Originally Published MDDI October 2001

WASHINGTON WRAP-UP

The appointment of a conservative chief counsel at FDA has industry wondering if it is the first in a series of moves designed to establish an attitude of less-rigorous enforcement at the agency.

James G. Dickinson

FDA Policy on SUDs Called 'Irrational | Industry Faults FDA Efforts to Ease Regulation | FDA Rejects TMJ Implants Protest | Heart Valve Took 15 Years to Approve

Washington circles that watch FDA closely have been rife with rumors about the Bush administration's plans for the agency. The longer FDA goes without a commissioner, the more the pressure to fill the vacancy grows, fueled by industry complaints that without a leader bureaucrats are becoming more unreasonable.

Along with more-frequent plant inspections and slower progress on "least burdensome" paperwork reforms, there have been episodes that some FDA-watchers characterize as device-review abuses. These include the TMJ Implants case, covered previously in this column, which has now moved into the political arena, and the even slower FDA approval of the MedicalCV Omnicarbon heart valve. (Both issues are covered below.)

These situations are extremes, of course, and most companies have fared better. But these examples add to the political static in Washington, and to expectations that new Bush appointees will "rein in" FDA. The biotech industry is even more impatient on this issue than the device industry.

In August, no strong front-runner had yet emerged in the quest for a commissioner. But the administration let go FDA's chief counsel of 11 years, Margaret Porter (appointed in the first Bush administration). Taking her place was conservative lawyer Daniel E. Troy, of the Washington law firm of Wiley Rein & Fielding. A former clerk of controversial conservative judge Robert Bork and a scholar at the conservative American Enterprise Institute, Troy has written strongly in favor of full constitutional protection for commercial speech in advertising. Such protection could stifle FDA and FTC regulation of promotional materials.

At first, Troy's appointment was seen as a move to curb FDA's excesses, crafted to get around Democratic opposition in the Senate to the likely nomination for commissioner. Earlier rumors that President Bush intended to nominate one of a clutch of industry-connected conservatives had provoked liberal senator Edward M. Kennedy and his allies on the committee that will confirm any new commissioner to protest in writing to President Bush.

Thus, Troy's appointment—which needed no advice and consent from the Senate—was seen as a reaction to that protest. Until Bush is able to place someone in the commissioner's office who will meet Kennedy's approval, perhaps Troy can bring about more regulatory circumspection at the agency.

In a brief statement to this writer, Kennedy said Troy was known to be "a staunch opponent of efforts to have vigorous FDA enforcement." Because this selection does not require Senate confirmation, he added, "there is nothing we can do about this." Kennedy said he disagrees with Republicans who think FDA is an agency that needs reduction.

A similar criticism came from Public Citizen Health Research Group director Sidney M. Wolfe. The Bush administration chose Troy, he said, "because they want to get in someone who represents the business interests, someone who believes that commercial free speech has got to be left so free that you can't come down on advertising." Wolfe said he had let it be known inside FDA's Office of Chief Counsel that he wants to be told if Troy "does things that are several standard deviations off of what they should be doing. If this person is not going to facilitate law enforcement, or is going to block it, then he needs to be pushed out as quickly as possible."

Such views of Troy were quickly counterbalanced by positive assessments, however. Peter Barton Hutt, dean of FDA lawyers, spoke enthusiastically of the appointment. "He's a superb lawyer, [he] comes with breadth of experience, he's a hands-on person. He reminds me a great deal of where I was when I came to the agency."

"When I came to FDA," Hutt said, "everybody predicted I was there as a token for the industry, and I think that was disproved pretty quickly. [Troy] wants to help the agency, he wants to work with the agency, he wants to learn a lot about it, and he wants to do a damn good job, like any good lawyer would want. I'm very enthused." Hutt said he had spent "quite a bit of time" with Troy discussing the position since his appointment became known. Troy, he said, is "going around town and meeting with all kinds of people" to learn about the job.

As for Troy's outspoken views on the First Amendment and criticism of FDA's attempts to restrict manufacturer support of educational and scientific materials, Hutt said: "He's right. FDA has had its head in the sand. They've lost every single court decision on this. They are destroying their credibility in the courts. You can't just pretend that the First Amendment doesn't exist—that's ludicrous. As long as FDA tries that, they aren't going to win a single court case, and they're going to have everybody in the country litigating against them."

