Breakthrough Device Designation

To qualify, a device must meet two key criteria:

• First Criterion: The device provides for more effective treatment or diagnosis of a life-threatening or irreversibly debilitating human disease or condition.
• Second Criterion: The device must satisfy one of the following:
  • Breakthrough Technology: No approved alternatives exist.
  • Significant Advantage: Offers a clinically meaningful advantage over existing approved alternatives.
  • Best Interest: Availability is in the best interest of patients.

This is not a lower standard for safety; statutory requirements for marketing authorization remain unchanged.

Designation grants access to several interactive and prioritized review features:

• Sprint Discussions: Timely, interactive communication with FDA reviewers to resolve clinical and regulatory issues quickly.
• Senior Management Engagement: Direct access to FDA senior management and a dedicated case manager.
• Priority Review: The marketing submission receives priority review status, placing it at the top of the review queue.
• Flexible Clinical Trial Design: FDA may accept a less burdensome clinical study design, such as the use of real-world evidence or intermediate surrogate endpoints, when scientifically appropriate.

A Breakthrough Device Designation Request should be submitted as a Q-Submission before filing a marketing application.

• When to Submit: Ideally before initiating the pivotal clinical trial, as early designation maximizes the benefit of interactive review on study design.
• Content: The request must include a detailed description of the device, the proposed intended use, a summary of the disease condition, and a data-driven rationale demonstrating how the device meets the qualifying criteria.
• Decision: The FDA aims to issue a decision within 60 calendar days of receiving a complete designation request.

The designation request must be supported by compelling, scientifically valid evidence. Acceptable data sources include:

• Non-Clinical Bench Testing: Demonstrating fundamental scientific principles.
• Animal Model Data: Showing proof-of-concept in a relevant disease model.
• Early Feasibility Clinical Studies: Initial human experience, even with a small sample size.
• Real-World Evidence: Historical data from similar devices or registry analyses.

The expectation is not a complete clinical data package, but rather a reasonable expectation that the device will provide more effective treatment or diagnosis.

Designation is not a guarantee of approval and carries ongoing responsibilities:

• Transparency: The FDA may publicly post information about the device's designation on its website.
• Continued Eligibility: If a predicate device is cleared via 510(k) or a De Novo is granted for the same intended use, the Breakthrough Device may lose its designation for that specific indication.
• Post-Market Data: The FDA may require robust post-market surveillance (PMS) as a condition of approval to confirm long-term safety and effectiveness in real-world clinical practice.

For Software as a Medical Device (SaMD), this pathway is particularly critical for AI/ML-enabled diagnostics:

• Iterative Improvement: The program's sprint discussions are vital for aligning on a Predetermined Change Control Plan (PCCP) for adaptive algorithms.
• Faster Patient Access: It significantly compresses the timeline for life-saving diagnostic AI, such as stroke detection or cancer screening tools, to reach clinical practice.
• Investment Signal: Designation is often viewed by investors as a strong signal of a device's clinical potential and regulatory viability, facilitating funding for pivotal trials.

A risk-based classification process for novel medical devices of low to moderate risk that lack a legally marketed predicate device. Unlike the 510(k) pathway, De Novo does not require proving substantial equivalence. It is often the final classification destination for a device that has successfully navigated the Breakthrough Device Designation program, establishing a new regulatory category and serving as a predicate for future devices.

The FDA's most stringent process of scientific and regulatory review to evaluate the safety and effectiveness of Class III medical devices. Breakthrough Devices that support or sustain human life and present a potentially unreasonable risk of illness or injury will be routed to the PMA pathway. This requires extensive clinical data from pivotal trials, though the Breakthrough program facilitates more interactive and expedited review of this data.

A premarket submission made to the FDA to demonstrate that a device is substantially equivalent to a legally marketed predicate device. While less common for truly novel Breakthrough Devices, a device may use the 510(k) pathway if a suitable predicate exists. The Breakthrough designation does not alter the fundamental requirement for substantial equivalence but can accelerate the interactive review of the submission.

An FDA-authorized plan detailing the types of modifications a manufacturer intends to make to a machine learning-enabled device without requiring a new marketing submission. This is a critical component for AI-driven Breakthrough Devices, allowing for iterative improvement based on real-world learning while maintaining regulatory compliance. The PCCP must be pre-specified and approved, outlining the scope of planned changes and the methods for validating them.

The statistical methodologies and trial protocols for proving diagnostic AI efficacy. For a Breakthrough Device, the clinical evidence must credibly demonstrate a clinically meaningful advantage over the current standard of care. This involves defining primary and secondary endpoints, establishing rigorous inclusion/exclusion criteria, and pre-specifying the statistical analysis plan to avoid bias and ensure the results are robust and generalizable.

Software intended to be used for one or more medical purposes that performs those purposes without being part of a hardware medical device. Many AI diagnostic tools, including those receiving Breakthrough Device Designation, are classified as SaMD. The designation applies to the software's intended function, and the regulatory pathway is determined by the risk of the information provided to the clinician or patient.