FDA's Statland Leaves Lasting Mark

Originally Published MDDI October 2002

NEWS & ANALYSIS

FDA's Statland Leaves Lasting Mark

Departing ODE director Bernard Statland broke impasse over TMJ product approval, setting a new standard for risk-based labeling.

James G. Dickinson

FDA and Department of Justice Investigate Guidant | Dental Device Guidance Issued | Media Flay FDA | Abbott Hires New Consultants | FDA Clarifies Conformity to Standards | Cochlear Implants' Link to Disease | Growth of 400% Predicted for ICDs

In little more than two years as director of the CDRH Office of Device Evaluation (ODE), Bernard Statland made a deep and lasting impression for his candor, openness, and innovative problem-solving. Then he announced in August that he was leaving to pursue a law degree at the University of Minnesota, where he started out 34 years ago. His deputy, surgeon Daniel Schultz, a 10-year FDA veteran, was named to succeed him.

Why did he resign? "I have been commuting from Minneapolis for two years now," Statland told me. The time finally came for him to choose between bringing his wife to Washington or going back home and finishing his law degree. Statland, who had been studying law at American University in Washington, DC, said he had two more semesters to go.

I will best remember Statland for breaking a traumatic impasse between CDRH reviewers and device maker TMJ Implants (Denver). The company had been shut down and its Fossa-Eminence prosthesis stalled for 20 months in a classification PMA review until Statland broke the logjam. His approval set a new "full disclosure" labeling standard that shifted some of the risk-benefit decisional burden from the agency to physicians and patients.

He and the agency took some flak for that from TMJ patients, but CDRH director David Feigal bravely backed him up. The disagreement reflected an intractable ideological split over the role of health product regulation. Statland's decision was a defeat for those who believe FDA's role is, or ought to be, to ensure absolute device safety and effectiveness. Instead, he sided with those who believe that the best that FDA can do is ensure full disclosure of information to the real risk takers: patients and their physicians.

More recently, Statland impressed attendees at the FDA–Orange County Regulatory Affairs Discussion Group annual meeting in California. In a colorful discussion on the differences between the review of drugs and devices, he issued a good-natured challenge to an FDA colleague from the Center for Drug Evaluation and Research: to explain why so many more high-profile drugs have been withdrawn from the market after lengthy premarket reviews than is the case for faster-reviewed medical devices. The FDAer from the drugs center ended up wishing his side could do a better job.

"I leave a legacy of openness and a pragmatic approach that I hope and feel sure Dan Schultz will continue," Statland told me. "Life is a journey. I don't know where I will go after I get my law degree. Maybe a big law firm? A medical device manufacturer? Or come back to government, FDA?"

Statland joined FDA in July of 2000, replacing former ODE director Susan Alpert. He earned his medical degree in 1968 from the University of Minnesota, and holds a PhD in biochemistry from the same school (1970). He served his residency in Denmark at the University of Copenhagen and was later the senior resident for clinical pathology at the University of Minnesota Hospitals.

FDA and Department of Justice Investigate Guidant

FDA's Office of Criminal Investigations and the U.S. Department of Justice are reportedly conducting an inquiry involving the Ancure arterial graft made by Guidant Corp. (Indianapolis).
Guidant disclosed the inquiry in a quarterly filing with federal securities regulators. The company said it believes the probe is related to a March 16, 2001, halt in production of the product after it was determined that sales staff were not reporting adverse events to FDA. These included severe vessel damage associated with deployment of the device.

At that time, CDRH advised medical professionals of serious problems with the device and said that patients who had received the graft should be carefully followed and should undergo periodic follow-up imaging. Guidant CEO Ronald Dollens has said the unreported adverse events did not involve injuries to patients but rather difficulties that doctors had in installing the graft.

The Ancure graft is a cylindrical fabric product designed to take pressure off arterial walls so the aorta doesn't rupture.

Dental Device Guidance Issued

CDRH issued a draft guidance in August that is intended to serve as a special control supporting classification of jaw-tracking and dental sonography devices into Class II. The draft guidance is entitled "Dental Sonography and Jaw Tracking Devices; Draft Guidance for Industry and FDA Reviewers." It focuses on dental sonography devices intended to interpret jaw sounds as well as on jaw-tracking devices intended to interpret mandibular jaw positions relative to the maxilla. Both devices are indicated, the guidance says, for the diagnosis of temporomandibular joint disorders and associated orofacial pain.

For manufacturers who intend to market such devices, the draft guidance provides information on abbreviated 510(k) submissions, including content and format. While the suggested format includes such items as a cover sheet, proposed labeling, and a summary report, the document stresses that a discussion of device-specific risks should be included in any 510(k). Other content-related items include a device description, and preclinical and clinical study information.

