By Mike Wolf, Maetrics
In December 2018, the U.S. Food and Drug Administration (FDA) published a guidance document explaining implementation of the Breakthrough Devices Program. The voluntary program is designed to streamline the market clearance/approval process for certain medical devices and device-led combination products in the United States.
Specifically, these products are novel or represent new technology that can assist high-risk patients suffering from life-threatening or irreversibly debilitating conditions by enabling more effective treatment or diagnosis. This proactive measure on the part of the FDA attempts to ensure that patients and healthcare providers have timely access to vital devices; meanwhile, well-prepared manufacturers can benefit from close collaboration with the FDA during the intensive process, propelling their products to market in a relatively short period of time.
A Two-Step Process With Two Main Criteria
The program consists of two main stages. In the first stage, the company or individual — referred to as the ‘sponsor’ — must submit a designation request to apply for entry into the program via the Q-Submission process (which has its own guidance document, issued in May 2019). This request can be sent at any time before a marketing submission — for example, premarket approval (PMA), premarket notification [510(k)], or a De Novo classification request.
The application must describe the device, its proposed indications for use, how it would benefit the target patient population, its regulatory history, and the type of marketing submission to be submitted to the FDA. Sponsors also must identify how the proposed device meets the Breakthrough Device acceptance criteria. The FDA intends to respond to designation requests within 30 days, generally requesting additional information the Agency deems necessary before making a decision about the device’s inclusion in the program. The FDA aims to reach a decision to grant or deny the request for designation within 60 calendar days of receiving the application.
Inclusion in the Breakthrough Device program is dependent on two criteria. First the device must provide for more effective treatment or diagnosis of life-threatening or irreversibly debilitating human disease or conditions. Second, the device must meet any one of the following: the device represents breakthrough technology; no approved or cleared alternatives exist; the device offers significant advantages over existing approved or cleared alternatives; or, device availability is in the best interest of patients.
Examples of devices that have been designated under the program include a device that could diagnose Parkinson’s disease at a much earlier stage than current diagnostic methods[i], an artificial intelligence tool enabling pathologists to become faster and more accurate in their diagnosis and treatment recommendations for cancer patients[ii], and a retinal imaging platform that uses artificial intelligence to aid in the diagnosis of Alzheimer's disease[iii]. Most recently, a test aimed at reducing unnecessary prostate biopsies became the first exosome-based liquid biopsy to be granted Breakthrough Device Designation.[iv]
In the second stage of the program, after the device has been accepted for inclusion, the FDA will assign special device review teams to evaluate submissions on a timely basis. This step includes senior management engagement to facilitate efficient development and regulatory review of the device, as well as to resolve issues.
The FDA is determined to deploy necessary resources internally, throughout submission processes, to work collaboratively with the sponsor, ensuring there is clear agreement every step on what is required and how those requirements can be met. The guidance document specifically states that submissions under this program will receive priority review from the FDA, and will therefore be at the head of the queue for evaluation.
As the program is barely seven months old, few examples exist of devices being designated under its umbrella, leaving new entrants with limited cases to reference. However, we anticipate that companies considering a submission to the program may face a number of challenges.
First, companies must realistically assess whether a device being developed addresses the target population and whether it truly improves treatment or diagnosis of a life-threatening condition or a serious deterioration of health. The FDA is likely to receive a number of submissions where the device’s importance has been overestimated by the developer or manufacturer, or the inclusion criteria are not met.
Though a complete set of clinical data is not required for Breakthrough designation, sponsors should identify a compelling need and demonstrate a reasonable expectation that the proposed device, used as intended, could effectively treat or diagnose the identified disease or condition in a new or better way. This argument is aided by citing relevant literature, providing supportive descriptions of unique design features, including meaningful discussion of patient perspectives, conducting risk-benefit analyses, and securing preliminary data from various sources.
An additional challenge is interacting with the FDA in the way the guidance document suggests. It is expected that interactions will be frequent and the process fast-paced; also, that the FDA may require detailed information at every meeting or discussion. Most companies are not accustomed to this level of interaction, so potential sponsors must prepare to be highly responsive and to produce requested information as swiftly as possible. The FDA anticipates providing rapid and thorough feedback within this program, and therefore expects the same speed of action and quality of information from sponsors.
For instance, one way of interacting with the FDA following designation is through ‘sprint’ discussions, intended to achieve timely resolution of potentially novel issues, with the goal of reaching mutual agreement on a specific topic within a set time period (e.g., 45 days). To facilitate these discussions and to ensure they are as effective as possible, sponsors should follow specific parameters outlined by the FDA.
Further, successful Breakthrough Device designation requires some behavioral modification from both sponsors and the FDA, as the process is expected to be intensive and demanding; the program is designed to be carried out as fast as the FDA can process information and make a decision.
The former Expedited Access Pathway and Priority Review for medical devices, which have been replaced by the Breakthrough Devices Program, did not have the same clear structure and well-communicated processes. Thus, the program represents a new approach for the FDA, requiring a shift in mentality and actual practice within the organization, matching the intent described in the guidance.
In addition to the obvious benefits to patients with debilitating or life-threatening conditions, manufacturers currently developing a new device stand to benefit from the expedited pathway created by the Breakthrough Device Program — provided their device fulfils the program’s criteria, enabling the manufacturer to market the device much sooner than has previously been possible. This pathway also offers the benefit of a collaborative partnership with the FDA, including participation from high-level managers, which may produce useful insights and experience for future regulatory submissions.
About The Author
Mike Wolf is Director of Solutions Delivery at Maetrics LLC, with more than 25 years of in line management and consultation roles. Mike has helped organizations design, implement, and improve quality management systems and processes, as well as achieve and maintain regulatory compliance, including market clearance for new devices and related international licenses or product registrations. Mike recently served as regulatory subject matter expert within a large-scale improvement project at a global orthopedic device company, leading the legacy review and remediation of labeling, regulatory assessment, and premarket product launch processes and records.