Palmer Smith, Associate, Spine Regulatory Affairs, MCRA LLC11.15.22
The U.S. Food and Drug Administration (FDA) introduced the Breakthrough Device Designation (BDD) Program in 2018 as a replacement for the Expedited Access Pathway and Priority Review for medical devices of all regulatory pathways. The program facilitates the development, assessment, and review of certain medical devices and device-led combination products that provide for more effective treatment or diagnosis of life-threatening or irreversibly debilitating diseases or conditions in order to improve patient care. To date, the program has helped both startups and well-established manufacturers as they navigate the regulatory process.
The Breakthrough Devices Program consists of two phases. The first is the Designation Request phase, in which an interested medical device manufacturer elicits Breakthrough Device Designation from the FDA through Q-submission. The second phase refers to the benefits and opportunities open to BDD sponsors that expedite development and facilitate review of the subject medical device. The designation itself provides an opportunity for sponsors to showcase the novelty and clinical promise of their device to investors and the public. The substantive benefits of a breakthrough device designation, however, stem from the second phase, when the sponsor is actively working towards clearance or market approval.
As of June 30, CDRH and CBER have granted 693 Breakthrough Device designations, including devices originally designated under the Expedited Access Pathway (EAP) program. Of those, “cardiovascular” has been granted 163, “neurology” has received 126, and “orthopedic” has been given 77. Other clinical panels granted designations include “gastroenterology and urology,” “general and plastic surgery,” and “immunology.” It is easy to see why the FDA has had success eliciting breakthrough device designation requests from medical device manufacturers—the program offers multiple benefits designed to provide for an efficient and effective review process, according to an FDA guidance. In summary, the program boasts:
Rather than being dictated by the review timelines established in the Q-Submission Guidance, these submissions require sponsors propose an interaction schedule with a defined end data (e.g., 45 days). As such, sprint submissions typically elicit FDA feedback and teleconferences earlier than a normal Q-Submission. (The sponsor's timelines in the sprint submission are subject to change based on FDA workload, but the agency tries its best to uphold the timelines). These submissions, however, are limited to one general topic (e.g., proposed non-clinical testing battery) and specific goals within that topic (e.g., determine primary endpoint evaluation for pivotal study). FDA works to provide feedback limited to those specific goals in the Q-Submission review process. But sponsors that want to engage FDA on multiple topics within one submission can submit a pre-submission per Q-Submission Guidance and request it be tracked as an “Interaction for Designated Breakthrough Device”; as such, a review team will prioritize the submission and work with its sponsor to develop a feedback timeline commensurate with commitments specified as part of the 2017 Medical Device User Fee Amendments.
Other key Breakthrough Device Program benefits include:
A breakthrough designation suggests the FDA agrees the subject device demonstrates a reasonable expectation in providing for more effective treatment or diagnosis of life-threatening or irreversibly debilitating diseases or conditions at the time of the request. The “reasonable expectation of more effective treatment or diagnosis” is a combination of design considerations and/or non-clinical and clinical data that show the device meets the required designation criteria.
Typically, manufacturers will elicit a breakthrough designation before generating the non-clinical and clinical data necessary for a marketing authorization submission or before finalizing the product’s indications for use/intended use, as these are informed by captured non-clinical and/or clinical data. As such, the arguments made in the designation request may not hold true at the time of a marketing application because only the full battery of data, and the indications for use it supports, paint the full image of the subject device.
The extent to which FDA will re-evaluate a breakthrough device designation at the time of marketing authorization submission remains to be seen. In June, FDA released a draft guidance outlining considerations for rescinding breakthrough therapy designation. One of the reasons given is “emerging data for the designated drug no longer support a finding that preliminary clinical evidence indicates the drug may demonstrate substantial improvement over existing therapies.” If carried over to the Breakthrough Device Program, this precedent could affect medical products under review whose data does not align with the arguments made in the designation request. This same criterion could be applied to any changes in device design or indications for use that call the breakthrough designation into question.
As more breakthrough devices come to fruition, sponsors will have a clearer picture of FDA’s handling of breakthrough designations in the marketing application review process. For sponsors seeking to maintain their breakthrough device designation post-marketing authorization, it is important to design and execute clinical studies with the potential to generate data that support the breakthrough device designation argument. Further, consider including a rationale for maintaining the designation in the marketing application. Understand what claims were made in the breakthrough designation request and whether those claims are supported or refuted by incoming non-clinical and/or clinical data, device design changes, or changes to the proposed indications for use.
Resources
Palmer Smith is a Regulatory Affairs associate at MCRA, supporting and advising clients in the completion of various regulatory submissions, specifically for spine and orthopedic implants, as well as wound care products. Palmer has supported projects including Breakthrough Device Designation requests, Investigational Device Exemptions, 510(k)s, Pre-Submissions, De Novos, Premarket Approvals (PMAs), and European Clinical Evaluation Reports. Palmer attended Clemson University and earned a master’s degree in biomedical engineering with a concentration in biomaterials.
The Breakthrough Devices Program consists of two phases. The first is the Designation Request phase, in which an interested medical device manufacturer elicits Breakthrough Device Designation from the FDA through Q-submission. The second phase refers to the benefits and opportunities open to BDD sponsors that expedite development and facilitate review of the subject medical device. The designation itself provides an opportunity for sponsors to showcase the novelty and clinical promise of their device to investors and the public. The substantive benefits of a breakthrough device designation, however, stem from the second phase, when the sponsor is actively working towards clearance or market approval.
