510(k) vs. De Novo: Key Differences in FDA Approval Pathways for Medical Devices

510(k) vs. De Novo: Key Differences in FDA Approval Pathways for Medical Devices

The U.S. Food and Drug Administration (FDA) offers two (2) principal Regulatory pathways for marketing non–PMA (Premarket Approval) medical devices: the 510(k) Premarket Notification and the De Novo Classification Request. These pathways cater to different types of devices, and choosing the correct one (1) is critical to ensuring a smooth market entry, Regulatory compliance, and long-term business success.

Overview of 510(k) and De Novo Pathways

510(k) Premarket Notification

The 510(k) pathway is appropriate when a device is substantially equivalent to a legally marketed predicate device. To demonstrate substantial equivalence, the device must have:

• The same intended use, and
• Either the same technological characteristics, or
• Different technological characteristics that do not raise new questions of safety or effectiveness.

Upon FDA review, if substantial equivalence is established, the FDA issues a Substantially Equivalent (SE) Letter, which constitutes formal FDA clearance. The device can then be marketed in the U.S.

Typical FDA Review Time: ~90 calendar days

De Novo Classification

The De Novo pathway is intended for novel devices that lack a predicate and present low to moderate risk. These devices do not qualify for 510(k) clearance but also do not require Premarket Approval (PMA).

Upon successful review, the FDA issues a De Novo Grant Order, which provides formal FDA authorization to market the device. The grant also:

• Establishes a new classification regulation (e.g., 21 CFR §xxx.xxxx) under Class I or Class II
• Assigns a new FDA product code specific to the device type
• Defines applicable general and/or special controls
• Creates a new regulatory foundation that can serve as a predicate for future 510(k) submissions

This regulatory action sets a precedent for subsequent devices of the same type and ensures consistent oversight of future products in the new category.

Device Types and Pathway Applicability

Note on Down-Classification of Class III Devices:
Certain Class III devices may be formally reclassified to Class II by the FDA through a reclassification order under Section 513(e) or 513(f)(3), or via a De Novo Grant under Section 513(f)(2) following a Not Substantially Equivalent (NSE) determination. These reclassifications require formal FDA action and cannot be assumed by the manufacturer without FDA confirmation.

Cost, Timeline, and Submission Complexity

Evidence Requirements

The type and extent of evidence required by the FDA differs significantly between the 510(k) and De Novo pathways due to the presence or absence of a predicate device.

• 510(k) Submissions
   The primary focus of a 510(k) submission is to demonstrate substantial equivalence to a legally marketed predicate device.
  • Bench testing: Evidence such as software validation, biocompatibility, electrical safety, electromagnetic compatibility (EMC), sterilization validation, and packaging integrity is typically required.
  • Clinical data: Not routinely required. However, clinical evidence may be necessary if differences in technology or intended use raise new questions of safety or effectiveness that cannot be resolved through bench testing alone.
• De Novo Requests
   For De Novo submissions, the device is considered novel, with no valid predicate. Therefore, the sponsor must provide valid scientific evidence to support reasonable assurance of safety and effectiveness.
  • Bench and clinical data: Both may be required depending on the device's risk profile, technological complexity, and intended use. This includes human clinical studies, usability testing, and real-world evidence, where appropriate.
  • Benefit-risk analysis: A structured assessment must demonstrate that the device's benefits outweigh the risks and that general and/or special controls are sufficient to mitigate those risks.
  • Pre-submission interaction: Early engagement with the FDA via the Q-Submission (Q-Sub) program is strongly recommended to align on evidence expectations, testing requirements, and overall submission strategy.

Strategic Pathway Selection

Choosing between the 510(k) and De Novo pathways is a strategic decision that hinges on both the regulatory landscape and the product’s business potential. The following considerations guide pathway selection:

1. Predicate Availability

   The first and most critical consideration in determining the appropriate FDA regulatory pathway is whether a legally marketed predicate device exists that shares the same intended use and similar technological characteristics.

   • If Yes → The 510(k) pathway is typically the preferred route. It is generally faster, less complex, and more cost-effective, as it relies on demonstrating substantial equivalence to the predicate device.
   • If No → The device is considered novel, and the De Novo pathway must be pursued, provided the device presents low to moderate risk and does not warrant the Premarket Approval (PMA) route. This path allows the FDA to establish a new regulatory classification for such devices.

