Welcome to our new website! If this is the first time you are logging in on the new site, you will need to reset your password. Please contact us at firstname.lastname@example.org if you need assistance.
Your membership opens the door to free learning resources on demand. Check out the Member Knowledge Center for free webcasts, publications and online courses.
Hear from leaders around the globe as they share insights about their experiences and lessons learned throughout their certification journey.
Posted 22 April 2014 | By Alexander Gaffney, RAC,
The US Food and Drug Administration (FDA) has released a long-awaited draft guidance document outlining an expedited approval pathway that can be used by sponsors of medical devices intended to treat life-threatening or "irreversibly debilitating" diseases or conditions.
The guidance, which for months has been rumored to be near completion, introduces the "Expedited Access Premarket Approval" program, or EAP for short. Regulatory officials said it is a continuation of FDA's earlier Innovation Pathway, a 2011 initiative meant to fast-track innovative medical devices.
FDA said it believes the program "will help patients have more timely access to these medical devices by expediting their development, assessment and review, while preserving the statutory standard of reasonable assurance of safety and effectiveness for premarket approval."
The program will involve sponsors and FDA working closely together, both to communicate and resolve issues as they arise and in the development of a "data development plan specific to the device" that will outline the clinical data that the sponsor intends to use in support of the device's approval and when that data will be collected (premarket or postmarket).
FDA called that data development plan a key aspect of the EAP, as it will "help assure predictable, efficient, transparent and timely device assessment and review." Especially crucial will be determining which data can be collected after the device is granted approval.
"Getting the right balance between premarket and postmarket data collection-specifically, where appropriate, a greater reliance on postmarket collection-can reduce the extent of premarket data submission and directly impact when patients will have access to high-quality, safe and effective medical devices," FDA wrote.
While the exact degree of certainty FDA requires to ensure that a healthcare product is safe and effective is difficult to quantify, and has been the bane of more than a few drugs and biological products seeking expedited approval, FDA said it would approve EAP devices if "uncertainty is sufficiently balanced by other factors," such as the device's likely benefit, controls on the device's use, and the benefit of early access to the device by patients.
FDA's guidance document, Expedited Access for Premarket Approval Medical Devices Intended for Unmet Medical Need for Life Threatening or Irreversibly Debilitating Diseases or Conditions, goes on to explain the requirements for participating in the EAP.
Sponsors will first need to request a designation from FDA that their device is an "EAP Device," known as "EAP Designation." If FDA grants that designation, the sponsor and FDA will then negotiate a Data Development Plan, which will lead to the submission and review of a premarket application (PMA) for the EAP Device.
If approved, FDA will then require robust postmarket data collection and evaluation.
Interestingly, FDA said it may, "at its discretion," permit device manufacturers to "provide less manufacturing information in their PMA application," or even skip premarket inspections of manufacturing sites. Those have traditionally been hurdles for manufacturers looking to bring their products to market very quickly, as sites are required to be inspected by FDA prior to a product coming to market. While FDA didn't say it would waive the requirements in all cases, some manufacturers-those with well-established manufacturing operations that have been inspected recently and without a Warning Letter or 483-might stand to benefit most of all. FDA said it will instead inspect the facilities soon after product approval.
Continuing approval of the devices will also depend on the sponsor meeting postmarket data collection commitments-an important requirement given the incomplete data FDA may be basing its approval decisions on.
Which devices qualify for "EAP Designation" as an "EAP Device?"
First, the device must be "intended to treat or diagnose a life-threatening or irreversibly debilitating disease or condition." While the definition of "life-threatening" is defined in the guidance and is relatively straightforward, the definition of "irreversible debilitating" contains some interesting leeway for sponsors.
For example, while FDA says that "short-lived and self-limiting" morbidities will not qualify a condition or disease for EAP status, "persistent or recurrent" conditions or diseases may qualify based on their debilitating (and perhaps cumulative) effects.
"Whether a disease or condition is "irreversibly debilitating" is based on its impact on such factors as survival, day-to-day functioning, and the likelihood that the disease or condition, if left untreated, will progress to a more serious disease or condition," FDA explained.
The second major qualification factor for EAP status is that the device needs to meet at least one of four criteria:
The fourth of these points includes several sub-considerations, such as whether the device can avoid major harms that exist with presently available therapies, whether the new device can improve adherence to therapies, or whether it can reduce adverse interactions which occur with other therapies.
FDA made clear that IVDs are eligible for this pathway, and may find their justification through this fourth criteria.
Third and finally, EAP status is contingent upon the submission of a data development plan, which must contain a description of data sufficient to determine if there is a reasonable assurance of safety and effectiveness. For example, a selected surrogate endpoint would need to be reasonably likely to predict clinical benefit in patients, FDA wrote.
The plan should also include a timeline for postmarket data collection.
FDA said it intends to accept surrogate endpoints, intermediate endpoints, smaller clinical trials, quicker clinical trials, and companion diagnostics to help bring devices to market more quickly. The acceptable use of each of these metrics is discussed at length in the guidance.
FDA also said it will take into account 10 factors when evaluating the probable benefit-risk ratio of a device:
Based on the data limitations, FDA said it may improve "certain labeling requirements" on the devices to explain to consumers the limitations of the data on which its approval was based. FDA recently approved a similar guidance document for drugs approved under expedited approval pathways.
In a statement, FDA regulators were quick to say that the EAP is "not a new pathway to market," but is instead meant to be a "collaborative approach to facilitate product development" using existing regulatory authority granted to it by Congress. "While other existing device programs have focused on reducing the time for the premarket review, EAP also seeks to reduce the time associated with product development," FDA explained.
However, EAP designation will afford companies an interactive review with FDA to support a "least burdensome" approach to development and regulatory review, priority review status, and potentially the involvement of senior FDA management officials and a cross-disciplinary case manager.
What remains to be seen is industry's interest in the programs, and whether FDA can support that interest. In the pharmaceutical sector, FDA's expanded use of expedited access programs has led to a slow decline in approval times as more and more products seek market access through the programs. Because the reviews require more FDA resources than traditional reviews, that means slower approvals for other applications seeking expedited approval. FDA may ultimately need additional resources to support the EAP program if it attracts similar amounts of interest from device manufacturers.
What also remains to be seen: Whether devices sponsors will meet their end of the bargain in collecting data in postmarket settings. It sometimes becomes difficult to enroll patients in trials once a product has been approved, meaning some sponsors-even those that try to collect data-may be unable to meet FDA's requirements, or meet them in the agreed-upon time. Whether FDA will be flexible or will readily revoke approval for devices which fail to obtain the agreed-upon data will be a major point to watch going forward.
FDA will be accepting comments on the guidance for 90 days.
Expedited Access for Premarket Approval Medical Devices Intended for Unmet Medical Need for Life Threatening or Irreversibly Debilitating Diseases or Conditions (FR)
FDA Press Statement on the EAP Program
Tags: EAP Device, EAP Designation, Expedited Access PMA, EAP, Expedited Approval, Latest News, PMA, draft guidance, guidance, medical device
Regulatory Focus newsletters
All the biggest regulatory news and happenings.