De Novo Program

November 4, 2014

Elias Mallis

Director

Division of Industry and Consumer Education

Office of Communication and Education

Center for Devices and Radiological Health

U.S. Food and Drug Administration
Learning Objectives

• Describe the legal and regulatory basis for the de novo 

program

• Describe the de novo submission process

• Assemble the materials that will lead to a good quality 

de novo submission

• Identify the resources useful in preparing a de novo

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What is a de novo? 

A classification process:

Ø using a risk-based strategy

Ø for new, novel devices whose type has not previously 

been classified

Ø would be classified into Class III

Ø to classify into Class I or II

3
What is a de novo? 

• an application sent by the medical device sponsor to FDA

• if granted:

Øestablishes new “device type” along with classification, 

regulation, necessary controls and product code

Ødevice is eligible to serve as a predicate for new medical 

devices, where appropriate [510(k) process]

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Federal Food, Drug, and Cosmetic Act 

(the FD&C Act)

Medical Device Amendments, 1976

Section 513

• classification of medical devices

• risk-based approach: 

– 513(a)(1)(A): Class I, “General Controls”

– 513(a)(1)(B): Class II, “Special Controls”

– 513(a)(1)(C): Class III, “Premarket Approval”

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Reference

Regulatory Controls (General, Special , PMA)

• http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidan

ce/Overview/GeneralandSpecialControls/default.htm

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FD&C Act

Medical Device Amendments (1976)

Section 513(a)(1)(C)

• Class III, require Premarket Approval

• devices with highest risk

• unable to rely on general and/or special controls

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FD&C Act

Medical Device Amendments (1976)

Section 513(f)(1): “new devices”

• post-Amendments Class III devices 

• a device not equivalent to a Class I or II device is classified into 

Class III: a “new device”

• regardless of risk

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FD&C Act – modified in 1997

Food and Drug Administration Modernization Act (FDAMA)

Section 513(f)(2): established de novo classification process

• also known as “Evaluation of Automatic Class III Designation”

• provided regulatory authority for FDA to classify devices that were 

automatically classified into Class III per Section 513(f)(1) (new devices)

• to Class I or II using criteria of Section 513(a)(1)(A-B)

Ø excludes devices already classified into Class III

(e.g., PMA-approved devices)

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De Novo Process, 1997

1. Sponsor submits premarket notification (510(k))

2. FDA issues final 510(k) decision of “not substantially 

equivalent” due to no predicate

3. Sponsor submits de novo request

4. FDA decides whether to classify device from Class III to 

Class I or II with new classification/regulation

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FD&C Act – further modified in 2012

Food and Drug Administration Safety and Innovation Act (FDASIA)

Section 513(f)(2) – de novo provision

What changed

• allowed alternative pathway that doesn’t require submission of 

a 510(k) prior to de novo request

• timeframe for review set at 120 FDA days

Ø goal: to streamline and increase efficiency in process

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FD&C Act – further modified in 2012

Food and Drug Administration Safety and Innovation Act (FDASIA)

Section 513(f)(2) – de novo provision

What didn’t change

• still only applies to Section 513(f)(1) (new devices)

• sponsor may still submit 510(k) first (e.g., FDAMA pathway an option)

• intent and decision-making threshold for de novo eligibility unchanged

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De Novo Process, 

effective 2012

1. Sponsor submits de novo request

2. FDA decides whether to classify device from 

Class III to Class I or II with new 

classification/regulation

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1998 De Novo Guidance, final

14

Note: Due to enactment of FDASIA 2012, some aspects of this 

guidance may no longer be current.
2014 De Novo Guidance, draft

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Reference

February 1998 Final Guidance

• http://www.fda.gov/downloads/MedicalDevices/DeviceRegulation

andGuidance/GuidanceDocuments/ucm080197.pdf

August 2014 Draft Guidance

• http://www.fda.gov/downloads/medicaldevices/deviceregulationa

ndguidance/guidancedocuments/ucm273903.pdf

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2014 De Novo Guidance, draft

• published August 14, 2014

• reflects proposed policy and procedures to implement 

changes to de novo program from FDASIA 2012

• draft guidance:

– not implemented at this time

– if finalized, will replace 1998 Guidance

– 90-day public comment period

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2014 De Novo Guidance, draft

Major Items

• explains changes to FD&C Act:

§ allowed alternative pathway that doesn’t require submission of a 

510(k) prior to de novo request

§ timeframe for review set at 120 FDA days

• Decision Options: grant or decline

• Pre-Submission meeting process

• new term: “direct de novo” (no 510(k) prior to de novo 

submission)

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De Novo

Submission Process
Submission Process:

Two Pathways

Pathway #1: 510(k) è de novo

• attempt 510(k) route with proposed predicate device

• submission found NSE, but candidate for de novo

Pathway #2: direct de novo

• useful if you believe proposed device is viable de novo 

candidate (esp. with feedback from Pre-Sub program)

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Submission Process:

Pathway #1: 510(k) è de novo

Ø When to use: You believe you have a suitable 

predicate device.

