WASHINGTON WRAP-UP

In response to a series of Seattle Times exposés about two unapproved medical devices, Timothy Ulatowski told the newspaper in December that the agency is taking action against the products. Ulatowski is CDRH compliance director. Both products are manufactured overseas. Both are considered risky and are being blocked by U.S. Customs from entry.

One device is the PAP-IMI ion magnetic inductor, manufactured in Greece by Panos Pappas and illegally marketed to clinics for pain relief. The other is the EPFX (electrophysiological feedback Xrroid), manufactured in Hungary by William Nelson and illegally marketed to hospitals and clinics to treat cancer and AIDS.

FDA turned over its 2001–2005 investigation of the PAP-IMI to the state of California—a decision that kept hundreds of the devices in use elsewhere. California regulators treated the device as an economic fraud rather than a health hazard.

Before FDA ceded its interest, CDRH Division of Bioresearch Monitoring director Michael Marcarelli declared the device “adulterated” in a letter sent to a Chatsworth, CA, address for Pappas, who is based in Athens. He also directed the manufacturer to “notify all involved IRBs [institutional review boards] of FDA's determination that your investigation is a significant risk device study” and said that the IRBs “must immediately discontinue enrollment of new subjects.”

In making this determination, CDRH effectively overruled Pappas's IRB, Texas Applied Biomedical Services, which Marcarelli acknowledged had “determined that these studies present a nonsignificant risk.” The Seattle Times reported that Pappas had shipped the devices—mislabeled as agricultural seed germinators—to his U.S. collaborator even though FDA denied him permission to market them in 1995.

His collaborator, salesman Charles Wallace, now deceased, set up Bio-Energy Services for the devices as a treatment clinic in Tarzana, CA. FDA investigators James Fleckenstein and Vanessa Mullen inspected the facility after being alerted by an anonymous whistleblower. In September 2002, they issued a damning establishment inspection report and a 14-observation FDA-483.

Fleckenstein told the Seattle Times that he was horrified by what he saw: a baby being pulsed by the PAP-IMI. “We went through the roof,” he told the newspaper. “We knew we had to pursue this.” The PAP-IMI was one of the most egregious cases in his 30-year career, he said.

FDA decided to turn the case over to the California Food and Drug Branch. Bio-Energy Services continued sales and treatments, and a patient died, the newspaper reported. FDA inspected three PAP-IMI clinics outside California, but the agency appears to have taken no enforcement actions against Pappas other than Marcarelli's untitled letter to him in 2005.

Meanwhile, with the PAP-IMI now denied admission into the United States, local entrepreneurs have been filling the void with imitation, and equally unapproved devices, the Seattle Times reported. One of these entrepreneurs, it said, is Mike Davis, president of PEMF Systems in Las Vegas, who is marketing imitation devices under a variety of names, including Magnapulse. He told the newspaper that he planned to get FDA approval to use the machines in a clinical study, but in the meantime has reportedly sold 300 worldwide, half of them in the United States. The original PAP-IMI is still being promoted at www.papimi.com.

In the case of the EPFX machine, the Seattle Times quoted Ulatowski as saying, “This is pure, blatant fraud. The claims are baloney.” FDA acknowledged that it took action as a result of the newspaper's reports.

Also in response, the House Commerce Subcommittee on Oversight and Investigations opened its own investigation into how these manufacturers have taken advantage of federal loopholes to profit from the machines. In addition, the Washington State Chiropractic Association asked its state regulatory board to ban the EPFX.

According to the Seattle Times, Nelson registered his company, Eclosion, with FDA in 1989. But within three years he was warned to stop making fraudulent claims that the EPFX could diagnose and heal. In 1996, the newspaper said, he fled the United States after he was indicted on nine counts of felony fraud and reestablished marketing operations in Budapest, where they continue.

