New FDA CDRH Final Guidances Present New Opportunities for Sponsors

On April 13, 2015, the Food and Drug Administration’s (FDA) Center for Devices and Radiological Health (CDRH) issued two final guidance documents based on draft guidances issued last year:

  1. Balancing Premarket and Postmarket Data Collection for Devices Subject to Premarket Approval
  2. Expedited Access for Premarket Approval and De Novo Medical Devices Intended for Unmet Medical Need for Life Threatening or Irreversibly Debilitating Diseases or Conditions

These two documents together represent the Agency’s current thinking on when data collection might be pushed from pre-approval to post-approval, with the second guidance focused on devices where there is a significant unmet medical need. The following is a summary of the information provided and recommendations for Sponsors looking to take advantage of opportunities to achieve earlier and less expensive medical device approval.

The first guidance does not appear to introduce any novel ideas, but rather reflects how CDRH has been utilizing postmarket data collection in recent years. Multiple examples are provided to describe types of data or situations where postmarket data collection is appropriate.

This guidance includes a brief discussion of the use of data collected outside the US, which may indicate increased flexibility in the type of data needed to establish safety and effectiveness of medical devices. The guidance describes the possibility of obtaining approval based on “long-term outside the US (OUS) clinical performance data” that is then either supplemented by limited clinical data collection from US patients prior to approval or US data collected post-approval. Sponsors who have tried this approach in the past should re-engage with their review branch in order to see if OUS data can be used to limit the US data development program. CDRH recommends that Sponsors submit a Pre-Submission (Pre-Sub) outlining and justifying the proposal for pre- and post-approval data collection.

The second guidance represents a significant opportunity for Sponsors to leverage a new CDRH program to gain earlier approval for their device or device modification. In this final guidance, CDRH introduces the Expedited Access Pathway (EAP) that is specifically for devices that address “unmet medical needs for life threatening or irreversibly debilitating diseases or conditions.” If a device is accepted in this pathway, the benefits appear to be significant, including:

  • More interactive review from FDA during both the IDE and PMA processes
  • Greater participation of Agency management
  • Case manager involvement where appropriate
  • Priority review
  • The opportunity to reduce manufacturing information requirements and push manufacturing inspections to after approval

However, the greatest potential benefit is the opportunity to work with the Agency on a mutually agreeable Data Development Plan, which identifies data to be collected premarket and postmarket. The goal of this plan is to identify data that can be gathered post-approval rather than pre-approval in order to significantly reduce the “time and cost from device development to FDA marketing decision.”

Inclusion in this program could lead to a product gaining approval one to two years earlier, with a significant proportion of the development costs pushed to the post-approval setting, where they can be balanced by commercial revenue. Because of this, Sponsors should be evaluating each development program to see if there is any opportunity to participate. To participate, the device or device modification has to fulfill these three criteria:

  • 1. Intended to treat or diagnose a life-threatening or irreversibly debilitating disease or condition
  • 2. Meet at least one criteria for addressing an unmet need
    • a. No appropriate alternative treatment or means of diagnosis exists
    • b. Breakthrough technology that provides a clinically meaningful advantage over existing legally marketed technology
    • c. Clinically meaningful advantages over existing legally marketed alternatives (may include superiority over current treatments for effects on serious outcomes, substantially less risk, addressing a known and important shortcoming, or ability to provide clinical benefit to patients unable to tolerate current treatments)
    • d. Availability of device is in the best interest of patients (e.g., addresses an unmet medical need)
  • 3. Sponsor submits an acceptable draft Data Development Plan

One open question with this program is how CDRH will handle Advisory Committee meetings (referred to as Panel meetings for medical devices). Devices that qualify for this program will almost certainly meet the criteria for a Panel meeting, yet Sponsors will not have generated the level of data that panelists are accustomed to seeing. The guidance is silent on this consideration, except to note that Panels can be used to evaluate data collected after approval for implications to labeling or the assessment of safety and effectiveness. Panels are currently used for this process, so this does not appear to be a unique feature of this program.

As an example of how this program could lead to earlier approval, consider a device that would typically require two years of clinical data before PMA submission. If the Sponsor can justify the approach, CDRH could accept the PMA for review with only six months of data while data collection continues through two years. Sponsors may also be able to better leverage OUS data and push collection of US data to the post-approval setting. Finally, CDRH may be more open to the use of surrogate endpoints or patient reported outcomes as the primary measures of effectiveness if there is a data-driven justification for doing so.

As with the first guidance, the second guidance recommends that interested Sponsors submit a Pre-Sub meeting request, including a detailed Data Development Plan. CDRH commits to providing feedback within 30 days on whether or not to grant EAP designation.

At this point, there does not appear to be a downside to participation in the EAP program; in fact, Sponsors should move quickly to submit proposals to participate as there are limited resources within CDRH to support this program. If your device is one that seems to be in the gray area – it may qualify, but it is not clear – begin a discussion with your review branch in order to assess participation criteria for your specific device type. Even if current projects don’t qualify, future projects should be continually assessed, as the program is intended to be ongoing if successful. Also, if accepted, Sponsors should be sure to have internal accelerated review processes so that they are able to match their reviewers’ attention and urgency. For smaller companies, this is not likely to be an obstacle, but could be an important consideration for larger companies with more rigid management review requirements.

The release of these two final guidance documents demonstrate CDRH’s current focus on their mission to provide patients and providers “timely and continued access to safe and effective and high quality medical devices.” Even an informal discussion with CDRH could provide insight into important opportunities for Sponsors to accelerate time to approval, while reducing costs pre-approval.



Amy TezelPhD, combines her extensive scientific background, regulatory experience across the entire FDA approval process, and an ability to communicate effectively to prepare clients for success. Amy’s experience in medical devices spans from pre-IDE, IDE, and PMA preparations to FDA advisory committee meetings and post-approval commitment negotiations. Amy is a former 3D employee, now at Alcon.