If N/A is 
selected, part i. below is omitted from the checklist 
i.  The De Novo request includes appropriate patent statement or         
certification and a statement that the applicant will give notice, 
as applicable. See section 503(g)(5)(A) & (C) of the FD&C Act. 
Comments: 
C.  Device Description 
1.  A complete description of the device (including, where applicable, pictorial         
representations, device specifications, and engineering drawings) and of its 
principles of operation. 
a.  Where necessary to describe the device, the device description includes         
pictorial representations, device specifications, and engineering 
drawing(s), which could include schematics, illustrations, photos and/or 
figures of the device. Alternatively, include a statement that 
engineering drawings, pictorial representations, etc. are not applicable 
to the device to justify their omission (e.g., the device is a reagent and 
figures are not pertinent to describe the device). 
 
In lieu of engineering drawings, pictorial representations, etc. of each 
device to be marketed, representative drawings, etc. may be 
provided, where representative is intended to mean that the drawings, 
etc. provided capture the differences in design, size, and other 
important characteristics of the various models, sizes, or versions of the 
device(s) to be marketed. 
19  Contains Nonbinding Recommendations 
 
Elements of a Complete De Novo Request 
Check Yes if item is present, N/A if it is not needed, and No if it is not 
included but needed. 
 
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identify the page numbers where requested information is located. Use the 
comments section for an element if additional space is needed to identify the 
location of supporting information. 
b.  A description of proposed conditions of use; surgical technique for         
implants; anatomical location of use; user interface; how the device 
interacts with other devices; and/or how the device interacts with the 
patient. 
Comments: 
2.  A complete description of 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. 
Comments: 
3.  A complete description of each of the functional components or ingredients         
of the device, if the device consists of more than one physical component 
or ingredient. This description includes any parts or accessories to be 
marketed with the device that are the subject of the De Novo request (e.g., 
the request seeks marketing authorization for a device and an accessory to 
that device). 
Comments: 
4.  A list of 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. 
Comments: 
D.  Alternative Practices and Procedures 
1.  The De Novo request contains a description of 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 and function of the body and that are 
known or should reasonably be known to the requester. 
 
If there are no known or reasonably known alternative practices or 
procedures, include a statement to that effect to justify their omission. 
Comments: 
E.  Classification Summary and Proposed Classification 
1.  For devices which were not the subject of a previous 510(k) submission,          
the De Novo request includes a classification summary with a complete 
description of the following: 
20  Contains Nonbinding Recommendations 
 
Elements of a Complete De Novo Request 
Check Yes if item is present, N/A if it is not needed, and No if it is not 
included but needed. 
 
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identify the page numbers where requested information is located. Use the 
comments section for an element if additional space is needed to identify the 
location of supporting information. 
a.  The searches used to establish that no legally marketed device of the         
same type exists. 
b.  A list of the classification regulations, PMAs, HDEs, EUAs, 510(k)s,         
and/or product codes regarding devices that are potentially similar to 
the subject device. 
c.  A rationale explaining how the subject device is different from the         
devices covered by the classification regulations, PMAs, HDEs, EUAs, 
510(k)s, and/or product codes identified in the list. 
Comments: 
2.  For devices which were the subject of a previous 510(k) NSE decision, 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. 
Comments: 
3.  Benefit-Risk: The De Novo request includes a discussion of the probable         
benefits to health from use of the device and any probable risks to health 
from such use. 
 
See the FDA guidance document entitled, Factors to Consider When 
Making Benefit-Risk Determinations in Medical Device Premarket 
Approval and De Novo Classifications, available at 
https://www.fda.gov/regulatory-information/search-fda-guidance-
documents/factors-consider-when-making-benefit-risk-determinations-
medical-device-premarket-approval-and-de. 
Comments: 
a.  The benefit-risk discussion addresses how the data and information in         
the De Novo request constitute valid scientific evidence within the 
meaning of 21 CFR 860.7(c). 
Comments: 
b.  The benefit-risk discussion addresses why the probable benefit to         
health from use of the device outweighs any probable injury or illness 
from such use, when subject to general controls or general and special 
controls. 
Comments: 
21  Contains Nonbinding Recommendations 
 
Elements of a Complete De Novo Request 
Check Yes if item is present, N/A if it is not needed, and No if it is not 
included but needed. 
 
