WASHINGTON WRAP-UP

When FDA gets questions it doesn't know how—or doesn't want—to answer, it often invokes a policy of silence. This may infuriate companies that feel truth is on their side. But in most cases, the firms just submit to the agency's authority because fighting FDA in court is not cost-effective.

It is now the first anniversary of the agency's federal court loss to Utah Medical Products. Utah Medical says FDA might have spared itself that defeat if it had engaged in meaningful dialogue with the company. However, FDA is again taking a policy of silence to a federal judge in a case involving TMJ Implants (TMJI; Golden, CO).

As in the Utah Medical case, the FDA Denver district office and CDRH compliance office are throwing the book at a small device firm.

In Utah Medical's case, the agency sued in federal court to shut the company down even though no safety and effectiveness issues were in question. In the TMJI case, FDA is suing before its own administrative law judge, Daniel Davidson. The agency is asking for $630,000 in civil monetary penalties because TMJI refused to file 17 adverse event reports. TMJI says it investigated the incidents and found that they did not involve faults with its devices. The case is scheduled to be heard November 30.

TMJI had insisted on a meaningful discussion with the agency before submitting the reports. FDA's refusal to discuss the substantive merits or demerits of its lower-level staffers' assessments is a central feature of both the Utah Medical and TMJI cases. In both cases, FDA's posture appeared to be that manufacturers must comply with its demands or go to court.

This is one face of a long-standing and broad FDA policy of silence that produces self-wounding losses in the court of public opinion as well as in courts of law. For example, public opinion of FDA has plummeted on issues such as drug safety and advisory committee conflicts of interest.

In a brief to Judge Davidson, TMJI scorns CDRH claims that regulators engaged in dialogue before suing. TMJI says that's not true. TMJI did not receive a substantive medical explanation from any agency personnel before FDA filed the complaint, according to the company. “Instead, TMJI received conclusory statements that simply mirrored the text of the MDR rule and that reflected a lack of understanding of the full range of medical issues involved. TMJI repeatedly attempted to engage in a dialogue with the agency at the medical expert level, but the agency refused.”

TMJI president Robert Christensen says he wanted to know who at CDRH was making the medical decisions that rendered each of the 17 events reportable. He wonders about the quality of their medical expertise as well. However, the center declined to respond.

Christensen says his stand was based on his knowledge as the device's inventor and his 40 years of experience as a manufacturer and implanting surgeon. He also based it on a history of alleged CDRH bias against his company. This includes alleged preferential treatment of a competitor and a 20-month delay in approving his two reclassified temporomandibular joint prostheses in 2002.

Despite that, Christensen says he would have submitted the reports if the center had warned him that civil monetary penalties would be sought. CDRH gave him no warning, he says. The center declined to provide its side of the matter for this story.

FDA's legal posture in the case suggests that it does not trust Christensen to be both judge and jury on whether an event should be reported and publicly posted on the MDR Web site. Christensen is also concerned with what his allegedly CDRH-favored rival, TMJ Concepts, would do in the marketplace with such a mass posting of what he calls “unwarranted” MDRs.

But there's more to this story. Both CDRH and TMJI filed briefing documents with Judge Davidson when the parties reached an impasse in 2004 on the MDR reportability of the events. At that time, TMJI decided to follow the advice of CDRH director Daniel Schultz and appeal to the commissioner.

However, after eight months of waiting for a response, TMJI was served with the complaint for civil monetary penalties. Three days later, it received a letter from the commissioner's office. The letter apologized for the delay and denied the appeal on grounds that a complaint for civil penalties had already been filed.

According to TMJI corporate attorney Lynn Watwood, the commissioner did not act in good faith. Agency documents show that eight months earlier, the commissioner was involved in the internal discussions about seeking civil monetary penalties against TMJI. This not only ignored due process but also violated the company's Fifth Amendment rights, Watwood says.

Longtime Christensen ally Roland Jankelson, whose own company, Myo-Tronics, bested CDRH in a similar battle in 1997, goes further. “It was the agency that instructed the company to appeal,” he says. “Then, while waiting for a response to its appeal, [TMJI] got hit with the [complaint]. I'd call that an ambush.”

CDRH told Judge Davidson in a brief that it was “entirely appropriate” to reject TMJI's petition. The center argued that it is within the commissioner's discretion whether to review any matter. “In this instance,” CDRH said, “several factors support the decision by the commissioner not to hear the appeal.

“First,” the center's brief said, “TMJI's disagreement with CDRH is one appropriately resolved at the center level. Accordingly, were it not for TMJI's stubborn refusal to accept the agency's reasonable interpretations of the MDR rule, which FDA was explicitly authorized to interpret and enforce, the issues here could have been resolved within CDRH.” But Christensen's view is that the center appeared to have no interest in resolving the issues. After all, he says, it was CDRH director Schultz who told TMJI he was not “the last word” on the matter and that TMJI could appeal to the commissioner.

Second, CDRH's brief continues, just because a company files an appeal “does not preclude FDA from initiating an action to enforce the MDR rule.”

Third, TMJI's dispute “does not involve policy questions or an unusual situation that required immediate review by the commissioner.” The brief continues that the dispute did not negate the commissioner's discretion to deny the appeal request. Besides, everybody else in the device industry was complying with CDRH's interpretations and requirements under the MDR rule.

On the basic issue of event reportability, TMJI believes that it is legally not required to report events it has determined were not caused by its device. A CDRH brief, however, takes the opposite view. It points out that during a May 10, 2004, meeting with representatives from FDA's Denver district, TMJI was told that “injuries that are symptomatic of TMJ disorder or intrinsically associated with the device are reportable.” The company was also told that Congress has “broadened the definition of what needs to be reported” through the MDR rule. Moreover, in July of that year, FDA told TMJI in writing that “definitive proof of causation was not a prerequisite for filing MDRs.”

