Published: February 21, 2008
The New York Times – WASHINGTON — Makers of medical devices like implantable defibrillators or breast implants are immune from liability for personal injuries as long as the Food and Drug Administration approved the device before it was marketed and it meets the agency’s specifications, the Supreme Court ruled on Wednesday.

The 8-to-1 decision was a victory for the Bush administration, which for years has sought broad authority to pre-empt tougher state regulation.

In 2004, the administration reversed longstanding federal policy and began arguing that “premarket approval” of a new medical device by the F.D.A. overrides most claims for damages under state law. Because federal law makes no provision for damage suits against device makers, injured patients have turned to state law and have won substantial awards.

The Bush administration will continue its push for pre-emption in another F.D.A. case that the court has accepted for its next term, on whether the agency’s approval of a drug, as opposed to a device, pre-empts personal injury suits. Drugs and medical devices are regulated under separate laws.

The case before the court concerned only medical devices that had gone through the premarket approval process specified by the Medical Device Amendments of 1976. Most devices now available reached the market through a different process, under which the F.D.A. found them to be “substantially equivalent” to those marketed before the 1976 law took effect.

The Supreme Court ruled in 1996 that this less rigorous approval process does not pre-empt state damage suits against the manufacturers of “grandfathered” devices.

Devices subject to the premarket approval process, and thus affected by the court’s opinion, tend to be more technologically advanced, expensive and, in some instances, risky.

Examples of devices that have been the subjects of recent lawsuits include an implantable defibrillator, a heart pump, a spinal cord stimulator, a drug-coated stent, an artificial heart valve, and prosthetic hips and knees.

It was not immediately clear how many of the thousands of lawsuits against medical device manufacturers would be affected, though some pending cases will almost certainly be nullified.

The decision, for example, does not foreclose lawsuits claiming that a device was made improperly, in violation of F.D.A. specifications. Cases may also be brought under state laws that mirror federal rules, as opposed to supplementing them.

Next Monday, the court will hear another F.D.A. pre-emption case, on whether a state case can be based on the claim that a drug maker committed fraud by misrepresenting or withholding information from the agency during the approval process. The administration is supporting the manufacturer in that case, Warner-Lambert Co. v. Kent, No. 06-1498, which concerns the diabetes drug Rezulin.

Writing for the majority in Wednesday’s case, Riegel v. Medtronic Inc., No. 06-179, Justice Antonin Scalia said that permitting state juries to impose liability on the maker of an approved device “disrupts the federal scheme,” under which the F.D.A. has the responsibility for evaluating the risks and benefits of a new device and assuring that it is safe and effective for its intended use.

A jury, looking only at the injured plaintiff, will tend to weigh only the dangers of a device and “is not concerned with its benefits,” Justice Scalia said, adding, “the patients who reaped those benefits are not represented in court.”

The decision affirmed the dismissal of a lawsuit by a patient who was injured during an angioplasty when a balloon catheter burst while being inserted to dilate a coronary artery. The device won F.D.A. premarket approval in 1994, two years before the incident. The patient, Charles R. Riegel, died after the lawsuit was filed, and the case was carried on by his widow, Donna.

The medical device statute contains a pre-emption clause that bars states from imposing “any requirement” related to a medical device that is “different from, or in addition to” a federal requirement. The question of statutory interpretation at the heart of the case turned on what Congress meant by “any requirement.”

Justice Scalia said that state tort law, by imposing duties of care on product makers, amounted to such an additional requirement. He said the 1976 law “speaks clearly to the point at issue,” regardless of the federal government’s previous or current positions.

Justice Ruth Bader Ginsburg, the solitary dissenter, said the court had misconstrued Congress’s intent in adding the pre-emption clause to the 1976 law. The purpose, she said, was to prevent individual states from imposing their own premarket approval process on new medical devices. Devices were not regulated under federal law at the time, and California and other states had stepped in to fill the vacuum by setting up their own regulatory systems.

That was all that Congress had in mind, Justice Ginsburg said, not “a radical curtailment of state common-law suits seeking compensation for injuries caused by defectively designed or labeled medical devices.” She said that Congress had passed the 1976 law “to protect consumer safety,” not to oust the states from “a domain historically occupied by state law.” The decision was at odds with the “central purpose” of the 1976 law, Justice Ginsburg added.

