Shifting the Device Risk Burden

Originally Published MDDI May 2001Washington Wrap-up Does a recent device approval indicate a softening of FDA's "appropriate use" worries?

10 Min Read
Shifting the Device Risk Burden

Originally Published MDDI May 2001


Washington Wrap-up

Does a recent device approval indicate a softening of FDA's "appropriate use" worries?

James G. Dickinson

More devices may be approved faster—without the need for drug-type user fees—with a risk-shifting labeling initiative promulgated at CDRH by director David Feigal and his new device evaluation director, Bernard Statland. The initiative was expressed in public statements by Feigal soon after his own appointment in 1998, and again in June 2000. In general terms, he advocated a more vigorous approach to opening CDRH device information to professional and patient access. The first practical implementation of the concept occurred last February when Statland applied it in a controversial device approval. In recent months, this column has included extensive accounts of the issues surrounding the review of the Fossa-Eminence prosthesis manufactured by TMJ Implants Inc. (Golden, CO). Although that process concluded with the approval of the device, it serves as evidence of this significant shift in thinking at CDRH.

According to the company's attorneys, Statland saw that instead of reviewers tying themselves in knots trying to guarantee there will be no inappropriate patient exposures to implanted devices—and stalling products in midreview as a result—FDA needed only to implement a "full disclosure" labeling standard to lift that self-imposed burden from the agency.

Attorney Mike Cole of Bergeson & Campbell states that the approval was the first he had seen where the agency stepped back from its "appropriate use" worries and allowed physicians and patients to make such assessments, based on full disclosure in labeling of the device's real-world limitations—including the availability of alternative therapies. The warnings section of the device's label includes a box that contains the heading "The medical literature reports" and the following four bulleted statements:

  • That many cases of internal derangement resolve after nonsurgical treatment, or, in some cases, with no treatment at all.

  • That the complexity of contributing factors in this patient population must be considered in the diagnosis and decision to surgically treat patients.

  • That replacement surgery, therefore, should be utilized only as a last resort after other treatment options are exhausted or determined not to be warranted in the medical judgment of the physician/dentist in consultation with the patient.

  • That the Wilkes classification is a guide in determining the severity of the disease. This classification should not be relied on as a sole criterion for surgical treatment.

"It really is a striking difference in philosophy," Cole says. "It discloses that a lot of patients have responded without surgery [and] describes situations where the doctor arrives at the diagnosis that surgery may be appropriate, but it doesn't prejudge [an off-label use]. Over the years, there have been all these notable instances of concern about off-label use of products and misuse of products. Part of it comes, I think, from a mentality that we have to be 100% sure that it will be used appropriately. As a result, manufacturers have started submitting applications with more, and more-restricted, indications statements in them because that can get through the system."

Cole and colleague David Rosen, of McDermott, Will & Emery, believe that the TMJ Implants submission had been in deadlock at FDA for so long simply because reviewers were afraid the products would be used inappropriately—an FDA syndrome that has affected many other products over the years. "A lot of times, what it really comes down to is demands for more data, more data, more data," Cole explains, "because the reviewers are not comfortable with the idea that the device ought to be on the market, or available." He suggests that "the way out of that has been to keep asking for more information."

Cole adds that in TMJ Implants' case, review leader Susan Runner "held what I think was a very honest and sincere concern about the device being used in cases where patients might respond without surgical treatment. Because the studies hadn't been set up to prove exactly what I think we had demonstrated, she had this really deep-seated concern about the product being used, and it just went round and round in circles. We had no apparent instances of misuse of the device, but we were getting nowhere."

Describing a meeting with the device evaluation director, Cole says Statland "got up with a whiteboard and started talking about the data, and he said to his people, 'You know, we've got a lot of information here. What we need to do is figure out how we're going to present this information to the doctor so that the doctor and the patient understand exactly where surgery fits in this, and make sure we discuss the limitations of the data.' For the first time that I've heard this in 25 years of dealing with CDRH, he said, 'We'll discuss this information in the labeling and we'll let the doctors and the patients decide whether they want to use the device—we won't decide for them.'"

Cole states that Statland stopped the reviewers' agonizing at the point where reasonable assurance of safety and efficacy had been demonstrated. This prevented the agency from continuing to stray into attempts to secure an absolute guarantee that the product would not be used improperly. "In a way it's a kind of subtle point," Cole explains, "but in a way it's also a sledgehammer point. When Dr. Statland said, 'This is what we're going to do,' it was over."

