With the advancements in technology and the advent of artificial intelligence, the medical device industry is flourishing. But regardless of the type of technology involved, the U.S. Food and Drug Administration must clear the device for marketing before any commercialization of a medical device.
There are typically three mechanisms for seeking FDA clearance for a medical device: a 510(k) submission, a de novo classification request and a premarket approval application. The FDA will not accept a 510(k) application unless the applicant can demonstrate that the device is at least as safe and effective (i.e., substantially equivalent to) a device that has already obtained FDA clearance (i.e., a predicate device).
At the other end of the spectrum, a PMA is the most stringent marketing application for a medical device and is required for Class III medical devices that are new concepts never previously marketed. For a PMA, the applicant must provide valid scientific evidence, such as laboratory studies and clinical investigations, to show safety and effectiveness for an intended use.
In between a 510(k) and a PMA is the de novo classification request; a pathway for novel Class I and Class II medical devices where general or special controls can assure safety and effectiveness for the intended use (such as labeling, device listing, registration requirements, quality systems, good manufacturing practices, post-market surveillance and data requirements, and performance standards), but for which no predicate device has been legally marketed.
The de novo classification allows the FDA to meet its public health interest by enhancing access to beneficial innovative medical devices, while at the same time reducing the regulatory burden for marketing clearance of those devices. The de novo classification also allows for predicate devices to get on the market more quickly, thereby allowing future related medical devices to use the more streamlined 510(k) submission procedure.
As part of the Medical Device User Fee Amendments of 2017, the FDA was tasked with providing guidance, including submission checklists, to facilitate efficient and timely review of de novo classification requests. Therefore, on Sept. 9, the FDA issued a final guidance document titled "Acceptance Review for De Novo Classification Requests."
This final guidance replaces the Oct. 30, 2017, draft guidance of the same name and describes the administrative steps the FDA will take to either refuse to accept, or RTA, or allow for substantive review for automatic Class III designated devices. This guidance also relates to combination products with a device constituent part.
More specifically, the FDA has provided a checklist of the information that is required to be included in a de novo application in order to be considered administratively complete and ready for substantive review. These types of acceptance-for-filing reviews of submissions to the FDA are not new. In fact, the FDA has had similar procedure in place for drug applications for years, as well as for 510(k) and PMA submissions. Placing the burden on the applicant to provide all relevant substantive information, in an organized fashion, significantly streamlines the process, and allows for the FDA to focus its limited resources on substantive review of the applications.
Under this final guidance, a de novo applicant must include each of the items on the acceptance checklist for de novo classification requests provided with the guidance. These items include: preliminary questions, organizational elements, "elements of a complete De Novo Request."
In order to facilitate the administrative review, the FDA requests that the location of supporting information for each checklist topic be provided. If any of these items are not relevant to a particular device or if the information is otherwise not available, the applicant must include a rationale for why those elements are not applicable or available.
FDA staff have some discretion on whether missing information is needed to ensure that the application is complete and may reach out for additional information before providing an acceptance or RTA. However, without any rationale for the missing information, the applicant runs the risk that it will receive an RTA. Should an RTA be issued, the FDA must include its reasoning and the applicant has 180 days to respond by providing any missing information.
Here is the preliminary information that you have to provide pursuant to the checklist:
- The type of device;
- Whether it is eligible for de novo classification;
- The appropriate center for the device (if it is a combination product, the lead center will be determined by the primary mode of action. If the PMOA is attributable to the biological product, the Center for Biologics Evaluation and Research will be the lead center; if the PMOA is attributable to the device, the Center for Devices and Radiological Health will be the lead center. This guidance, published by both CDRH and CBER, would apply to the device component of the combination product in either case);
- Whether a request for designation was submitted;
- Whether a combination product includes a drug product for which the active pharmaceutical ingredient has exclusivity;
- Whether the requester is subject to the application integrity policy for data called into question by wrongful acts;
- Whether there is a pending 510(k) or PMA application for the same device with the same indication for use; and
- If the de novo requester has a pending 510(k) or PMA for the same device for the same indication of use, the de novo request will be placed on hold until the proper application pathway is determined. That being said, a pending de novo request for the same device form a different requester will not alone result in an RTA.
The organizational elements required in the checklist include a table of contents, headings or tabs, and numbered pages.
Other requirements in the checklist include a description of intended use with prescription or over-the-counter designation, combination product request (including any patent certification or statement, as required), a device description, a description of the technology, proposed conditions for use, a list and description of component parts, and a description of any general or specific controls that will provide reasonable assurance of safety and effectiveness.
In addition, information concerning sterilization requirements and methods, shelf life summary, biocompatibility, software, electrical safety and electromagnetic compatibility, animal studies, clinical studies, literature, benefits and risks to health from use and financial disclosures must be provided.
An acceptance review of this information will be conducted within 15 calendar days of receipt of the de novo classification request, user fee payment and a validated e-copy. Further, if neither an acceptance or RTA are received within 15 days, the application automatically gets moved to a substantive review.
However, an acceptance for filing or default substantive review does not change the process by which medical devices are classified. Because the quality and adequacy is of data is not reviewed at this stage, an acceptance for filing and default substantive reviews also do not ensure that the FDA will not request additional information and do not ensure that the product will ultimately be cleared by the FDA. Nevertheless, the FDA anticipates that adherence to the checklist will provide for more quality applications.
To further its goal of efficient review of de novo requests, FDA has also provided a recommended checklist for additional information that applicants should consider including.
These items include information that the FDA finds is commonly missing or deficient during the substantive review, such as the application being in English, device trade/proprietary name, identification of related submissions for the same device, assigned reference numbers for accessories or components, alternative practices or procedures, classification summary, summary of probable risks, executive summary of supporting data, summary and full study report for nonclinical, animal, and clinical studies, labeling, and any statements, certifications and declaration of conformity.
Not including such recommended information will not lead to an RTA, but it will slow down the FDA's classification of the product, may lead to the request being placed on hold, or may lead to a "decline" decision.
If an applicant disagrees with the RTA, the FDA recommends that the applicant reach out to the initial reviewer.
The FDA plans a 60-day transition period. Pending de novo requests, and those filed during the transition period, will not be subject to RTA review. That being said, it is in an applicant's best interest to comply with the requirements set forth in the RTA checklist if is files a de novo application during the transition period.
The FDA's guidance shows its continued emphasis on transparency. For example, by providing the acceptance and recommended checklists, medical device companies now have insight into the exact information that the FDA requires to be included in a de novo application and the information most likely to be deficient.
In other words, the FDA has provided a roadmap to the information that it deems most important and crucial to any de novo application. It may take time and expense for companies to set up policies and procedures to comply with the checklists provided in this guidance.
However, after these policies and procedures are set up, the entire de novo application process will become less cumbersome. That, coupled with shortened timelines for review, makes the de novo classification process more enticing to companies that otherwise might wait for a predicate device to come on the market, saving the expense of a de novo review.
The end result will be smoother and quicker responses from FDA and more novel medical devices coming on the market sooner, which is a win for medical device companies and patients needing access to life changing innovation.
This was originally published in Law360.
Disclaimer: This Alert has been prepared and published for informational purposes only and is not offered, nor should be construed, as legal advice. For more information, please see the firm's full disclaimer.