The Food and Drug Administration (FDA) released a draft guidance on April 23, 2014 titled Expedited Access for Premarket Approval [of] Medical Devices Intended for Unmet Medical Need for Life Threatening or Irreversibly Debilitating Diseases or Conditions - Draft Guidance for Industry and Food and Drug Administration Staff 1 and is accepting comments through July 22, 2014.2 In the draft guidance, the FDA proposes the Expedited Access PMA Program (the “EAP Program”), which is a voluntary program intended to expedite Premarket Approval of medical devices that address unmet medical needs for “life threatening or irreversibly debilitating diseases or conditions.” The goal is to provide patients with more timely access to these medical devices (“EAP Devices”).
Device sponsors must request participation in the EAP Program, which is subject to FDA approval of the EAP Designation. The request should be submitted to the Agency in a Pre-Submission (“Pre-Sub”) in accordance with the Guidance for same, Requests for Feedback on Medical Device Submissions: The Pre-Submission Program and Meetings with Food and Drug Administration Staff. Generally, the sponsor should submit the Pre-Sub EAP Designation request “prior to commencement of an IDE pivotal study.” The Pre-Sub should include a “discussion of why the device meets the EAP criteria” and a Draft Development Plan, discussed below.
The following are the criteria for EAP Designation:
1. The device is intended to treat or diagnose a life-threatening or irreversibly debilitating disease or condition.
2. The device meets at least one of the following criteria for addressing an unmet need:
a. The device represents a breakthrough technology that provides a clinically meaningful advantage over existing technology.
b. No approved alternative treatment or means of diagnosis exists.
c. The device offers significant, clinically meaningful advantages over existing approved alternatives.
d. The availability of the device is in the best interest of patients (e.g., addresses an unmet medical need).
3. The sponsor submits an acceptable draft Data Development Plan.
The FDA will issue written notification of its determination of whether it is granting EAP Designation. If the FDA grants the EAP Designation request, the Agency intends to provide the EAP Device sponsor with an FDA point of contact for Agency interaction.
The FDA intends to execute the EAP Program through “more interactive communications” and interactive planning and development between the EAP Device sponsor and the Agency. For example, the FDA proposes to work with sponsors to create a Data Development Plan that would detail (1) all clinical and nonclinical data required for approval, premarket, and postmarket, (2) a timeline to expedite the introduction of the device to market, and (3) proposed labeling.
In accordance with the requirements of the Food, Drug, and Cosmetic Act (the “FDCA”), the FDA will seek the “least burdensome appropriate means of evaluating device effectiveness” to obtain device approval. The FDA anticipates accepting less certainty with regard to the benefit-risk profile of EAP Devices at the time of PMA and approving the EAP Device if data supports a “reasonable assurance of safety and effectiveness.”
It also anticipates accepting less certainty by relying on “assessments of a device’s effect on an intermediate or surrogate endpoint that is reasonably likely to predict clinical benefit.” The FDA defines the term “intermediate endpoint” as “a measurement of clinical benefit or risk concerning a symptom or measure of function that is not the ultimate outcome of the disease.” Examples of intermediate endpoints include, but are not limited to, symptoms of hyperglycemia or angina frequency. The FDA defines “surrogate endpoint” as “a substitute which is reasonably likely to predict clinical benefit, based on epidemiologic, therapeutic, pathophysiologic or other scientific evidence.”
“The types of measurements which may be used as a surrogate endpoint are in vitro laboratory or medical imaging measurements, or physical signs (e.g., blood pressure measurements in trials of antihypertensive therapeutics, as a surrogate for clinical endpoints such as stroke, myocardial infarction, or mortality).” The FDA intends to utilize postmarket requirements, such as post-approval studies, to establish the more complete benefit-risk profile. Therefore, the FDA may condition the PMA of EAP Devices on postmarket requirements.
Additional conditions of PMA may include post-approval non-clinical studies, “continuing evaluation and periodic reporting on safety, effectiveness, and reliability,” and restrictive labeling that may be updated “to reflect the population and condition for which a clinical benefit was directly established in the post-approval stud(ies).”
The FDA may forgo premarket inspection of manufacturing facilities as part of the EAP Program. However, if an inspection is not conducted premarket, the Agency will conduct the inspection within the first twelve (12) months of device approval.
The FDA may revoke EAP Designation on written notice to the EAP Device sponsor if the Agency concludes any of the following:
The information submitted in support of a request for EAP Designation, including, without limitation, the Pre-Sub package, or any related premarket submission contained an untrue statement of material fact or omitted material information, including false statements relating to data collection; or
Based on evidence available, the device is no longer eligible for an EAP Designation according to the EAP criteria ….
The FDA may withdraw PMA if the Agency subsequently concludes any of the following:
On the basis of the data from the required post-approval study(ies), or other new information with respect to such device, evaluated together with the evidence available to FDA when the PMA application was approved, FDA finds that there is a lack of a showing of reasonable assurance that the device is safe or effective under the conditions of use
prescribed, recommended or suggested in the labeling;
The sponsor fails to meet any post-approval requirement imposed by the PMA approval order…; or
On the basis of new information, evaluated together with the evidence available to FDA when the PMA was approved, FDA finds that the labeling, based on a fair evaluation of all material facts, is false or misleading … and such labeling is not corrected within a reasonable time after receipt of written notice from FDA.
Prior to withdrawing a PMA, FDA will afford an opportunity to the EAP Device sponsor to voluntarily request withdrawal.
The FDA is requesting comments to the Draft Guidance by July 22, 2014. The EAP Program will assist to address unmet medical needs for life threatening or irreversibly debilitating diseases or conditions.
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