Clinical Trials Sought For Atherectomy Device 510(k)s In FDA Guidance

New US FDA draft guidance on 510(k)s for peripheral vascular atherectomy devices asks sponsors to submit clinical trial data due to lack of a good animal model.

US FDA issued a draft guidance document July 27 for peripheral vascular atherectomy devices, asking sponsors submit clinical evidence to help prove the new devices are substantially equivalent to their predicates.

While clinical trial data is not requested for a majority of 510(k) devices, clinical data in about 10% to 15% of cases, according to FDA.

Atherectomy devices are used to remove plaque from diseased arteries. Versions used for the coronary arteries are considered class III devices, requiring a PMA, but those that target the peripheral vasculature rely on the 510(k) route and are the subject of this guidance. The devices work in several ways, including by cutting, shaving, sanding or vaporizing the plaque, and can be further categorized as directional, orbital, rotational or laser devices based on the design. 

The draft guidance applies to devices regulated under 21 CFR 870.4875, “intraluminal artery strippers.” Devices cleared in this category include Avinger Inc.'s Patheris System, Cardiovascular Systems Inc.'s Diamondback 360 Peripheral Orbital Atherectomy System and Spectranetics Corp.'s Turbo-Power catheters.

The document explains that multicenter clinical testing may be necessary to ensure device safety and effectiveness.

“A diseased-animal model with clinically relevant challenging anatomy and lesions does not currently exist,” FDA explains in the draft guidance. “We believe a clinical study evaluating multiple operators, patient demographics, and lesion characteristics represents the least burdensome approach to demonstrate substantial equivalence. Therefore, we recommend that you conduct in vivo (i.e., clinical) studies to evaluate device safety and effectiveness for new and modified peripheral vascular atherectomy devices.”

The document further states that FDA is most likely to ask for clinical trial data if devices are new, have been modified in design or functionality, or the sponsor is proposing a new indication or labeling that suggest improved clinical performance. In some cases, real-world data may be enough to support a new indication for use. Sponsors should talk to FDA during the pre-submission process to see what kind of clinical testing might be needed, the draft guidance states.

FDA asks that trial data for peripheral vascular atherectomy devices intended to be used as the primary treatment demonstrate that the device is as safe and effective as the standard of care. If the device is intended for use with another therapy, the contribution of the device should be demonstrated “in a clinically meaningful way,” FDA says. Further, the data should support the use of the atherectomy device for any specific lesion types listed in labeling, such as below-the-knee lesions.

The guidance document also includes recommendations for bench and animal testing. Bench testing should include simulated-use testing in which the device is visualized with imaging guidance, and sponsors should evaluate whether the device will resist kinking in a way that could lead to device failure or patient injury even under the worst device curvature anticipated during clinical use.

“For example, we recommend that you consider wrapping the catheter around a series of mandrels with successively smaller radii until the catheter kinks or the lumen collapses,” FDA says.

Similarly, sponsors should look at the peak temperature reached by devices during use and whether the device can withstand typical torsional forces.

The guidance document recommends caution on animal testing, noting that no animal model exactly matches the human disease progression of atherosclerotic disease. If it’s used, the agency suggests sponsors use pigs or cows because their coronary systems are most like those of humans. Sponsors doing animal trials should capture both acute data, such as the ease of use and procedural safety associated with the device, and chronic data, such as clinical observations and necropsy data focused on vascular treatment sites, major organ systems and downstream tissue beds for thromboembolic events.

Many of the other recommendations made in the draft guidance document are routine for 510(k)s, including detailed descriptions of the mechanism of operation and the technological characteristics, as well as identification of configurations and models and a listing of materials. Additionally, sponsors should submit a full description of any software or firmware used with the device that complies with FDA’s current software guidance. The agency is also requesting that sponsors perform biocompatibility, sterility and pyrogenicity testing, as well as battery-life testing that takes the device lifespan and performance at extreme temperatures into account.

The guidance also lists examples of device changes that would typically trigger a new 510(k), such as changes in device dimension or changes to the component or mechanism used to remove plaque from the arteries.

From the editors of the Gray Sheet