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FDA Enforcement: When Less Is More

    Originally Published MDDI September/October 2003 WASHINGTON WRAP-UP   A white paper issued by Mark McClellan attempts to defend FDA's enforcement activities under the Bush administration. But agency watchdogs and former officials declare it "a joke."

Originally Published MDDI September/October 2003


A white paper issued by Mark McClellan attempts to defend FDA's enforcement activities under the Bush administration. But agency watchdogs and former officials declare it "a joke."

James G. Dickinson

New Magnetic Resonance Diagnostic Guidance | Abbott Ready for New FDA Inspection | First West Nile Test OK'd | Consult FDA Early on Combination Products | SUD Reprocessing Guidance | Guidance on Manufacturer Identification

Despite a demonstrable decline in FDA enforcement activity under President Bush, new agency commissioner Mark McClellan took the astonishing step in July of issuing a white paper asserting the very opposite.

He did so to rebut critical conclusions drawn in an extensive New York Times investigative report by staff reporter Melody Petersen. The story, "Who's Minding the Drugstore?" (June 29), was published just four days after the agency's most senior policy and enforcement leaders had been accused by Congress of ineptness in keeping illegal drugs out of the country. The theme of Petersen's article was that the Bush administration had weakened FDA's enforcement posture by reducing the number of actions it takes against product marketers and by relaxing its vigilance over the promotion of unapproved indications.

Longtime FDA-watchers and former enforcement officials declared McClellan's white paper, titled Protecting the Public Health: FDA Pursues an Aggressive Enforcement Strategy, a joke. They said it whitewashed an enforcement strategy that is far from aggressive. What's more, it used misleading statistics in the effort, they added.

McClellan's paper tackled Petersen's statements only indirectly, by asserting broadly that the agency is "committed to pursuing Food, Drug, and Cosmetic Act violations." It cited the issuance of warning and untitled letters, injunctions, recalls, arrests, and convictions that, it said, "point to dramatically increased enforcement...."

The statements implied that the "dramatic increase" engineered at FDA by the Bush administration was measured from the end of the Clinton administration. The figures cited in the white paper, however, began within the Clinton administration, using a 1998–2002 time frame. During this time, injunctions rose from 11 to 15 and convictions from 194 to 317. (In the first eight months of this fiscal year, FDA has secured nine injunctions and 148 convictions.)

Thus, prosecutions that typically have a three- to four-year time frame per case were launched by FDA under Clinton but were concluded to the accidental credit of the Bush administration—hardly an effective rebuttal of Petersen's argument.

Even more misleading was McClellan's use of product recalls as an indicator of FDA's aggressiveness in enforcement. In the same 1998–2002 period, McClellan claimed, recalls increased from 3532 to 5025. However, except in food cases and rarely invoked recent statutory power over medical devices, FDA has no authority to order product recalls. Recalls for drugs, biologics, veterinary medicines, and the overwhelming majority of devices are voluntary actions by industry. (Sometimes they are extra-legally coerced by FDA, however.) Companies that elect to recall products for safety reasons are legally obliged to report such actions to FDA, and only when they neglect to report does FDA take enforcement measures.

FDA is probably responsible for the confusion that exists on this subject. Seldom known to shed presumed powers it doesn't actually have, the agency for many years has counted recalls along with its enforcement statistics, and it lists them in its Weekly Enforcement Report.

But instead of offering proof of FDA's Bush-era enforcement aggression, the recent rise in product recalls actually may suggest the opposite—a surge in defective products resulting from a major decline in FDA compliance and enforcement activities. These would include FDA-conducted inspections and the prompt issuance of warning letters. (Recent data compiled by FDA's Office of Resource Management show a modest increase in inspections, from 15,146 in 2000 to 18,572 in 2002, but these data absorb an undisclosed but reportedly large number of inspections done for FDA by state agencies and foreign governments under contract. An authoritative source says FDA's own inspections have plummeted in this period and that FDA no longer compiles breakdown statistics that would show this.)

The number of warning letters issued, usually pursuant to an inspection, is widely regarded by FDA lawyers as a more reliable measure of enforcement activity than injunctions and convictions. The incubation time frames for warning letters are much shorter and more current.

