FDA Rebukes Edwards for Late Reporting of Adverse Events With Valve Devices, Including MYXO Ring

Shelley Wood

April 07, 2010

April 7, 2010 (Silver Spring, Maryland) — An FDA inspection of medical-device maker Edwards Lifesciences has turned up six complaints of adverse events relating to use of mitral annuloplasty rings and pericardial prosthetic heart valves that were not reported to the FDA within the 30-day window required by the agency. That's the upshot of a letter posted on the FDA's website today.

One of the event reports cited in the letter relates to the "McCarthy MYXO ETLOGIX annuloplasty ring" (now known as the Edwards dETlogix 5100)--the device at the center of a regulatory hullaballoo first reported by heartwire .

Timothy A Ulatowski, director of the FDA's Office of Compliance at the Center for Devices and Radiological Health, sent the letter to Edwards Lifesciences Chair and CEO Michael A Mussallem on March 1, 2010.

"Our inspection revealed that your annuloplasty ring devices and your pericardial heart valve device are misbranded" under the section of the regulation that governs medical-device reporting, "in that your firm failed or refused to furnish material or information respecting the device that is required by or under section 519 of the act," the letter reads. "Significant deviations include, but are not limited to, the following: Failure to report to us no later than 30 calendar days after the day that you receive or otherwise become aware of information, from any source, that reasonably suggests that a device that you market may have caused or contributed to a death or serious injury."

Ulatowski then provides six examples of complaints that were not reported within 30 calendar days "that resulted in a death or serious injury."

"You should take prompt action to correct the violation addressed in this letter," he continues. "Failure to promptly correct this violation may result in regulatory action being initiated by the Food and Drug Administration without further notice."

Edwards Responds

Edwards swiftly issued a comment, acknowledging receipt of the FDA warning letter and stating that the company "corrected" training procedures on the [medical device reporting] MDR process during the FDA's inspection and notes that the FDA has since issued an establishment inspection report (in October 2009) concluding its inspection.

According to Edwards, the delay in reporting the events ranged from six to 29 days beyond the 30-day reporting requirement.

In an email to heartwire , Ulatowski noted that compliance with the specific FDA regulation governing medical-device reporting is evaluated by the agency in "many inspections" and "is not a rare event."

However, he added, "Reporting violations are serious and [are] often associated with problems in other areas covered by our quality system regulation (like corrections and removals, complaint handling)."   

Adverse Events

The adverse event concerning the dETlogix (Myxo) 5100 ring, given as one of the six examples in the FDA letter, involved a patient whose device was explanted after a duration of "zero days, due to an unsuccessful ring repair." The operative report explains that, "because of a very small p1 segement [sic], this repair had significant insufficiency. Next I took off the triangular ring and replaced it with a posterior band." The patient reportedly was in stable condition after the operation.

Two of the six events noted in the letter pertained to the use of a different annuloplasty ring (the Carpentier-McCarthy-Adams IMR ETLOGIX). In one instance, the device was explanted after 41 months due to mitral regurgitation, mitral insufficiency, and dehiscence of the mitral ring from the anterior leaflet portion. In the second, the device was explanted after "zero days due to unsuccessful ring repair."

The remaining three events--including one death--occurred after implantation of pericardial bioprosthetic replacement heart valves.

More of a Muddle for the Myxo?

Publication of the FDA letter and any heat this is causing for Edwards comes as the company is celebrating a number of milestones in its percutaneous-valve business. Last month, the company's Sapien XT transcatheter aortic heart valve--a new and improved version of its original Sapien device--and delivery systems received CE Mark approval in Europe. And last week, on US soil, a federal jury ruled that Medtronic had willfully infringed on an Edwards transcatheter-valve patent, awarding the latter $74 million in damages.   But the rumblings over Edward's annuloplasty rings--not in the limelight as much as the company's surgical and new transcatheter valves--keep resurfacing. Controversy over the Myxo annuloplasty ring, in particular, centered initially on whether it was an investigational device when used at Northwestern Memorial Hospital in April 2006, as reported by heartwire in October 2008. A patient who received the ring in 2006--implanted by Dr Patrick McCarthy, the device inventor--is suing McCarthy and Edwards because she believes a series of adverse events she experienced after undergoing device implantation was related in part to the fact that the device was investigational and required further testing. As previously reported, Edwards had sold the device for two and a half years without 510(k) clearance, after determining from an FDA document that a new 510(k) wasn't needed. Within weeks of heartwire 's original story, however, the company submitted a new 510(k), and the device was ultimately cleared by the FDA in April 2009.

As reported by heartwire, however, the FDA also concluded that Edwards erred when it initially decided the device did not need a new 510(k) application but felt the company had made an "honest attempt" to adhere to the FDA's guidance and would face no sanctions for having sold the ring since March 2006.

The twisted tale has become the target of an FDA investigation, and a subsequent US Senate inquiry--this letter from Ulatowski is just the latest to weigh down the mailbags of postal workers trudging between FDA headquarters, Senate offices, and Northwestern.