FDA Admits Error in Approving Knee Implant

In a rare acknowledgement of misguidedness, the U.S. Food and Drug Administration (FDA) is revoking approval of an orthopedic knee device that has become the poster child for a highly criticized product approval process used by the agency.

FDA officials admitted late last week that they made a mistake in approving the Menaflex Collagen Scaffold in December 2008 for repairing and reinforcing meniscal tissue in the knee. The surgical mesh, manufactured by Hackensack, N.J.-based ReGen Biologics Inc., is designed to stimulate the growth of new meniscal tissue in damaged knees.

Jeffrey Shuren, M.D., director of the FDA’s Center for Devices and Radiological Health (CDRH), called the move an “unusual, unique” circumstance. Though it is not uncommon for the FDA to revoke approval for a device based on new safety data, it is rare for the agency to consider the entire approval process flawed and re-evaluate a product.

The FDA’s reversal on Menaflex, together with its decision to withdraw the obesity drug sibutramine (Meridia; Abbott Laboratories) from the market last week, demonstrates that the agency is more militant about patient safety than it had been during the George Bush administration, said Diana Zuckerman, Ph.D., president of the nonpartisan National Research Center for Women and Families, a Washington, D.C.-based group that specializes in health issues.

“The new FDA leadership under [President Barack] Obama is more public-health oriented. They’re more willing to admit a mistake,” Zuckerman told Medscape Medical News, adding that FDA decisions to rescind a drug or device approval are rare.

The FDA uses two different processes to approve products: the premarket approval process, in which a manufacturer must provide evidence that its product is safe and effective; and 510(k) premarket notification, in which a manufacturer needs only to show that its product substantially is the same as a “predicate” drug or device already approved by the FDA—and therefore is as safe and effective.

The 510(k) premarket notification process has been a boon to manufacturers, but critics (including U.S. Sen. Charles Grassley (R-Iowa) and some FDA scientists) have insisted the less stringent vetting method has allowed unsafe products to enter the market and be used by consumers.

Menaflex won FDA approval through 510(k) premarket notification. But the decision soon came under fire by members of Congress who questioned whether the agency had properly followed its procedures and succumbed to undue pressure from the manufacturer. In September 2009, the FDA agreed to reevaluate its decision.

“There were in fact numerous departures from the review process,” Shuren said at the time about the CDRH’s 2008 decision. “There is no adequate information in the record establishing why the device was approved.”

That same month, the FDA commissioned the Institute of Medicine (IOM) to study its 510(k) approval process. The IOM is scheduled to publish a final report in March.

After reevaluating its decision, the FDA said it concluded that Menaflex was “technologically dissimilar” from other surgical-mesh devices the agency had approved, and it embodied differences that could affect its safety and effectiveness. Unlike predecessor products that repair or reinforce damaged tissue, for example, Menaflex helped the human body grow new meniscal tissue.

“Because of these differences, the Menaflex device should not have been cleared by the agency,” the FDA said in a news release.

Regen Biologics’ chief executive blamed the FDA’s decision on politics.

“The agency’s clearance of Menaflex has become a political football and the FDA is not playing by the rules,” CEO Gerald Bisbee said in a statement. “Regen has invested 58 months and more than $30 million to meet (the center’s) requirements only to have the agency reverse decisions made by previous officials by stating that they were in error with no substantial evidence that is true.”

Bisbee said the company is evaluating its options. Executives already are investigating ways of financing its Europeon subsidiary, ReGen Biologics AG, so it can continue to market Menaflex outside the United States. Menaflex has been sold in parts of Europe for the past nine years.

Revoking FDA approval can take as long as a year and does not preclude the manufacturer from reapplying for market approval. Until revocation is made final, Menaflex will remain on the market, and physicians are free to implant it during that time, according to the agency.

Because the surgical mesh is resorbed and replaced with meniscal tissue, removing it in light of the impending rescission generally would be unnecessary, the FDA stated. However, surgeons should speak to their patients with implanted Menaflex devices about any steps they might need to take.