New FDA Program to Expedite the Approval of 'Breakthrough' Medical Devices

The US Food and Drug Administration (FDA) has put the finishing touches on two policies intended to expedite access to potentially life-saving devices meant for patients with life-threatening diseases or conditions.

Background

FDA's Center for Devices and Radiological Health (CDRH) has for several years been putting the finishing touches on two conceptually related guidance documents:

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

The documents collectively outline a policy by which CDRH says it will allow some medical devices to be approved more quickly and with less data than it would ordinarily require of similar devices. Similar programs, including FDA's accelerated approval pathway, already exist to expedite the approval of pharmaceuticals.

Understanding the EAP

The first guidance document establishes FDA's "Expedited Access Pathway" program, or EAP in the agency's abbreviated parlance. As explained in FDA's April 2014 draft guidance document, the EAP is intended to "help assure predictable, efficient, transparent and timely device assessment and review."

Read our extensive explanation of the draft guidance document here.

As with FDA's accelerated approval pathway, an approval through the EAP will rely on less evidence than would ordinarily be required for approval. In return, FDA will require the sponsor of the approval EAP device to conduct rigorous post-market surveillance and studies on its product to ensure it is as safe and effective as was intended. FDA's requirements and philosophy toward this postmarket collection of data are explained at length in its second guidance, Balancing Premarket and Postmarket Data Collection for Devices Subject to Premarket Approval.

More on FDA's data collection requirements here.

Also similar to FDA's accelerated approval process will be the limitations on the types of devices which may participate under the program. FDA's guidance says it will only permit devices which are "intended to treat or diagnose a life-threatening or irreversibly debilitating disease or condition." In addition, the device will need to meet at least one of four criteria:

• The device represents a breakthrough technology that provides a clinically meaningful advantage over existing legally marketed technology.
• No approved alternative treatment or means of diagnosis exists.
• The device offers significant, clinically meaningful advantages over existing legally marketed alternatives.
• The availability of the device is in the best interest of patients (e.g., addresses an unmet medical need).

EAP Details: Who and How

The pathway will also accept either Premarket Approval Applications (PMAs) or requests for de novo classification (i.e. a previously unapproved device that is not perceived to be high-risk). FDA's guidance says it will not accept 510(k) applications through its EAP. That's because once one 510(k)—also known as a premarket notification—is approved, it can serve as the basis for other 510(k) approvals by becoming what is known as a "predicate" device. FDA's guidance explains it doesn't want EAP devices serving as predicates until they are shown (through postmarket monitoring) to be safe and effective.

De novo products are "not eligible for the full scope of the EAP program," FDA noted.

Combination products, meanwhile, may qualify for review under the EAP, but the qualification will depend upon the combination device's primary mode of action (PMOA), FDA said. Companies interested in qualifying their combination product for the EAP should contact FDA "as early as possible," FDA said.

Devices approved through FDA's EAP will also need to demonstrate "reasonable" assurance that a device is safe and effective for its proposed indication. While FDA concedes there "is never 100% certainty when determining reasonable assurance of safety and effectiveness of a device," it still wants the preponderance of the evidence to indicate patients will likely benefit.

FDA's EAP will also bring in other elements familiar to the pharmaceutical sector, including "a more interactive communications" process and "a more interactive review" of a device's clinical trial applications, which are known as Investigational Device Exemptions (IDEs). Devices given EAP designation will also be eligible for priority review under Section 515(d)(5) of the Federal Food, Drug and Cosmetic Act, FDA said.

Sponsors will need to explicitly request EAP Designation and agree to a data development plan prior to participating in the program, FDA's guidance document states.

Other EAP Requirements

EAP designation will not be available to every company or every device, FDA explains in its guidance. Companies will need to meet certain conditions of participation, including:

• Premarket (clinical or non-clinical) data demonstrate that the probability of serious harm is low.
• Postmarket patient exposure to the device prior to the required submission of postmarket data to FDA will be small.
• The sponsor has a proven track record of a robust quality system.
• A Data Monitoring Committee (also called Data and Safety Monitoring Board) will be used in the postmarket study to evaluate adverse events.
• User training to help mitigate the probable risks of the device, which is described in the proposed labeling for the device.
• The sponsor will provide patient labeling.
• There is valid scientific evidence to demonstrate that the intended patient population is willing to tolerate the probable harm of the device in light of the level of uncertainty about the probable benefits and/or probable risks of the device.
• There is a high likelihood that postmarket surveillance can quickly identify instances of serious patient harm.
• There is a high likelihood that the required postmarket data collection will be completed in a timely manner.
• The proposed postmarket data study is well-designed and feasible, taking into account the likelihood that patients will participate in the study once the device has been approved.

FDA added that, like its accelerated approval program for pharmaceuticals, its EAP program will consider surrogate and intermediate endpoints.

The EAP program will be open for participation as of 15 April 2015, CDRH Director Jeffery Shuren said in a blog posting on FDA's website.