CDRH Announces Expedited Access PMA Program to Speed Development and Approval of Devices that Treat or Diagnose a Life-Threatening or Debilitating Disease and Meet an Unmet Medical Need

By Jamie K. Wolszon –

Earlier this month, FDA’s Center for Devices and Radiological Health (“CDRH”) announced a new voluntary “expedited access premarket approval (“PMA”) program” intended to speed development and approval of devices that treat or diagnose a life-threatening or debilitating disease and fulfill an unmet medical need.  Among other provisions, the Expedited Access PMA (“EAP”) program, which is detailed in an FDA guidance, would embrace the use of intermediate or surrogate endpoints combined with additional reliance on post-market data, and a possible reduction in manufacturing information required in the PMA application, as well as moving the preapproval inspection of the facility to post-approval.

The program also would provide for eligible applicants: interactive review of device development, including a Data Development Plan; senior CDRH management involvement; a case manager; and priority review.

CDRH already has established an expedited review program (also known as priority review).  Under that expedited review program, PMA applications that meet the requisite criteria are placed at the beginning of the appropriate review queue and receive additional review resources.  This new expedited access PMA program, which is modeled on the drug accelerated approval and breakthrough therapies provisions, would broaden CDRH’s efforts to expedite development and approval. 

Devices eligible for the program would need to meet the same criteria as those for CDRH’s currently existing expedited review program.  Those criteria are as follows: The device is intended to treat or diagnose a life-threatening or irreversibly debilitating disease or condition, and addresses an unmet medical need.  FDA defines an unmet medical need as one of the following: The device represents a breakthrough technology that provides a clinically meaningful advantage over existing technology; no approved alternative treatment or means of diagnosis exists; the device offers significant, clinically meaningful advantages over existing approved alternative treatments; or the availability of the device is in the best interest of patients. FDA provides in the guidance examples and explanation for each criterion. 

The program would allow FDA to rely on “assessments of a device’s effect on an intermediate or surrogate endpoint that is reasonably likely to predict clinical benefit (on the condition that remaining uncertainty about the predictive relationship between a surrogate and clinical benefit is minimized through confirmatory post-approval studies or on the condition that clinical benefit is verified through confirmatory post-approval studies).”  A surrogate endpoint, as described in the guidance, is “not itself a measure of clinical benefit, but is used in trials 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 program includes increased reliance on post-market data.  As explained in the guidance, “FDA may accept less certainty regarding the benefit-risk profile of these devices at the time of premarket approval, and approve an EAP Device, as long as the data still support a reasonable assurance of safety and effectiveness. That is, FDA intends to approve an EAP Device if the uncertainty is sufficiently balanced by other factors, including the probable benefits of the device, the probable benefits of earlier patient access to the device, and postmarket controls, to support premarket approval.”  CDRH also issued a corresponding guidance on post-market data.

One interesting aspect of the EAP program relates to the possibility of reduced manufacturing information in the PMA application.  PMA applications must provide extensive design, manufacturing, and labeling information, and FDA generally inspects the facility that will manufacture the device prior to approval of the device.  Providing this information involves significant preparation.  Under the program, on a case-by-base basis, CDRH would allow a sponsor to provide less manufacturing information in their PMA application, when the sponsor has a good track record for quality systems and there are not new, unique manufacturing issues that could adversely impact product quality or performance.

Moreover, FDA may also at its discretion, forgo preapproval inspection of certain manufacturing sites and instead conduct those inspections after product approval, in which case it would inspect the facility within twelve months after approval. The guidance details factors the agency would consider in deciding whether to forgo preapproval inspection.

Participation in the EAP program is only at the request of the sponsor and with FDA’s agreement. CDRH outlines a four-step process that would include: (1) a request for designation as an EAP Device (an “EAP Designation”); (2) agreement upon a Data Development Plan; (3) review of a PMA application for an EAP Device; (4) If approved, postmarket data collection and evaluation.

Comparable Drug Provisions.  As mentioned above, the EAP PMA program is modeled on drug breakthrough therapies and accelerated provisions for drugs that treat serious conditions and meet other criteria (see our previous post here). 

Breakthrough Therapies: The drug breakthrough therapies program was created by the Food and Drug Administration Safety and Innovation Act ("FDASIA") that was signed into law on July 9, 2012.  The benefits of breakthrough therapy designation include the features of fast track designation (described below), “intensive” guidance on developing an efficient drug development program, beginning as early as Phase 1, and organizational commitment from FDA involving senior managers.

Accelerated Approval: Accelerated approval provides for drug approval based on an effect on a surrogate or intermediate clinical endpoint that is reasonably likely to predict a drug’s clinical benefit.

Fast-Track: The fast-track program includes frequent interactions with the FDA drug review team, priority review, and rolling review.