Table of Contents
- When does PMA vs. De Novo apply?
- Device Classification
- Advantages of a De Novo vs. PMA
- How Does De Novo Compare to PMA?
- De Novo vs. PMA Postmarket Requirements
- PMA vs. De Novo Submissions
- Regulatory Submission Strategy
- Frequently Asked Questions (FAQs)
When does PMA vs. De Novo apply?
Per the FDA medical device regulations, “De Novo” and “PMA” refer to distinct pathways for obtaining marketing approval. PMA is the most rigorous and typically used for high-risk devices, while De Novo offers a streamlined route for novel, low to moderate risk devices with no existing equivalent. De Novo devices are initially “granted approval” as Class III and if the device remains a Class III, then the PMA pathway will apply. The level of controls is deemed much higher for Class III than for Class II. The table below provides a comparison between the two pathways and defines the regulatory requirements between a high-risk device (PMA) vs. a novel device (De Novo).
Table 1. PMA vs. De Novo Pathways and definition of the regulatory requirements
Class III Devices
| High-Risk Devices (FDACA 513(a)(1)(C) and 21 CFR 860.3(c)(3)) | Novel Devices (Automatic Class III Designation) (FDCA 513(f)(1)) |
| 1. Not Class I: General controls are insufficient | 1. Not marketed prior to 1976 Medical Device Amendments (postamendments device) |
| 2. Not Class II: Special controls and general controls are insufficient | 2. Not reclassified into Class I or II |
| 3. One of the following: – Life-supporting – Life-sustaining – Of substantial importance in preventing impairment of human health, or – Presents a potential unreasonable risk | 3. Not found SE to an unclassified preamendments device or a device in Class I or Class II |
For novel devices, which are new devices that have not been classified by the FDA, the De Novo regulatory pathway may be an alternative if the novel device is low or moderate risk. Choosing the right submission pathway depends on various factors, including your device’s risk level, the availability of predicates, and the resources you have available. Understanding the device classification process and the requirements for each class is helpful to ensure your device is safe and effective.
Device Classification
Federal law (Federal Food, Drug, and Cosmetic Act, section 513) establishes the risk-based device classification system for medical devices. Each device is assigned to one of three regulatory classes:
- Class I (Low to moderate risk): General Controls
- Class II (Moderate to high risk): General Controls and Special Controls
- Class III (High risk): General Controls and Premarket Approval (PMA)
Key Points about General Controls
Devices are classified according to the degree of difficulty in assuring their safety and effectiveness. Class I, which is synonymous with General Controls, is the least stringent of the three device classes. Before placing a device in Class I, the FDA must first determine that there is sufficient information available to support such a classification decision. Second, the FDA must decide that General Controls are sufficient to provide reasonable assurance of the device’s safety and effectiveness. Class I devices are not subject to the restrictions of Class II- Special Controls or Class III-Premarket Approval. General Controls apply to all three classes of medical devices; however, they are the only level of controls that apply to Class I devices. General Controls include:
- Adverse event reporting
- Recall reporting
- GMP requirements
- Premarket notification
Key Points about Special Controls
Special Controls are regulatory requirements for Class II devices and are device specific. The FDA classifies into Class II devices for which General Controls alone are insufficient to provide reasonable assurance of safety and effectiveness of the device, and for which there is sufficient information to establish Special Controls to provide such assurance. Special Controls are usually device specific and include:
- Performance standards
- Post-market surveillance
- Patient registries
- Special labeling requirements
- Premarket data requirements
- Guidelines
Key Points about PMA Controls
Premarket Approval (PMA) for medical devices is a rigorous process required by the U.S. Food and Drug Administration (FDA) for high-risk, Class III, medical devices. It ensures that these devices are safe and effective before they are marketed to the public. The PMA process involves a detailed review of the device’s design, manufacturing processes, clinical data, and labeling, as well as pre-approval inspections. Due to the level of risk associated with Class III devices, the FDA has determined that General and Special Controls alone are insufficient to assure the safety and effectiveness of Class III devices. PMA Controls are above and beyond General and Special Controls. PMA Controls includes:
- Premarket review process
- Manufacturing information
- Pre-approval inspection
- Express pathway contracts to other pathways (Conditional Approvals)
- Post-market requirements (Post approval study)
- Restriction on use of a device (require certain restrictions are addressed before use)- restrict a user population
- Most, if not all, post-market changes require prior approval from the FDA
PMA is the most stringent device marketing pathway. PMA Controls are necessary for the Class III highest risk device.