Warning letters issued in the first half of calendar year 2003 totaled 264 (30 for medical devices). There were 219 such letters (31 for medical devices) issued in the same period last year, when the full impact of Bush administration FDA chief counsel Daniel Troy's review of all such letters in the Office of Chief Counsel (OCC) was first felt. The corresponding number in the first half of FY 2001—a year more typical of FDA enforcement than those that have followed Troy's appointment—was 765 (73). Thus, warning letters have declined by more than 50% since Bush took the White House.

McClellan's white paper skirted Petersen's account of the decline in warning letters and the reason for routing all drafts through Troy's office—high-level HHS concern about the "hodgepodge" nature of FDA's letters to industry, as revealed to MD&DI in a December 6, 2002, conversation with HHS deputy secretary Claude Allen.

Instead, McClellan claims legal reviews in the OCC have "enhanced the legal foundation of the that they can provide a solid basis for court action." (MD&DI, however, was unable to find any court actions based on warning letters since the reviews began.) The white paper states OCC reviews have "not appreciably reduced the number of letters on promotional activities being issued," but Petersen's report said the letters have fallen to two per month so far this year, from about 10 per month previously.

Neither McClellan nor Troy, who were each sent prepublication versions of this article, responded to requests for comment.

New Magnetic Resonance Diagnostic Guidance

In a July 14 guidance for industry and FDA staff, CDRH has increased its recommendation for the main static magnetic field strength of magnetic resonance diagnostic devices from 4 T to 8 T for most patient populations. Titled Criteria for Significant Risk Investigations of Magnetic Resonance Diagnostic Devices, the document supersedes Guidance for Magnetic Resonance Diagnostic Devices—Criteria for Significant Risk Investigations, issued in September 1997. The updated guidance describes "the device operation conditions . . . that FDA considers a significant risk for the purposes of determining whether a clinical study requires agency approval of an Investigational Device Exemption (IDE)."

CDRH recommends that the following operating conditions be considered when assessing whether a study may pose a risk: (1) main static magnetic field, (2) specific absorption rate, (3) gradient fields' rate of change, and (4) sound-pressure level. "These criteria," it says, "apply only to device operating conditions. Other aspects of the study may involve significant risks and the study, therefore, may require IDE approval regardless of operating conditions." The guidance may be accessed at

Abbott Ready for New FDA Inspection

Abbott Laboratories says that it is on track to be reinspected by FDA by the end of the year, under its GMP consent decree. The company continues to meet "periodically and productively" with FDA, and it is making significant progress on quality and compliance initiatives, said investor-relations vice president John Thomas during an earnings conference call on July 10. He added that the company's diagnostics division is meeting its internal targets.

Earlier this year, Abbott Medical Products Group president Rick Gonzalez said the company had been working in concert with its new regulatory consultants and FDA in "devising solutions to our quality systems that are simple, systemic, and sustained." One such solution, he noted, is the initiation of "quality systems remediation efforts." According to Gonzalez, Abbott has been progressing through the implementation phase of those efforts. "Our regulatory consultants are conducting rolling audits to ensure that we are fully prepared for a facility inspection shortly after the completion of this phase," he added.

In 1999, the company was fined $100 million as part of a consent decree with FDA for continuing compliance problems at its diagnostic manufacturing operations in Lake County, IL. Then, in 2002, Abbott was hit with a $112 million disgorgement penalty after it failed a reinspection and was found out of compliance with the consent decree.

First West Nile Test OK'd

In July, FDA cleared a PanBio Ltd. (Windsor, Brisbane, Australia) 510(k) application for the first test to aid in the clinical laboratory diagnosis of West Nile virus infection. Named West Nile Virus IgM Capture ELISA, the device is intended for use in patients "with clinical symptoms consistent with viral encephalitis/meningitis," according to an FDA news release.

The test works by detecting levels of antibody (IgM) to the disease in a patient's serum. IgM antibodies can be detected within the first few days of the onset of illness and, according to FDA, can assist in diagnosing patients. FDA said the West Nile assay was evaluated using more than 1000 patient sera, which were tested at four different clinical sites. The PanBio test "correctly identified antibody in up to 90–99% of West Nile virus disease cases," added the agency.