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identify the page numbers where requested information is located. Use the 
comments section for an element if additional space is needed to identify the 
location of supporting information. 
4.  The De Novo request includes a summary of the probable risks to health         
associated with use of the device that are known or should reasonably be 
known to the requester and the proposed mitigation measures, including 
general controls and, if recommended to be a class II device, special 
controls, for each identified risk. For each mitigation measure that involves 
specific performance testing or labeling, the De Novo request provides a 
reference to the associated section or pages for the supporting information 
in the De Novo request. 
Comments: 
5.  The De Novo request identifies a recommended class (I or II). If class I, the         
De Novo request provides a description of why general controls provide 
reasonable assurance of safety and effectiveness. If class II, the De Novo 
request identifies proposed special controls and describes how general 
controls and special controls provide a reasonable assurance of safety and 
effectiveness. 
Comments: 
F.  Summary of Studies 
1.  The De Novo request includes a summary of the results of the technical          
data contained within the De Novo request. 
Comments: 
2.  Each study summary includes 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. 
Comments: 
3.  The summary of studies includes a summary of each nonclinical study         
submitted in the De Novo request. 
 
Nonclinical test report summary content recommendations can be found in 
FDAs guidance Recommended Content and Format of Non-Clinical 
Bench Performance Testing Information in Premarket Submissions, 
available at https://www.fda.gov/regulatory-information/search-fda-
guidance-documents/recommended-content-and-format-non-clinical-
bench-performance-testing-information-premarket. 
Comments: 
22  Contains Nonbinding Recommendations 
 
Elements of a Complete De Novo Request 
Check Yes if item is present, N/A if it is not needed, and No if it is not 
included but needed. 
 
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identify the page numbers where requested information is located. Use the 
comments section for an element if additional space is needed to identify the 
location of supporting information. 
4.  The summary of studies includes a summary of each clinical investigation         
submitted in the De Novo request and identifies any clinical investigations 
conducted under an IDE. 
Comments: 
5.  The summary of each clinical investigation involving human subjects         
submitted in the De Novo request includes 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. 
Comments: 
G. Nonclinical Studies 
1.  The De Novo request provides a protocol and complete test report         
(including results) for each nonclinical study provided in the De Novo 
request (including any testing described below in Items G.2-G.5 and any 
animal studies provided in the request). 
 
Protocol and complete test report content recommendations can be found in 
FDAs guidance Recommended Content and Format of Non-Clinical 
Bench Performance Testing Information in Premarket Submissions, 
available at https://www.fda.gov/regulatory-information/search-fda-
guidance-documents/recommended-content-and-format-non-clinical-
bench-performance-testing-information-premarket. 
 
In the event that an applicant is appropriately declaring conformity with a 
voluntary consensus standard that FDA has recognized pursuant to section 
514(c) of the FD&C Act to meet applicable requirements, it may not be 
necessary to submit full test reports with respect to those requirements. 
Refer to Item I.1.a of this Checklist; see also FDAs guidance Appropriate 
Use of Voluntary Consensus Standards in Premarket Submissions for 
Medical Devices, available at https://www.fda.gov/regulatory-
information/search-fda-guidance-documents/appropriate-use-voluntary-
consensus-standards-premarket-submissionsmedical-devices. 
23  Contains Nonbinding Recommendations 
 
Elements of a Complete De Novo Request 
Check Yes if item is present, N/A if it is not needed, and No if it is not 
included but needed. 
 
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identify the page numbers where requested information is located. Use the 
comments section for an element if additional space is needed to identify the 
location of supporting information. 
Comments: 
The submission includes, as appropriate:         
 
