On October 3, 2011, FDA issued a draft guidance entitled, “De Novo Classification Process (Evaluation of Automatic Class III Designation).” In the guidance, FDA described the submission and review of petitions under the de novo classification process in section 513(f)(2) of the Federal Food, Drug, and Cosmetic Act. Under the de novo process, a low to moderate risk medical device that FDA found to be not substantially equivalent (“NSE”) to a legally marketed predicate device based on a 510(k) notice can be reclassified from Class III to Class I or Class II. Reclassification allows immediate marketing of the device that is the subject of the de novo review petition (“the new device”) and its use as a predicate device.

  1. Criteria for De Novo Review

Medical devices must meet two threshold criteria for de novo review: (1) the new device is not within a device type that has been classified based on risk; and (2) FDA has stated that the new device is automatically classified into Class III in a NSE letter issued within the last 30 days. The basis for FDA’s NSE determination must be that the device lacks an identifiable predicate, has a new intended use, or has different technological characteristics that raise new questions of safety and effectiveness, and not the absence of, or issues with, performance data. The new device should be low to moderate risk and likely to meet the standards for Class I or Class II classification, and the requestor should be able to explain the risks and benefits of the new device so that the risks can be sufficiently addressed through use of general and/or special controls.

  1. Pre De Novo Submission

If the draft guidance is finalized, there would be two de novo review options: (1) a pre de novo submission (“PDS”) followed by the concurrent submission of a 510(k) notice and de novo petition (“the PDS/concurrent submissions option”); or (2) a de novo petition submitted after receiving an NSE determination regarding a 510(k) notice (“the sequential submissions option”). FDA currently requires sequential submissions. FDA expects the proposed PDS/concurrent submissions option to streamline the de novo review process.

Under the first option, requestors who believe that a new device meets the criteria for de novo review would submit a PDS. FDA would analyze whether the new device appears to be suitable for the de novo process based on the PDS and, if it is suitable, advise the requestor regarding the data and other information needed in the 510(k) notice and de novo petition. FDA recommends that the requestor wait to submit a PDS until it has determined the device’s proposed intended use and technological characteristics so that FDA can provide more specific guidance.

Upon receipt of a PDS, FDA will assess whether the submission contains adequate information for a suitability review. Requestors can ask to meet with FDA to discuss the submission at least 30 days after the date of submission. FDA intends to ask for any additional information within 60 days of the initial PDS submission or the most recent complete response to a previous request for information. If information is not received within 180 days of the request, FDA will consider the PDS to be withdrawn. Once FDA has adequate information, it will analyze whether a predicate device exists for the new device, if it is the type of device that FDA has classified as Class III by regulation, or if the Agency has approved a PMA for the same type of device without a classification regulation. If FDA determines that the new device has a predicate or is currently regulated as a Class III device (by regulation or through an approved PMA), the Agency will stop the review and send a letter explaining why the new device is not suitable for de novo review. If the device appears suitable for de novo review, FDA will then analyze whether general and/or special controls are likely to provide reasonable assurance of safety and effectiveness. If general and/or special controls are unlikely to be adequate, FDA will issue a letter explaining that the device is not suitable for de novo review. If FDA issues a non-suitability letter, the requestor may submit a new PDS containing additional evidence to address FDA’s concerns.

FDA intends to issue a suitability letter within 60 days of receiving all information necessary for review of the PDS indicating whether the device appears to be suitable for consideration through the de novo process and if so, its likely class, any special controls, and necessary performance data. Requestors who are informed that their new device is suitable for the de novo process should concurrently submit a 510(k) notice and de novo petition containing data described in the suitability letter. There is no time limit for their concurrent submission. FDA intends to conduct a review for completeness of 510(k) notices submitted with de novo review petitions within 20 days of their receipt. FDA suggested that the submitter identify sections of the 510(k) notice that are not relevant because it is seeking concurrent review of a de novo petition. FDA will then analyze complete submissions to determine whether a predicate device exists for the new device, e.g., if FDA has reclassified a new device via the de novo process since the Agency responded to this device’s PDS. If so, FDA will notify the requestor that the de novo petition has not been filed and request information for review of the 510(k) notice under the substantial equivalence standard. If a predicate device likely does not exist, FDA will issue a NSE determination regarding the 510(k) notice within 60 days of receipt of the complete submission and indicate that the de novo petition has been filed for review.

  1. De Novo Petition

The second option for the de novo process is the current process of submitting a de novo petition within 30 days of receiving a NSE determination in response to a 510(k) notice. FDA will determine whether the petition contains adequate information for a de novo review within 30 days of its submission. FDA will issue a denial of the petition if the petition is missing significant information or data is needed to determine whether general and/or special controls can provide reasonable assurance of safety and effectiveness for the new device. Requestors will then need to file another 510(k) (possibly with a preceding PDS) to reinitiate the de novo review process.

If the petition contains sufficient information, FDA will continue its review and determine whether general and/or special controls will be adequate to provide a reasonable assurance of safety and effectiveness. If not, FDA will issue a denial and the device will remain in Class III and require premarket approval prior to marketing. If general and/or special controls will be adequate, FDA will grant the de novo petition and issue a written order granting the petition and classifying the device as Class I or Class II. The new device may be immediately marketed upon receipt of the written order. FDA will then follow the order with a notice in the Federal Register announcing the identification and classification of the device, as well as the special controls if it is a Class II device. FDA may describe the special controls in the classification regulation for the device instead of issuing a special controls guidance document if the controls are straightforward or if the Agency believes that there are unlikely to be many devices of that type.

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The PDS/concurrent submissions option could lead to shorter overall FDA review time and total review time (the FDA review time plus the hold periods) for 510(k) notices and de novo review petitions combined if the Agency concludes that a device is suitable for de novo review, the type and amount of clinical data that the Agency requests is reasonable, and the Agency does not decide during its review of the concurrent submissions that additional or different clinical data is needed. The target time for FDA to make a final decision on a 510(k) notices is shorter for concurrent submissions than sequential submissions (60 versus 90 days), but the Agency could extend that period in either situation by requesting additional information. The PDS/concurrent submission option might also make the de novo process more predictable by providing early feedback from FDA. For these reasons, we expect that most companies seeking de novo review will choose the PDS/concurrent submissions option if the guidance is finalized. We also believe that the inclusion of special controls for Class II devices in the classification regulation would shorten de novo review times for Class II devices regardless of their de novo review options. Thus, this guidance could make the de novo review process a more reasonable regulatory route for new devices.

FDA is soliciting comments on the draft guidance by December 2, 2011.