Ulatowski told the newspaper that Nelson's registration as a medical device manufacturer has recently been revoked, allowing the agency to seize the EPFX machines at U.S. borders. Five of Nelson's six largest distributors are in the United States.

FDA Preemption Backed by Bush Administration

The Bush administration told the Supreme Court in December that the federal preemption clause in the Medical Device Amendments of 1976 protects device companies from being sued in state courts by patients allegedly injured by an FDA-approved device. Arguing in Riegel v. Medtronic, U.S. deputy solicitor general Edwin Kneedler told the nine justices that there would be a “serious undermining of FDA's approval authority and its balancing of the risks and benefits, if a state jury could reweigh those.” The case involves a New Yorker who was treated with a Medtronic balloon catheter that burst, necessitating emergency bypass surgery. He subsequently died.

Medtronic's lawyer, Theodore Olson, argued that state tort claims would be preempted even in situations in which the manufacturer became aware of a new risk and failed to share it with FDA. “(T)hat's a judgment that Congress made, because the manufacturer would then be violating the law by failing to tell FDA what was going on, perhaps committing fraud, and be subject to criminal penalties, recall penalties, and civil penalties.”

Several of the justices asked for clarification from Olson about what happens when significant risks are discovered about a device in the marketplace, and whether device makers are liable when injuries occur before devices are modified to address the new risks. Olson said preemption would still apply to such claims. “And the reason for that is that someone must make a judgment that the information the manufacturer may have learned may [compromise] some aspect of the safety or effectiveness of the device, but it still might be the best product available. As the government points out in its brief, there are some devices that are used in situations [in which] a child might die. There's a 50% mortality rate even with using the device. So there have to be individual judgments with respect to variations of risk and safety and availability.”

Arguing on behalf of the injured patient, Public Citizen Litigation Group's Allison Zieve said that although FDA approved the device, if the device maker knew of a risk and could have made it safer by modifying the label or changing the design, those changes should have been made. It's negligence on the manufacturer's part to market a device—even if it was approved by FDA—when there is a better one that would reduce the risks, she said. Chief Justice John Roberts interrupted her for clarification: “It's not that it is not reasonably safe, it's that another design would be safer?” he asked. “And you think that's a basis for negligence because you say, yes, FDA approved it, but that doesn't mean [the agency] required the manufacturer to market that device?” That's right, Zieve responded.

The Supreme Court is expected to issue its opinion before July 2008.

Revoking FDA's Self-Policing Power May Not Be Enough

FDA's authority to investigate itself when employee misconduct is alleged was rescinded in November when the HHS Office of the Inspector General (OIG) reclaimed that authority. However, Roland Jankelson quickly told the House Energy and Commerce leadership that this step may not be enough to prevent continuing abuses. He cited alleged CDRH abuse of TMJ Implants (TMJI; Golden, CO) and his own company, Myotronics Inc. (Kent, WA), in 1997.

OIG improperly abandoned a strong case it had built several years ago against CDRH employees in the TMJI matter, Jankelson wrote in a letter to committee chairman John Dingell (D–MI) and Subcommittee on Oversight and Investigations chairman Bart Stupak (D–MI).

OIG had been “presented with compelling evidence of multiple abuses—[including] conflicts of interest and manipulation of the premarket approval [PMA] process to assure a desired outcome,” Jankelson wrote. He said this abuse included the “manipulation and stacking of a review panel and treating TMJI's PMA review with different (harsher) standards than the review of another company favored by the lead reviewer.” OIG's investigator, Matthew Kochanski, informed Jankelson on several occasions “that the investigation was nearly complete and would provide findings of criminal wrongdoing,” but then Jankelson was no longer able to make contact with Kochanski and “no results were ever made public. Someone had the capability to ‘bury' these findings from ever being revealed.” Kochanski is no longer listed in the HHS employee directory.

“Hopefully,” Jankelson's letter concluded, “the Office of the Inspector General will not be allowed to be just another level of bureaucracy behind which misbehaving FDA employees can hide.”

