Public FDA Meeting Tackles 510(k) Review Process

Medical device tax looming as healthcare reform debate continues.

As part of the ongoing saga of the U.S. Food and Drug Administration’s (FDA) 510(k) medical device clearance program, a public meeting was held recently to discuss the state of the agency’s embattled review process.

Agency officials said the meeting would help inform an internal task force charged with highlighting changes the agency can make with existing powers. An outside report from the Institute of Medicine, due in March next year, will focus more broadly on the FDA’s device division and what additional power or changes it needs.

The 510(k) program often is incorrectly described a “fast-track” process because it relies on previous approvals of similar or “predicate” devices. A device applying for 510(k) clearance must show “substantial equivalence” to a device already given the OK by the agency (compared to higher classes of devices or novel technology that must undergo the more rigorous premarket approval process, which often required years of research and clinical data). Ostensibly, devices that undergo 510(k) review aren’t as high-risk, though critics claim some such devices have fallen through the bureaucratic cracks—a report issued by the Government Accountability Office last year highlighted some of higher-risk devices approved by 510(k). High-risk devices tend to be ones that are implanted in the body or that are life-sustaining. Only 8-10 percent of 510(k) submissions have required patient data, according to the agency.

About 3,500 devices are cleared every year under the 510(k) system. Meanwhile, about 50 devices are approved each year under the more stringent PMA system. Supporters of the 510(k) program say the review process is thorough and scientifically sound, while detractors claim the process isn’t as rigorous as it could be. All parties seem to agree, however, that some sort of review of the program certainly couldn’t hurt.

According to Donna-Bea Tillman, Ph.D., director of the FDA’s Office of Device Evaluation in the Center for Devices and Radiological Health (CDRH), the regulatory process must keep pace with evolutionary changes to medical devices. Tillman resigned shortly after the meeting.

“As science evolves, our regulatory approach also needs to evolve,” she said at the meeting. “We need to be continually assessing the regulatory framework for the review of medical devices to ensure that it is still accomplishing our fundamental mission to promote and protect public health.”

Heather Rosecrans, director of the 510(k) staff at the CDRH, highlighted the importance of ensuring that device regulations are clear and consistent.

“Developing clear definitions, guidance and additional authorities may be required,” Rosecrans said. “Utilizing rational application of guiding principles is vital.”

Though the FDA defended its current review process, the agency acknowledged that it faces difficulties in reviewing certain medical devices, hurdles that may call for additional regulations and authorities. Often, according to agency officials, it can be difficult to tell if a new device is truly similar to an approved product or if there are enough differences to classify it as an entirely new product, particularly given the pace of innovation in the medical device sector. Difficulty inspecting device makers and a high number of proposed new products are other issues to be considered, according to FDA staff.

Device companies, industry consultants and investors said some smaller changes could improve the current process. They cautioned, however, that a major overhaul could stifle innovation and prevent newer technologies from reaching patients and doctors. Firms also are worried that they could see longer review times, higher costs and other hurdles that may make it harder to get their products on the U.S. market. The threat of greater regulation affects smaller manufacturers as well as larger ones—though smaller companies could be at a greater disadvantage. Companies could be asked to submit more data to win approval, requiring more research and development spending.

Some critics argued that an examination of the review process also is necessary to determine links to product recalls. FDA staff said most devices are recalled because of manufacturing or design problems, and that most likely would not change even if the agency implemented changes to the approval process. The FDA could issue more guidelines for companies to follow and focus more on staff training, other industry experts said.

Officials at the Advanced Medical Technology Association (AdvaMed), the industry’s largest trade group, said the 510(k) process is “already robust” and provides “strong protections” to American patients and promotes medical innovation.

