WASHINGTON WRAP-UP

FDA and industry recently got together to negotiate renewal of medical device user-fee legislation. However, they left out any provision for postmarket surveillance.

Such a provision had been included in the original Medical Device User Fee and Modernization Act of 2002 (MDUFMA), but the Republican-led Congress did not fund it.

Most mass media headlines faulting FDA's performance on postmarket product safety have focused on drugs. However, agency deficiencies in the device industry have also been featured. Drug-eluting stents, defibrillators, breast prostheses, heart valve implants, infusion pumps, and contact lens solutions have all captured media attention.

Indeed, concerns have been intense enough to prompt CDRH to commission a study on bar coding for medical devices. And, last November, center director Daniel Schultz announced a Postmarket Transformation Leadership Team to enhance device safety in the marketplace.

So why was this entire issue left out of the second round of user-fee legislation?

Enter the new Democratic majority on Capitol Hill in the form of House Committee on Energy and Commerce Health Subcommittee chairman Frank Pallone (D–NJ). In a May 16 hearing on MDUFMA II, as the reauthorization is called, he described postmarket surveillance activities as “noticeably absent from this proposal.”

Asked to explain their absence, FDA assistant commissioner for policy Jeffrey Shuren explained the agency's position. “If we can ensure adequate funding for the agency,” he said, “we will be in a fairly good place for postmarket safety.”

Although the user-fee reauthorization does not specifically address postmarket activities, the fees will still support necessary surveillance activities, he explained. For example, Shuren said, past funding has allowed the agency to hire experts. These experts provide “greater expertise in a variety of fields that is then integrated into our postmarket safety activities. In addition, we have a little more protection on appropriations that will go to the rest of the program, which will cover the remaining postmarket safety activities.”

Pallone asked whether the agency would support a congressional mandate that earmarked user fees for postmarket surveillance issues. Shuren said that FDA “would prefer [to] have the funding and then apply it as [it sees] fit.”

In explaining the reauthorization, Shuren said, “MDUFMA was about growth. It was about progressively increasing the size of the device review program through rapidly increasing funding linked to progressively more-aggressive performance goals. For MDUFMA II, we are recommending changes to fine-tune the program.” This includes getting funding to maintain a stable device review program and continuing to improve performance that is attainable through seasoned review staff and process efficiencies.

Shuren also highlighted three areas for refinement. “First, for premarket review performance, we are proposing to meet more-rigorous goals that build on the progress we made in the first medical device user-fee program,” he said. “The result would be a shortened decision time for several types of applications, including those for the most innovative devices. In addition, we are proposing several qualitative goals to continue to enhance the device review process and to make it more transparent.” For example, FDA has proposed additional steps to facilitate the informal interactions with manufacturers called interactive reviews. Such steps would make public more information about FDA's performance.

“Second, to ensure financial stability for the review program, we are recommending a reasoned increase in user-fee revenues in the first year,” Shuren said, “followed by annual increases of 8.5% for the four years thereafter.” This system could help ensure that FDA has adequate resources to maintain a device review program, while providing the predictability and the fees for the duration of MDUFMA. Also, the establishment of two new fees will generate about 50% of the total fee revenue. (The additional fees are an annual establishment registration fee and an annual fee for filing periodic reports.) This revenue should stabilize FDA's funding, enable it to lower the application fees, and provide a larger fee discount for small businesses.

“Third, we are recommending modest changes to the third-party inspection program,” Shuren explained. The changes are designed to encourage industry participation while maintaining safeguards against conflicts of interest. In addition, he said, a successful third-party inspection program will enable FDA to better focus its inspectional resources on high-risk devices.

Subcommittee member Henry Waxman (D–CA) urged that FDA be given more resources for device inspections. Since 2003, FDA has reduced medical device field investigators from 482 to 413, making it more difficult to perform mandated biennial GMP inspections. Shuren said that domestically, about 5500 facilities making Class II and Class III devices are eligible for biennial inspections. However, the agency is inspecting these firms only about once every four years.

National Research Center for Women and Families president Diana Zuckerman urged lawmakers to add more device safety provisions in the legislation. She cited Bausch & Lomb's recent problems with its 510(k)-cleared contact lens solution that caused eye infections and blindness. She said the agency should require clinical trials when potentially dangerous devices are modified. “MDUFMA II should make sure that the approval process protects consumers,” she said, complaining that performance goals would drastically speed up the 510(k) clearance process. (The goals would require 90% of 510(k)s to be reviewed within 90 days.) For premarket approval (PMA) application devices, review goals would also be faster. For those devices, 60% of PMAs and supplements would need to be completed within six months. Those time frames are considerably faster than what's expected of drugs, she noted.

