FDA Approvals for Tweaked High-Risk Devices Need Revamping

March 24, 2014

SAN FRANCISCO, CA — The US Food and Drug Administration's (FDA's) premarket approval (PMA) pathway, which allows currently approved medical devices to undergo modifications without the need for a rigorous review, needs to be changed, says one critic of the process[1].

According to Dr Rita Redberg (University of California, San Francisco), the existing PMA supplement pathway, which is the process required by the FDA for alterations "affecting the safety and effectiveness of the device for which the applicant has an approved PMA," needs to be changed so that clinical data are more commonly submitted as part of the PMA supplement.

"Some devices have hundreds of PMA supplements," said Redberg. "One of major challenges is that these changes can be iterative, with literally changes on top on changes, so that you have a device that looks very different from the original device. I understand the critical importance of trying to get these devices on the market, but if there turns out that there is a problem with the new design, these things are not like cars or trucks on the market. They're implanted in people. We can't just get them back."

Writing in the "Ideas and Opinions" section of the March 25, 2014 issue of Annals of Internal Medicine, Redberg, along with coauthor Sarah Zheng (University of California, San Francisco), state that high-risk medical devices (class III), "those that support or sustain human life," are generally approved by the FDA with a PMA that requires the submission of clinical data to assess safety and effectiveness.

However, as Redberg points out, changes to the device can be approved with a PMA supplement, a process that does not require the same level of evidence. In order to allow for quick approval of design improvements, the PMA supplement allows for changes to the device without the need for device manufacturers to undergo another rigorous PMA. This PMA supplement pathway allows for improvements or minor changes to the device and has fewer evidence requirements than the original PMA.

Multiple PMA Supplements With One Device

To heartwire , Redberg said nearly all medical devices approved with a PMA, everything from knee replacements to infusion pumps, often have multiple supplements attached to the original PMA. The companies usually submit changes to the device one supplement at a time instead of submitting multiple changes to the device in one application, a process that allows each change to be reviewed separately.

These things are not like cars or trucks on the market; they're implanted in people. We can't just get them back.

However, approving such design improvements of existing devices in this way can introduce previously unknown risks to the patients. For example, Redberg cites the Sprint Fidelis defibrillator lead (Medtronic, Minneapolis, MN), a lead that underwent changes to the original via several PMA supplements. None of the changes required the submission of clinical data, and yet the final iteration of the Fidelis lead differed substantially from the lead design originally approved. The Fidelis lead was ultimately recalled because of an increased risk of lead fractures, which was previously reported by heartwire .

Similarly, 20 models of the Riata (St Jude Medical, St Paul, MN) family of defibrillator leads received approval for changes with six PMA supplements. These leads were also recalled because of a high rate of failure in the outer insulation layer.

To heartwire , Redberg said she began to look more closely at the process of PMA supplements around the time of the Fidelis and Riata recalls. Looking at the approval process, she noted that the leads had undergone numerous changes to the original device and that these changes had been approved via PMA supplements.

"The PMA supplement pathway encompasses a lot of different things, and it's designed to allow manufacturers to make small improvements to the devices without having to go through the laborious PMA process," said Redberg. "It can include anything from a small label change, a change in the color of different parts, to something clinically meaningful like a change in the design of the device."

Asked about the issues raised by Redberg, Janet Trunzo, senior executive vice president of technology and regulatory affairs at AdvaMed, a trade association that represents medical-technology companies, said the PMA-supplement process does require that companies submit data to demonstrate the safety and effectiveness of their products and that the FDA can request any information it feels is necessary, including clinical data, to support the changes requested with the PMA supplement.

"In fact, the FDA typically requires clinical data for PMA-supplement changes that could impact patient care, including a different patient population, a significant modification of a technology, different surgical procedures, different conditions of use, and different physiological location on or in the body," according to Trunzo. She added that the FDA can mandate a full PMA review by an outside advisory panel if it deems it necessary.

Redberg has previously argued for rigorous standards of safety and effectiveness in clinical drug trials, with studies of sufficient power designed to test standardized end points. Medical devices, she said, should undergo similar testing of the same rigor. While the process for overseeing changes to devices needs to be flexible to allow improvements to get to market quickly, this needs to be balanced with patient safety. She suggests companies provide clinical data supporting any changes that aren't cosmetic before supplement approval as well as a postapproval registry to ensure the modified device is safe and effective in wider and long-term use.

As Redberg points out in the editorial, collecting additional data might be "cumbersome and costly" for industry, but postmarket surveillance could help get devices to market quickly while still ensuring that data are continuing to be collected and analyzed. Such a robust registry might have detected Riata and Fidelis lead problems sooner, she adds.

To heartwire , Trunzo said AdvaMed said that registries can be an important source for gathering information about the safety and effectiveness of a device or diagnostic technology, but they're not a "silver bullet" to address all of the issues involving device performance. In addition, they provide appropriate information only if they are carefully designed, implemented, maintained, and adequately governed.

Redberg and Zheng report no conflicts of interest.

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