The US Food and Drug Administration (FDA) on Tuesday issued a draft guidance detailing the agency's new program for breakthrough medical devices created by the 21st Century Cures Act.
The new breakthrough devices program supersedes and combines several of the agency's existing programs to speed access to new devices.
"Earlier and more frequent interaction between the FDA and manufacturers … should allow manufacturers to make the best use of their resources to bring state-of-the-art medical technologies to the market faster," FDA Commissioner Scott Gottlieb said.
The program applies to devices subject to FDA's premarket approval (PMA), de novo, and 510(k) pathways, and all devices accepted to the program are guaranteed priority review status.
Unlike FDA's priority review program for drugs, which offers designated products a shorter review period than standard applications, devices granted priority review are placed at the top of the review queue and are assigned additional review resources but are not guaranteed a faster review. FDA also notes that breakthrough devices may actually take longer to review than other devices due to novel scientific issues.
When multiple breakthrough devices are under review at the same time, FDA says it will prioritize applications based on a first-in-first-reviewed basis.
When it comes to clinical trials for breakthrough devices, FDA says it will consider certain clinical study features to ensure "efficient and flexible" studies, including: Prespecified endpoints regarding the minimum clinically meaningful impact;Intermediate and surrogate endpoints where evidence is provided to support the endpoint as reasonably likely to predict the clinical benefit of a device;Composite endpoints with an explicit rationale for the meaningful effect size; andPhased study design
As for the reviewers assigned to oversee breakthrough therapy submissions, FDA says its staff will be "experienced with innovative approaches to regulatory science" and will undergo regular training to ensure that review teams are up to date on the program as well as scientific and technological advances in their respective areas of expertise.
Once a device has been designated as a breakthrough device, FDA says sponsors can select one or more features of the breakthrough program for additional interactions with the agency.
First, sponsors can request to have "sprint" discussions with FDA on novel issues related to their device, with the goal of reaching mutual agreement with the agency within a set time period. FDA says that sprint discussions should focus on a single topic and follow a defined schedule.
Sponsors can also request FDA to coordinate with them on a data development plan (DDP).
"The DDP is a high-level document intended to help ensure predictable, efficient, transparent, and timely device assessment and review by outlining data collection expectations for the entire product lifecycle," FDA writes, noting that the DDP may also detail the balance of premarket and postmarket data collection.
Lastly, sponsors can request that FDA agree in writing to a proposed clinical protocol. Such agreements are considered binding on both FDA and the sponsor, unless a change is agreed to in writing by both parties or the director of the office reviewing the submission determines that "a substantial scientific issue essential to determining the safety or effectiveness of the device exists."
In order for FDA to change the protocol unilaterally, the agency must first give the sponsor an opportunity to discuss any new scientific issues, and the office director must provide his or her decision to the sponsor in writing.
Additionally, FDA says that sponsors can agree to have regular check-ins with the agency via email, teleconference or face-to-face meetings to discuss their product or application's progress and plan for upcoming meetings.
For breakthrough medical devices subject to PMAs, FDA says the breakthrough program will provide some additional benefits.
FDA says it plans to rely more heavily on postmarket data collection to balance out uncertainty at the time of approval for breakthrough PMAs.
But FDA says this does not mean it is changing its standards for approval and that the agency will only approve PMAs "if it determines that there is a reasonable assurance of safety and effectiveness" at the time of approval.
FDA also says it plans to "expedite the review of manufacturing and quality systems compliance" for breakthrough PMA submissions that require a preapproval inspection. And, on a case-by-case basis, FDA says it will allow breakthrough PMA sponsors to submit less manufacturing information in their submissions, such as in cases where the sponsor "has a good track record for quality systems compliance and there are no new manufacturing issues that could adversely impact product quality or performance."
In cases where FDA does not conduct a preapproval inspection, the agency says it will conduct postapproval inspection within 12 months.
Draft Guidance, Statement