We remember the late Jimmy Buffett who sang in his 1977 classic, “Changes in latitudes, changes in attitudes; Nothing remains quite the same.” Demonstrating a change in attitude, in September, the Food and Drug Administration issued a new Final Guidance relating to its Breakthrough Devices Program, clarifying that certain devices for life-threatening or irreversibly debilitating diseases or conditions may now qualify for the program. The updated final guidance, “Breakthrough Devices Program,” supersedes the previous guidance of the same name issued on December 18, 2018.¹

One of the major changes from the superseded guidance is the emphasis on health equity. The guidance explains how the Breakthrough Devices Program may also apply to innovative medical devices that may address health inequities (to be defined), aligning with the Center for Devices and Radiological Health’s (“CDRH”) Strategic Priority to Advance Health Equity. CDRH’s Strategic Priority to Advance Health Equity recognizes that CDRH can advance the development of technologies to meet the needs of all patients and consumers.² FDA defines health equity as the absence of unfair, avoidable, and remediable differences in health status among groups of people.

In addition, consistent with the SUPPORT Act, the updates clarify that the Breakthrough Devices Program may be available for certain non-addictive medical products to treat pain or addiction.³ This Bulletin provides a high-level overview of the 31-page final guidance and our observations.⁴

Guidance Overview

• The Breakthrough Devices Program is comprised of two phases:
  • The Designation Request phase, in which a sponsor of a medical device requests that FDA grant Breakthrough Device designation.
  • The phase that discusses actions to expedite development and the prioritized review of subsequent regulatory submissions.
• FDA intends to make the aforementioned types of devices more readily available.
  • FDA will provide interactive and timely communication with Breakthrough Device sponsors, which may help ensure that clinical study designs are prepared to maximize best results.
  • The agency notes that it may require consultation with external experts or an Advisory Committee, when appropriate.
  • The Program also supersedes the Expedited Access Pathway and the Priority Review Program.

Breakthrough Device Designation

• Breakthrough Device designation criteria, as defined in section 515B(b) of the Federal Food, Drug, and Cosmetic Act, are as follows:

(1) [Devices] that provide for more effective treatment or diagnosis of life-threatening or irreversibly debilitating human disease or conditions, and one of the following:

(2)(A) that represent breakthrough technologies;

(B) for which no approved or cleared alternatives exist;

(C) that offer significant advantages over existing approved or cleared alternatives, including the potential, compared to existing approved alternatives, to reduce or eliminate the need for hospitalization, improve patient quality of life, facilitate patients’ ability to manage their own care (such as through self-directed personal assistance), or establish long-term clinical efficiencies; or

(D) the availability of which is in the best interest of patients.

• A sponsor should make clear the proposed indications for use when submitting the designation request.
• In determining whether the device meets condition (1) above, FDA will consider the following three factors:
  • Whether a device provides for a “more effective” treatment or diagnosis.
    • The sponsor should demonstrate a reasonable expectation that the device could function as intended and, by this demonstrated function, that the device could more effectively treat or diagnose the identified disease or condition.
      • FDA’s interpretation of “more effective” is based upon the totality of available information about the device, including the function, the potential for technical and clinical success, the potential for the device to make a clinically meaningful impact, and the risks and benefits compared to standard of care.
      • FDA may consider improved accessibility of a device to populations facing health inequities and related unmet needs when evaluating whether it could meet this criterion.
    • Whether a disease or condition is “life -threatening” (e.g., acute stroke, cancer).
    • Whether a disease or condition is “irreversibly debilitating” (e.g., amyotrophic lateral sclerosis (“ALS”)).
  • The device must also meet one of the four criteria under condition (2) above, as further described below:
    • Device Represents Breakthrough Technology
      • “[W]hether the medical device represents novel technology or novel application of an existing technology that has the potential to lead to a clinical improvement in the diagnosis, treatment (including monitoring of treatment) cure, mitigation, or prevention of the life-threatening debilitating disease of condition.”
    • No Approved or Cleared Alternatives Exist
      • “[W]hether there is a drug, biological product, device, or combination product that has received FDA marketing authorization after premarket review for the same indication(s) being considered (e., whether there is an alternative product that FDA has approved, cleared, or licensed, or for which FDA has granted a De Novo request)”
      • The product should also be consistent with the current stand of care for the relevant disease or condition.
    • Device Offers Significant Advantages Over Existing Approved or Cleared Alternative
      • Whether, compared to existing approved or clear alternatives, the device has the potential “to reduce or eliminate the need for hospitalization, improve patient quality of life, facilitate patients’ ability to manage their own care (such as through self- directed personal assistance), or establish long-term clinical efficiencies.”
    • Device Availability Is in the Best Interest of Patients
      • “[W]hether the proposed device and indications for use provide another type of specific public health benefit,” such as a device that can conduct simultaneous tests where such testing is usually conducted individually, a device that offers an alternative to an existing therapy that is not well-tolerated for certain patients, or a device that otherwise addresses an unanticipated serious failure in an approved or cleared device for which there are no alternatives.