In other words, CDRH's interpretation is final, and no discussion of it will be entered into. In Christensen's mind, the absence of scientist-to-scientist discussion between the company and CDRH about the real nature of the 17 contested events is a pivotal issue. Substantive silence had been the center's Achilles's heel in the Utah Medical case and nine years before in the Myo-Tronics case as well.

At the time of his firm's win, Utah Medical CEO Kevin Cornwell said, “It is impossible to constructively resolve differences when one side simply shuts off all dialogue. For years, our repeated requests for feedback regarding our detailed written responses to largely sham FDA-483 observations were ignored. FDA's mission in this case was not to protect public health, but to show who is boss.”

Asked to comment, all FDA and center officials who were approached invoked the agency's silence policy.

Marketing Combination ASRs Can Void Exemption Status

FDA says that marketing a Class 1 510(k)-exempt analyte-specific reagent (ASR) in combination with other devices or tests can void the ASR's exemption status. A new draft guidance, “Commercially Distributed Analyte Specific Reagents: Frequently Asked Questions,” has been issued. It says the following scenarios are inconsistent with what FDA views as the proper marketing of a 510(k)-exempt ASR:

• Combining, or promoting for use, a single ASR with other products such as other ASRs, general-purpose reagents, controls, laboratory equipment, software, etc.
• Promoting an ASR with specific analytical or clinical performance claims, instructions for use in a particular test, or instructions for validation of a specific test using the ASR.

The guidance says that when an ASR is marketed in ways described above, the product is no longer considered an ASR as defined by 21 CFR 860.4020. Instead, it would be considered part of a test system. To view the guidance, visit www.fda.gov/ohrms/dockets/98fr/06d-0336-gdl0001.pdf.

Jail Time for Two Abtox Medical Execs

In September, Chicago federal judge Ruben Castillo sentenced Ross Caputo, president and CEO of now-defunct Abtox Medical, to 10 years in federal prison. Caputo and his vice president, Robert Riley, who received a six-year sentence, were convicted for illegal sales of sterilizers to hospitals. The sterilizers were reported to have caused 18 people to lose sight in one eye.

Caputo and Riley were jointly ordered to pay more than $17 million to hospitals that purchased the sterilizers.

The Chicago Tribune reported that Castillo characterized Caputo as a man who might be a brilliant scientist but could not be considered a medical doctor. “While I don't consider you to be totally evil,” the newspaper quoted him as telling the defendant, “I do consider you to believe you are somehow above the law.”

Rejecting the pair's late plea for a new trial, Castillo called Riley “a dupe whom Caputo used at Abtox and during the trial,” the Tribune said.

The ruling also seems to endorse the hard-line approach taken three years ago by FDA deputy chief counsel for litigation Eric Blumberg. The judge's sentence recalls Blumberg's comments in Chicago at the Association of Food and Drug Officials national meeting in 2003. As if to counter a weakening trend in FDA enforcement resources, Blumberg warned senior managers in attendance that his agency would hold them accountable if they did not respond properly to FDA warnings.

Abtox was located less than 40 miles from the meeting's downtown venue. However, it's unlikely that anybody from the company was there to hear Blumberg review the Supreme Court rulings on the 1975 Park decision and the 1943 Dotterweich decision. Both cases dealt with strict liability. They established that persons in a position of authority in a company regulated by FDA must accept this strict liability. Those persons can also be held accountable if they fail to correct violation of the Federal Food, Drug, and Cosmetic Act or fail to ensure that violations do not occur in the first place.

Assistant U.S. Attorney Michael Gurland said the prison sentences would send notice through the device industry that lying to FDA or violating its regulations will not be tolerated. This statement adds weight to Blumberg's predictions made in 2003.

Wallach Surgical Warned by FDA

A June inspection at the Wallach Surgical Devices manufacturing facility in Orange, CT, found CGMP violations for the company's Endocell endometrial cell sampler, Inseminator catheter, and LL100 cryosurgical system. A recent warning letter from FDA's New England district office listed multiple violations (see sidebar on this page).

FDA district director Gail Costello said a written response from the company made general commitments to certain FDA-483 inspection items. However, it failed to address specific systemwide corrective actions necessary to bring the company into compliance. She said the response also did not document corrections made.

Wallach Surgical was told to respond within 15 working days with a list of additional steps taken to correct the problems. The agency also expects an explanation of how the firm would prevent the violations from happening again.

U.S. Marshals Seize Alaris Infusion Pumps

At FDA's request, U.S. marshals in San Diego seized $1.8 million worth of Cardinal Health's Alaris Signature Edition Gold infusion pumps (Models 7130, 7131, 7230, and 7231) in August. A design defect called key bounce prompted the action. Key bounce may cause drug overinfusion. “This seizure was intended to ensure that infusion pumps located at Alaris's manufacturing facility are not distributed unless the problem is corrected,” an FDA release said. Agency inspections found that Alaris failed to follow the quality system regulation.

A key bounce occurs when the pump registers a command twice, although the operator has only pressed the command key once. “If a key bounce occurs and is not detected during programming verification, it may result in an infusion rate at least 10 times the intended infusion rate,” FDA said.

Warning letters were issued to Alaris in August 1998 and again 14 months later. The company was also “given opportunities to correct the violations, but failed to take appropriate actions,” FDA said. A company product recall letter in August provided users with ways to minimize key entry errors until the problem could be corrected.

In a statement issued after the seizure, Cardinal Health said it had suspended the pump's production, sales, repairs, and installations. It estimated that about 1300 pumps were seized. It said manufacturing and distribution would resume pending resolution of the issue with FDA.

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