Crucial Democratic lawmakers appear to agree with Justice Ginsburg, including Senator Edward M. Kennedy, Democrat of Massachusetts, who heads the Health, Education, Labor and Pensions Committee and was the sole Senate sponsor of the 1976 legislation in question.

“In enacting legislation on medical devices, Congress never intended that F.D.A. approval would give blanket immunity to manufacturers from liability for injuries caused by faulty devices,” Mr. Kennedy said in a statement. He added: “Congress obviously needs to correct the court’s decision.”

Representative Henry Waxman, the California Democrat who is chairman of the House Committee on Oversight and Government Reform and was on the House panel that approved the 1976 bill, expressed a similar view.

“The Supreme Court’s decision strips consumers of the rights they’ve had for decades,” Mr. Waxman said. “This isn’t what Congress intended, and we’ll pass legislation as quickly as possible to fix this nonsensical situation.”

The Food, Drug and Cosmetic Act of 1938, under which the F.D.A. regulates pharmaceuticals, does not contain a pre-emption clause. Nonetheless, the administration is arguing in the case the court has accepted for its next term, Wyeth v. Levine, No. 06-1249, that pre-emption is implicit in the structure of the statute.

The Supreme Court’s interest in pre-emption is not limited to the medical arena. In a similar case decided on Wednesday, this one unanimously, the court ruled that the federal law that deregulated the trucking industry in 1980 pre-empted two recent laws adopted by the State of Maine to regulate the shipment of tobacco products into the state.

The state laws were intended to prevent children who were not of legal age to buy cigarettes from ordering them over the Internet. The laws placed responsibility on shippers and delivery companies to verify the recipient’s identity and age.

Justice Stephen G. Breyer, writing for the court in this case, Rowe v. New Hampshire Motor Transport Association, No. 06-457, said the state law “produces the very effect that the federal law sought to avoid, namely, a state’s direct substitution of its own governmental commands for competitive market forces” in a deregulated environment.

The active UHF RFID system, marketed by RFID ProSolutions, is designed to protect newborn babies, Alzheimer’s patients and other individuals staying in health-care facilities.
By Beth Bacheldor
Copyright RFID Journal LLC 2008, Used With Permission

RFID Journal – Feb. 13, 2008—RFID ProSolutions, a Canadian startup company specializing in RFID systems and integration, is now reselling an RFID-enabled system designed to protect newborn babies, Alzheimer’s patients and other individuals staying in health-care facilities. The BlueTag system, from Paris-based BlueLinea, leverages active ultrahigh-frequency (UHF) RFID tags embedded in bracelets and is currently used in 50 maternity wards in 10 countries around the world.

According to Jebb Nucci, RFID ProSolutions’ VP of RFID, the BlueTag system incorporates interrogators with integrated antennas, a computer and Blue Tag software, which contains a repository of each tag’s unique ID number and associated patient information. The RFID-enabled bracelet is hypoallergenic and waterproof, and can be worn on the wrist or ankle. Removing the device without authorization—if, for instance, someone were to cut the bracelet off—triggers an audible alarm. An alarm also sounds if anyone wearing the bracelet passes through a doorway equipped with the readers.

Four hospitals in France are presently using the BlueTag system, Nucci says, including the American Hospital of Paris and Montfermeil Hospital. “Montfermeil Hospital had some issues with babies being taken from their maternity ward over the past five years,” Nucci notes. “It is now considered one of the safest and most secure maternity wards in the greater Paris area. This new system has put their patients and staff more at ease, and has helped rebuild the hospital’s positive brand.”

Nucci says one key feature of the BlueTag system is that it helps prevent mothers and babies from prematurely leaving maternity wards. “Both [of the French] hospitals had experienced a high level of mothers and babies who would leave the ward before being properly discharged,” Nucci explains. “This was a major problem for nurses, because they would spend so much time looking for mothers and babies that were already gone. With the system in place, a mother and her baby must go see the nurses before leaving so they can deactivate and remove the baby’s tag to avoid sounding the alert on their way out.”

Since announcing the availability of the BlueTag system in the North American market in January, Nucci says, RFID ProSolutions has had several hospitals and retirement homes in the Montreal area express interest. “We are forecasting our first installation of the system in the spring of 2008,” he states.

