It’s a common misconception that FDA De Novo content is very different from FDA 510k submission content, but is that true?
What do you think the De Novo content differences are?
Most people think the difference between a 510k and a De Novo is time and money. That conclusion is based upon a very important assumption: a 510k will not require clinical data, and a De Novo will require clinical data. That assumption is not always correct. 10-15% of 510k submissions include clinical data to support the performance claims, and last year our team submitted three De Novo submissions that did not include any clinical data. So what are the differences between a 510k and a De Novo content?
We use the same FDA eSTAR template for both types of FDA submissions, and on the first page of the eSTAR template, we identify if the submission is a 510k or De Novo. If we select De Novo, the eSTAR will be pre-populated with four unique De Novo content requirements that are not found in a 510k. The four unique requirements are:
- identifying alternative practices and procedures for the same indications
- recommending a classification, providing a justification for that classification, and explaining what efforts were taken to identify a suitable 510k product code
- providing a written benefit/risk analysis starting with the clinical benefits of your device
- recommendations for special controls for your new product code based upon the risks to health and the mitigation measures for each risk
What alternative practices and procedures are currently available?
The unique De Novo content requirement is to provide a description of alternative practices and procedures for treatment or diagnosis of the same indications that you are proposing for your subject device. This is a subsection of the device description section in the FDA eSTAR template. Your should description should include other 510k-cleared products, drugs, and even products that have similar indications but are not identical. The description of alternative practices and procedures must also be attached as a document in the section for benefits, risks, and mitigation measures. To maintain consistency throughout your submission, you should create the document for attachment first and copy and paste the content into the text box at the end of the device description section.
You need to recommend a classification in your De Novo
The unique De Novo content requirement is found in a section titled “Classification.” There is a shorter classification section included in 510k submissions, but the 510k version only has four cells. The first three are populated by selecting one of the options from a dropdown menu, and the fourth cell is only used if your subject device includes other product classification codes.
The De Novo version of the eSTAR is identical for the first row of the classification section, but then you must select a proposed product classification (i.e., Class 1 or Class 2) in accordance with FDA Classification Procedures (i.e., 21 CFR 860). The third cell is a text box for you to enter your justification for the proposed classification. Next, the FDA requires you to enter a proposed classification name. Finally, at the end of the classification section, the FDA requires that you provide a classification summary or reference to a previous NSE 510k submission.
A Benefit/Risk Analysis is required in the De Novo Content
For new devices, the FDA uses a benefit/risk analysis to decide if a device should be authorized for marketing in the USA. This process includes humanitarian device exemptions, De Novo applications, and Premarket Approval submissions. The FDA has a guidance document that provides guidance for FDA reviewers and the industry. The most important aspect is, to begin with, the benefits of the device and to provide a quantitative comparison of benefits and risks. Many De Novo submissions have been rejected because the submitter did not provide objective evidence of clinical benefits for the subject device.
The FDA guidance documents are helpful for creating a benefit/risk analysis, but you can also find information in the ISO/TR 24971:2020–the guidance for the application of ISO 14971:2019. Our company also includes a template for a benefit/risk analysis as part of our risk management procedure (i.e., SYS-010).
What are your recommended Special Controls?
In FDA De Novo Classification Decision Summaries, there is a table provided that identifies the identified risks to health and the recommended mitigation measures for each risk category. In the FDA eSTAR, you are required to add a similar table for De Novo content. The only difference between the table in summary and the eSTAR is that the eSTAR table has a third column where the FDA wants you to reference the supporting data provided for each mitigation measure–including the document and page within the document. The FDA also provided an example table in the eSTAR, copied below.
The above table for the risks to health and mitigations needs to be translated into a list of recommended Special Controls for Class II devices. Since most De Novo applications are for Class II devices, you will need to convert each of your mitigations into a corresponding Special Control and type these controls into the text box provided in the FDA eSTAR.
What else is different from a 510k?
There are no additional mandatory elements that you need to include in a De Novo application, but there are several elements of a 510k submission that are not included in a De Novo. The most obvious of these sections is the Substantial Equivalence Comparison Table in the section labeled “Predicates and Substantial Equivalence.” Another difference is that you are more likely to need clinical data to support a De Novo application than for a 510k submission. It is also possible that subsequent 510k submissions for the same product code may not need to provide clinical data because the 510k process only requires a demonstration of substantial equivalence rather than clinical benefits outweighing risks to health. The FDA review time for a Traditional 510(k) varied between 190 and 210 days in 2022, while the De Novo review timeline averaged 390 days in 2022. Finally, the FDA user fees for 510k submissions are far less than those for a De Novo application.