510(k): What Happens When the Fox Guards the Chicken Coop

Although there have been about 100 legally questionable 510(k) rescissions, this is the first in which the agency admits error on its part. ReGen’s December 18, 2008–cleared device became the center of a political firestorm at the height of the Obama inauguration season in 2009 when nine dissident CDRH scientists blew the whistle on alleged industry and political interference in device reviews.

Both of ReGen’s home state New Jersey U.S. senators and two of its congressmen had written and called FDA over two years to unblock the protracted and tortured Menaflex review. Always at issue was whether the device should have gone through premarket approval instead of cleared via a 510(k).

In a lucid illustration of what can happen when the proverbial fox is sent in to guard the chicken coop, Republican commissioner Andrew von Eschenbach and CDRH director Daniel Schultz acceded to the pressure and the clearance was pushed through over staff reviewers’ objections.

The Menaflex 510(k) submission listed 11 predicate devices—an indication of what critics have termed “predicate creep”—but none of them satisfied the reviewers, who continued to complain that ReGen “did not provide adequate preclinical mechanical testing data to clearly demonstrate safety against mechanical failure of the [collagen scaffold] device.”

Belatedly agreeing with them after nearly two years of intensive internal self-examination, FDA this past October issued its historic “we were wrong” admission. It based this conclusion on a reevaluation of the scientific evidence undertaken after a September 2009 internal report identified problems in the clearance—problems that included political interference. FDA’s admission came just as Washington was abuzz with reviews of a new book by Harvard University government professor Daniel Carpenter, Reputation and Power, which analyzes the etiology of FDA’s Bush-era reputation dive.

Carpenter could have made much of the Menaflex case, but it came too late. Instead he had to content himself with other examples of FDA losing its reputation and consequently much of its effective power—such as the politically influenced Plan B “morning after” emergency contraceptive.

FDA’s decision to rescind Menaflex’s 510(k) is not without its problems (see the company’s response in the sidebar). For one, the agency does not have explicit authority to rescind 510(k)s, although it says it has done so about 100 times. On January 16, 2001, in the final days of the Clinton administration, it proposed to give itself such explicit authority in a Federal Register notice that responded to a Health Industry Manufacturers Association (now AdvaMed) petition asking it to formally declare that it has no such authority.

As the Bush administration took over FDA and industry expressed vigorous resistance to the 510(k) rescission proposal, the idea was deep-sixed.

Nevertheless, there are apparently other ways to skin this cat. In an e-mail response to me, agency press officer Dick Thompson did not respond to a question about the proposal’s fate but instead asserted:

Agencies have authority to reconsider their decisions in certain circumstances, including fraud, error, or correction of mistakes. FDA has rescinded 510(k) decisions in the past—approximately 100—including some partial rescissions. The 510(k) report CDRH issued earlier this year contains a recommendation that CDRH consider issuing a regulation that defines the scope and procedures for rescission. This recommendation is not to clarify whether the agency has the authority to rescind a 510(k) but rather to clarify the circumstances and procedures associated with rescission. With or without a regulation, the FDA can rescind 510(k) decisions.

Apparently FDA is not eager to upset the industry as it did in January 2001; it can achieve its ends less confrontationally. An agency news release said it would begin the process of rescinding the Menaflex 510(k) by meeting with ReGen to “discuss the appropriate marketing pathway for the device and what data it would need to provide a reasonable assurance of safety and effectiveness.” This is the initial step in the rescission process FDA proposed but never finalized in 2001.

The release said FDA has now concluded that the device is intended to be used for different purposes and is technologically dissimilar from predicate devices now available. The differences can affect the safety and effectiveness of the ReGen device, the release said. FDA added that it probably wouldn’t be necessary to explant devices now in use because the device is resorbed and replaced with new tissue. However, it said, patients who have had the ReGen device implanted should talk with their surgeon or other healthcare professional about what steps, if any, should be taken.

Lawmakers Critique FDA’s 510(k) Proposals

A bipartisan group of 12 House members said in October they had identified 5 of FDA’s 60 proposals for reforming the 510(k) process that are controversial and could disrupt the device review process, depending on how FDA implements them.

In a letter to FDA commissioner Margaret Hamburg, the 12 urged her to follow the process she described in a briefing for the staff of two House committees. The plan entails first focusing on recommendations that have consensus among interested parties and then soliciting additional input from stakeholders, including the committees, for recommendations that are controversial.

The proposals identified by the representatives involve rescission authority, split and multiple predicates, clarifying intended use and indications for use, mandatory premarket inspections and mandatory clinical information for a subset of Class II devices, and proprietary information.

“Depending on how FDA implements these recommendations, they could prevent companies from using important evidence in product applications, delay the introduction of innovative new therapies, increase the cost and time associated with new product development, and potentially upset the delicate balance that exists between providing information to the public and protecting intellectual property,” the 12 wrote. They said they don’t necessarily oppose the recommendations, but believe that more transparency from FDA is needed so they have specifics on which to assess the full effect of the recommendations.

The representatives also asked Hamburg for the following:

Meanwhile, comments formally received by FDA in response to its proposals showed a wide variation in opinion between the medical device industry and consumer advocates. Industry comments cautioned that many of the proposals could hurt the efficient review and clearance of low- and moderate-risk medical devices, while nonindustry reform advocates said the current 510(k) system has failed to protect public health and requires a major overhaul.

