Acceptance Review for De Novo Classification Requests

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

[email protected].

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 [email protected].

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[email protected] 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, [email protected], 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.

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.

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 Agency’s 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),

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).

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.

“Medical Device De Novo Classification Process” (86 FR 54826)

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.

See Title II of the FDA Reauthorization Act of 2017 (Public Law 115-52).

https://www.fda.gov/media/102699/download

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, FDA’s 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

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,

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

Please refer to the final rule (86 FR 54826) published on October 5, 2021 and available at

https://www.federalregister.gov/d/2021-21677.

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.

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 staff’s 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

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.

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 electronically

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 Center’s Document Control

Center (DCC)

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.

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

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.

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.

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.

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 Center’s 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 reviewer

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 reviewer’s 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 request’s

administrative file and are not posted publicly when FDA makes the RTA designation.

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).

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).

IV. RefusetoAcceptPrinciples

In order to use this guidance appropriately, FDA staff should review the following basic

principles regarding FDA’s 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 FDA’s 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

CBER will accommodate the use of faxes; submitters may also wish to provide a fax number.

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 continue

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.

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.

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”

Contains Nonbinding Recommendations

decision. Please see “De Novo Classification Process (Evaluation of Automatic Class III

Designation)”

for additional information regarding this situation.

6. Is the requester subject to the Application Integrity Policy (AIP)?

The lead reviewer should refer to the AIP list.

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

FDA’s 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 FDA’s 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

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/de-novo-classification-process-

evaluation-automatic-class-iii-designation

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.)

https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/application-integrity-

policy/application-integrity-policy-list

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.

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),

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.

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.

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.

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,

See also FDA’s 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.

Contains Nonbinding Recommendations

indicating the submission is a De Novo request.

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

[email protected]

Form FDA 3514, available at https://www.fda.gov/media/72421/download.

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).

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

uest

ons

Answers in the shaded blocks indicate consultation with a Center advisor is needed.

(Boxes checked in this section represent FDAs preliminary assessment of these

questions at the time of administrative review.)

Yes No N/A

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 Officer’s

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 Officer’s determination. If the De Novo request

should not be reviewed by your Center, mark “No.”

☐

Comments:

Contains Nonbinding Recommendations

Preliminary

uest

ons

Answers in the shaded blocks indicate consultation with a Center advisor is needed.

(Boxes checked in this section represent FDAs preliminary assessment of these

questions at the time of administrative review.)

Yes No N/A

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 th

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 a

inform your management. Provide summary of Product Jurisdiction Officer’s

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.

☐

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.

*Requesters including the checklist with their De

Novo request should

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.

Yes No N/A

*Page

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.).

☐

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.

*Requesters including the checklist with their De

Novo request should

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.

Yes No N/A

*Page

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 device’s 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:

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.

*Requesters including the checklist with their De

Novo request should

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.

Yes No N/A

*Page

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.).

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:

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.

*Requesters including the checklist with their De

Novo request should

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.

Yes No N/A

*Page

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.

☐

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.

*Requesters including the checklist with their De

Novo request should

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.

Yes No N/A

*Page

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:

☐

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.

*Requesters including the checklist with their De

Novo request should

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.

Yes No N/A

*Page

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:

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.

*Requesters including the checklist with their De

Novo request should

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.

Yes No N/A

*Page

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 eac

h 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

FDA’s 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:

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.

*Requesters including the checklist with their De

Novo request should

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.

Yes No N/A

*Page

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

FDA’s 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 FDA’s 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.

☐

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.

*Requesters including the checklist with their De

Novo request should

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.

Yes No N/A

*Page

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 sys

tem,

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:

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.

*Requesters including the checklist with their De

Novo request should

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.

Yes No N/A

*Page

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.

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:

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.

*Requesters including the checklist with their De

Novo request should

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.

Yes No N/A

*Page

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 FDA’s 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.

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:

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.

*Requesters including the checklist with their De

Novo request should

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.

Yes No N/A

*Page

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.

☐

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.

*Requesters including the checklist with their De

Novo request should

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.

Yes No N/A

*Page

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:

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.

*Requesters including the checklist with their De

Novo request should

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.

Yes No N/A

*Page

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 t

o 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.

☐

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.

*Requesters including the checklist with their De

Novo request should

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.

Yes No N/A

*Page

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:

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.

*Requesters including the checklist with their De

Novo request should

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.

Yes No N/A

*Page

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:

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.

*Requesters including the checklist with their De

Novo request should

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.

Yes No N/A

*Page

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: