If you’re developing a new medical device and there’s no clear predicate on the market, you may be wondering whether the FDA’s De Novo pathway is the right route forward. The process can feel confusing at first glance.
How does De Novo differ from a 510(k)? What evidence will the FDA expect? And how do you prepare without over-complicating things?
This article breaks down the essentials: what a De Novo submission is, when it applies, and the practical steps to take for a smoother review. Along the way, we’ll highlight common challenges and how teams can set themselves up for success with the right documentation strategy.
What is a De Novo Submission?
A De Novo submission is a regulatory submission pathway created by the FDA for novel medical devices that don’t have a legally marketed predicate. It provides a way to classify low- to moderate-risk devices that don’t fit into an existing category, without forcing sponsors into the more burdensome Premarket Approval (PMA) process.
In practice, the De Novo pathway is often used by teams developing innovative devices that are first-of-their-kind. While a 510(k) relies on showing substantial equivalence to an existing device, a De Novo request asks the FDA to create a brand-new classification. If granted, this classification can then serve as the predicate for future 510(k) submissions.
Some examples of devices that have been cleared through the De Novo process include:
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Digital therapeutics for conditions like substance use disorder.
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Wearable sensors that continuously monitor health metrics in new ways.
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AI-based software that supports diagnostic decision-making.
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Novel surgical instruments with functions not previously available on the market.
These examples highlight the FDA’s intent with the pathway: to support innovation while ensuring that appropriate controls are in place for safety and effectiveness.
When Should You Consider the De Novo Pathway?
The De Novo pathway is designed for medical devices that are new, innovative, and lack a clear predicate. If you attempt a 510(k) submission and the FDA determines that no suitable predicate exists, you may be directed toward De Novo. Alternatively, you can pursue De Novo from the outset if it’s clear your device is first-of-its-kind.
You should consider the De Novo pathway if:
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No legally marketed predicate exists. Your device is unlike anything currently cleared under 510(k).
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The risk profile is appropriate. The device can be reasonably controlled through general or special controls, without requiring the PMA process.
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You want to establish a new classification. A granted De Novo request not only clears your device, it creates a new regulatory category that future devices can use as a predicate.
For example, companies developing AI-driven diagnostic tools often pursue the De Novo pathway. There isn’t always a predicate device to compare against, but the risk profile can still be managed with the right controls.
Similarly, novel digital therapeutics or wearable devices that apply new technology to established clinical needs are common De Novo candidates.
How the De Novo Process Works
While every device has its own unique considerations, most De Novo submissions follow a clear sequence of steps.
1. Pre-Submission (Pre-Sub) Meeting with FDA
Sponsors often begin by requesting a Pre-Sub meeting. This gives your team the chance to present the device concept, discuss testing plans, and get FDA feedback before committing resources.
2. Evidence Development
The FDA expects data demonstrating that your device is safe and effective for its intended use. Depending on the device, this may include bench testing, animal studies, or clinical trials. The scope of evidence should match the risk profile. Not every De Novo device requires extensive clinical data.
3. Preparing the Submission Package
A complete De Novo request includes administrative elements (cover letter, forms, eCopy) and technical sections (device description, labeling, testing results, risk analysis, and proposed special controls). Organizing this package carefully is key to avoiding review delays.
4. FDA Review
Once submitted, the FDA conducts a substantive review of the package. By statute, review timelines are targeted at 150 days, but can extend if additional information is requested.
5. Decision
If granted, the FDA creates a new classification regulation for the device type, allowing future devices in the same category to use the 510(k) process. If declined, the sponsor may need to consider the PMA pathway.
Challenges Teams Commonly Face
Even when the De Novo pathway is the right choice, teams often run into obstacles that can slow down the process or lead to unnecessary rework. Understanding these challenges upfront makes it easier to plan around them.
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Demonstrating the right risk classification. One of the most common hurdles is showing that your device can be adequately regulated through general or special controls. If the FDA feels your evidence doesn’t support this, the submission can stall.
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Gathering the right level of evidence. Sponsors sometimes over- or under-invest in testing. Too little data leaves gaps the FDA will flag. Too much data can waste valuable time and resources. Finding the balance is critical.
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Managing timelines and resources. For smaller teams, preparing a De Novo request can stretch limited staff and budgets. Coordinating across regulatory, quality, and clinical functions adds complexity, especially if documentation is scattered across systems.
These challenges don’t mean the De Novo pathway is unmanageable. With early planning, FDA engagement, and a strong documentation strategy, sponsors can reduce the risk of delays and keep their submission moving forward.
How FDA Reviews a De Novo Request (with Examples)
Once a De Novo submission is under review, FDA examiners assess whether your evidence and controls justify classifying the device under Class I or II, without needing a full PMA. Key evaluation dimensions include safety, effectiveness, risk controls, labeling, and benefit-risk balance.
Below are illustrative examples showing how FDA decisions have turned on these factors.
1. Safety and Effectiveness Based on Real-World Evidence (RWE)
In one De Novo submission for a mobile fertility application (DEN170052), the sponsor analyzed retrospective usage data from ~15,000 users to support claims of safety and effectiveness. That RWE was used as a primary source of clinical evidence.
In another case (DEN170058), a next-generation sequencing (NGS) tumor profiling assay used retrospective clinical data from medical records at Memorial Sloan Kettering to validate cut-off thresholds and support claims.
2. Device Reclassification via New Generic Device Type
A notable example is DEN150049, which was granted for a neurovascular mechanical thrombectomy device (used in acute ischemic stroke). The device was reclassified as Class II under new generic controls.
Another is DEN150011, approved in 2015 for a high-intensity ultrasound ablation system intended for prostate tissue. FDA reclassified it as Class II under new special controls.