The 747-bed Boston hospital has installed an RFID-based real-time location system throughout its 17 floors, enabling it to track thousands of medical devices.
By Beth Bacheldor
Copyright RFID Journal LLC 2008, Used With Permission

RFID Journal – Feb. 20, 2008—With a months-long successful pilot now complete, Brigham and Women’s Hospital (BWH) in Boston is taking its active RFID tracking system to new heights. The 747-bed nonprofit teaching hospital, affiliated with Harvard Medical School, has wired each of its 17 floors with a real-time location system (RTLS) and plans to expand the system to an adjoining facility opening this spring.

Altogether, about 8,000 medical devices will be tagged and tracked using the RTLS. Those devices include infusion pumps, continuous veno-venous hemofiltration (CVVH) machines for removing waste products from blood, and pulse oximeters that measure the oxygen saturation of a patient’s blood.

Radianse’s active RFID tags operate at 433 MHz and communicate with Radianse receivers via a proprietary air-interface protocol. The receivers—small box-shaped devices typically mounted on walls—communicate with BWH’s wireless local area network and relay the collected RFID data to a Radianse server. The receivers can interrogate a tag from up to 50 or 60 feet away, and can pinpoint its location within an accuracy of up to 3 feet. When three or more receivers pick up a tag’s ID number, Radianse software determines its location based on signal strength.

The system is in use within the hospital’s emergency department, surgery units, cardiac care, perioperative units and common areas. It will also operate throughout the new facility, the Carl J. and Ruth Shapiro Cardiovascular Center, which will connect to the main building via a bridge and tunnel.

The hospital’s initial deployment of the Radianse system took place in 2005. During that nine-month pilot, says Steve Schiefen, Radianse’s chief operating officer, BWH tagged five types of equipment, covering about 350 devices. To date, says Michael Fraai, the hospital’s director of biomedical engineering, BWH has tagged approximately 4,000 items.

Printed on each tag is a label printed with a bar-coded number identical to the unique ID number encoded onto the tag’s RFID chip. When staffers affix an RFID tag to a device, they use a handheld bar-code scanner to record the tag’s bar code. By using a bar-code reader, employees know with 100 percent certainty that the device is correctly matched to the ID of its own tag, and not to the ID number of another nearby tag.

“Bar-code readers have become very inexpensive and easy to use,” Schiefen says, making them an ideal solution to affix and associate RFID tags on devices that will be tracked by an RFID-enabled RTLS. Once a tag’s bar code is scanned, details about the tagged device, such as its make, model and assigned location—much of which the staff accesses from the hospital’s inventory management system—are then input and stored in the Radianse system.

According to Fraai, the system is already helping improve patient care, streamline patient flow and save the hospital money. “For tagging,” he says, “we identified the critical devices that can compromise patient flow—those are the devices that, if you can’t find them, patients can’t be treated.” Staff can use a nearby computer to access the Radianse application and select the device being sought. The software then locates the item and indicates its location, down to the room level.

The hospital is now starting to collect usage data that will help it determine just how many of each device it needs to maintain in inventory, as well as whether some items could just be leased. “Let’s say you need 10 IV pumps, but you can only get your hands on eight,” Fraai says. “So you keep 12 in inventory because with that many, you think you will be able to get your hands on at least 10.” But with real-time location data, the hospital will be able to keep close tabs on where each of the 10 IV pumps is at any given time.

And with the historical data, the hospital will be able to track how often each device is in use, and decide whether it would be more cost-effective to lease rather than buy. “Take the CVVH machines, for example,” Fraai explains. “According to the clinicians, they are always in use, but this system will provide us with data that is non-biased. “We might discover that 75 percent of the time, three of the CVVH machines were just sitting in the holding area. So maybe we’d decide to lease, rather than buy, additional machines.”

Additionally, Fraai adds, the hospital hopes to eliminate incidents in which devices simply go missing. For a while, staffers suspected some items were ending up in the laundry room after inadvertently being wrapped up in dirty linens as rooms were cleaned. To prevent this from occurring, the hospital has installed receivers in the laundry rooms. “We haven’t found any devices yet that I’m aware of,” he notes, “but that is why we put the antennas there.”