Precision Biometrics Warned About Off-Label Claim

CDRH has issued a warning letter to Precision Biometrics (San Carlos, CA), alleging that the firm has been marketing its MyoVision 8000 Static Surface EMG system and Dynamic Surface EMG system for diagnostic uses that go beyond its 510(k) marketing clearance. The letter said the MyoVision received a 1988 substantial equivalence determination as a biofeedback device.

However, CDRH said, the company's Web site contains statements indicating that the devices can be used in evaluating the areas or levels of the nervous system that are adversely affected by vertebral subluxations. CDRH said that such language indicates a major modification in the devices' intended use and requires a new premarket submission.

The company was told to immediately stop marketing the systems for diagnostic use and to submit a letter describing intent to comply.

FDA Seeks More Data on Stimulator

FDA has asked Cyberkinetics Neurotechnology Systems (Foxborough, MA) for additional analyses and data for a humanitarian device exemption (HDE) marketing application. The application is for the Andara oscillating field stimulator system, which is a nerve growth stimulator designed to treat acute spinal cord injuries. The company said agency approval may be delayed until at least the first half of 2008 while it provides the additional information.

The Andara device is designed to be implanted in patients within 18 days of a spinal cord injury to stimulate nerves to regrow across the injury area. Although the device is removed after 15 weeks of treatment, the company says improvement in sensory and motor function may continue for months or even years as nerves form new connections to transmit information to and from the brain.

Company officials said FDA had identified additional information related to clinical and engineering data that must be provided before agency review can be completed. The officials said they would work with FDA to fully understand the requirements and believe the information can be included in an amendment to the HDE application early in 2008.

New FDA Warning on Vail Beds

An updated FDA public health notification says that anyone who has a Vail enclosed bed system should stop using it. Patients should be moved to alternative beds. The notice was directed to hospitals, nursing homes, and consumers.

Vail enclosed bed systems are canopy-like padded beds covered with nylon netting that is zipped into place. They are used for at-risk patients with cognitive impairment, unpredictable behavior, spasms, seizures, and other disorders. They are used as an alternative to physical or chemical restraints in preventing patients from falling from the bed or wandering.

Vail Products Inc. (Toledo, OH) stated on June 16, 2005, that it had permanently ceased manufacture, sale, and distribution of the enclosed bed systems and can no longer provide accessories, replacement parts, or retrofit kits. A June 24, 2005, FDA public health notification warned that the systems pose a health risk because patients can become trapped in them and suffocate.

FDA says it is aware of at least 30 adverse-event reports, including at least eight deaths, resulting from entrapments, falls, and other incidents. More than half of the incidents involved children age 16 and younger.

Safety Precautions

The latest notification says that if the Vail bed is the only option, these safety precautions recommended by Vail should be followed:

Cardinal Health Recalls Alaris Pump Modules

Cardinal Health has recalled all Alaris Model 8100 pump modules (also known as Medley pump modules) shipped before September 27, 2007, because of potential problems related to misassembled springs during manufacturing or servicing.

A company recall notification stated that Cardinal has received reports of inaccurate flow rates due to a misassembled spring. The company said that it has implemented a new manufacturing inspection process for Alaris pump modules that eliminates the potential problem for new products shipped as of September 27.

The company plans to inspect each Alaris module at the customer site and remove any modules with misassembled springs. Acceptable devices may be placed back in service, the company said.

Until all devices can be inspected, Cardinal recommends that customers perform an occluder pressure test every six months to confirm the occluders are functioning properly as of the test date. The firm said lack of occluder pressure is a strong indicator of a misassembled spring, warranting removal from patient use for further inspection.

Last year, FDA and Cardinal agreed on a consent decree involving the Alaris SE pumps. The company had to recondition 1300 Alaris Signature Edition Gold drug infusion pumps. The issue then was with the pumps' keypads, which had the potential to stick, creating the risk of overinfusion.

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