Regulatory Focus™ > News Articles > Regulatory 'Loophole' Allowing Unsafe Devices to be Marketed, Say Researchers

Regulatory 'Loophole' Allowing Unsafe Devices to be Marketed, Say Researchers

Posted 10 January 2013 | By

A "loophole" in the way in which some medical devices are regulated is allowing unsafe devices to reach-and harm-patients, argues a new editorial published in the New England Journal of Medicine.

The loophole stems from the 1976 Medical Device Amendments, which established for the first time in the US a system for the regulation of medical devices.  The system classified medical devices into three general categories: Class I for low-risk devices, class II for moderate risk devices and class III for high-risk devices such as implantable devices.

Because many medical devices had already been on the market, Congress proposed-and the US Food and Drug Administration (FDA) implemented-a compromise: Some class III devices could be reviewed under the 510(k) substantial equivalence pathway, avoiding the more rigorous premarket approval (PMA) pathway that would require data from clinical trials to support an application.

"Congress had always intended class III devices to undergo PMA, and in 1990, it directed the agency to establish a schedule to finish the transition to PMAs for all devices that were to remain in class III," explained authors Brent Ardaugh, Stephen Graves and Rita Redberg in their 10 January opinion piece. "As of December 19, 2012, however, the FDA still had not completed this transition to PMA for high-risk devices, although it had stated its intention to clear proposed rules for all remaining class III preamendment devices by December 31, 2012."

This is significant, they continued, because some of those devices continue to be marketed under the 510(k) pathway, and some of those devices have been the subject of significant safety concerns both in the US and around the world.

Case in point: metal-on-metal hip implants, such as DePuy's ASR XL Acetubular System. The device was cleared through FDA's 510(k) pathway in 2008 after regulators found it substantially equivalent to predicate devices by virtue of its surface, metal-on-metal articulation and similar (but larger) femoral head sizes, the researchers said. Though all three characteristics were independently similar to predicate devices, they had never before been used in conjunction with one another in a device. The researchers referred to this as a "split predicate."

The devices would eventually be voluntarily recalled by DePuy after concerns were raised about high rates of required surgical revisions and the potential for metal (chromium) shavings to come off the metal joints and become lodged in tissue elsewhere in the body.

This, the researchers said, raised a larger question: If the device was found to be safe by virtue of its equivalence to earlier devices, had its predicates also been found to be safe? The answer, they found, was no.

"Ultimately, clearance was based on the claim that these predicate devices were substantially equivalent to three prostheses that were used before 1976: the McKee-Farrar, Ring, and Sivash metal-on-metal total hip prostheses. It is important to note that these three devices were discontinued long ago (and well before clearance of the ASR XL) because their risk of revision was so much higher than that of other hip prostheses."

In other words, the devices were cleared by regulators under the assumption that they were based on previously cleared (and thus safe) devices which had been withdrawn from the market for safety reasons.

The researchers' observation is not a new one. In the lead-up to the authorization of the FDA Safety and Innovation Act by Congress, patient safety advocates and even the director of FDA's Center for Devices and Radiological Health, Jeffery Shuren, identified the loophole and called for it to be closed.

At present, Shuren said in remarks to Bloomberg News in February 2012, CDRH is legally required to "approve devices that cite an eligible predicate unless the older device has been ordered off the market by the agency or a court order."

Because those devices are citing ones which were voluntarily withdrawn from the market, and not as the result of a court order or by the agency, subsequent devices are still able to obtain approval from FDA regulators.

FDASIA (§608(a))contains some provisions that will reportedly allow FDA to close such loopholes, though it does not do so as directly as some advocates, including Ed Markey (D-MA), had called for.

Advocates had also called for FDA to establish a database of medical devices withdrawn from the market, including information regarding the reason for the recall (safety vs. market or manufacturing reasons)-an idea that the NEJM authors threw their support behind. "There would be value in an FDA-sanctioned registry," they said. FDASIA does not contain language supporting the formation of such databases, though it would be well within FDA's existing statutory authority to create one.

For the NEJM authors, though, the entire episode speaks to the necessity of requiring more clinical trials for certain devices.

"This ancestry reveals serious flaws in the 510(k) procedure for metal-on-metal hips, which resulted in clearance of a new device that was never shown to be safe and effective," they wrote. "A clinical trial might have identified the high revision rate of the ASR, which became evident after 9 months when it was compared with all other total conventional hip prostheses in the Australian Joint Registry and which precipitously worsened over time."

"As thousands of Americans are painfully learning, there are unknown risks with devices that enter the market without clinical data showing safety and effectiveness, and implanted body parts cannot be recalled as easily."


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