As of June 30, CDRH and CBER have granted 693 Breakthrough Device designations, including devices originally designated under the Expedited Access Pathway (EAP) program. Of those, “cardiovascular” has been granted 163, “neurology” has received 126, and “orthopedic” has been given 77. Other clinical panels granted designations include “gastroenterology and urology,” “general and plastic surgery,” and “immunology.” It is easy to see why the FDA has had success eliciting breakthrough device designation requests from medical device manufacturers—the program offers multiple benefits designed to provide for an efficient and effective review process, according to an FDA guidance. In summary, the program boasts:
- Interactive and timely communication
- Pre/post-market balance of data collection
- Efficient and flexible clinical study design
- Review team support
- Senior management engagement
- Priority review
- Manufacturing considerations for PMA submissions
Rather than being dictated by the review timelines established in the Q-Submission Guidance, these submissions require sponsors propose an interaction schedule with a defined end data (e.g., 45 days). As such, sprint submissions typically elicit FDA feedback and teleconferences earlier than a normal Q-Submission. (The sponsor's timelines in the sprint submission are subject to change based on FDA workload, but the agency tries its best to uphold the timelines). These submissions, however, are limited to one general topic (e.g., proposed non-clinical testing battery) and specific goals within that topic (e.g., determine primary endpoint evaluation for pivotal study). FDA works to provide feedback limited to those specific goals in the Q-Submission review process. But sponsors that want to engage FDA on multiple topics within one submission can submit a pre-submission per Q-Submission Guidance and request it be tracked as an “Interaction for Designated Breakthrough Device”; as such, a review team will prioritize the submission and work with its sponsor to develop a feedback timeline commensurate with commitments specified as part of the 2017 Medical Device User Fee Amendments.
Other key Breakthrough Device Program benefits include:
- Data Development Plan (DDP): Sponsors may coordinate with the agency regarding a DDP—a high-level document intended to help ensure predictable, efficient, transparent, and timely device assessment and review by outlining data collection expectations for a product’s entire lifecycle (including pre-and post-market authorization).
- Clinical Protocol Agreement: Sponsors can obtain a written agreement from the agency for clinical protocols that will be considered binding to both the sponsor and the FDA; any changes to previous protocols must be agreed upon in writing by FDA, the sponsor, and the director of the office responsible for reviewing the device—as long as the latter determines that a substantial scientific issue exists that is essential to determining the safety and effectiveness of the device.
- Regular Status Updates: FDA and the sponsor may agree to have regular status updates where the parties can discuss general progress of the project and next steps or plans for future discussions.
A breakthrough designation suggests the FDA agrees the subject device demonstrates a reasonable expectation in providing for more effective treatment or diagnosis of life-threatening or irreversibly debilitating diseases or conditions at the time of the request. The “reasonable expectation of more effective treatment or diagnosis” is a combination of design considerations and/or non-clinical and clinical data that show the device meets the required designation criteria.
Typically, manufacturers will elicit a breakthrough designation before generating the non-clinical and clinical data necessary for a marketing authorization submission or before finalizing the product’s indications for use/intended use, as these are informed by captured non-clinical and/or clinical data. As such, the arguments made in the designation request may not hold true at the time of a marketing application because only the full battery of data, and the indications for use it supports, paint the full image of the subject device.
The extent to which FDA will re-evaluate a breakthrough device designation at the time of marketing authorization submission remains to be seen. In June, FDA released a draft guidance outlining considerations for rescinding breakthrough therapy designation. One of the reasons given is “emerging data for the designated drug no longer support a finding that preliminary clinical evidence indicates the drug may demonstrate substantial improvement over existing therapies.” If carried over to the Breakthrough Device Program, this precedent could affect medical products under review whose data does not align with the arguments made in the designation request. This same criterion could be applied to any changes in device design or indications for use that call the breakthrough designation into question.
As more breakthrough devices come to fruition, sponsors will have a clearer picture of FDA’s handling of breakthrough designations in the marketing application review process. For sponsors seeking to maintain their breakthrough device designation post-marketing authorization, it is important to design and execute clinical studies with the potential to generate data that support the breakthrough device designation argument. Further, consider including a rationale for maintaining the designation in the marketing application. Understand what claims were made in the breakthrough designation request and whether those claims are supported or refuted by incoming non-clinical and/or clinical data, device design changes, or changes to the proposed indications for use.
Resources
- www.fda.gov/medical-devices/how-study-and-market-your-device/breakthrough-devices-program#s9
- https://www.fda.gov/media/108135/download
- Considerations for Rescinding Breakthrough Therapy Designation (fda.gov)
Palmer Smith is a Regulatory Affairs associate at MCRA, supporting and advising clients in the completion of various regulatory submissions, specifically for spine and orthopedic implants, as well as wound care products. Palmer has supported projects including Breakthrough Device Designation requests, Investigational Device Exemptions, 510(k)s, Pre-Submissions, De Novos, Premarket Approvals (PMAs), and European Clinical Evaluation Reports. Palmer attended Clemson University and earned a master’s degree in biomedical engineering with a concentration in biomaterials.