While this test is considered a valuable aid in diagnosing West Nile, FDA says there is a need to confirm positive results by an additional test or by using the current CDC diagnostic guidelines for diagnosis of this disease, because of West Nile's similarities to other viruses in the same family.

Consult FDA Early on Combination Products

"Take the initiative. Ask FDA for its opinion, advice, and guidance early in the product development process." This was the overarching message to manufacturers delivered by FDA speakers at a session on drug-device combination products at the Drug Information Association's annual meeting in San Antonio, TX, in June. CDRH chemistry–team leader Kasturi Srinivasachar pointed out that development of drug-device combination products, unlike drugs or devices alone, represents "constantly moving targets." He emphasized that chemistry and manufacturing control (CMC) procedures must be flexible enough to take this fact into account. FDA's regulatory requirements must take it into account as well, he added. CDRH biomedical engineer Jonette Foy agreed: "Combination products are, by their nature, complex—and will become more so in the future, when they may well utilize two or even three drugs in combination with a device," she said.

According to Srinivasachar, FDA is seeking ways to design "risk-based product reviews" to evaluate CMC issues in the manufacturing process. Combination products containing elements deemed "low-risk"—for example, drugs known to be "robust," stable, and for which there is a long history of safety and efficacy in clinical use—may receive less scrutiny than others whose characteristics are not as well defined. Srinivasachar said the effort to identify criteria for defining "low-risk" products is now under way, and he insisted that such criteria, in all cases, be "science-based."

Shortly after these presentations, Becton Dickinson Medical Systems regulatory affairs director Keith M. Smith conducted a workshop in Bethesda, MD, on innovative drug-biologic delivery systems. He told those in attendance that FDA should retain its current interpretation of "primary mode of action" when deciding which center has primary jurisdiction over a new combination product. Speaking on AdvaMed's behalf, Smith said the group's members have come to rely on interpreting primary mode of action by analyzing the combination product as a whole and by its intended function. This analysis has allowed many "innovative and important combinations to reach market using device jurisdictional standards," he said.

AdvaMed is opposed to any change in interpretation of primary mode of action that would shift innovative technology–based products currently reviewed by CDRH to either CDER's or CBER's jurisdiction, Smith said. "Innovation has been fostered because of the legal and policy initiatives that are uniquely available under our device premarket review structure," he added.

SUD Reprocessing Guidance

CDRH has released a guidance on the content and format of cleaning, sterilization, and functional-performance validation data in 510(k) applications required by the Medical Device User Fee and Modernization Act (MDUFMA) for reprocessed single-use devices. Titled Medical Device User Fee and Modernization Act of 2002, Validation Data in Premarket Notification Submissions (510(k)s) for Reprocessed Single-Use Medical Devices, the document supersedes "any other guidance document that recommends less complete data and information than [CDRH has] described in this document." For example, it says, "Blue Book document K90-1 describes information on sterilization processes that FDA recommends manufacturers submit in 510(k)s. Section 302(b) of MDUFMA and this guidance supersede K90-1 as it relates to the scope of the validation data to be submitted in 510(k)s on the cleaning, sterilization, and functional-performance aspects of reprocessed SUDs that require the submission of such validation data." The new guidance may be accessed at

Guidance on Manufacturer Identification

FDA has released a draft guidance for industry and FDA staff titled Compliance with Section 301 of the Medical Device User Fee and Modernization Act of 2002 —Identification of Manufacturer of Medical Devices. The new statute requires that a device, or an attachment to a device, bear the name of the manufacturer, a generally recognized abbreviation of the name, or a unique and generally recognized symbol that identifies the manufacturer. The legislation becomes effective on April 26, 2004, for devices introduced or delivered for introduction into interstate commerce after that date.

The guidance, according to FDA, says that when exercising enforcement discretion, the agency intends not to raise objections if a manufacturer has not implemented the changes required by Sec. 301 for devices introduced after April 26, 2004, for a period of up to 18 months after FDA issues final guidance on its interpretation and implementation of that section of MDUFMA. The guidance may be accessed at

Copyright ©2003 Medical Device & Diagnostic Industry

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