1.  Reprocessing and Sterilization: If device is intended to be sterile or is 
reusable: 
a.  Identification of the components and/or accessories for which 
reprocessing and/or sterilization are applicable. 
b.  Sterilization method, parameters, validation method, and Sterility 
Assurance Level (SAL). 
c.  Reprocessing information, including the protocols and test reports of 
the validation of the reprocessing instructions (see the FDA guidance 
document entitled, Reprocessing Medical Devices in Health Care 
Settings: Validation Methods and Labeling, available at 
https://www.fda.gov/regulatory-information/search-fda-guidance-
documents/reprocessing-medical-devices-health-care-settings-
validation-methods-and-labeling). 
d.  Pyrogenicity test information for the following: 
i. implants; 
ii. devices in direct or indirect contact with the cardiovascular system, 
the lymphatic system, or cerebrospinal fluid (CSF), regardless 
of duration of contact; or 
iii. devices labeled non-pyrogenic. 
e.  Packaging information, including materials and package test methods. 
Comments: 
24  Contains Nonbinding Recommendations 
 
Elements of a Complete De Novo Request 
Check Yes if item is present, N/A if it is not needed, and No if it is not 
included but needed. 
 
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*Requesters including the checklist with their De Novo request should  Yes  No  N/A 
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identify the page numbers where requested information is located. Use the 
comments section for an element if additional space is needed to identify the 
location of supporting information. 
The submission includes, as appropriate:         
 
2.  Shelf Life: 
a.  An evaluation to establish that device performance is not adversely 
affected by aging, or a rationale for why the storage conditions are not 
expected to affect device safety or effectiveness. 
OR 
b.  A proposed shelf life, as well as an evaluation to establish that device 
safety and effectiveness will not be adversely affected throughout the 
proposed shelf life. 
 
The submission may include only a summary of the evaluation methods 
used, if a justification for omission of a protocol and complete test report is 
provided in accordance with 21 CFR 860.220(c). 
Comments: 
The submission includes, as appropriate:         
 
3.  Biocompatibility: If the device includes patient-contacting components: 
a.  Identification of each patient-contacting device component and 
associated materials of construction. 
b.  Identification of contact classification (e.g., surface-contacting, less 
than 24-h duration) for each patient-contacting device component (e.g., 
implant, delivery catheter). 
c.  Biocompatibility assessment of patient-contacting components. 
Comments: 
The submission includes, as appropriate:         
 
4.  Electrical Safety and Electromagnetic Compatibility: Electrical safety 
and/or electromagnetic compatibility evaluation, including: 
a.  Evaluation of electrical safety (e.g., per IEC 60601-1 or equivalent 
FDA-recognized standard), OR evaluation using alternate methods or 
standards with a rationale. 
b.  Evaluation of electromagnetic compatibility (e.g., per IEC 60601-1-2 
or equivalent FDA-recognized standard), OR evaluation using alternate 
methods or standards with a rationale.  
Comments: 
25  Contains Nonbinding Recommendations 
 
Elements of a Complete De Novo Request 
Check Yes if item is present, N/A if it is not needed, and No if it is not 
included but needed. 
 
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identify the page numbers where requested information is located. Use the 
comments section for an element if additional space is needed to identify the 
location of supporting information. 
H. Software 
1.  For all devices that incorporate software, all relevant software information         
and testing is provided, including: 
a.  Software level of concern and rationale for the software level of 
concern. 
c.  Appropriate device hazard analysis, hardware, and system information 
as described in the FDA guidance document entitled, Guidance for the 
Content of Premarket Submissions for Software Contained in Medical 
Devices, available at https://www.fda.gov/regulatory-
information/search-fda-guidance-documents/guidance-content-
premarket-submissions-software-contained-medical-devices, OR an 
alternate approach to such documentation with a rationale. 
Comments: 
I.  Standards and Declarations of Conformity 
1.  Does the De Novo request utilize voluntary consensus standards? (See         
section 514(c) of the FD&C Act). This includes both FDA-recognized and 
non-recognized consensus standards. 
a.  The submission cites FDA-recognized voluntary consensus standard(s)         
i.  The submission includes a Declaration of Conformity (DOC) as         
outlined in FDAs guidance Appropriate Use of Voluntary 
Consensus Standards in Premarket Submissions for Medical 
Devices, available at https://www.fda.gov/regulatory-
information/search-fda-guidance-documents/appropriate-use-
voluntary-consensus-standards-premarket-submissions-medical-
devices.  
OR 
ii.  If citing general use of a standard, the De Novo request 
provides information to demonstrate how the device meets, or 
justify any deviation from, the referenced standard. 
b.  The submission cites non-FDA-recognized voluntary consensus         
standard(s) 
i.  The De Novo request provides information to demonstrate how         
the device meets, or justify any deviation from, the referenced 
standard. 
Comments: 
26  Contains Nonbinding Recommendations 
 
Elements of a Complete De Novo Request 
Check Yes if item is present, N/A if it is not needed, and No if it is not 
included but needed. 
 