“[The 510(k) program] gives FDA the flexibility it needs to ensure the safety and effectiveness of incremental changes made to low- and moderate-risk medical devices whose risks are well-understood from experience with similar devices," according to AdvaMed officials. “It is important for patients to know that devices cleared via the 510(k) process undergo thorough FDA review. It has erroneously been called a fast-track process by too many in the media. That is an inaccurate characterization. The length of review is determined by FDA and based on potential impact to public health and on technological complexity. It is also important to note that FDA has total authority under the 510(k) process to require whatever evidence is necessary to assure a product’s safety and effectiveness, including clinical data when it deems this data to be necessary to assess the risks and benefits of a product.”

Kelly Slone, director of federal life science policy for the National Venture Capital Association based in Arlington, Va., said changes to the system could endanger innovation driven by small startup firms.

“These young companies, as years go on, get more fragile and harder to raise money and invest in even though they have great ideas,” Slone said. “A critical part of the innovation ecosystem is at risk. VCs, when looking at innovative technologies, have to make a judgment on risk assessment to invest in novel technologies. We believe 510(k) is workable, but over three years there's been a disturbing trend on impeding innovation. Why is this happening? We believe it's because a burdensome regulatory environment has greatly reduced innovation.”

Not just a matter of consideration for industry insiders, the 510(k) program also has garnered attention on Capitol Hill. On Feb. 16, Sen. Charles Grassley (R-Iowa) sent a letter to the FDA asking for an update on its plans to issue new 510(k) guidelines.

“Over a year ago, I wrote to the FDA regarding serious allegations that an annuloplasty ring used in heart valve repair was being implanted in patients even though the device was allegedly not cleared for marketing by the FDA. The FDA concluded that the company had made the wrong decision when it marketed the product without first seeking clearance from the agency,” Grassley wrote. “That device has since been cleared by the FDA, but as I stated in my letter to the FDA last April, the fact remains that for more than two years, patients … were being implanted with the device before a 510(k) was submitted to the agency.”

Grassley wants a response from the FDA by early this month, answering questions about how and when manufacturers are required to update their device listings with the agency, how patients and doctors can “obtain information about the status of a device other than from the manufacturer itself” and whether manufacturers must update their listings if device names are changed without modifications to the product, or if modifications are made that don’t require a new 510(k) application.

After the meeting, Jeffrey Shuren, the new head of CDRH, said the agency could make some changes before the Institute of Medicine releases its report next year. FDA officials have said they will accept public comments for the next month before making its task force's recommendations public in June.

Any substantial new FDA authority over devices, however, would require action by Congress.

In related news, according to an FDA memo leaked to The Wall Street Journal, the agency is concerned about the use of third-party contractors hired by device makers to review products before a 510(k) application.

“If the third party signs off on the device, the FDA may approve it without much further scrutiny,” the newspaper reported. The memo indicated that third-party review may be perceived by the industry as a way to “sneak things in,” according to the Journal.

Third-party reviewers “often just repeat what is in the submission” without further scrutiny, according to the leaked memo, which could lead to the FDA limiting the devices it allows to be reviewed by outside contractors. Approximately 300 applications were reviewed by third parties during fiscal 2008, up nearly 63 percent since 2003, the paper said.

Smith & Nephew Loses Legal Battle to KCI; Patients Sue Zimmer

While one orthopedic giant deals with a legal defeat, another is gearing up to defend itself against two patients.

A U.S. District Court jury has concluded that a wound therapy product sold by Smith & Nephew plc infringes two patents owned by Wake Forest University Health Sciences, which are exclusively licensed to Kinetic Concepts Inc. (KCI).

KCI will be seeking an injunction in the United States District Court in post-trial proceedings to prevent further infringement by Smith & Nephew of its V.A.C. technology, according to the San Antonio, Texas-based company.

“The outcome of this trial exemplifies the protections provided to innovators like Wake Forest and KCI under the U.S. patent system,” said Catherine Burzik, KCI’s president and CEO.

KCI manufactures medical devices for the wound care, tissue regeneration and therapeutic support system markets. Smith & Nephew, which manufactures devices for the orthopedics, wound management and endoscopy markets, is headquartered in London, England, with its U.S. base in Memphis, Tenn.