3. Review Timeline Extremes and Software Devices
Although the target review period is 150 days, actual times vary widely. Apple’s De Novo for its Apple Watch ECG app was cleared in just 28 days, and its irregular rhythm notification feature in 33 days.
That said, many submissions take far longer. The same study showed median De Novo decision times around 309 days (mean ~338 days), with some taking over 30 months.
4. Declines Due to Insufficient Controls or Evidence
If FDA determines that general or special controls are not enough to ensure reasonable assurance of safety and effectiveness or the data are insufficient, the De Novo request may be declined.
When FDA grants a De Novo request, it issues a written order that creates a new classification regulation (and special controls, if needed) and allows that device to serve as a future predicate under 510(k).
If the request is declined, FDA provides reasons in writing (e.g., gaps in performance, benefit-risk issues), and the sponsor may need to collect more data or switch to the PMA route.
Tips for Making Your Submission Stronger
The De Novo process can feel uncertain, especially for smaller teams bringing a first-of-its-kind device to market. But the sponsors who succeed tend to follow a consistent set of best practices. These steps help reduce friction, avoid unnecessary delays, and build FDA confidence in the submission package.
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Engage FDA early. Use the Pre-Submission process to confirm expectations before you invest heavily in testing. Early dialogue helps you align on evidence requirements and reduce surprises.
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Leverage regulatory intelligence. Review past De Novo decisions for similar device types. This can guide your testing strategy, risk analysis, and labeling approach.
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Keep documentation consistent. Make sure regulatory, quality, and clinical teams are working from the same set of documents. Discrepancies in labeling, risk files, or test reports are common causes of review delays.
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Right-size your evidence. Focus on the level of testing that matches your device’s risk profile. Over- or under-investing can both create problems.
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Plan for resourcing. Submissions often stretch small teams. Building in project management support and using tools that centralize your documentation can keep your submission on track.
By approaching De Novo preparation with these principles, sponsors can shift the review from a stressful, reactive process to one that feels structured and manageable. The result is more predictable timelines and a higher likelihood of FDA clearance on the first try.
How Kivo Helps Teams Preparing for De Novo
Preparing a De Novo submission requires coordination across regulatory, quality, and clinical teams. For many sponsors, especially those working with lean resources, the biggest challenge isn’t generating the data, it’s keeping regulatory documentation organized and consistent from start to finish.
Kivo was designed to solve exactly this problem. By storing regulatory, clinical, and quality documentation in a single, validated system, Kivo helps teams eliminate silos and reduce version conflicts. That means the device description in your De Novo package matches the labeling in your QMS, and your risk file aligns with the testing reports submitted to FDA.
Some of the ways sponsors use Kivo to support their De Novo pathway include:
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One source of truth. No more reconciling files across SharePoint, spreadsheets, and local drives.
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Flexible workflows. Configure processes to fit your team’s approach instead of being forced into a rigid template.
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Audit-ready documentation. Ensure that every file in your submission package is tracked, validated, and inspection-ready.
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Cross-functional visibility. Regulatory, quality, and clinical contributors can work from the same system without duplicating effort.
Companies like Elpida and Elevar have used Kivo to accelerate their submissions and scale operations without losing control of compliance. Their results highlight how a modern, unified platform can keep even complex regulatory pathways on track.
By reducing the administrative burden, Kivo allows sponsors to focus on what really matters: generating the evidence FDA needs and getting innovative devices to patients faster.
Conclusion
The De Novo pathway can feel daunting for teams bringing a novel medical device to market. Without a predicate, there’s more uncertainty, more decisions to make, and greater pressure to align your submission with FDA expectations. But with the right preparation, De Novo doesn’t have to be an obstacle. It can be the clearest route to getting your innovation into the hands of patients.
By engaging FDA early, aligning your evidence to the right level of risk, and keeping documentation consistent across regulatory, quality, and clinical teams, sponsors can make the process more predictable and less stressful. Tools like Kivo help simplify that alignment, giving you one source of truth for everything that goes into your submission.
If your team is preparing for a De Novo submission, now is the time to make sure your documentation strategy supports your pathway forward. Schedule a demo with Kivo to see how we can help you prepare with confidence.
FAQ: De Novo Submissions
Here are some answers to commonly asked questions about De Novo submissions.
1. What is the purpose of a De Novo submission?
The De Novo pathway gives device sponsors a way to bring innovative, low- to moderate-risk devices to market when no predicate device exists. It allows the FDA to classify a novel device and establish the regulatory requirements (general and special controls) that will apply to future devices in the same category.
2. How is a De Novo different from a 510(k) submission?
A 510(k) is based on showing that your device is “substantially equivalent” to a legally marketed predicate. If no predicate exists, you can’t use the 510(k) route. The De Novo pathway is designed specifically for these situations, allowing FDA to create a new device classification instead of forcing you into a higher-risk PMA process.
3. What data do I need for a De Novo submission?
The FDA expects evidence that demonstrates your device is safe and effective for its intended use. This can include bench testing, animal studies, or clinical data depending on your device and risk profile. The key is to provide enough data to justify classification under general or special controls without over-investing in unnecessary studies.
4. How long does FDA review of a De Novo submission take?
The FDA review timeline is typically 150 days, though the process can extend if additional information is requested. Planning ahead, engaging in pre-submission meetings, and submitting a complete, well-organized package can reduce delays.
5. Can a De Novo submission be rejected?
Yes. If the FDA determines your device is too high-risk for general or special controls, or if the evidence doesn’t support safety and effectiveness, the request may be declined. In that case, the device may need to go through the PMA pathway. Early engagement with FDA and careful preparation are the best ways to avoid this outcome.