*Page 
*Requesters including the checklist with their De Novo request should  Yes  No  N/A 
# 
identify the page numbers where requested information is located. Use the 
comments section for an element if additional space is needed to identify the 
location of supporting information. 
J.  Animal: The De Novo request provides the results as well as a protocol and         
complete test report for each animal study provided. 
Comments: 
1.  Each study includes a statement that the study was conducted in         
compliance with the Good Laboratory Practice (GLP) for Nonclinical 
Laboratory Studies regulation (21 CFR part 58), OR if the study was not 
conducted in compliance with the GLP regulation, a brief statement of the 
reason for the noncompliance. 
Comments: 
K. Clinical: The De Novo request contains results of each clinical investigation         
of the device, including for each investigation: 
Comments: 
1.  Study protocols. (If performed under an approved IDE application         
submitted under 21 CFR 812.20, this should be the final FDA-approved 
version of the clinical study protocol, incorporating any Notices of 
Changes.) 
Comments: 
2.  Number of investigators and subjects per investigator.         
Comments: 
3.  Investigation design, including study population and investigation period.         
Comments: 
4.  Subject selection and exclusion criteria.         
Comments: 
5.  Tabulations of data from individual subject report forms.         
Comments: 
6.  Effectiveness data.         
Comments: 
7.  Safety data, including all adverse reactions and complications, deaths,         
subject discontinuations and subject complaints, device failures (including 
unexpected software events if applicable), and replacements. 
Comments: 
8.  Copies of individual subject report forms for patients who died or who did         
not complete the investigation. 
 
Check N/A only if no patients died or were discontinued. 
27  Contains Nonbinding Recommendations 
 
Elements of a Complete De Novo Request 
Check Yes if item is present, N/A if it is not needed, and No if it is not 
included but needed. 
 
*Page 
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identify the page numbers where requested information is located. Use the 
comments section for an element if additional space is needed to identify the 
location of supporting information. 
Comments: 
9.  A statement that each investigation has been completed per the protocol or         
a summary of any protocol deviations. 
Comments: 
10. The results of any statistical analyses performed.         
Comments: 
11. Contraindications, warnings, precautions, and other limiting statements         
relevant to the use of the device type, based on the clinical investigation. 
Comments: 
12. If a De Novo request 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. 
Comments: 
13. A discussion of how the investigation data represent clinically significant         
results, pursuant to 21 CFR 860.7(e). 
Comments: 
28  Contains Nonbinding Recommendations 
 
Elements of a Complete De Novo Request 
Check Yes if item is present, N/A if it is not needed, and No if it is not 
included but needed. 
 
*Page 
*Requesters including the checklist with their De Novo request should  Yes  No  N/A 
# 
identify the page numbers where requested information is located. Use the 
comments section for an element if additional space is needed to identify the 
location of supporting information. 
14. Statements of Compliance for Clinical Investigations         
 
Select N/A if the submission does not contain any clinical data from 
investigations (as defined in 21 CFR 812.3(h)) to support the recommended 
classification. 
 
For multicenter clinical investigations involving both United States (US) 
and outside the United States (OUS) sites, part (a) should be addressed for 
the US sites, and part (b) should be addressed for the OUS sites. 21 CFR 
812.28 applies to all OUS clinical investigations that enroll the first subject 
on or after February 21, 2019. 
 
Please refer to the guidance document entitled Acceptance of Clinical 
Data to Support Medical Device Applications and Submissions - 
Frequently Asked Questions, available at https://www.fda.gov/regulatory-
information/search-fda-guidance-documents/acceptance-clinical-data-
support-medical-device-applications-and-submissions-frequently-asked, 
for more information. 
a.  For each clinical investigation conducted in the US, the De Novo         
request includes either a statement that the investigation was conducted 
in compliance with 21 CFR parts 50, 56, and 812 (or, with respect to       
part 56, that it was not subject to the regulations under 21 CFR 56.104 
or 56.105), OR a brief statement of the reason for noncompliance with 
21 CFR parts 50, 56, and/or 812. 
Select N/A if the clinical investigations were conducted solely OUS. 
29  Contains Nonbinding Recommendations 
 
Elements of a Complete De Novo Request 
Check Yes if item is present, N/A if it is not needed, and No if it is not 
included but needed. 
 