“MDUFMA II has performance goals for speed, but it needs performance goals for public health as well,” Zuckerman told the hearing. She noted that the user-fee reauthorization also lacks any fees for direct-to-consumer advertising reviews and adverse-event analyses. In addition, there are no fees for analyses to ensure that postmarketing commitment studies prove that products are safe. “Although FDA has flexibility to spend user-fee money however it wants, there's just not enough money for all it needs to do.”

FDA Alliance executive director Steven Grossman echoed the concerns about resources. He said that since 2003, FDA has “lost about 20% of its buying power and has nearly 1000 fewer employees supported by appropriated dollars.” These deficits make it hard for FDA to recruit and retain the “best and brightest.”

Grossman said a $450 million increase in appropriated funding is needed to restore the agency to operational levels achieved in 2003. Of this, CDRH and related field activities should receive an increase of $72 million in FY 2008. “This would bring the center from its current $230 million to $302 million, not including user fees. Because devices employ cutting-edge science, CDRH needs these non-user-fee monies for additional staff to perform product reviews, assure pre- and postmarket safety, and facilitate innovative technology coming to market.”

Utah Medical CEO Decries FDA-AdvaMed Collaboration

FDA should not be collaborating with organizations like AdvaMed to educate industry about FDA regulations, according to Utah Medical Products CEO Kevin Cornwell. This activity, he says, may work to create new standards and law outside the statutory framework.

A recent FDA solicitation urged device makers to attend an FDA-AdvaMed– sponsored industry education meeting in Denver in May. Commenting on the solicitation, Cornwell recalled FDA testimony during its unsuccessful 2005 GMP case against his firm. The testimony stated that the way companies learn industry standards, “which are required,” is by going to industry meetings. “The federal court exhaustively examined the technical facts relating to FDA's claims that Utah Medical was not in compliance with the QSR. It ruled against FDA on each of its claims and held that Utah Medical is in full compliance with the QSR,” he said.

“Since FDA couldn't find any law or regulation which Utah Medical violated, FDA's QSR case against us boiled down to FDA claims that the firm was violating so-called industry standards,” Cornwell said.

“Going to industry meetings to learn industry standards was rejected by the court as a basis for compliance with the QSR,” continued Cornwell. “When FDA's chief witness, Kim Trautman, was questioned by the judge, she could not come up with any written industry standards regarding validation of injection molding and extrusion (because there aren't any), which was their chief claim.”

Also, he said, FDA brought in so-called expert witnesses who had never visited the company to testify on its state of compliance. “The court found that these experts' opinions about Utah Medical's alleged lack of compliance were not correct. But these are some of the very people that AdvaMed is retaining in seminars to tell industry participants what they need to do to be in compliance. These experts have been proven to not know what is in compliance and what is not in compliance when adjudicated in federal court.”

Cornwell said AdvaMed “is not representing the interests of its members, the industry, or the American people by being complicit with the so-called FDA education process.”

He cited language from a statement issued on the collaboration by CDRH director Dan Schultz. In it, Schultz says, “the medical device industry learns about our regulatory requirements while hearing about the real-world application of these requirements.” This, Cornwell said, “is another way of saying that they are setting regulatory requirements outside the legal process. They are attempting to tell people ‘how' instead of ‘what.' The ‘what' is the law. The QSR is a general document that is easy to read and understand.”

On the other hand, he said, “the ‘how' are the opinions expressed in [these] conferences. They are based on statements from the so-called experts. FDA has no business engaging in and funding this activity—particularly when we hear the drumbeat over and over that they don't have enough resources for proper enforcement activities.”

TMJ Implants's People Also Liable

Individuals at device firms can be held liable for their participation in device-related violations. That's the bottom line of a two-page order written in May by FDA administrative law judge Daniel J. Davidson in the TMJ Implants (TMJI) case. He denied motions by company president Robert Christensen and regulatory affairs director Maureen Mooney to be dismissed as individual respondents to CDRH's complaint for civil money penalties. Davidson was expected to rule on the agency's $630,000 civil money penalties claim in mid-June if the parties didn't settle before then.