AdvaMed said that any changes should build on the current program’s strengths. “The association is concerned [that] the number and scope of FDA’s recently proposed 510(k) changes could negatively impact the agency’s mission to ensure American patients have timely access to safe and effective medical technologies,” the group said.

According to the comments, FDA recommendations that could have a negative effect on medical innovation and the flow of improved products to patients while providing no corresponding public health benefits include redefining fundamental terms, limiting use of predicates, consideration of off-label uses, and greater authority to rescind 510(k)s.
AdvaMed also questioned the proposal to establish a separate category of 510(k) devices that would be subject to additional regulatory requirements.

“While AdvaMed supports identifying a small focused subset of Class II device types that would be subject to special requirements, we do not support the Class IIb category as defined in FDA’s recommendations,” says AdvaMed executive vice president Janet Trunzo. “FDA’s Class IIb proposal appears to include a much broader category of device types and the proposed additional requirements for this category are unreasonably burdensome.”

Likewise, the Medical Device Manufacturers Association (MDMA) said that it supports FDA’s overall efforts to bring more clarity to the 510(k) process but cautioned that some agency proposals would impose unnecessary barriers to development of and access to medical devices.

“MDMA supports meaningful, predictable, and transparent improvements to the premarket review process that foster innovation, encourage advances in science and medicine, and focus on the public health,” says MDMA president Mark Leahey. “Regulatory confusion and inconsistency often result in patients not having timely access to the therapies they need. It also leads to more expensive products for device manufacturers and ultimately for patients.”

TMJ Implants Sold to Crocker Ventures

FDA-besieged TMJ Implants Inc., of Golden, CO, has been purchased at bankruptcy auction for $455,000 by Salt Lake City–based health science investment company Crocker Ventures.

The long-established maker of temporomandibular joint prostheses took refuge in Chapter 7 bankruptcy in June after being pressed by FDA to pay $340,000 in civil money penalties for not reporting 17 disputed adverse events. The company’s unsecured liabilities were listed at $962,997 in the bankruptcy, including the civil money penalties; the agency did not object to it and so apparently was not paid.

In a news release, Crocker Ventures said TMJ Implants “has proven to have the best implant products on the market and a solid position and reputation as a leader in the industry.” As part of the acquisition, it said, a new production facility was being constructed in Golden and would be completed this fall.

“It will house manufacturing, order processing, and customer service for the company, while sales, marketing, and administration will be conducted from Salt Lake City, where Crocker Ventures is headquartered. The company’s Colorado employees will continue to produce the high-quality joint replacement prosthesis for which TMJ Implants has become known.”

No mention was made in the news release of the company’s founder and CEO, 85-year-old Robert W. Christensen, who was initially cited for personal liability in the civil money penalties ($170,000). Christensen told me he expects to have a continuing role as medical consultant, but he was unclear about specifics. He has yet to file for personal bankruptcy and could not say how the court would disburse to creditors, including FDA. He has begun writing a book about his experiences.

Rising Recalls Troubles New FDA Compliance Chief

New CDRH Office of Compliance director Steve Silverman is taking aim at recalls after seeing a troubling trend with significant increases in Class I recalls. Speaking at the FDLI Enforcement and Litigation Conference in October, Silverman showed in his presentation that he has hit the proverbial road running and is not wasting any time in sinking his teeth into certain troubling compliance issues after being on the job for barely a month.

There were 14 Class I recalls in FY 2008, and this more than doubled to 32 in FY 2009. While official numbers for FY 2010 are not out yet, he said preliminary reports place them between 45–50 recalls. Additionally, he said Class II recalls are also on rise.

“So what does this mean?” Silverman asked. “This is an area of significant concern for us. And in the case of 510(k)-cleared devices, for example, it raises questions on our part about whether manufacturers are rushing products to market at the cost of product integrity and basically working out product quality problems in the marketplace in order to garner market share.”

Silverman said CDRH will be taking a “comprehensive look at our recall process and looking at a number of different perspectives. From an internal perspective, we want to see what the process map looks like when we look at a recall notification by a manufacturer to an FDA district office and the time it takes for that notification to be communicated publicly when public notification is the appropriate course to follow. And from that point, how long does it take for the agency to classify that recall? We have a lot of efficiencies that can be gained.”

On transparency efforts, Silverman told FDLI that his office wants to see whether there are aspects of its recall classification process that can be made more transparent. “For example,” he said, “the criteria we apply when determining whether there is a reasonable versus remote risk for significant injury may be made public. This is an area we will be looking at in the coming year.”

Additionally, Silverman said his office has heard from manufacturers about some confusion with the distinction between enhancement of a compliant product and recall of a violative product, and the line between those two activities being somewhat blurred. “So our expectation is that we will issue guidance in the coming year to provide greater clarity on this,” he said.

Silverman replaces retiring director Tim Ulatowski, who has moved to a senior advisor role for enforcement in Silverman’s office until his official retirement in January after 36 years with agency. Previously, Silverman, who is a lawyer, served as a senior advisor to center director Jeff Shuren.

Earlier in his career, Silverman served as Office of Compliance assistant director in FDA’s drug center. He also had a stint in the agency’s Office of Chief Counsel where he focused on dietary supplement enforcement issues.