Hutt predicted that Troy will be sympathetic to strong FDA enforcement. Noting that this was just as he himself had always been, Hutt took the opportunity to lambaste Congress for "strangling FDA to death."

Two other former FDA chief counsels, Tom Scarlett (Reagan administration) and Nancy Buc (Carter), also expressed optimism about the appointment.

Scarlett said he expected that Troy "is probably going to be a good chief counsel." He agreed with Troy's criticisms of FDA's "uphill climb" in arguing against the Washington Legal Foundation.

Although coming from the opposite side of the political spectrum, Buc warmly applauded the choice, saying Troy "is a terrific lawyer."

FDA Policy on SUDs Called 'Irrational'

CDRH's policy on single-use devices (SUDs) is irrational, unlawful, and in the absence of adequate safety and effectiveness data, fails to protect patients, asserts the Association of Disposable Device Manufacturers (ADDM) in an August 3 citizen petition. The group is requesting that FDA regulate SUDs as reusable medical products. In addition, the agency should refuse to approve PMAs or 510(k)s for reprocessed SUDs that are labeled "single use only," ADDM claims.

The petition says that giving premarket approval to multiple-use devices labeled as single-use is both false and unlawful because the conditions of use stated in the product's labeling are not those under which the devices are intended to be used. In fact, the group says, since these devices are not shown to be equivalent to other multiple-use devices, they are actually unapproved Class III devices, and therefore adulterated under FDA's own standards.

ADDM's petition faults FDA's premarket guidance and other agency correspondence that allow a reprocessor to label a reprocessed SUD "single use only" even when the device has not only been previously used, but will be reprocessed again after the current use. "The practical effect of this policy is that, unlike submissions for all other reusable devices, reprocessors' premarket submissions will not contain data demonstrating that the device is safe and effective after multiple reprocessing procedures, or data establishing the maximum number of reuses for a given device."

Industry Faults FDA Efforts to Ease Regulation

An FDA draft guidance on the least burdensome ways of regulating medical devices must be aggressively implemented or the benefits of the principles in the document will not be realized, says industry association Adva-Med. The group's comments came in a July 30 response letter to a draft FDA document, "The Least Burdensome Provisions of the FDA Modernization Act of 1997: Concept and Principles." The association said that if these principles were "applied within the spirit in which they were written, then a productive collaboration between FDA and industry representatives could result."

AdvaMed's letter said it approves of the agency's interpretation of the least burdensome concept and the scope of its application to all medical devices, including in vitro diagnostics and all pre- and postmarket activities. However, the group stressed the need for training and follow-up activities within the agency. "The least burdensome concept represents a cultural shift within FDA and this shift will occur only through effective training activities conducted at periodic intervals with appropriate follow-up and reinforcement," the group said.

Similarly, AdvaMed recently told FDA in a June 26 letter that its requirements for hepatitis C assay PMAs as outlined in a new guidance document are excessive, considering that these products have been marketed without significant problems for some time. The object of AdvaMed's remarks was the document, "Guidance on Premarket Approval Applications for Assays Pertaining to Hepatitis C Viruses (HCV) That Are Indicated for Diagnosis or Monitoring of HCV Infection or Associated Disease." It should be revised to allow the use of well-characterized stored samples to demonstrate the safety and effectiveness of these products, the group said. "We believe that this concept for sample bank correlation studies should be added to the next draft of the guidance, with the stipulation that each stored sample have sufficient patient clinical information so that the patient information can be used for discrepant resolution when the tests being compared do not give the same answer."

The group complained that the guidance was overly burdensome. For example, the document recommends that many studies be performed in each matrix to be claimed (serum and each plasma type). "This should only be necessary if differences in performance are demonstrated during serum/plasma equivalence studies," Advamed said. "Where equivalent performance has been demonstrated, it would be overly burdensome and unnecessary to perform stability, analytical sensitivity, interference, reproducibility, etc., on each matrix type."

FDA Rejects TMJ Implants' Protest

Relationships that the lead reviewer of TMJ Implants Inc.'s devices had with a variety of individuals and entities during the review "do not constitute a violation of the 'conflict of interest' criminal statutes or regulations." So wrote FDA Office of Internal Affairs special agent in charge Donald L. Briggs, Jr., in a July 25 letter to company president Robert W. Christensen. He was replying to complaints Christensen had made about the reviewer, Susan Runner, and her prior relationships with a consultant to a trade competitor, two FDA advisory panel members, a temporomandibular joint (TMJ) patients' support group, and FDA's Office of Women's Health.

