FDA’s Breakthrough Devices Program

To its credit, the FDA has developed a number of programs to increase, or speed, the availability of medical devices, drugs, and biologics under special circumstances. The Orphan Product Designation grants special status to a drug or biological product to treat a rare disease or condition. Emergency Use Authorizations during Covid are another example. The Humanitarian Use Designation for was developed for devices intended to treat or diagnose a disease or condition that affects or is manifested in not more than 8,000 individuals in the United States per year.

Another such FDA program worthy of note is the Breakthrough Devices Program. This program is intended to expedite the approval of devices and device-led combination products intended to treat critically ill patients. The Breakthrough Devices Program implements Section 360e-3 of the Federal Food, Drug, and Cosmetic Act (FD&C Act). The stated purpose of Section 360e-3 is:

360e–3. Breakthrough devices (a) Purpose The purpose of this section is to encourage the Secretary, and provide the Secretary with sufficient authority, to apply efficient and flexible approaches to expedite the development of, and prioritize the Food and Drug Administration’s review of, devices that represent breakthrough technologies.

Although the Breakthrough Devices Program was initiated in 2017, the concept was in place, in one of three programs, as early as 2011. The Innovation Pathway (IP) was piloted in 2011. The IP was established to facilitate the development and create a priority review program for pioneering technologies. The IP pilot was later ended. The Priority Review Program (PRP) which was implemented in 2013 established priority review for medical device premarket submissions and was structured to realize efficiencies in the review process. The Expedited Access Pathway (EAP) was launched in 2015. The EAP was an expedited market access program for certain high-risk devices targeting life-threatening diseases or ailments. Both the PRP and the EAP were replaced by the Breakthrough Devices Program. The current Breakthrough Devices Program incorporates elements of all three of the previous FDA programs.

The Breakthrough Devices Program is a two-step process. The first step is the Designation Request. The second step is the actions the FDA will take to speed the development of the device and give the device priority in the submission review process.

In order to be designated as a Breakthrough Device, a device must meet the following criteria, as stated in Section 360e-3(b) of the FD&C Act:

(1) that provide for more effective treatment or diagnosis of life-threatening or irreversibly debilitating human disease or conditions; and

(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.

In this Designation Request step, the device sponsor requests that the FDA designate the device a Breakthrough Device. A Designation Request is submitted as a Q-Submission. The Q-Submission must include a device description, the indications for use, the regulatory history of the device, and the regulatory pathway the sponsor intends to pursue, i.e., PMA, De Novo Request, or 510(k). And most importantly, it must also demonstrate how the device and its indications for use meet Criterion (1) and one of the four elements of Criterion (2).

Once a device is designated as a Breakthrough Device, the specific features of the Program begin:

Interactive and timely communication
FDA consultation with external experts or an FDA advisory Committee
Postmarket data collection
- allowing for postmarket data collection to speed the development and review of the device
- accepting more uncertainty in the device risk-benefit profile provided it is balanced by other factors
Efficient and flexible clinical study design
FDA review team support
Senior FDA management engagement
Priority review of all submissions
Manufacturing considerations for PMA submissions
- less QMS and manufacturing information if certain requirements are met
- in certain circumstances, deferring the manufacturing site inspection for as long as 12 months after the device has been approved

The Breakthrough Devices Program has become increasingly popular, with more sponsors taking advantage of the Program each succeeding year. A study by Johnston et al.¹ found that as of January 1, 2020, the FDA had granted 248 Breakthrough Devices and approved PMA’s or cleared 510(k)’s for 15 Breakthrough Devices. Through May of 2020, there had been 298 Designations². The breakdown is as follows:

Time Period	Designations
Prior to Dec 13, 2016 (EAP)	26¹
Dec 13, 2016 – Dec 31, 2018 (EAP and BDP)	84¹
Jan 1, 2019 – Jan 1, 2020 (BDP)	138¹
Jan 2, 2020 – May 27, 2020 (BDP)	50²

The Breakthrough Devices Program is beneficial both to patients and to sponsors. It offers the advantage of FDA advance agreement on issues such as clinical trial design and data to be collected so that there are no surprises in the review process. The flexibility built into the Program and the FDA support and input invaluable. Frequent interaction with the FDA is also an advantage due to the information it provides. The sponsor and the FDA have formed a partnership, as it were. Both parties are heavily invested in making the device available to the patients who need it.

¹ Johnston, J.L., Dhruva, S.S., JS Ross, J.K., and Rathi, V.K. Early experience with the FDA’s Breakthrough Devices program. Nature Biotechnology – nature.com (2020)
²starfishmedical.com/blog/fda-breakthrough-devices-program/

Mike Andrews, Ph.D., former Vice President, Regulatory and Quality, Boulder iQ