In his order, Davidson cited the statutory and regulatory language of 21 USC 333(g)(1)(A) and 21 CFR Part 17. He said that it is “abundantly clear that corporate officers and employees may be liable in their individual capacities for device-related violations.”

He also cited an April 17 hearing transcript in the case. He used it to assert that both Christensen and Mooney had roles in the company's decision-making process that was used to decide not to file the 17 contested medical events as MDRs. At that hearing, Davidson urged the parties to settle.

However, TMJI's settlement offer to the agency was swiftly rebuffed over the issue of money.

On May 4, FDA's Office of Chief Counsel insisted that any settlement between the parties involve monetary payment. It opposed TMJI's contention that a settlement cannot involve monetary payment. The company contends such payment would force it to close.

In a statement, Christensen said his offer to FDA was to sit down and discuss each case the agency thought should have been filed as a MDR. From there, the two parties could make a determination based upon medical facts. “TMJI agreed that if this process determined that any of those cases should have been filed as MDR reports, the company would immediately do so,” Christensen said.

However, he said, FDA's response suggests that “even at this late date, the agency cannot find medical expertise to support its position and cannot admit its mistakes.” Furthermore, Christensen says, FDA “continues to insist on financial penalties that can only be seen as a design to punish TMJI because [the company] questioned what we believe are medically unsupportable positions. We hope that the agency will rethink its response to the administrative law judge's encouragement of settlement and approach settlement in a more constructive way, which would be to deal with medical facts rather than heavy-handed misuse of enforcement tools.”

Meanwhile, Republican members of the House Energy and Commerce Committee have challenged FDA's legal tactic. They have questioned the agency's motive in demanding civil monetary penalties from TMJI before dealing with an appeal by the company to the FDA commissioner on the MDR issue. The members acted partially out of concern that FDA's civil money penalties demand could close the company.

FDA Panel Rejects Cardima Microcatheter

FDA's Medical Device Dispute Resolution Panel has voted not to recommend approval of Cardima's PMA for the Revelation Tx Microcatheter System. The panel said in April that it believed that efficacy data were not clear and supportive for approval.

In briefing documents released before the meeting, FDA said Cardima did not collect required clinical trial data. The firm should have collected data on the “atrial electrogram amplitude as required by the protocol, as well as other procedural data required in the case report forms.”

CDRH had previously issued two “not approvable” letters on the device. The briefing documents said the uncollected data included “numbers of ablation burns completed per lesion line, temperature set-point used, actual temperature achieved, power used, etc. Therefore, it is not possible to determine whether any study subject had a successful ablation procedure with the Revelation Tx as defined in the investigational protocol.”

Additionally, FDA said, there were no recorded procedural data. Without it, FDA was unable to determine the true safety of the catheter. “For example, if all the investigators had used the Revelation Tx catheter aggressively to achieve a 50% decrease in atrial electrogram amplitude, it is possible that there may have been a higher adverse-event rate.”

FDA Releases Guidance on IVD Labeling

A new CDRH guidance provides recommendations to industry on labeling requirements for IVDs intended to detect influenza A (or A/B) virus in human specimens. The guidance is aimed particularly at devices that test for avian influenza (H5N1, H9N2, H7N7).

The document also outlines the premarket regulatory path for devices intended to generally detect influenza A viruses, or those intended to detect and differentiate a specific novel influenza A virus infecting humans, the agency says. It includes broad recommendations on the necessary information for assessing the clinical performance and utility of such devices.

The guidance can be found at www.fda.gov/cdrh/oivd/guidance/1594.html.

FDA Guidance Supports Labor Monitor Classifications

CDRH has issued a guidance called Class II Special Controls Guidance Document: Computerized Labor Monitoring Systems. It is designed to support classification of computerized labor monitoring systems into Class II (special controls). The systems are intended to continuously measure cervical dilation and fetal head descent as well as provide a display indicating labor progress. They include a monitor and ultrasound transducers.

The guidance identifies risks to health from the use of such systems as patient injury, electrical hazards, and acoustical, or ultrasound, tissue damage. Also mentioned are electromagnetic interference and electrostatic discharge hazards, mismanagement of patients, adverse tissue reactions, and infections. The guidance also covers recommended measures to mitigate these risks.

The guidance may be accessed at www.fda.gov/ohrms/dockets/98fr/2007d-0122-gdl0001.pdf.

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