Interactive and Timely Communication

The FDA believes such communication during development and throughout the review process for Q-Submissions, IDEs, 510(k)s, De Novo requests, PMAs, and certain PMA supplements has significant value. To facilitate this, the FDA recommends the use of “tracked changes” and redlined versions of previously reviewed documents, summary tables to points of agreement from previous interactions, and communication regarding the goals of interactions and response timelines.

Pre/Postmarked Balance of Data Collection

Timely postmarked data collection for PMA devices facilitates expedited and efficient development and review of the breakthrough device. The FDA recognizes that the benefits of the breakthrough device may outweigh the risks of delaying the availability of the device. However, it will depend on the benefit-risk analysis, non-clinical data, and clinical data available for the device.

Efficient and Flexible Clinical Study Design

To ensure the design of clinical trials is as efficient and flexible as practicable, the FDA will consider various types of endpoints such as prespecified, intermediate, surrogate, composite, and adaptive study designs.

Review Team Support

A lead reviewer is assigned based on training, expertise, experience, and the ability to resolve complex issues quickly and interactively. Staff are also experienced with innovative approaches to regulatory science and clearly communicate the FDA’s expectations during the device development process.

Senior Management Engagement

Senior FDA officials are involved in the process to help resolve issues during development and review. Breakthrough device manufacturers have the opportunity to interact with senior FDA officials, including the Center Director and the Office of Combination Products, to help resolve issues and expedite the approval process.

Priority Review

A review of the submission is placed at the top of the review queue, and additional review resources are allocated.

Manufacturing Considerations for PMA Submissions

An expedited review of manufacturing and quality systems compliance is performed, including acceptance of less quality and manufacturing information if statutory and regulatory requirements are satisfied, using an alternative approach to submitting all items listed in relevant FDA guidance documents.

By providing manufacturers with additional support and resources, the program aims to bring breakthrough medical devices to patients in need as quickly and safely as possible.

Sprint Discussion

Sponsors needing timely resolution of novel issues can interact with the FDA every week to discuss a single topic with specific goals. During a sprint discussion, a defined interaction schedule is developed and agreed upon, after which documentation is provided to the FDA for interactive feedback.

Data Development Plan (DDP)

This high-level document helps ensure that expectations for the entire product lifecycle are aligned with those of the FDA and the sponsor. The FDA suggests DDP discussions be one of the first submissions after a breakthrough device designation has been granted.

Clinical Protocol Agreement

This binding agreement between the sponsor and the FDA on a clinical protocol typically includes details such as the study design, patient population, endpoints, statistical analysis, and other key elements of the trial, such as provisions for monitoring and reporting adverse events, as well as plans for ensuring patient safety during the trial.

Other Pre-Submission for Designated Breakthrough Device

This option can be utilized to engage with the FDA on multiple topics in a single pre-submission.

Regular Status Updates

This informal communication (email, meetings, etc.) discusses the timeframe for a planned marking submission, the next steps, or plans for future discussions. Such high-level communication fosters transparency and allows the identification of potential hurdles.

• Devices provide for more effective treatment or diagnosis of life-threatening or irreversibly debilitating human disease or condition; and

• a. that represent breakthrough technologies;
  b. for which no approved or cleared alternatives exist;;
  c. that offers 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 patient.

More Effective

Due to the nature of these designation requests, the FDA recognizes it is appropriate to consider whether there is a reasonable expectation that a device could provide more effective treatment or diagnosis relative to the current standard of care. It’s important to understand the current standard of care and compare your device against it.

Devices that receive breakthrough designations remain a mystery until the point at which they are granted marketing authorization (https://www.fda.gov/medical-devices/how-study-and-market-your-device/breakthrough-devices-program) . As such, the industry has been putting pressure on the FDA for additional transparency into how a device received breakthrough designation, which in turn has increased the scrutiny the FDA is placing on such designations.

The “more effective” criterion is one of the areas that has had the most impact. Although the guidance indicates clinical data is not required, recent breakthrough designations have been required to include clinical data.

Breakthrough Technology

The FDA will consider the novelty of the device, including a novel application of an existing technology. If you have discovered a new way to use an old or existing device, it could still qualify for a breakthrough designation.

No Approved or Cleared Alternatives

Even though you’re applying for a device designation, the FDA will look at drugs, biological products, other devices, or combination products that have received marketing authorization for the same indications proposed for your device. It’s important to remember your comparison is not just to other devices, so make sure your discussion includes all possible standard-of-care options, including drugs.

You might find yourself in an interesting situation where there is a cleared predicate for a device you are attempting to get a breakthrough designation for. In this case, you may need to prove that the predicate device, although cleared, is no longer available on the market and could not be considered the standard of care. This will not be an easy argument to make, but you need to remember to think outside the box and make your case to the FDA as strong as possible.

Significant Advantages

To leverage this criterion, your breakthrough device needs to reduce or eliminate the need for hospitalization, improve the patients’ quality of life, facilitate their ability to manage their own care, or establish long-term clinical efficiencies when compared to existing approved or cleared alternatives. Remember, this, too, can include drugs and biologics.

Best Interest of Patients

This criterion is very much open to interpretation, and the FDA provides a few different examples in their guidance, including patient perspective, devices that address a national security issue, or a serious unanticipated failure in a critical component of an approved or cleared device.