A Guide to US FDA De Novo Submission Process and Timeline

US FDA De Novo submission is a regulatory route for low to moderate-risk medical devices that lack a predicate device. It enables manufacturers to classify novel devices into Class I or Class II. This allows the device to be marketed in the US. Additionally, it can potentially serve as predicates for future 510(k) submissions. Thus, the De Novo submission pathway has been formulated for novel devices that are not high-risk but lack predicate. Notably, the De Novo pathway is more rigorous than the FDA 510(k) submission. It requires extensive data, including benefit-risk analysis and classification justification.

What is US FDA De Novo submission?

The De Novo pathway is designed for novel devices that lack a predicate for comparison but are low to moderate risk. If the device is determined to be of low to moderate risk, the FDA may assign it to Class I or II, thereby bypassing the need for premarket approval (PMA). This route enables innovative technologies to enter the market with appropriate regulatory controls. The De Novo pathway creates a new classification regulation for future predicates. Notably, it is ideal for digital health, diagnostics, and emerging tech. Moreover, it requires robust risk mitigation and regulatory intelligence.

Eligibility criteria for De Novo pathway

• The medical device must be novel with no suitable predicate.
• Risk level must be low (Class I) or moderate (Class II).
• Risks must be characterizable and mitigable.

3 Key points to remember for FDA De Novo application

1. Benefit-risk analysis: De Novo submissions require detailed benefit-risk analysis.
2. Justification for classification: Extensive justification is required for the proposed FDA medical device classification (Class I or II).
3. Additional requirements: Additional testing requirements are needed for FDA De Novo application.

When should you opt for the De Novo pathway?

You should opt for the US FDA De Novo submission under the following conditions:

• When there is no existing device that can serve as a predicate device for your new device
• The device does not qualify for US FDA premarket approval (PMA), which is primarily intended for Class III or high-risk devices.
• You need to establish a new regulatory medical device classification for similar future devices.
• General and special controls are sufficient for ensuring safety and effectiveness of the medical device.

De Novo classification request

Submissions must be prepared using the eSTAR template and submitted electronically via the CDRH Customer Collaboration Portal.

An US FDA De Novo submission request is appropriate when:

• Your device is a novel medical device with no legally marketed predicate.
• The device is classified as low-risk (Class I) or moderate-risk (Class II), and no suitable predicate exists.
• If neither condition applies, the device is considered high-risk (Class III) and requires a Premarket Approval (PMA).

Applicants submitting a De Novo request are subject to applicable user fees. For current fee details, please refer to the MDUFA User Fees page.

Content and format of the De Novo request

The structure of an US FDA De Novo submission format closely mirrors that of a traditional or abbreviated 510(k) application. However, certain sections are excluded due to the unique nature of the De Novo pathway. The section 5, which is the 510(k) summary or statement, is not required, as the De Novo process is distinct from the 510(k) pathway. Additionally, the Section 12, which is substantial equivalence comparison, can be omitted. This is because De Novo submissions do not rely on predicate devices for equivalence. We have provided an overview of the content and format of the De Novo request.

1. Table of contents: Clearly organize the submission with volume and page numbers.
2. Administrative information: Name, address, phone, and email of the requester will be required along with U.S. representative details, if applicable.
3. Device description: Detailed description of the device, including components, principles of operation, and intended use has to be provided.
4. Classification summary: Proposed classification (Class I or II) has to be mentioned. Additionally, justification for classification based on risk and controls has to be provided.
5. Benefits and risks: Summary of known and potential benefits and risks have to be included. Additionally, risk mitigation strategies have to be mentioned.
6. Performance data: Nonclinical testing (bench, software, biocompatibility, etc.), clinical data (if applicable), and summary of test methods and results have to be provided.
7. Labeling: Draft labelling, including instructions for use, indications, warnings, and promotional materials, has to be included.
8. Summary of standards: List of recognized standards used and declarations of conformity have to be provided.
9. Justification for not using a predicate: A proper explanation as to why no predicate exists and the absence of a comparative study have to be provided.
10. Proposed special controls: If the medical device belongs to Class II, proposed special controls to ensure safety and effectiveness have to be mentioned.

US FDA De Novo submission process and timeline

The US FDA De Novo submission process shares structural similarities with the 510(k) pathway. The technical documentation must be compiled in PDF format and submitted electronically. Upon receipt, the FDA reviews the submission and ultimately issues a decision to either grant or decline the request.

 Key milestones

• Day 1: Submission receipt: The FDA receives the De Novo request and assigns a unique submission number beginning with “DEN” followed by six digits. This number is included in the acknowledgment letter sent to the applicant.
• Day 15: Acceptance review: The FDA conducts an initial review to assess completeness and administrative acceptability. If deficiencies are found, the submission is placed on RTA (Refuse to Accept) hold. Once the missing information is provided, the FDA proceeds to substantive review.
• Day 60: Substantive review: The FDA evaluates whether similar marketed devices exist and assesses the safety and effectiveness of the proposed device. Any deficiencies identified are communicated via an Additional Information (AI) request letter. The applicant must respond within 180 calendar days. Failure to respond results in automatic withdrawal of the submission.

Final FDA decision

• Grant: The device is classified into Class I or II. It may be legally marketed and used as a predicate for future 510(k) submissions. Once the US FDA De Novo submission is approved, the medical device can be immediately marketed in the US. The classification will be published in the Federal Register. Furthermore, once the De Novo is granted, the device will be permitted to serve as a predicate for future 510(k) applications.
• Decline: If the data is insufficient to support classification, the device remains in Class III and cannot be legally marketed. Moreover, if the De Novo pathway application is rejected, the device cannot be marketed without further efforts by the applicant and acceptance by the FDA.

Withdrawal Conditions

The FDA may withdraw a De Novo request under two circumstances:

• The applicant voluntarily submits a written withdrawal notice.
• The applicant fails to respond to an additional information (AI) request within 180 days.

Review Timeline

• The FDA aims to complete its review within 150 calendar days, excluding any time the submission is on hold due to AI requests.
• The review clock starts on the date the FDA receives the submission and stops when a final decision is issued.

We specialize in navigating the US FDA De Novo submission process to ensure clearance for novel medical devices. Our team has extensive knowledge of the requirements and application process. We guarantee a swift De Novo submission, enhancing your prospects for a favourable De Novo approval. Drop an email at [email protected] or call/Whatsapp on 9996859227 to let us help you get started.