1. Sponsor submits 510(k) submission

– this should be a complete 510(k) submission

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Submission Process:

Pathway #1: 510(k) è de novo

2. FDA reviews 510(k) submission; makes NSE 

finding due to lack of predicate

• lack of predicate = proposed predicate device does not have same 

intended use and technological characteristics as new device.

• FDA may choose to indicate in NSE letter that new device may be 

appropriate de novo candidate (based on risk-benefit profile, not adequacy 

of data submitted)

Ø the suggestion for de novo is not binding

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Submission Process:

Pathway #1: 510(k) è de novo

3. Sponsor submits de novo application

• reference prior 510(k)

• provide additional evidence to demonstrate safety and 

effectiveness of new device, as appropriate

• address any differences and evidence gaps between 510(k) 

device and de novo: provide added testing, S&E information as 

needed

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Submission Process:

Pathway #1: 510(k) è de novo

3. Sponsor submits de novo application:

• characterize risks to health associated with use of new device

• characterize how the risks may be mitigated

• provide rationale for why device does not fit into an existing 

regulation

• if propose Class II classification, then identify the special controls 

to mitigate the risks to health

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Submission Process:

Pathway #1: 510(k) è de novo

4. FDA reviews de novo application

• may interact with sponsor, ask for additional information

• render final de novo decision: grant or decline

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Submission Process:

Pathway #2: direct de novo

Ø When to use:

1. You believe you don’t have a suitable predicate 

device either based on your own assessment or 

through FDA feedback AND

2. You believe the device may be classified into Class 

I or II per de novo.

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Submission Process:

Pathway #2: direct de novo

1. Sponsor submits de novo application:

• evidence that establishes reasonable assurance of safety and 

effectiveness of new device

§ most information typically submitted in traditional 510(k) submission

§ device description

§ labeling

§ performance testing (bench, animal, clinical)

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Submission Process:

Pathway #2: direct de novo

1. Sponsor submits de novo application:

• characterize risks to health associated with use of new device

• characterize how the risks may be mitigated

• provide rationale for why device does not fit into existing regulation 

(either 510(k) or PMA)

• if propose Class II classification, then identify the special controls 

to mitigate the risks to health

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Submission Process:

Pathway #2: direct de novo

2. FDA reviews de novo application

• may interact with sponsor, ask for additional information

• render final de novo decision: grant or decline

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2014 De Novo Guidance, draft

New Flowchart

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Getting Informal Feedback:

Pre-Sub

FDA strongly encourages sponsors to use Pre-Sub 

program for potential de novos!

• after device design and intended use are established

• after sufficient information has been collected regarding safety and 

effectiveness (e.g., test methods)

• useful for novel devices with no FDA regulatory history, based on 

your research

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Reference

Pre-Submission Program Guidance

• http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Guidanc

eDocuments/ucm310375.htm

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What happens after

a de novo is granted?
After de novo is granted

• New Device is Legally Marketed

– subject to post-market requirements applicable to that device 

and class (including general controls, special controls as 

applicable)

• New Device Establishes New Classification 

Regulation

– new device is eligible to serve as a predicate for future similar 

devices

• follows standard 510(k) process
After de novo is granted

• FDA publishes order announcing new 

classification, controls

• FDA generates decision summary that is 

publicly available
After de novo is granted
Resource

FDA Transparency Website

www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProducts

andTobacco/CDRH/CDRHTransparency/ucm232269.htm
After de novo is granted
Classification Order (pages 1, 3)
Decision Summary (1st 2 pages)
De Novo Database

launched August 2014
Reference

De Novo Database

• http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMN/denovo.cfm

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Submission Identification

DENXXZZZZ*

• DEN = de novo

• XX = year of submission (e.g., 14 = 2014)

• ZZZZ = submission increments from 0001

* Naming structure effective with new submissions as of Aug 2014.