According to the draft guidance, preclinical considerations include device comparison, biocompatibility, software validation, electrical shock, interference with a pacemaker or other electrical stimulatory devices, and device interpretation functions. Clinical information should show that a diagnostic endpoint exists and that, based on that endpoint, the device can differentiate between healthy and unhealthy patients.

Proposed classifications, product codes, and classification definitions for both Class I and Class II dental sonography and jaw-tracking devices are also included in the draft guidance, which has been posted to CDRH's Web site at http://www.fda.gov/cdrh/ode/guidance/1393.html.

Media Flay FDA

Medical device regulation at FDA is losing a public health battle against defective or inadequate products. So argued an investigative journalism article published by Newhouse News Service on August 11, 2002. The exposé prompted at least one newspaper, the influential Cleveland Plain Dealer, to write in an editorial that "lack of staff and lack of money are rendering the FDA incapable of doing a proper job of testing and inspecting medical devices."

CDRH director David Feigal, away on vacation, was unavailable for comment.

The article was written by Washington correspondents Robert Cohen and J. Scott Orr and based, they said, on thousands of pages of FDA documents and interviews. According to the authors, 98% of devices, "including implants," enter the market without clinical study. CDRH inspection resources, they said, have dwindled while implanted device recalls have soared from an average of 40 per year between 1992 and 1998 to 117 last year. The recalls, according to the article, encompassed nearly 800,000 cardiac pacemakers and defibrillators over the past decade (40% of all implants recalled), as well as 470,000 fasteners, such as bone screws and plates (23%).

Of 573 recall notices covering more than 2 million implants issued in the past decade for "lapses such as mislabeling, structural failure or manufacturing error," the article said only one was issued by FDA itself — "the rest came from manufacturers." The article did not explain that FDA only won the statutory authority to force product recalls in 1997.

The Newhouse correspondents asked CDRH director David Feigal why the number of recalls is increasing even though the number of implantable devices on the market remains roughly the same. He shook his head, the article said. "It is something that seems to be a particular problem in devices; I don't think we really know why," it quoted him as saying.

As the most serious cases of implanted device recalls, the article cited the 1986 Bjork-Shiley heart valve involving a reported 248 patient deaths, and the Vitek Proplast Teflon jaw implant, involving "hundreds" of failures that forced the company into bankruptcy in 1990. Other companies named in the article were Centerpulse (formerly Sulzer Orthopedics), St. Jude Medical, Boston Scientific, Medtronic, and Guidant.

Whether or not more bad products are being made, the article said, "it isn't the FDA that has pulled them off the market. In virtually every case, the recall has been initiated by the manufacturer. In its entire regulatory history, the FDA has recalled only six medical devices."

The article quoted former CDRH medical officer Suzanne Parisian as saying, "The system has significant flaws. . . . FDA is not set up to act quickly on safety issues, and there are so many roadblocks that occur."

Addressing the level of scrutiny most devices receive from FDA before entering the market, it quoted Parisian as saying that the agency "works on the assumption that manufacturers are telling the truth. They have a low level of suspicion, and they don't have the people to check things out." She was also quoted as saying that FDA's system would work all right "if everybody told the truth. . . . But there are so many places where truth can be lost."

Abbott Hires New Consultants

Abbott Laboratories has hired two third-party GMP consulting firms to assist it in reaching compliance under a 1999 consent decree with FDA.

Abbott began looking for alternatives to Quintiles Consulting after Abbott failed a long-awaited GMP inspection by FDA of its Lake County, IL, diagnostics manufacturing operation. It subsequently had to pay a $112 million disgorgement penalty for not being in compliance.

According to Abbott spokesman Don Braakman, the company retained Plantation, FL–based AccuReg and Beltsville, MD–based Bio-Reg to address FDA's latest concerns. AccuReg will assist the company in developing and implementing a GMP–quality system plan, while Bio-Reg will perform third-party audit functions. Both consultants, Braakman says, have extensive in vitro diagnostic regulatory and compliance expertise. The first order of business, he adds, will be to develop a plan for FDA to review and approve. No timeline for the completion of the plan has been set.

Contrary to earlier reports, Abbott did not "fire" Quintiles, but retains its services in addition to the new consultants, Braakman said.

FDA Clarifies Conformity to Standards

Device manufacturers can declare conformity to a standard even when their devices are not listed in a particular standard's supplemental information sheets. So states a July 22 FDA publication, "Frequently Asked Questions on the Recognition of Consensus Standards; Guidance for Industry and for FDA Staff." In such situations, the Office of Device Evaluation will determine whether conformity with the standard meets regulatory device requirements.

