CRT: FDA sheds light on percutaneous heart valve approval process

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WASHINGTON, D.C.—Sonna M. Patel-Raman, of the FDA’s Center for Devices and Radiological Health, explained the FDA application process for new medical devices, such as transcatheter heart valves, from pre-submission to investigational device exemption (IDE) to application submission during a Feb. 6 presentation at the Cardiovascular Research Technologies (CRT) meeting.

The role of the FDA is to ensure that the intended uses, labeling and packaging of medical devices are “truthful and informative,” according to Patel-Raman, but the FDA’s job is a “balancing act” in evaluating the benefits and risks.

On the benefit side, the FDA wants “to ensure that we’re getting safe and effective devices to the U.S. market as quickly as possible, and ensure that the devices already on the market remain safe and effective,” said Patel-Raman, adding that this is where pre- and post-market studies become important.

The FDA uses a risk-based paradigm to classify devices, and transcatheter heart valves are designated as Class III devices.

Generally, the pre-submission pathway is the first step in gaining FDA approval. Patel-Raman said that the term pre-submission will be used “more often, because it has replaced the pre-IDE process.” The pre-submission process is a time in which any topic can be addressed with regards to the technology being submitted. 

For the example of a pre-submission application for transcatheter heart valves, she suggested that the FDA would expect to see preclinical testing summaries, a clearly defined patient population expected to be enrolled in the study, specific endpoints (including vascular complications, neurological events and/or hospitalization) and a statistical analysis plan with the proposed hypothesis.

After the pre-submission process and the IDE is ready to be submitted, the FDA is interested in some “key components of the clinical study,” according to Patel-Raman. This woulde include trial conduct, utilization of pre-specified event risk definitions and consideration of a registry to capture data on smaller subgroups of data that the study may not be powered for, such as valve-in-valve and severe mitral regurgitation. Also, if there are changes from the pre-submission process, the IDE submission process is the time to discuss those changes with the FDA.

When the IDE is completed, the labeling of the device needs to “accurately reflect the clinical data collected during the IDE study,” she said. After this, there are two applications for approval: pre-market application, in which the device must demonstrate a reasonable assurance of safety and effectiveness, or humanitarian device exemption (HDE), in which the data need to demonstrate a reasonable assurance of safety and probable benefit.

“What is unique about an HDE is that you first need to submit a humanitarian use designation to the Office of Product Development, and demonstrate to that office that the device is intended to treat a patient population of less than 4,000,” she said.

In her conclusion, Patel-Raman encouraged anyone seeking to submit new transcatheter heart valves for approval to engage with the FDA “early and often” before the IDE is even begun, and throughout the IDE process.