Table 2. PMA vs. De Novo Safety and Effectiveness Controls
Safety & Effectiveness of Device Can Be Assured With:
| General Controls | X | X | X |
| Special Controls | X | ||
| PMA Controls | X | ||
| Marketing Pathway | Low risk device De Novo Class I | Moderate risk device De Novo Class II | PMA Class III |
PMA applications require extensive clinical data and evidence to demonstrate the device’s safety and effectiveness. However, most De Novo requests require clinical data and approximately 80% have provided clinical studies to support the submission application.
In the table below, the top three regulatory pathways are the most used. 510(k) submissions rely on the substantial equivalence to a predicate device and are the most common route for approval. The number of applications received by the FDA for De Novo and PMA submissions in FY2024 is very similar. De Novo submissions establish a new classification for devices without predicates and are considered low to moderate risk devices. PMA submissions are intensive and required for high-risk devices without any predicates. They involve comprehensive clinical data and evidence to demonstrate safety and effectiveness.
Table 3. Number of applications received by FDA for YR2024
| PATHWAY | Received at CDRH in FY2024* |
| 510(k) (CDRH) | 3643 |
| De Novo | 78 |
| Premarket Approval (PMA) Original PMAs and Panel-track Supplements | 69 |
| Humanitarian Device Exemption (HDE) ** | 2 |
| Product Development Protocol (PDP) (3 completed since 1796)** | 0 |
| *Fiscal year 2024 ran from Oct. 1, 2023 to Sept. 20, 2024. Data extracted from FDA MDUFA V Performance Report dated Nov. 22, 2024 **Number approved per FDA HDE webpage (pathway not covered by MDUFA Performance Reports: number approved usually smaller than received. |
Advantages of a De Novo vs. PMA
The De Novo pathway offers several advantages, especially for devices without a predicate. It provides a streamlined regulatory pathway, reducing the time and resources required to obtain FDA approval. This expedited process can be particularly beneficial for manufacturers eager to bring their innovative devices to market and positively impact patient care.
Upon successful review of a De Novo Request, the FDA will create a classification for the device, a regulation if necessary, and identify any special controls required for future premarket submissions of substantially equivalent devices. The De Novo Classification allows the device to be used as predicate for future devices, making it easier for other manufacturers to approve similar devices.
How Does De Novo Compare to PMA?
If you have a novel new device, it’s recommended to review the De Novo regulatory pathway to determine if this is the better path forward compared to a PMA. A comparison between the PMA requirements for FDA approval to the De Novo requirements is depicted in the table below.
Table 4. PMA vs. De Novo Requirements
Compared to PMA, De Novo will generally entail
| 1. Less clinical data? | Not likely |
| 2. Less pre-clinical (bench/animal) data? | Not likely |
| 3. Less details in labeling? | Not likely |
| 4. Less scrutiny of manufacturing? | Likely (no review of QSR compliance) |
| 5. Shorter FDA review time? | Potentially (user fee commitment 70% within 150 days) |
| 6. Less expensive? | Likely (FDA user fees much lower) |
| 7. More flexibility for changes? | Yes (510(k) modification standard) |
| 8. Lower barrier to entry for subsequent devices? | Yes (510(k) pathway) |
De Novo vs. PMA Postmarket Requirements
Upon device approval, PMAs are subject to greater user fees over the device lifespan compared to De Novos. PMA change control is more stringent compared to 510(k)s. If you recall, as part of the De Novo submission process, the data submitted to support the device claims of safety and effectiveness are reviewed after the application is granted approval. The FDA reviews the application again to determine whether the device meets the requirements for a new classification. This rigorous evaluation ensures that only devices meeting the necessary standards are approved. If successful, the sponsor will receive a De Novo classification order, allowing marketing of your device in the United States.