Christensen had contended that Runner's relationships with these entities were evidence of bias against his two pre-1976 prostheses, which FDA had forced from the market for 20 months pending a problem-plagued review of their PMA applications. The devices were ultimately approved last February.

In his letter to Christensen, Briggs said his office "is declining to investigate these matters. However, since your letter indicates you are seeking an HHS Office of Inspector General investigation, I am forwarding your letters, with attachments, to the HHS Office of Inspector General, via this letter, for any action they deem appropriate."

However, like Briggs's office, the Inspector General's office has declined to investigate Christensen's complaints, except in the context of a broad examination of CDRH device-review practices.

Briggs's letter crossed in the mail a letter Christensen faxed to CDRH integrity officer Carl De Marco. In it he criticized both De Marco and CDRH ombudsman Les Weinstein for claiming an inability to investigate allegations of wrongdoing by FDA employees. By taking this stance, he said, the two "have become deflection officers whose functions appear to have been to protect the bureaucracy, including perhaps supervisors who failed to address employee misbehavior when evidence of that behavior is so strong."

Christensen wrote that FDA has "a history of cover-up," not only in his case but also in a 1995 case involving the Tukwila, WA, dental monitors manufacturer Myotronics, which was investigated by a House subcommittee. In that case, Christensen told De Marco, "chairman Joe Barton (R–Texas) made it abundantly clear that the [Office of Internal Affairs] did not have the ability to investigate FDA wrongdoing and thus referred it to the IG. . . . If you are sincere in your desire to see the TMJ Implants Inc. case objectively investigated, you will assist the company in its efforts to compel both congressional hearings and an IG investigation."

Christensen copied his letter to 17 senators and representatives, including Barton.

Heart Valve Took 15 Years to Approve

FDA moved too slowly to approve a heart valve device that could have saved thousands of lives, the Competitive Enterprise Institute (CEI) complained in a July 27 statement. The statement coincided with the device's approval after a 15-year review. The conservative think tank said MedicalCV's Omnicarbon heart valve has been available on the European and Japanese markets since 1986.

According to CEI, Medical Incorporated, now MedicalCV, filed its PMA application in 1986. FDA denied it in 1989, however, requesting more information from the company. "Ironically," says the Institute, the device was developed in the United States, and "for at least 15 years has been manufactured here and exported with FDA approval. Only now, however, will it actually be available to physicians and patients in this country."

"The Omnicarbon's pyrolite construction significantly reduces embolism risk," said CEI. Citing the statistic that approximately 16,000 heart valve recipients a year die from bleeding complications in the United States, the group argued that the Omnicarbon valve offers major life-saving benefits. These benefits were denied to the American public due to FDA's 15-year delay, said CEI.

According to MedicalCV, the now-approved device is a monoleaflet (tilting-disk) mechanical valve, with both the disk and the housing ring constructed from pyrolytic carbon. It is rotatable, causes minimal cardiac energy loss, and has a particularly low complication rate for both thromboembolism and hemorrhage, the company said.

CDRH Office of Device Evaluation deputy director for clinical policy Dan Schultz described the Omnicarbon review as an "aberrant" case that involved an "excessive amount of time." Not many people in the center remember the early difficulties that faced the PMA application when it was submitted, but they do recall that the aftershocks of the Shiley heart valve failures were still affecting the reviews of all heart valves. "There was an attitude of relative conservatism," Schultz said.

In addition, there were scientific disagreements about the clinical data submitted by the sponsor. As time passed, interpretation of the data became increasingly difficult in light of changes in medical practice and the design of clinical protocols. "If you don't get an early approval, and the review extends to 3, 4, or even 5 years, these difficulties become greater," Schultz said. There were also periods when the company "was not terribly responsive" to reviewers' concerns.

Finally, the review took so long that, paradoxically, those disagreements about the data were gradually overtaken by accumulated clinical evidence from the trials. This event finally enabled the center to approve the device despite those data-oriented concerns.

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

Copyright © 2001 Medical Device & Diagnostic Industry