On Monday, 3 October 2011, the Food and Drug Administration's (FDA or "the Agency") Center for Devices and Radiological Health (CDRH) issued a draft guidance regarding the submission and review of petitions under section 513(f)(2) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), also known as the de novo classification process. The draft guidance, titled Draft Guidance for Industry and Food and Drug Administration Staff - De Novo Classification Process (Evaluation of Automatic Class III Designation), addresses the review process for novel low to moderate risk devices that lack a predicate device. These devices are now automatically placed in class III due to the lack of a predicate, despite their low to moderate risk. According to an Agency press release, the de novo program has been "under-utilized because of process inefficiencies." This draft guidance provides recommendations and intended timelines for more efficient interactions with FDA for companies seeking de novo classification. Once this document is finalized, it will take experience with the new process to evaluate whether the proposed changes to the current process decrease the de novo classification petition review times, which recently have increased to 18 months and in many instances longer.

Under the current section 513(f)(2), the de novo process may be utilized only after receipt of a not substantially equivalent (NSE) determination for a 510(k) submission. Therefore, even if there is no known predicate device, the company must submit a 510(k) submission and wait for the Agency to issue an NSE determination. The draft guidance proposes another pathway for the de novo process, which is initiated with a pre de novo submission (PDS). The PDS submission would allow companies to engage in early discussions with the Agency about the suitability of the device for de novo classification. Companies could then file a concurrent 510(k) notice with a de novo petition after this initial review if the device appears suitable for the de novo process. This preliminary interaction with the Agency is designed to allow companies to obtain earlier feedback on the likely classification and the likely performance and/or clinical data necessary to support the de novo petition. Alternatively, under the draft guidance, a company may continue to utilize the existing de novo pathway by choosing not to submit a PDS and instead submitting a de novo petition within 30 days of receiving an NSE determination.

The draft guidance describes the format and content suggested by the Agency for a PDS submission. Within 60 days of the initial PDS submission, FDA may request additional information. Additionally, the company may request a meeting with the Agency to discuss the PDS. FDA will issue a non-binding suitability letter within 60 days after receipt of all necessary information, which will specify whether or not the device appears to be suitable for the de novo process, and if so, the likely special controls and performance data necessary to obtain de novo downclassification. The Agency will indicate the reason for a determination that a company's device likely is not suitable for de novo downclassification in the non-binding suitability letter to the company. PDS submissions may be resubmitted for the same device if a company collects additional evidence to address FDA's concerns outlined in an original PDS letter of non-suitability.

It is important to note that for 510(k) notices submitted concurrently with a de novo petition following a PDS suitability review, FDA intends to first complete a screening review within 20 days of receipt of the concurrent submission to assure that a manufacturer has submitted the necessary data. FDA will begin an in-depth review of the submission upon successful completion of the screening review. FDA plans to notify companies that the de novo petition has not been filed if a likely predicate device exists. If no likely predicate device exists, FDA plans to issue an NSE determination for the 510(k) notice within 60 days of receipt of a complete concurrent submission.

The NSE letter will indicate that the Agency filed the de novo petition and will continue to review it. Under either pathway (i.e., 510(k)) notice followed by de novo petition or PDS followed by concurrent 510(k)/de novo petition), FDA may issue an additional information (AI) letter or request information via interactive review if the Agency identifies issues requiring clarification after the petition has been filed. FDA's issuance of an AI letter resets the review clock, and once the manufacturer provides the requested information, the review cycle is an additional 60 days. The target time for FDA to make a final decision regarding clearance of a device is shorter for concurrent submissions compared to sequential submissions (i.e., 60 versus 90 days), but the Agency easily could extend that period in either circumstance by requesting additional information. The Agency has stated that the concurrent submission route could potentially shave 90 days off the review period for some devices.

In sum, this draft guidance describes a mechanism intended to provide greater clarity regarding the suitability of a device for de novo review, and hopefully, more timely input on the type of data necessary to support de novo classification of an eligible device. Unfortunately, the draft guidance maintains the two-step 510(k)/petition process, which has been part of the reason for the extended delays in obtaining the ultimate downclassification. It is noteworthy that the Novel Device Relief Act of 2011 introduced recently by Representative Brian Bilbray of California proposes to eliminate the need to submit a 510(k) notice when pursuing de novo downclassification. While it is fair to say that the draft guidance is a step in the right direction, it remains to be seen whether there will be any significant decrease in the time to downclassification of de novo devices.

This draft guidance is one of 25 action items listed in the FDA's Plan of Action for Implementation of 510(k) and Science Recommendations launched earlier this year to improve the predictability, consistency, and transparency of the Agency's premarket review programs. The FDA has opened public dockets for comments on this draft guidance and will be accepting comments until 30 December 2011. Electronic comments on Docket No. FDA-2011-D-0689 can be submitted at www.regulations.gov. Written comments can be submitted to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Room 1061, Rockville, MD 20852.