Once a De Novo is approved, the device becomes a 510(k) and follows the 510(k) process for changes throughout its lifecycle. In 2017, the FDA released a guidance: Deciding When to Submit a 510(k) for a Change to an Existing Device for post-market devices changes. The guidance contains various flow charts that help in the evaluation and final decision process. The Sponsor’s risk assessments and the outcome of verification and/or validation for the changes will determine if a “letter for file” can be filed for the change instead of filing a new submission to the FDA. Unlike 510(k), postmarket changes for PMAs require submissions for all changes to the device. Changes that do not have any potential to impact product safety and/or effectiveness can be implemented prior to reporting in the annual report. A change assessment should be completed per FDA guidance: Modifications to Devices Subject to Premarket Approval (PMA)–The PMA Supplement Decision-Making Process.
Table 5. PMA vs. De Novo User Fees*
| Purpose | De Novo | PMA | |||
| Standard | Small Business | Type of Submission | Standard | Small Business** | |
| New/Novel Device | $162,235 | $40,559 | ORIGINAL | $540,783 | $135,196 |
| Change to Indications | New Indication: Submit 510(k) | Panel-Track Supplement | $432,626 | $108,157 | |
| Manufacturing Change(s) (no fee for site change) | Follows 510(k) Guidance Document and processes | 30-Day Notice | $8,653 | $4,326 | |
| 135-Day Supplement | No fee (already paid with the 30-day notice) | ||||
| Minor Design and/or Labeling Changes | Real-Time Supplement | $37,855 | $9,464 | ||
| Significant Design and/or Labeling Change(s) | 180-Day Supplement | $81,117 | $20,279 | ||
| Periodic Reporting | Not applicable | Annual Report | $18,927 | $4,732 | |
*FY2025 user fees shown
**Requires a Small Business Designation
PMA vs. De Novo Submissions
PMA and De Novo submissions have unique characteristics, but they also share some commonalities.
- Both pathways require detailed information about your device, including its intended use, design features, and manufacturing processes.
- Each submission type necessities supporting data to demonstrate safety and effectiveness, although the required evidence level varies.
- Regardless of the pathway, all submissions undergo a rigorous review process by FDA.
However, there are also significant differences between the pathways. As a reminder, PMA submissions are intended for high-risk devices, whereas De Novo and 510(k) are suitable for lower-risk device with suitable predicates.
Choosing the right submission pathway depends on various factors, including the device’s risk level, the availability of predicates, and the resources that are available. Now, let’s discuss how you can make an informed decision.
Regulatory Submission Strategy
Determining the appropriate submission strategy for your device is a critical decision. Here are some factors to keep in mind:
- Evaluate your device’s risk level: If your device is high-risk or substantially different from any existing device, a PMA submission may be the best choice.
- Assess the predicate availability: If a suitable predicate is available and is low to moderate risk, a 510(k) submission may be a viable option.
- Consider resources and timelines: PMA submission typically requires more time, money, and resources than De Novo and 510(k) submissions. Assess your capabilities and evaluate whether you can meet the requirements of each pathway.
By carefully weighing these factors and consulting with regulatory experts, you can make an informed decision that maximizes your chances of FDA approval and successful market entry.
Frequently Asked Questions (FAQs)
What are the advantages of a De Novo request?
A De Novo request can lead to a lower-risk classification for the product, which may result in less stringent regulatory requirements and a faster path to market. Additionally, a device granted De Novo status can serve as a predicate for future 510(k) submissions.
What is a De Novo classification request?
A De Novo request is a process used by the FDA to classify novel medical devices that don’t have a legally marketed predicate device. It’s a pathway for these devices to obtain marketing authorization as Class I or Class II, which requires demonstrating that general controls, or general and special controls, provide reasonable assurance of safety and effectiveness for the intended use.
Why is a De Novo process used?
De Novo is used for medical devices that are not substantially equivalent to any existing device on the market, meaning they don’t have a suitable predicate. It’s a way for these innovative devices to gain market access without needing to relay on a 510(k) submission that requires demonstrating substantial equivalence to a predicate.
How long does the De Novo process take?
The timeline varies by pathway. On average, 510(k) submissions take 90 to 180 days, PMAs may take 180 days to a year or more, and De Novo submissions take approximately 150 to 270 days.