Unpainted Lead Container Hazard

FDA warned dental health professionals of the potential for harmful lead exposure from dental films stored in tabletop containers lined with unpainted lead. In a March 13 letter, CDRH director David Feigal warned that dental films stored in lead-lined containers have been found to be coated with a whitish film that is about 80% lead. He added that, "In many cases there are highly dangerous levels of lead on the films, enough to potentially cause serious adverse health effects in patients and healthcare professionals." Potential adverse effects include anemia and serious neurological damage. Feigal advised dental health professionals to discard such film and properly dispose of the boxes, and follow manufacturer-recommended instructions for storing dental film.

Harmonizing Approvals with Canada

As part of an ongoing effort to attain global harmonization of device premarket applications, FDA has initiated a pilot project with the Canadian Medical Devices Bureau for joint review of PMA applications for implantable cardiac devices. CDRH cardiovascular and respiratory devices director James Dillard says the pilot program expands one started about two years ago for orthopedic and ENT devices that was "pretty successful in terms of sharing resources and ideas."

In the latest effort, the two agencies sent letters about four months ago to most implantable device manufacturers offering them the opportunity to submit applications to both agencies simultaneously. In addition, reviewers at the agencies were authorized to talk with their counterparts during the review process. A small number of companies have already taken advantage of the program and have reviews being processed, says Dillard. He explains that a few other firms have expressed interest.

Dillard says such a joint review represents progress toward a global premarket submission system in which a single form would contain the information required by any of a number of regulatory bodies. The program also increases the ability of officials in both the United States and Canada to learn more about each country's regulatory approach and process. He explains that although it would be good if a single application could lead to faster reviews or other efficiencies, it is too soon to say if that would ever be a possibility. "We still don't know if we'll be able to develop a common application, much less what efficiencies that might produce," Dillard states.

New Guidance Defines "Guidance"

Warning letters and other communications directed to individuals or firms are not considered guidance documents, CDRH says in a new guidance for agency staff. According to Good Guidance Practices (GGP) Regulations; Final Guidance for FDA Staff, "documents directed to FDA staff that also provide guidance to applicants/ sponsors or the public are guidance documents." Such documents may include internal memos and outlines of operating procedures. Examples of internal documents that are not guidance documents include:

  • Staff guides on personnel or leave policies.

  • Directives on routing documents for assignment or review.

  • Documents relating to internal FDA procedures.

  • Agency reports.

  • Informational documents provided to consumers and health professionals.

  • Speeches.

  • Journal articles and editorials.

  • Media interviews and press materials.

In the guidance, the agency says it "may not use documents and other means of communication that are excluded from the definition of guidance documents to informally communicate new or different regulatory expectations to a broad public audience for the first time." The agency is required to follow the GGP regulations whenever it first communicates regulatory expectations "that are not readily apparent from the statute or regulations to a broad public audience." The guidance may be downloaded from the FDA Web site at

Guidance on Home-Use Uterine Monitors

Special controls for home-use uterine activity monitors are provided in an FDA draft guidance, Class II Special Controls Guidance for Home Uterine Activity Monitors. The guidance document describes the regulatory controls that FDA applies to home uterine activity monitors and recommends the different types of information that should be included in a sponsor's 510(k) submission. The guidance document may be downloaded from

Death of Peter Maxim

CDRH chief of immunology and molecular diagnostics Peter E. Maxim died of a heart attack on February 27 while serving as a chaperone for his youngest daughter's sixth-grade field trip. A Youngstown State University graduate in biology with MS and PhD degrees in medical microbiology from West Virginia University, Maxim worked for eight years in industry before joining FDA in 1990.

A CDRH statement called Maxim "a superb scientist, a balanced regulator respected by healthcare and industry professionals alike, a skilled administrator, and a hard-working and caring coworker." He was designated the lead scientist within the Division for Clinical Laboratory Devices for international harmonization activities in 2000. In 1999, Maxim was awarded FDA's Outstanding Achievement Award for his "leadership as the agency lead in developing new policy and review procedures for processing tumor markers for diagnostic use."

James G. Dickinson is a veteran reporter on regulatory affairs in the medical device industry.

Copyright ©2001 Medical Device & Diagnostic Industry

Sign up for the QMED & MD+DI Daily newsletter.

You May Also Like