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Submission Identification

• 510(k)s that lead to de novos - both 510(k) and 

DEN numbers

• Direct De Novos – no 510(k) number

• DEN process began August 2014

– retroactively assigned DEN ID to prior de novos

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Suggested Information for 

Inclusion in De Novo Application
Content Information -

from 2014 Draft Guidance

Disclaimer:

• not for implementation (draft)

• however, may contain useful information to consider 

for inclusion in your submission
Suggested Information

1. Administrative Information:

• applicant name

• contact name

• address

• contact information (phone, fax, email)

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Suggested Information

2. Regulatory History:

Prior submissions to FDA for same device

• prior 510(k)s and related NSE decisions

• IDEs

• Pre-Submissions (Pre-Subs)

• previously withdrawn/declined de novos

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Suggested Information

3. Device Information and Summary

• device name

• device description

• intended use/indications for use statement

• technological characteristics

• labeling (directions for use)

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Suggested Information

4. Classification Summary

– review of FDA classifications, regulations, and approved PMAs to 

confirm that your device has not already been classified

• in other words, confirmation that this is a “new device”

5. Recommended Classification

– Class (i.e., either Class I or II)

– exempt or not-exempt

– justification for recommended classification, controls, and 

exemption (as applicable)

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Suggested Information

6. Proposed Special Controls

• applicable to Class II devices ONLY

7. Supportive Evidence

• methods, data, results

• testing to include: pre-clinical, animal, clinical, where appropriate

• correlation between evidence and classification recommendation

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Suggested Information

8. Summary of Benefits

9. Summary of Known/Potential Risks to Health

10. Risk and Mitigation Information

– discussion of each risk, mitigation measure, and evidence

– mitigation to include general and/or special controls

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Suggested Information

11. Benefit-Risk Considerations

Discuss how benefits, with recommended general/special 

controls, outweigh risks

12. Device Labeling

per Section 201(m) of FD&C Act

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Best Practices/Helpful Hints
Best Practices/Helpful Hints

1. Do your homework and regulatory 

research to show your new device is 

eligible for de novo.

– Verify that your new product is not already classified

– Research all available databases (510(k), PMA, classification) and 

prior decisions

Ø Especially important if you pursue direct de novo
Best Practices/Helpful Hints

2. Be specific with and finalize the device 

description and intended use.

– The specifics of the device description and intended use will determine 

whether the new device has a predicate to which it may be compared.
Best Practices/Helpful Hints

3. Complete all required performance testing 

prior to submission of de novo. 

• De Novo application should be best effort to include all necessary information 

for FDA to make final de novo decision.

• Testing may include bench, animal, in vivo, in vitro, clinical.

• Each de novo will need the level of testing to characterize level of risk of device, 

demonstrate reasonable assurance of safety and effectiveness, and (as 

applicable), the appropriateness of special controls.

• Clinical testing not always be required, but likely in many cases. 
Best Practices/Helpful Hints

4. Ensure that data support proposed 

intended use.

• If you propose intended use for multiple patient populations, provide 

evidence for all groups (or justification for not directly testing patient 

population)
Best Practices/Helpful Hints

5. Correlate each risk to health with a 

mitigation. 

• Consider similarities of new device risk with mitigation used for similar 

devices

ü Tip: Review special controls used for other granted de novo applications

• Address each risk to health with at least one mitigation
Best Practices/Helpful Hints

6. Being Low Risk helps support de novo 

eligibility, but isn’t sufficient to be 

granted a de novo. 

A new device that is low risk may be eligible for a de novo only:

• if able to characterize risks to health and

• provide reproducible controls to manage those risks.
Does My Device Qualify for a De Novo?

1. Has the Device Type already been classified by FDA?

– Device Type includes both intended use and technological characteristics

– 510(k) Pathway: Is there an applicable predicate device?

– PMA Pathway: Has the device type been approved under PMA?

2. Factors to Consider for the New Device

– Does the device present low risk or moderate risk?

– Can we identify the risks to health associated with the new device?

– Can we identify the necessary controls (general and/or special) to mitigate the 

risks?
Conclusion

1. De Novo provides a means for a new medical device to get to market.

2. The eligibility for a de novo is based on several factors, such as FDA 

precedent, level of risk and the ability to characterize and mitigate risks 

of device.

3. The information needed in a De Novo includes evidence that 

demonstrates safety and effectiveness of new device and classification 

information.

4. Several key resources such as FDA Pre-Submissions and public 

domain information on web may be useful.
Providing Industry Education

1. CDRH Learn – Multi-Media Industry Education

§ over 80 modules - videos, audio recordings, power point presentations, software-based 

“how to” modules

§ accessible on your portable devices http://www.fda.gov/Training/CDRHLearn

2. Device Advice – Text-Based Education

§ comprehensive regulatory information on premarket and postmarket topics

http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance

3. Division of Industry and Consumer Education (DICE)

§ If you have a question - Email: DICE@fda.hhs.gov

§ Phone: 1(800) 638-2014 or (301) 796-7100 (Live Agents 9am – 4:30 pm EST)

Web Homepage: 

http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/ContactUs--

DivisionofIndustryandConsumerEducation/default.htm

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Thank you

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