FDA STeP Program Offers Expedited Review

The STeP program is one of several that falls under the FDA’s medical device safety action plan, which the agency announced in 2018. Device-led combination products are eligible for the STeP program, although these products are eligible only to the extent that the device component is demonstrably safer.

Both the September 2019 STeP draft and the final guidance point to the breakthrough devices program as a model for the STeP program’s design. Unlike the breakthrough devices program, STeP is not for devices that treat life-threatening or potentially debilitating conditions, but rather is focused on devices that offer a significantly improved benefit-risk profile for a device-associated hazard.

In terms of procedure, the manufacturer would notify the agency of its interest in taking part in STeP via the Q-submission mechanism. Incidentally, the guidance for the Q-sub program was modified in January 2021, although the change was limited to an explicit inclusion of the STeP program. At the date of publication, the STeP guidance was subject to the regulatory freeze announced Jan. 20, by the Biden administration, which specifically calls out agency guidance as under the scope of the freeze order.

Safety/Performance Trade-offs not Permitted

Program eligibility is generally limited to devices and diagnostics that are subject to the three main premarket review channels, the de novo, 510(k), and PMA pathways. There are several general considerations for eligibility, such as that the device “should be reasonably expected to make a clinically meaningful improvement” in the rate of occurrence and/or the severity of a known safety issue. However, this improvement should not be offset by a negative effect on the product’s effectiveness, nor should the modification increase the rate of occurrence of a different type of safety issue.

Another general factor for eligibility is whether the device improves the benefit-risk profile via “substantial safety innovation.” This is defined as any innovation that incorporates an innovative technological feature or constitutes an innovative use of an existing technology to achieve the improvement in safety. Among the examples of the first of these is the use of a new material in the device, and an example of the second is a modification of software.

Before approaching the FDA for entry into the program, the sponsor should have documented the principles of operation of a device, and should already possess any preliminary data from clinical or non-clinical sources. Any appropriate literature searches should already be on hand as well, but a complete data set derived from a full-blown clinical evaluation or clinical trial is not needed to qualify.

The manufacturer has four specific means of demonstrating their device is eligible for inclusion in the STeP program, such as that the device provides;

• A reduction in the occurrence of a known serious adverse event (AE);
• A reduction in the occurrence of a known device failure mode;
• A reduction in the occurrence of a known use-related hazard or use error; or
• An improvement in the safety of another device or intervention.

The manufacturer will have to consider both acute and long-term AEs to meet the condition of a reduction in the occurrence of a known serious event. The guidance provides a few examples of how this might be brought about, such as an in vitro diagnostic (IVD) that eliminates AEs by eliminating any interference a drug therapy is imposing on existing diagnostics.

The guidance offers little in the way of insight into the known failure mode question, other than to state that the failure mode should be associated with AEs such as death or long-term injury. Hypothetical failure modes do not fulfill this criterion.

The third factor will be met when the sponsor can demonstrate that the device’s design addresses any hazards associated with either user errors or hazards attendant to routine use of the device. Human factors studies will likely play a key role in at least some of the devices that claim this improvement for entry into the STeP program, but a sponsor cannot use a mere change in labeling or in the instructions for use to qualify.

Risk Classification Unaffected by Entry into STeP

There are several potential ways to qualify under the category of an improvement in the safety of an intervention or another device. One is a device that can prevent the need for one or more downstream interventions or surgeries. An IVD that can eliminate the need for invasive test methods, such as biopsies, might also qualify. Medical device accessories could gain entry under this rubric, although acceptance into the program does not determine whether the product qualifies as an accessory.

Similarly, acceptance into the program does not take up the risk category of the device, or whether there is a predicate. In addition, sponsors should be aware that any design changes they undertake to an existing 510(k) clearance may require filing of a new 510(k). In that instance, the final STeP guidance refers to the 2017 version of the “510(k) changes” guidance.

While there are a number of benefits for participation, the manufacturer that successfully brings a device through the STeP program cannot claim via labeling or other promotional material that the device is “safe,” or is safer than a competitor’s devices. There are also a few potential issues of timing that manufacturers may want to consider. One is that the benefit of expedited review may be lost unless the sponsor applies for admission into the STeP program substantially prior to filing the standard regulatory submission for that device.

Also, while the FDA is not entirely averse to including two devices into the program that address the same safety issue or offer the same improvement, each individual sponsor can apply only once for that safety issue or improvement. The agency will decide within 60 days whether to accept an application, and will pass along any requests for additional information within 30 days of the sponsor’s request for inclusion under the Q-sub mechanism.

While those requests from the FDA staff do not affect the 60-day clock, the agency asks sponsors to respond quickly to those requests, which helps the FDA to keep all applications on clock. Furthermore, the guidance advises that a failure to respond within a “timely manner” may result in denial of entry into STeP. Precisely what constitutes a “timely” response, however, is not at all clear.