Smith & Nephew was not immediately available for comment.

In other orthopedic legal wrangling, two patients are suing Zimmer Holdings over what they claim is a defective hip implant.

The lawsuits filed by a truck driver and former nurse claim an artificial hip socket manufactured and sold by the orthopedic device behemoth was defective and subjected them to chronic pain.

Todd Lovelace of Elizabethtown, Ky., and Christine Walker of West Palm Beach, Fla., filed their lawsuits separately in federal district courts in their respective states. Both blame the faulty hip socket for “debilitating injuries” that eventually led to the loss of their careers.

Walker, 53, a former nursing director, underwent hip replacement surgery in December 2007. Surgeons replaced her hip socket with the Durom Acetabular Component, also known as the Durom Cup, a device that minimizes bone removal and promised patients “an increased range of motion with greater stability.” The device was designed to bond to the hip bone. Walker’s lawsuit, however, claims the cup had the opposite effect: It resisted bone growth and popped free from the hip.

Zimmer declined to comment on the lawsuits filed by Walker and Lovelace. The company stopped selling the Durom Cup in the United States in July 2008 so it could update labeling to provide more detailed surgical technique instructions and establish a surgical training program.

Zimmer said it conducted a comprehensive review of clinical experience and product conformance to specifications in the United States and Europe and found no evidence of a defect in materials, manufacture or design of the Durom Cup.

Lieff Cabraser Heimann & Bernstein LLP, the West Palm Beach, Fla.-based law firm that filed the lawsuits on behalf of Walker and Lovelace, claims that more than 24 percent of patients who received the Durom Cup will be forced to undergo revision surgery.

Doctors performing Walker’s revision surgery in December 2008 discovered the Durom Cup had become completely detached from the hip. She still suffers from leg and hip pain, and relies on a walker to walk long distances.

Lovelace’s hip surgery left him with similar debilitating injuries, according to his lawsuit (filed Feb. 26). The 45-year-old former truck driver underwent hip replacement surgery in May 2008 but months of excruciating pain forced him to undergo a revision procedure on Dec. 22 of that year. Like Walker, the Durom Cup implanted in Lovelace had become completely loose.

Stryker Releases New Hip System; Officials Show Enthusiasm About Product Offerings

Stryker Corp. rolled out its third major hip product in the past year during the recent American Academy of Orthopaedic Surgeons (AAOS) annual meeting in New Orleans, La. The company’s ADM X3 Mobile

The ADM X3 Mobile Bearing Acetabular System. Photo courtesy of Stryker Corp.

Bearing Acetabular System, is hip-replacement technology designed to minimize risks, according to the Kalamazoo, Mich.-based firm.

The Mobile Bearing Hip system is made possible by the company’s X3 Advanced Bearing technology, which is manufactured of highly crosslinked polyethylene. It has been used in knee systems as well, and is designed to increase the longevity of the implant.

According to the company, lab tests have shown a 97 percent reduction in volumetric wear compared to conventional polyethylene.

While total hip replacement is one of the most successful surgical procedures performed today, dislocation remains one of the top reported complications. To address dislocation, conventional designs focus on the use of metal-on-metal large-head technologies that, based on recent studies, suggest added risk due to metal ion release. Company officials claim that by combining an evolution in design with the only anatomic dual mobility acetabular system and its patented X3 Advanced Bearing Technology, the Mobile Bearing Hip addresses dislocation without the risk of metal ion release.

ADM’s anatomic design also has the potential to increase mobility and reduce groin pain, according to Stryker. Its dual points of articulation help accommodate multi-directional movement, which provide greater range of motion than fixed implant designs based on laboratory testing. In addition, the anatomic cup design has an iliopsoas tendon cutout aimed at reducing iliopsoas tendon impingement, a key cause of post-operative groin pain, according to the firm.