*Page 
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identify the page numbers where requested information is located. Use the 
comments section for an element if additional space is needed to identify the 
location of supporting information. 
b.  For each clinical investigation conducted OUS, the De Novo request         
includes a statement that the clinical investigations were conducted in 
accordance with good clinical practice (GCP) as described in 21 CFR       
812.28(a)(1), OR a waiver request in accordance with 21 CFR 
812.28(c), 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. 
Select N/A if the clinical investigations were conducted solely inside 
the US. 
Comments: 
L.  Financial Disclosure Information 
1.  For a De Novo request that includes clinical studies, financial disclosure         
information is provided. 
 
As required by 21 CFR part 54, the requester must either provide: 
  a signed and dated Certification Form (Form FDA 3454); or 
  a signed and dated Disclosure Form (Form FDA 3455). 
 
For additional information, see the FDA guidance document entitled 
Financial Disclosure by Clinical Investigators, available at 
https://www.fda.gov/regulatory-information/search-fda-guidance-
documents/financial-disclosure-clinical-investigators.  
Comments: 
a.  For a Certification Form (Form FDA 3454): Is the required list of all         
investigators and sub-investigators attached to the form? 
Comments: 
b.  For a Certification Form (Form FDA 3454): If box (3) is checked, does         
the form include an attachment with the reason(s) why financial 
disclosure information could not be obtained? 
Comments: 
30  Contains Nonbinding Recommendations 
 
Elements of a Complete De Novo Request 
Check Yes if item is present, N/A if it is not needed, and No if it is not 
included but needed. 
 
*Page 
*Requesters including the checklist with their De Novo request should  Yes  No  N/A 
# 
identify the page numbers where requested information is located. Use the 
comments section for an element if additional space is needed to identify the 
location of supporting information. 
c.  For a Disclosure Form (Form FDA 3455): Does the requester provide         
details of the financial arrangements and interests of the investigator(s) 
or sub-investigator(s), along with a description of any steps taken to 
minimize potential bias? 
Comments: 
M. Other Information 
1.  A bibliography of all published reports, outside of the data described         
above, 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. 
 
If there are no additional published reports, include a statement to that 
effect to justify their omission. 
Comments: 
2.  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. 
Comments: 
31  Contains Nonbinding Recommendations 
 
Elements of a Complete De Novo Request 
Check Yes if item is present, N/A if it is not needed, and No if it is not 
included but needed. 
 
*Page 
*Requesters including the checklist with their De Novo request should  Yes  No  N/A 
# 
identify the page numbers where requested information is located. Use the 
comments section for an element if additional space is needed to identify the 
location of supporting information. 
N.  In Vitro Diagnostic (IVD) Devices: If the device is an IVD, the labeling         
submitted in the De Novo request provides information describing the 
performance characteristics of the device, including as appropriate, such things 
as: 
 
1.  Precision/reproducibility 
2.  Accuracy 
3.  Specificity 
4.  Sensitivity (detection limits, Limit of Blank (LoB), Limit of Detection 
(LoD), Limit of Quantitation (LoQ) where relevant for the device type). 
 
The technical sections of the De Novo request provide the results of the 
studies, as well as associated protocols and line data, corresponding to the 
information on performance characteristics of the device (such as 
precision/reproducibility, accuracy, specificity, and sensitivity), including, as 
appropriate, linearity, calibrator or assay traceability, calibrator and/or assay 
stability protocol and acceptance criteria, assay cut-off, method comparison or 
comparison to clinical outcome, matrix comparison, and clinical reference 
range or cutoff. 
Comments: 
O. Labeling 
1.  The De Novo request includes 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. 
 
See 21 CFR parts 801 and 809, as applicable. 
Comments: 
 
 
32