2. De Novo Pathway Options

    A. Post-NSE De Novo (Section 513(f)(2))

   This pathway follows an unsuccessful 510(k) submission, in which the FDA concluded that the device is Not Substantially Equivalent (NSE) to any legally marketed predicate.

   • Sponsors first submit a 510(k) application attempting to demonstrate substantial equivalence.
   • If the FDA issues an NSE Letter, the sponsor may then submit a De Novo Classification Request, referencing that NSE determination under Section 513(f)(2).

   If the De Novo is granted, the FDA will issue a De Novo Grant Letter, formally authorizing the device for marketing and establishing a new classification regulation and product code.

   B. Direct De Novo

   When the sponsor determines from the outset that no suitable predicate exists, they may bypass the 510(k) process and submit a Direct De Novo request.

   • This proactive approach is often used to avoid the time and cost associated with an anticipated NSE determination.
   • The sponsor must provide sufficient valid scientific evidence to support classification of the device as Class I or II.

   Upon successful review, the FDA issues an official De Novo Grant Letter, which formally authorizes the device for marketing, establishes a new classification regulation under 21 CFR, assigns a unique product code, and may define special controls applicable to the device type.

Regulatory Cost vs. Strategic Value

While the 510(k) process is quicker and less expensive, the De Novo pathway can offer long-term strategic value—especially for breakthrough or AI-based technologies—by defining a new product classification and setting the regulatory precedent for future competitors. A successful De Novo defines the Regulatory foundation (special controls, classification) for future devices, setting the standard for competitors.

Postmarket and Compliance Obligations

Achieving FDA clearance through the 510(k) pathway or authorization via the De Novo process is a critical milestone—but regulatory responsibility continues long after market entry. Both pathways require robust postmarket compliance to ensure ongoing safety, effectiveness, and quality.

1. Quality System Regulation (QSR)

   All manufacturers must comply with 21 CFR Part 820, which governs Quality System Requirements. Key obligations include:

   • Design Controls and Design History File (DHF)
   • Corrective and Preventive Actions (CAPA)
   • Process Validation and Change Management
   • Production and Process Controls
   • Management Review and Internal Audits

   The FDA may inspect facilities at any time to verify QSR compliance.

2. Medical Device Reporting (MDR) and Adverse Event Monitoring

   Manufacturers must implement procedures to monitor and report device-related adverse events in accordance with 21 CFR Part 803. This includes:

   • Mandatory reporting of serious injuries, deaths, or device malfunctions
   • Maintaining MDR records for FDA audits
   • Timely submissions of reports within the required timeframe

3. Unique Device Identification (UDI) and Labeling Compliance

   Devices cleared or authorized under either pathway must meet UDI labeling and GUDID submission requirements. Proper labeling ensures traceability and enables adverse event tracking.

4. Special Controls (For De Novo Devices)

   Devices authorized under the De Novo pathway may be subject to special controls, in addition to general controls. These may include:

   • Postmarket clinical follow-up studies
   • Performance testing data for future submissions
   • Specific labeling elements
   • Additional quality system requirements

   Special controls are defined as part of the De Novo classification and are legally enforceable.

5. Device Modifications and Change Management
   • For 510(k)-cleared devices, any significant design or labeling changes must be evaluated to determine if a new 510(k) submission is required.
   • For De Novo devices, modifications must still be assessed under QSR, and future submissions may reference the original De Novo decision or require new 510(k)s.

6. Enforcement Risks

   Failure to comply with postmarket obligations may result in:

   • FDA Form 483 observations
   • Warning letters
   • Recalls or removal from the market

Summary: Choosing the Right Path

Selecting the appropriate FDA regulatory pathway is a critical decision that impacts both compliance and commercial success. Manufacturers must evaluate the novelty of the device, regulatory expectations, and business objectives before proceeding.

• The 510(k) pathway is well-suited for devices that are modifications or equivalents of existing products, where substantial equivalence can be demonstrated.
• The De Novo pathway is essential for innovative technologies that lack a valid predicate but pose only low to moderate risk, avoiding the need for the more rigorous PMA process.

Choosing the correct path from the beginning ensures regulatory alignment, accelerates market entry, and supports long-term product success.

Need guidance? Whether you're pursuing a 510(k) or De Novo submission, our Regulatory experts can support you in navigating FDA requirements with clarity and confidence. Contact us to initiate your submission strategy.