BWH expects its RTLS will save it $300,000 annually. Fraai says the equipment deployed for the 2005 pilot paid for itself within 15 months, and he expects the hospital to recoup the costs of implementing the RTLS throughout its facility (excluding the adjoining cardiovascular center) in about three years. “This system is relatively easy to use,” he says. “The staff that is using it, love it now.”

The light microscope launched modern biology in the seventeenth century, letting scientists view the components of life that exist far beyond the range of unaided human vision. But light travels in waves, and its wavelength prevents researchers from focusing on details below a certain size limit without creating interference. As a result, light microscopes cannot show details that are less than about 200 to 300 nanometers apart. This is fine for viewing a single cell, but look inside it and things blur. Even a cluster of proteins, each a mere three to 10 nanometers in size, appears as an indistinct blob. (A nanometer is a billionth of a meter; a human hair is 80,000 nanometers in width.)

Creative new techniques developed in the past few years, however, have extended the boundaries of what these microscopes can reveal. The latest approach, from the lab of Xiaowei Zhuang, professor of chemistry and chemical biology at Harvard and a Howard Hughes Medical Institute investigator, uses fluorescent molecules that can be switched on and off to create images with more than 10 times the resolution of traditional light microscopes.

Zhuang says that light, despite its limitations, has important advantages for viewing cells. Electron microscopy, though more powerful in resolution, requires that cells be killed and chemically fixed. With electron microscopy, she says, “You’re looking at a still image,” rather than capturing activity in a cell. Light, on the other hand, is noninvasive, so it can be used to image live cells; scientists can use a variety of stains and fluorescent tags that let them view specific proteins or structures of a cell in different colors. Ideally, Zhuang says, “one would want to have a method that combines the merits of both”: the high resolution of electron microscopes paired with the flexibility of optical microscopes.

Image courtesy of Xiaowei Zhuang
Using conventional imaging techniques, a circular piece of DNA (bottom left) appears as an indistinct blob when magnified (center). A new technique permits three-dimensional resolution 10 times better, revealing the crisp ring structure of the object (upper right).

The new technique, which Zhuang developed with graduate students Michael Rust and Mark Bates, makes use of fluorophores—molecules that absorb light and then fluoresce, emitting light at a different wavelength. Fluorophores have been used in microscopy for many years because they can be attached to specific molecules in cells, allowing scientists to track their location.

Normally, when a sample of fluorophores is exposed to light, they fluoresce in unison. Under an optical microscope, this sea of individual spots cannot be resolved if they are densely packed. Even so, Zhuang says, scientists have known how to determine mathematically the position of a single, isolated fluorophore by calculating the center of the fuzzy spot of light detected by the microscope. The trick was to find a way to turn the lights out on a group of fluorophores, allowing only a few at a time to light up so that the microscope could pick out individual spots.

Several years ago, Zhuang’s group discovered a fluorophore that has an on-off switch—when exposed to red light, it is inactive, but when exposed to green, it has the ability to fluoresce. “This was the additional step that allowed us to control how many molecules are active,” she says. Using this molecule, they can first turn off all the fluorophores with a red light, and then expose the sample to a small amount of green light—so small that only a few of the fluorophores will activate at a time. An image of those scattered fluorophores can then be made and their positions determined to within nanometer accuracy. By repeating this process many times to locate the position of all fluorophores, the scientists can create a whole image.

Zhuang’s team calls the method stochastic optical reconstruction microscopy, or STORM, and published a demonstration in a recent edition of Nature Methods. With this technique, “You’re going to get many of the advantages of optical imaging, but sharper and crisper by more than an order of magnitude [10 times],” she says. As an example, her team attached 20 to 40 fluorophores to a circular string of DNA and proteins and was able to resolve its ring-like structure, where conventional microscopy would have shown only a blob. Zhuang’s team is now hunting for other fluorophores that have the same ability to switch on and off, but in different colors.

The main drawback of the technique is the time it takes to gather multiple views and stitch them together. Creating an image can take a few minutes, making it best for viewing fixed structures. But Zhuang’s team hopes to improve it further, to be able to capture the movements of molecules in cells, which happen on the order of seconds to milliseconds. She says STORM is one of a few promising approaches that have the potential to turn high-resolution still images of the cell into live action. “We’d like to look at events in live cells with nanometer resolution, in real time,” she says. “That’s the hope.”