On October 25, 2017, FDA released a critical draft guidance on the breakthrough medical device pathway established by the 21st Century Cures Act (the “Cures Act”). The Draft Guidance For Industry, Breakthrough Device Pathway (“Draft Guidance”) reflects FDA’s proposal regarding the process by which a sponsor may seek a designation as a breakthrough device, assigning a team of staff to review devices designated for expedited development and priority review; and information about the criteria that will be used in evaluating a request for designation (the “Breakthrough Devices Program”). This new Breakthrough Devices Program will supersede the current Expedited Access Pathway (“EAP”), which FDA launched in 2015. It will also supersede FDA’s Priority Review Program, which implemented statutory criteria for granting priority review to premarket submissions.

As an initial matter, the Draft Guidance clarifies that FDA will approve Breakthrough Devices subject to a Premarket Approval Application (“PMA”), only if it determines there are reasonable assurances of safety and effectiveness. But it also signals that FDA may accept a greater degree of uncertainty of the benefit-risk profile for Breakthrough Devices so long as that uncertainty is sufficiently balanced by other factors, including the probable benefits for patients to have earlier access to the device and adequate postmarketing controls. Furthermore, sponsors can still look to FDA’s “Balancing Premarket and Postmarket Data Collection for Devices Subject to Premarket Approval” for guidance on FDA’s policy regarding balancing premarket and postmarket data collection during PMA review.

The Draft Guidance outlines the process a sponsor should follow in order to request designation of a Breakthrough Device. A designation request must be submitted prior to the sponsor’s marketing application submission. The request must indicate which marketing application type the sponsor intends to submit, and the rationale for this decision. All designation requests should be submitted as a Q‑Submission following the process outline in FDA’s Pre-Submission Guidance. FDA will grant or deny designation requests within 60 calendar days of receipt.

The Draft Guidance emphasizes FDA’s intent to provide interactive and timely communication with sponsors during device development and review processes, including assigning staff to be available to address questions by institutional review committees within a reasonable time. FDA will assign an FDA manager to each breakthrough device application, who will in turn assign the most appropriate person within FDA to review the application; and the Draft Guidance assures industry that staff reviewing Breakthrough Device applications will be experienced with “innovative approaches to regulatory science.” To meet that goal, FDA review teams will undergo regular training, including team meetings, sponsor engagement, and patient interactions. Senior management also will remain involved throughout the review process.

Additionally, FDA will take measures to expedite the review of Breakthrough Devices, including assigning priority review status to all Breakthrough Device applications. If more than one such application is submitted in a review cycle, the applications will be reviewed based on a first-in-first-reviewed basis. Furthermore, FDA will expedite review of manufacturing and quality systems during preapproval inspections, and even forgo inspection of certain manufacturing sites prior to approval where appropriate. FDA’s decision to inspect a manufacturing site will depend on the date of the site’s last inspection, and the results of that inspection.

For sponsors seeking approval of a Breakthrough Device, FDA will offer three options for accelerated discussions:

  • “Sprint” Discussions: To support sponsors needing timely resolution of potentially novel issues, FDA will offer “sprint” discussions. These discussions will occur with a goal of reaching mutual agreement on a specific topic within a set time period (e.g., 45 days). The number and format of these discussions, supporting material needed, and timing, will vary based on the project. Similarly, the topic of the discussions should be focused in one general area (e.g., animal study protocol design). The discussions will end with written feedback from FDA to the sponsor.
  • Early Agreement on Data Development Plan (“DDP”): A sponsor can submit a DDP containing both clinical and nonclinical testing approaches, and describing the balance of premarket (and postmarket, if available) data. A DDP is a high-level document intended to help ensure predicable, efficient, transparent, and timely device assessment and review by outlining data collection expectations for the entire product lifecycle. FDA will review the DDP following the same model as its “sprint” discussion model, with a goal to reach early agreement on the DDP.
  • Clinical Protocol Agreement: Sponsors can seek written agreement from FDA on clinical protocols. FDA will document its agreement with a letter.

A sponsor can choose from any of these three options at any point prior to submitting a marketing application for a device. In addition to these three options for accelerated discussion, FDA and the sponsor can engage in regular status updates to discuss the progress of the project and next steps.

FDA also provided guidance on the criteria it will apply to determine whether a device qualifies as a Breakthrough Device. Its guidance is broken down by the categories created in the Cures Act:

  • Devices Providing for More Effective Treatment: FDA will consider, among other things, whether there is a reasonable expectation that a device could provide for more effective treatment or diagnosis relative to the current standard of care. A complete set of clinical data will not be required for this assessment. The device can treat a life-threatening condition, which FDA defines as a disease or condition for which the likelihood of death is high, unless the course of the disease is interrupted. Alternatively, such condition must have a substantial impact on day-to-day functioning in order to qualify as irreversibly debilitating.
  • Device Represents Breakthrough Technology: FDA will consider the potential for a device to lead to clinical improvement in the diagnosis, treatment, or cure of a life-threatening or irreversibly debilitating condition.
  • No Approved or Cleared Alternatives Exist: FDA will consider whether there is a drug, biological product, or device that has received FDA marketing authorization for the same indications as the proposed breakthrough device. To qualify as an approved or cleared alternative, the product also must be consistent with the current standard of care. If that standard is not well defined, FDA may consult with experts to determine whether the product is an approved or cleared alternative.
  • Device Offers Significant Advantages over Existing Approved or Cleared Alternatives: FDA will consider whether a device reduces or eliminates the need for hospitalization, improves patient quality of life, facilitates the ability of patients to manage their own care, or establishes long-term clinical efficiencies when compared against an existing approved or cleared alternative. One example provided by FDA is an in vitro diagnostic product for earlier diagnosis of preeclampsia.
  • Device Availability Is in the Best Interests of Patients: FDA also will consider the extent to which the device and its proposed indications for use provide another type of specific public health benefit; provide a benefit to patients who are unable to tolerate or are not responding to available therapy; and/or address an unanticipated serious failure in a critical component of an approved device, when alternative treatment would present substantial risk of morbidity to the patient.

FDA has solicited comments on its Draft Guidance, which can be submitted within 60 days of its publication of the Draft Guidance, or by December 24, 2017. An analysis of the key provisions in the Cures Act related to drug, device, and biologic development and approval can be found in Reed Smith’s Client Alert, 21st Century Cures Act.