March 3, 2022

Demystifying De Novo

What You Need To Know About The De Novo Review Pathway

You’ve spent months, if not years, finetuning a concept you want to bring to market to improve the lives of patients. 

Maybe you’re having trouble finding a substantially equivalent predicate device, so a 510(k) is out of the picture.

And your product isn’t Class III, so no need for a PMA.

Going De Novo could be the answer for you.

Let’s get a better look at the De Novo pathway with insight into what it is and how it works.

What is De Novo?

A De Novo submission is a pre-market submission type for novel moderate risk (or Class II) devices with no legally marketed predicate.

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Before the introduction of the De Novo program, novel devices had two possible paths to get to market:

  1. Going the 510(k) route and receiving an NSE (not substantially equivalent) determination

OR

  1. Applying for a PMA

However, neither of these options were ideal for low and moderate-risk, novel devices.

This changed with the implementation of De Novo in 1997 and is improved with the latest rule update in 2022. 

We’ll discuss more of the Final Rule Update below.

Criteria Eligibility – How to know if your product is right for De Novo

Before you submit your De Novo application or engage in any Q-Sub meetings, it’s important to know your device’s risk assessment and its overall safety and effectiveness (via bench testing, preclinical testing, and clinical testing).

To qualify for De Novo, make sure your device meets the following requirements:

  • Falls under either Class I or II with no appropriate predicate
  • The proposed special controls are sufficient
  • The benefits of your device outweigh the risks

To start confirming these elements, a thorough regulatory review of currently marketed products should be conducted to determine those most similar to your product. Then, an analysis of the substantial equivalence of these products should be performed.

If no products are substantially equivalent but most similar products fall into Class I or II, you’ve likely addressed Bullet 1.

Further confirmation of your rationale can be obtained from a pre-submission meeting with FDA during which you can discuss your regulatory pathway. During this meeting with FDA, you may also discuss your testing, which will inform your special controls, and your benefit-risk assessment.

FDA will provide you feedback on these elements which you can then use to support a future De Novo submission.

Filing A De Novo Request

There are two ways to go about filing a De Novo request.

Option One: The first is a Post-NSE ruling of a 510(k). This is the traditional and more circuitous way of requesting a De Novo.

Under this option, you would first file a 510(k). Then after receiving a not substantially equivalent determination, you will need to generate and file an entirely new submission.

This effectively means you will be pulling together two submissions—one 510(k) and one De Novo—and submitting both to FDA. Both will be subject to user fees, and the review clock restarts after the NSE.

Our advice is to stray away from this option, if possible, to avoid the unnecessary time, costs, and burden. One way to avoid filing an unnecessary 510(k) is to have a pre-submission meeting in which you can discuss your regulatory pathway.

You can learn more about pre-submissions here.

Option Two: The other option is to go the Direct De Novo request filing route.

This path avoids the need for a 510(k) submission. If your device is, in fact, a De Novo device, then this pathway will be more efficient and cost-effective than Option 1.

Following this pathway, you will only need to generate one submission, pay one MDUFA user fee, and undergo one review (assuming you’ve got all your ducks in a row).

Similar to the above statement, a pre-submission meeting is still recommended even if you’re pretty confident that you are going to follow the De Novo pathway. In this pre-submission, you may confirm the pathway and your testing plans.

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FDA Review of De Novo Request

There are two different parts of the review process with the De Novo review request.

1st Part - The first leg of review is the Acceptance Review. The acceptance review assesses the completeness of the application and whether it meets the threshold of acceptability.

In 15 days, FDA will supply one of the following:

  1. Acceptance for substantive review 
  2. Not accepted (RTA) and the requester has 180 days to address the RTA
  3. Request is under substantive review & FDA didn’t complete acceptance review within the 15-day timeline

After the FDA accepts the De Novo request for review, Substantive Review begins.

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2nd Part - Substantive Review is when the FDA first conducts a classification review to see if an existing legally marketed device of the same type exists. They will also decide whether the special controls outlined are adequate for your device and review all your testing data in support of those special controls.

During this time in the review process, the FDA may identify deficiencies in the submission. 

For example, if your submission is missing testing information and data needed for the FDA to make their decision— this would be considered a deficiency. 

At that point, you would have 180 days to submit additional information. 

If you have supplied the appropriate and necessary information and the FDA determines your device to be safe and effective— you’ll be on the way to getting your De Novo granted.


Final Rule Update – October 2021


In October of 2021, the FDA released what they called the “Final Rule” for De Novo.

This update cemented common practices that were not clearly defined in guidance documents but are now listed as accepted practices.

  • Refuse-to-Accept (RTA) Checklist Updates

One of the biggest changes in the update is the acceptance checklist. Previously, the RTA checklist had two sections: 

Appendix A – require and Appendix B – Recommended

With the latest update, almost all of the elements from both sections are now required. Some of the newly required elements include the classification summary and device labeling.

  • Premarketing Manufacturing Inspection

This change affects only a small number of De Novo requests. If the device has critical or novel manufacturing processes that could affect the safety and efficacy of the device, the FDA may inspect the facility for data integrity concerns and quality system regulation.  

The FDA suggests discussing questions about whether a premarketing manufacturing inspection would be required and its scope in a pre-submission meeting.

  • Marketing Language Requirements

Since De Novo is not a PMA, the FDA recommends using marketing language like “granted De Novo” or “granted marketing authorization” rather than “FDA approved.”

Going De Novo can be just what you need to get your novel device to market.

If you want a smooth experience without any unexpected surprises, rely on an experienced CRO that is familiar with the De Novo review and submission process and can guide you with success.

Contact Proxima CRO for all of your regulatory and clinical needs.

Reference:

  1. Food & Drug Administration: Center for Devices and Radiological Health.(2018, January 4). De Novo Program - Transcript. U.S. Food and Drug Administration. https://www.fda.gov/training-and-continuing-education/cdrh-learn/de-novo-program-transcrip
  2. De Novo Classification Request
    . https://www.fda.gov/medical-devices/premarket-submissions-selecting-and-preparing-correct-submission/de-novo-classification-request
  3. Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program. https://www.fda.gov/media/114034/download
  4. Medical Device De Novo Classification Process. https://www.federalregister.gov/documents/2021/10/05/2021-21677/medical-device-de-novo-classification-process
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