Medical device makers have spent the last year urging U.S. officials to approve high-risk products faster, like their European counterparts. A scandal over leaking breast implants made in France may make the argument harder.
French and German officials last month recommended thousands of women have surgery to remove implants made by Poly Implants Protheses SA, after reports the products were leaking industrial silicone inside patients. The mishaps have heightened scrutiny of European Union rules for medical devices that already faced calls from doctors for an overhaul.
While the devices were never approved for use in the U.S., they may alter the debate over regulations there as well. Congress faces a September deadline over whether to revamp U.S. device rules, and industry allies in both parties have pointed to Europe’s speedier reviews as a model to follow. The tales of leaking implants, along with other EU device failures, should give lawmakers pause, said Carl Heneghan, an Oxford University teacher who has studied device recalls.
“All the industry guys in the U.S. say, ‘we should have access to these products much sooner, like in Europe,’” he said. “The flip side is, the European people are being used as guinea pigs.”
Heneghan, a physician who runs Oxford’s Centre for Evidence-Based Medicine, is among a growing chorus of doctors, regulators and even device makers calling for changes to Europe’s system, which relies on private reviewers hired by manufacturers to vet products. The European Commission is expected to recommend changes by the end of June.
“The PIP breast implant scandal is an inevitable result” of regulators’ “paralysis and inability to correct the failings of a flawed system,” Richard Horton, the editor of the British medical journal The Lancet, said in an editorial released yesterday. European approval “does not guarantee safety.”
On the other side of the Atlantic, U.S. device makers have complained for years about slow reviews and inconsistent standards at the Food and Drug Administration. At the same time, the agency has faced criticism after high-profile recalls of technology it cleared for sale, from Johnson & Johnson hip implants to Medtronic Inc. defibrillators.
In a series of Capitol Hill hearings last year, industry supporters often cited the EU as a better model. Its speedier reviews were luring companies away, taking “good-paying American jobs” with them, said Representative Joseph Pitts, a Pennsylvania Republican, in a typical warning last February. A Stanford University survey of manufacturers, released in 2010, found complex devices reach the EU two years faster on average.
“The industry is rapidly moving outside the United States,” said Steve Ferguson, chairman of Bloomington, Indiana-based Cook Group, the world’s largest closely held device maker, in a telephone interview. For American patients, “the human cost of not having access to that technology is enormous.”
The Cook Group, which had $1.9 billion in sales in 2011, once made 75 percent of its revenue in the U.S. That fell to 44 percent last year thanks in part to lower taxes and faster reviews in the EU, he said.
More than a dozen bills have been introduced to rewrite FDA rules. “You can carry this business of safety to a ridiculous level,” Representative Phil Gingrey, a Georgia Republican who sponsored one of the proposals, said in an interview last month before the European governments recommended removal of the PIP implants. “We’ve got to be responsible and safe, but we’ve got to understand that you can completely price these innovators out of the market.”
Gingrey, in an e-mail today, said, “We must do everything in our power to prevent instances like those in France from occurring. On the other hand, we must also do everything possible to prevent the FDA from standing between patients and life-saving treatments.”
The debate may reach a climax this year, said Ira Loss, an analyst at the investment research firm Washington Analysis. Congress faces a Sept. 30 deadline to renew industry fees that fund device reviews. The legislation is expected to become the arena for a broader fight over whether to push for quicker approvals, said Loss, an FDA watcher for three decades.
Unlike the FDA’s government-run reviews, the EU relies on a decentralized network of about 70 “notified bodies.” The closely held, mostly for-profit firms are hired by companies to check their products. The reviewers must be accredited by one of the union’s 27 member nations. Approval by any one of them allows companies to sell a device throughout the EU.
Safe and Effective
There’s another key difference, Oxford’s Heneghan said in a telephone interview. While the EU and U.S. require manufacturers to prove new products are safe, only the FDA mandates they also show devices are effective. That means studies for European approval are typically less in-depth than those required in the U.S, Heneghan said.
The European system sets up “an inherent conflict of interest” where companies can shop for the most amenable reviewers, said Deborah Cohen, an editor at the London-based British Medical Journal, which publishes drug and device research. In May, the 70,000-member European Society of Cardiology also called for changes, writing in its journal that notified bodies need higher standards and more transparency.
The Poly Implants Protheses breast implants were cleared by TUEV Rheinland, a notified body based in Cologne, Germany. TUEV Rheinland said in a Dec. 29 statement that its inspectors had been misled when PIP substituted industrial silicone for a medically approved variety after an inspection. Following EU device rules, the manufacturer had been told in advance about the inspection, TUEV said.
Implants with industrial silicone are more likely to rupture, leaking a gel that can cause scar tissue and inflammation, the French Health Ministry said in a Dec. 23 statement. The silicone is more typically used to make mattresses, the British Association of Aesthetic Plastic Surgeons said in its statement Dec. 3. PIP sold more than 300,000 of the implants during the past 12 years, mainly in Spain and the U.K., the group said.
The case underscores the need for changes in Europe’s system, said John Brennan, regulatory-affairs director at device industry trade group Eucomed. The Brussels-based association supports the creation of a central advisory committee to hold notified bodies to more consistent standards, he said. Approval and recall data also should be more accessible.
“People expect to know about the products that are being put in their bodies,” Brennan said in an interview. “We should have the equivalent transparency as the U.S.”
PIP, based in Toulon, France, was liquidated in March 2010 after French authorities banned the company’s implants. Yves Haddad, an attorney for company founder Jean-Claude Mas, didn’t respond to messages left at his office in Toulon.
The implants are the latest example of devices that reached Europe’s market too quickly, said Cohen, the British Medical Journal editor. In 2007, Dublin-based Covidien Plc won EU approval for PleuraSeal, a sealant designed to help doctors plug tiny holes in the lungs after surgery. A follow-up trial to win U.S. approval found three times as many patients developed air leaks with PleuraSeal than with sutures, Covidien said in a statement. The product, which never reached American patients, was recalled worldwide in October 2010.
The FDA, in a memo to Congress last year, cited more than a dozen other categories of “problematic devices” that reached Europe but never won U.S. approval. Along with PIP’s products, the list included inaccurate blood-sugar monitors, ineffective heart stents and an aortic graft linked to blood clots.
Covidien introduced PleuraSeal in the EU because it felt the market there was more attractive, Bruce Farmer, a spokesman, said in an e-mail. “Our commitment to patient safety cannot be compromised,” he said. “All of our products meet or exceed the safety requirements of the market where they are sold.”
Last January, an industry-sponsored study by the Boston Consulting Group found little difference in the number or severity of recalls in the two systems, suggesting the EU’s speedier approvals don’t sacrifice safety. The FDA and Oxford’s Heneghan questioned the report, saying a lack of disclosure and differing definitions of recalls in Europe make it impossible to draw meaningful conclusions.
Measure of Safety
The study “made assumptions that all serious problems are being reported” and “then did an extrapolation to come up with a number,” said Jeffrey Shuren, director of the agency’s device-review center, in an interview. “It’s just not a good measure of safety.”
The FDA, while acknowledging industry concerns about U.S. regulation, defends its system as better for patients. The European process makes it impossible to track approvals, side effects or recalls, Shuren said. Unlike in the U.S., there’s no central website where the public can find reports of adverse events or product withdrawals, he said.
Notified bodies often lack the expertise the FDA has gained after years of checking thousands of devices, Shuren said.
“The answer at the end of the day isn’t to scrap the U.S. standard of safety and effectiveness,” Shuren said. “The answer is to keep the U.S. standard but let us do our job to improve the program.”