FDA says that conforming to recognized consensus standards will in most cases eliminate the need for an agency review of the actual test data for those aspects of the device addressed by the standards. A declaration of conformity may also be submitted if a device falls outside the stated scope of a standard, as long as the manufacturer justifies why the standard applies to the device in question.

In addition, FDA will request the submission of data involving a declaration of conformity to standards that constitute actual test methods. According to the guidance, FDA will require the series of tests chosen from the standard, as well as the results of the actual testing.

The guidance also addresses how changes to recognized standards can affect a declaration of conformity. Such changes do not retroactively affect the clearance or approval status of a product. But if changes made to a product result in a less-than-accurate declaration of conformity, the manufacturer must document whether the declaration of conformity still applies to the product. If changes do not affect device safety or efficacy, the manufacturer should maintain records detailing the changes that were made, along with the rationale for why a premarket submission is not needed, and then submit those records to FDA for review.

The guidance is available at http://www.fda.gov/cdrh/ost/guidance/109.pdf.

Cochlear Implants' Link to Disease Suspected

Electrode design is a possible factor in a reported link between cochlear implants and bacterial meningitis, CDRH said in an August 15 notification on its Web site.

According to the center, 52 cases of meningitis have been reported to Advanced Bionics Corp. (Sylmar, CA) and Cochlear Corp. (Englewood, CO) over a period of 14 years. These cases have occurred in children and adults ranging in age from 21 months to 72 years who have undergone cochlear implantation for severe to profound deafness; 9 cases were identified in patients with the Advanced Bionics Clarion device and 15 cases with the Cochlear Nucleus device.

According to the Web site notice, the Clarion device differs from currently marketed cochlear implants in that it uses an additional piece (i.e., a positioner) that is placed into the cochlea next to the electrode to help transmit sound information to the auditory nerve.

During a July 5 ad hoc meeting in Amsterdam, CDRH said, a group of European physicians concluded there were more meningitis cases with the Clarion device than with other cochlear implants and that the use of the positioner may be to blame. Meeting organizers recommended discontinuing use of the positioner and, according to this notice, European regulatory authorities have accepted the recommendations.

Advanced Bionics has agreed to discontinue positioner use in its European-marketed devices. The company said it would also market one of its current electrode systems, the HiFocus, without a positioner. Additionally, CDRH said, Advanced Bionics has initiated a recall of any unimplanted Clarion devices in the United States and says that it will be seeking FDA approval of the HiFocus without an included positioner.

According to the notice, Cochlear Corp., in reviewing its Nucleus device data, claimed to have an overall incidence of reported meningitis comparable to meningitis in the general population. The company said the majority of reported meningitis cases in implanted patients resulted from predisposing factors, such as Mondini deformity or a prior history of meningitis.

To view the updated CDRH notice, visit http://www.fda.gov/cdrh/safety/cochlear.html.

Growth of 400% Predicted for ICDs

FDA expects to see an increase of up to 400% in the number of annual implantable cardioverter defibrillator (ICD) procedures. The agency based this conclusion, reported in a talk paper, on its approval in July of Guidant Corp.'s ICDs for expanded use in patients who have had a previous heart attack and have an ejection fraction less than or equal to 30%. According to CDRH medical officer Helen Barold, the current number of ICD procedures in the United States is estimated to be about 100,000 per year.

Guidant's ICDs were previously approved for patients who had survived cardiac arrests or who had undergone invasive electrical testing to determine their suitability for the devices. The company explains that an ejection fraction of 30% or less is an indication of impaired heart function that puts heart attack survivors at increased risk for sudden cardiac arrest.

Barold said that Guidant's approval does not require any additional postmarketing surveillance. The ICDs will continue under an existing device-tracking order initiated when the devices were first approved in the 1990s. She said it was too difficult even to estimate how many patients now have an ICD.

Approval for the expanded indication was based on results from a multicenter, randomized, controlled clinical trial, the talk paper says. The trial involved more than 1200 patients; 742 received an ICD, while 490 patients were treated with medical therapy alone. According to Guidant, the trial showed that use of its implantable defibrillator reduced the risk of death by 31% for heart attack survivors with compromised heart function compared to the risk for those in the medical therapy group. Only 3% of patients experienced complications with the device, according to the talk paper.

Guidant plans to launch several educational outreach programs for patients and physicians, following an on-line survey of heart attack survivors in which 55% of respondents did not know their ejection fraction. According to the company, these outreach programs are an effort to increase awareness of this important health indicator.

FDA's talk paper can be accessed at http://www.fda.gov/bbs/topics/ANSWERS/2002/ANS01159.html.
 

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