Potential Benefits

• Similar to any device subject to a Premarket Approval application, Breakthrough Devices subject to a PMA application must meet statutory standards of reasonable assurance of safety and effectiveness.
  • When scientifically appropriate, FDA intends to use timely postmarket data collection to facilitate expedited and efficient development and review of Breakthrough Devices.
  • As part of its benefit-risk determination, FDA may accept a greater amount of uncertainty in the benefit-risk profile for a Breakthrough Device subject to a PMA application, if appropriate.
  • The agency will weigh the device’s impact on patient health, including the probable benefit of earlier access to the device, against the probable risk of harm to patients from the device, should subsequent data collection demonstrate that the device is ineffective or unsafe.
• All submissions designated as Breakthrough Devices will receive priority review. The submission will go to the front of the line of the appropriate review queue and receive additional review resources, if needed.
  • The agency notes that, while the Program is intended to expedite review, the review may still take longer than many because of the complex issues that could arise.
• Where appropriate, generally based on the sponsor’s past quality system and manufacturing history, FDA may decide not to conduct an inspection of certain manufacturing sites prior to approval of a Breakthrough Device.
• FDA clarifies that Breakthrough Device designation may be granted for multiple devices with the same proposed intended use, and a Breakthrough Device designation will not be revoked solely because another designated device obtained marketing authorization.
  • However, when a Breakthrough Device has been approved or cleared or has had a De Novo request granted, no additional devices with the same intended use can obtain a Breakthrough Device designation, unless the criteria for designation above are still met despite the Breakthrough Device’s market availability.
• This final guidance explains how FDA will consider technologies and device features that may help address health and healthcare disparities, and provide more effective treatment or diagnosis in various populations that exhibit healthcare disparities.
  • The guidance provides sponsors with resources regarding the evaluation and reporting of various health equity data points within medical device clinical studies.

Process and Communications

• To obtain Breakthrough Device designation, a sponsor should submit a “Designation Request for Breakthrough Device” Q-Submission.
  • FDA will issue a grant or denial decision for each Breakthrough Device designation request within 60 calendar days of receiving such a request.
  • FDA intends to interact with a sponsor by day 30 regarding any requests for additional information needed to make the designation decision.
• A Breakthrough Device sponsor is offered several unique pre-submission (or pre-submission-like) options by which they may request feedback from FDA:
  • Breakthrough Device Sprint Discussions
    • Discussions between FDA and the sponsor designed to reach mutual agreement on a specific topic within a set timeframe (e.g., 45 days).
  • Data Development Plans (“DDP”)
    • Documented plans to help ensure predictable, efficient, transparent, and timely device assessment and review, by outlining data collection expectations for the entire product lifecycle.⁵
  • Clinical Protocol Agreements
    • Agreements between FDA and the sponsor for clinical protocols, which are binding on both parties.
  • Other Pre-Submissions Tracked as an “Interaction for Designated Breakthrough Device”
    • Submissions titled as such in the cover letter will receive priority review.

AGG Observations

• It is important for companies to recognize that, while the Breakthrough Device designation provides for Priority Review, which is intended to expedite the development review process, these types of devices are often more complex; so review times for these device applications may still be longer than the average review time for other products.
• These updates from the superseded guidance documents are focused on FDA’s efforts to increase health equity by rewarding innovation where it will help populations affected by health and healthcare disparities.
• We recommend early consultations with FDA if a company wants to proceed through the Breakthrough Devices Program to evaluate if its understanding of whether a device may qualify is similar to FDA’s interpretation.
• While we doubt Mr. Buffett will review this latest guidance, as he is likely eating a cheeseburger in paradise and lounging in Margaritaville, those in the medical device industry should see how the guidance affects their company and potential device projects.

[1] The final guidance is available here: https://www.fda.gov/media/162413/download.

[2] FDA’s Strategic Priority outlines are available here: https://www.fda.gov/media/155888/download.

[3] Section 515B of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. § 360e-3)).

[4] On Tuesday, November 14, 2023, at 1 p.m. EST the FDA will host a webinar for the medical device industry and others interested in learning more about the updated final guidance.

[5] FDA provides a DDP example approach in the guidance.