Parting the ReGen Clouds?

The FDA's top device regulator, Jeff Shuren, M.D., J.D., informed ReGen Biologics on October 14 that he intends to rescind the 510(k) clearance granted the company's Menaflex device by his predecessor Dan Schultz, M.D., in December 2008.

Jeff Shuren, MD, JDShuren wrote that his decision is based on the fact that the device "does not have the same intended use as any of the identified predicate devices. Alternatively, even if the device had the same intended use as any of the identified predicate devices, the differences between the technological characteristics of the device and each of the predicate devices raise different questions of safety and effectiveness."

He may have, however, offered a potential olive branch.

Subject to Special Controls?

"Before we take any action on your clearance, " wrote Shuren, "we would like to discuss the appropriate marketing pathway for the device and data requirements...If there is sufficient information to establish special controls to provide reasonable assurance of the safety and effectiveness of the device, FDA may classify the device in class II, subject to special controls.

Source:  Mark DuVal

The safety of ReGen's Menaflex has never been an issue. Two FDA orthopedic panels meeting in 2008 and 2010 told the FDA that the device was safe but that the device’s effectiveness was unclear.

Rescission Power

Rescission is a rare and seldom used enforcement tool. The FDA's authority to rescind a previously cleared device is uncertain and Shuren has made the clarification of the agency's rescission authority a top priority in recommendations to revamp the entire 510(k) program. Shuren's boss, FDA Commissioner Margaret Hamburg, M.D. told an audience of device manufacturers on October 20 that rescission should be used for "public health protection."

Mark DuVal, a Minnesota attorney who specializes in FDA and regulatory issues put it more succinctly:

"ReGen followed the rules. ReGen lawfully obtained a clearance in 2008. Yet FDA plans to rescind their clearance. We are not sure what FDA’s theory for rescission is, but we are confident, absent fraud, FDA does not have the legal grounds for rescission. What FDA seems to be confident in is that ReGen may not have the financial wherewithal to defend itself. If so, a clearly inappropriate and illegal rescission challenge may stand. FDA’s use of publicity has certainly destroyed the market for the product anyway—a case of being judged guilty before the opportunity to prove innocence.

"In the wake of FDA activity lays a suffering patient population with few treatment options for meniscus repair, patients with permanent implants from a company that will probably disappear because of the rescission, and laid-off ReGen employees looking for work in a suffering economy. Who gains? If a CDRH (Center for Devices and Radiological Health) Director and two expert panels determined the device was “safe, ” why is it being taken off the market? Out of concerns of efficacy? Aren’t practicing physicians in the marketplace capable of determining a device’s efficacy?"

CMS Non Coverage

Then there is the issue of the CMS (Centers for Medicare and Medicaid Services) non-coverage determination for the device this past June. Very few, if any, of the devices are implanted in patients over 65. According to the company, the device is designed to guide new tissue growth using the body’s own healing process to reinforce and repair the meniscus in patients with an irreparable meniscus tear or loss of meniscus tissue. The device provides a resorbable scaffold for the growth of new tissue in the meniscus.

The company did not request coverage from Medicare and a company spokesperson tells OTW that he understands the coverage determination was generated from staff within CMS.

A Way Out

Gary Bisbee, Jr., Ph.D.Since protecting the public's health doesn't appear to be at issue here, has Shuren found a way out of one of the most painful, confusing and acrimonious device reviews in recent memory?

Gary Bisbee, Jr., Ph.D., ReGen's Chairman and CEO told OTW in an interview on October 19, that if Shuren's offer to meet and see if the device can get cleared subject to special controls, is genuine, the company would be satisfied.

Bisbee: Politics Not Science

Bisbee's initial reaction to Shuren's letter was not quite as measured however.

On October 18, Bisbee issued a statement saying that politics, not science was driving FDA's actions.

Bisbee said,

For CDRH to arrive at the decision that the device has a new intended use four years after two senior CDRH officials informed the company that the device could be reviewed through the 510(k) program is totally unbelievable.

“The [Center] rigorously reviewed and cleared the [device] for use in the U.S. after the first independent Advisory Panel Meeting in November 2008, ” said Bisbee. “Since then the FDA has created storylines about the review process to discredit this clearance, as well as taken numerous actions that are illegal or well outside its existing statutory authority.”

The storyline referred to by Bisbee includes allegations that the company hired lobbyists and made campaign contributions to Congressmen and Senators who strong armed the agency into clearing the device. This storyline has been perpetuated by stories in the Wall Street Journal citing leaked government documents.

The agency's own legal counsel said in a review of the ReGen case that the company did nothing wrong. In fact, the reports confirmed that the agency's reviewers were applying the wrong standard to the device. Repeated requests from OTW to the agency for details of alleged and improper influence on the agency's reviewers have been met with vague and unsubstantiated references.

Bisbee says the FDA’s determination that the device could be reviewed under 510(k) criteria as a surgical mesh was made in November 2006 by the director of the agency’s Office of Device Evaluation.

"Contrary to the story that FDA is telling, that determination could not have been affected by any political influence because ReGen did not seek the assistance of New Jersey legislators until almost a year later, in late 2007. Even then, it was only after receiving a rejection of its submission based on an illegal review standard, following nearly two years of review. These members of Congress asked the FDA to examine the ReGen matter and insure that the review was treated fairly and consistent with existing agency regulations."

Bisbee pointed to a larger agenda on the FDA's plate. “The politics surrounding changes suggested in the 510(k) program appear to underlie FDA actions, for example, a group of dissident FDA reviewers has sought legislative intervention because of their dissatisfaction with the current regulations and agency management." He says the agency’s clearance of his device has become a political football and the FDA is not playing by the rules.

ReGen Ready to Meet

The company will meet with Shuren within the next 30 days and see if Shuren's offer is the real deal or a simple boilerplate response to all companies that are told their device is not substantially equivalent to a predicate device.

Bisbee told OTW that ReGen has never looked to pick a fight with the FDA and if Shuren's suggestion of considering a different regulatory pathway comes to fruition, the company will be satisfied.

The product continues to be marketed and sold in Europe, but the supply is dwindling down as the company has been forced to lay off employees and close down its manufacturing plant in Redwood City, California.

The cloud of the FDA stopped the company's ongoing surgeon training programs, continuing sales in the U.S. and raising capital. After spending $30 million to get clearance, this device has not only been the most studied 510(k) in history, but probably also the most expensive.

Bisbee says if the company can get out from under this FDA cloud, they will be able to resume production, resupply their European shelves, resume U.S. surgeon training and raise capital from investors.

Solomon or McCarthy

The pages of OTW have been filled with stories accusing the FDA of being arbitrary, capricious, violating the equal protection and due process rights of ReGen and strong warnings from industry representatives that such unprecedented actions could only serve to stifle innovation in the U.S. The comparison to the McCarthy era of the 50’s was even noted.

Is this Shuren’s opportunity to clean up a previous FDA administration’s mess, demonstrate his commitment to innovations as he seeks to reform the 510(k) program, placate his whistleblowing scientists, promote the public’s access to new devices and demonstrate how his proposal for a new Class IIb category might have prevented this?

We asked Dr. Shuren for comment, but received no response.

Device manufacturers will be watching as leaders measures Shuren’s credibility in how he deals with one of industry’s weakest members.

As Shuren attempts to reform the 510(k) program, ReGen becomes his real-world test of whether he and his agency are more like Solomon than McCarthy.