“By developing an implant that addresses adverse outcomes associated with hip replacement surgery, we are not only helping surgeons to treat their patients more successfully, but we are also striving to reduce global healthcare costs by minimizing surgical complications,” said Bill Huffnagle, vice president and general manager of hip reconstruction at Stryker Orthopaedics, based in Mahwah, N.J.

During the AAOS meeting, Huffnagle told Orthopedic Design & Technology that he and the company were “very exited” about this latest product launch.

“We’ve got a lot of momentum,” he added. “And people are enthusiastic to see Stryker headed down such new and innovative pathways. I’m really looking forward to the possibilities of this product.”

Patrick Treacy, vice president and general manager of Stryker’s knee business, told ODT that the company is in a “strong position” with both its hip and knee offerings.

“This could be one of the few times where we see one of the major players in the industry being strong in both hip and knee momentum,” he said. “Over the years, if you look at hip and knee growth, they sort of move at opposite trends. And there are various reasons for that—product launch cycles, focus of sales forces, etc. But when you look at what Bill’s team is doing, and certainly where we’ve been in market leading growth for the last 16 quarters, with the Triathlon [total knee replacement system] and X3 technology, we’ve got a lot of momentum.”

Treacy and Huffnagle also noted that Stryker’s recent acquisition in November last year of OtisMed, a privately held developer of patient-specific knee implantation instrumentation, will factor heavily in the company’s joint reconstruction business going forward.

“We have the opportunity to revolutionize how total knee surgery is done,” Treacy noted. “There are others that use preoperative imaging data to create cutting blocks, but nobody is doing what OtisMed had invented and pioneered which is really looking at that unique way to orient components to the individual patient.”

At present the OtisMed technology will be used with the company’s Triathlon knee system, and Stryker is currently seeking 510(k) approval from the U.S. Food and Drug Administration for the use of the OtisMed system with Triathlon.

“It wasn’t an accident that OtisMed sought out the Stryker design philosophy to implement their technology,” Treacy explained. “They look to place the femoral component in a unique way for that patient—for how the knee actually flexes and extends. And it is only a single-radius design philosophy that would allow you to maximize that design opportunity. So from the design philosophy and the technology itself, it was the perfect fit. We are incredibly excited about this technology and what it can do. Not just from the efficiency point of view, but the real special way they treat each individual patient.”

Treacy noted that the company already is evaluating the technology for use with other replacement implants—both large and small joint.

“We believe that we might have a bit of a jump on other folks in this area,” he said.

A ReGen Redo Scheduled by the FDA

The Menaflex implant manufactured by ReGen Biologics went before the U.S. Food and Drug Administration's (FDA) Orthopaedic and Rehabilitation Devices Panel in late March after months of controversy surrounding the clearance process for the device, which is used to repair torn knee cartilage. The controversial knee implant has been at the heart of many critics’ calls for a revamp of the agency’s 510(k) review process.

"The panel discussed and decided that there was insufficient evidence that the device, at time zero, reinforces and repairs soft tissue injuries," according to a summary of the panel's findings posted on the FDA's Web site. It concluded the Menaflex implant "can be viewed as reasonably safe, but the device's effectiveness would need to be analyzed further."

The implant was cleared by the FDA’s Center for Devices and Radiological Health in 2008, over the objections of some FDA scientists. The FDA admitted that it perhaps was in error when it approved the device. According to reports, FDA’s former director Daniel Schultz and four New Jersey legislators had pressured investigators to hustle Menaflex through the clearance process. ReGen is based in Hack-
ensack, N.J. The clearance came despite the fact that the device often failed and required second operations, agency reviewers claimed.

An FDA report called pressure from four New Jersey Democrats “extreme, unusual and persistent” and said it helped lead agency managers to overrule the agency’s scientists. Sens. Robert Menendez and Frank Lautenberg and Reps. Frank Pallone Jr. and Steven Rothman have said they had acted appropriately and were not influenced by any campaign contributions made by ReGen, according to The New York Times.

Company officials insist that Menaflex is safe and effective, and deny allegations made by the FDA.