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One of the issues AdvaMed and FDA have been discussing as part of FDA’s Postmarket Transformation Initiative is the question of when is the best time to file complex Medical Device Reports, said AdvaMed’s Jeff Secunda at an AdvaMed media briefing on postmarket issues. If an incident with a complex device occurs, only sketchy information will be available at first, he said. Should firms stick with rules that require them to report information immediately, even if it’s incomplete, or should they be allowed longer time for MDR preparation?”

You must [file MDRs] immediately, but it might be more effective to report more complete information and open up the reporting timeframe if the product requires extensive analysis,” he said. “We want to identify those that might benefit from longer reporting timeframes.”

That, he said, is the “most interesting and challenging” issue on the postmarket-discussion table right now.

– From MD&DI’s blog.

FDA and AdvaMed on April 16 made public the agreement that should form the basis for the reauthorization of the Medical Device User Fee and Modernization Act (MDUFMA). The new user fee scheme will promote a 6.4% increase each year between FY 2008 and FY 2013. It significantly reduces application fees but adds two new fees. The details can be found in a notice of a public meeting to be held on April 30 for discussion of the topic.

As expected, MDUFMA II eliminates the adjustments that made the year-to-year use fee increases so volatile. Instead, to promote more consistent funding, the proposal recommends two new fees that wouldn’t change much from year to year and would generate about 50% of total fee revenue. They are an annual establishment registration fee and an annual fee for filing periodic reports.

The annual establishment fee would in FY 2008 be $1706 per device manufacturer, single-use reprocessor, and specification developer. A firm would not be considered legally registered without paying this fee. It is expected to generate around $21.8 million in FY 2008. The periodic-report fee would start at $6,475 in FY 2008 and, assuming 425 devices are subject to it and most don’t qualify for the small-business rate, would generate about $2.5 million in FY ‘08.

These allow application fees to be reduced. PMA fees would be $185,000 in FY 2008, a 34% reduction from this year. Panel-track supplement fees would be reduced 51%, 180-day PMA supplement fees by 54%, real-time supplement fees by 36%, and 510(k) fees by 18%. However, there would now be fees for 30-day notifications and 513(g) classification requests, which are free currently. The small-business discount, for firms with less than $100 million in annual revenues, remains in effect.

CDRH’s performance goals have been modified to focus on the time it takes to make a final decision, rather than interim goals. Significantly, the goals include for the center to make decisions on 50% of PMAs, panel-track supplements, and premarket reports within 180 days, and 90% within 320 days.

The matter is now in the hands of Congress, which will likely combine it with a measure to reauthorize pharmaceutical user fees. The Senate was expected to start tackling it on April 18.

AdvaMed is happy with the agreement — read its press release to see for yourself.  Same for FDA.

– From MD&DI’s blog.

FDA has released proposed and final documents prepared by three study groups of the Global Harmonization Task Force and will receive comments on them through May 7. Accessible at www.fda.gov/OHRMS/DOCKETS, the documents represent a harmonized proposal and recommendation from the study groups. Governments that are developing and updating medical device regulatory requirements may find the documents useful.

The documents were developed by Study Groups 1, 2, and 4. Study Group 1 was to identify differences between various regulatory systems. It would then propose areas of potential harmonization for premarket device regulations and possible guidance to help lead to harmonization. The group has developed a proposed document, the Role of Standards in the Assessment of Medical Devices, which provides guidance to manufacturers designing a medical device. It also offers guidance when firms are demonstrating that the device conforms to relevant essential safety and performance criteria.

Study Group 2 was charged with developing guidance documents to be used for exchanging adverse-event reports. Its document is called Medical Devices Post Market Surveillance: Global Guidance for Adverse Event Reporting for Medical Devices. It provides guidance on the types of adverse events that should be reported by a manufacturer to a national competent authority.

Study Group 4 looked at developing guidance documents on quality system auditing practices. The document that it developed is called Guidelines for Regulatory Auditing of Quality Management Systems of Medical Device Manufacturers—Part 3: Regulatory Audit Reports. It suggests a structure for audit reports used in multiple jurisdictions, promoting consistency and uniformity.

- James G. Dickinson

When it comes to off-label promotion, FDA and industry have been engaged in a cat-and-mouse game for years. And in March, Congress got involved, too.

The House Committee on Oversight and Government Reform wrote to Johnson & Johnson and Boston Scientific to announce an investigation into the marketing of drug-eluting stents. Committee chairman Henry Waxman (D–CA) was inspired by the December hearings on drug-eluting stent safety, in which it was revealed that the products are used off-label about 60% of the time. If the percentage of off-label use is so high, Waxman deduced, then perhaps the manufacturers are doing something improper to encourage it. The firms announced they would comply with the investigation.

Just days later, CDRH officials met with manufacturers of coronary and bile-duct stents to remind them about guidelines against off-label promotion. In particular, the agency warned against promoting bile-duct stents for coronary applications, and it admonished some firms for advertising them at a cardiology meeting. According to one published report, 90% of bile-duct stent sales are to catheterization labs, where presumably they are used primarily for vascular applications. Again, by deductive reasoning, authorities must figure that if that number is so high, there must be some off-label promotion going on. It gave bile-duct stent manufacturers three weeks to change their marketing tactics.

“People had known for a long time that a lot of stents are used off-label,” says attorney Robert J. Klepinski of Fredrickson & Byron (Minneapolis). “This news is not a surprise, but I wasn’t expecting it to happen right now.” Klepinski is an expert on promotion and marketing of devices.

This sort of give-and-take has gone on for years. Device manufacturers are not allowed to promote off-label uses directly. But the federal courts have held that some forms of indirect off-label promotion, such as certain kinds of references to independent studies of off-label uses, are allowed. FDA is not allowed to regulate the practice of medicine. It has no control over what doctors do, but it does have control over what manufacturers do. Therefore, FDA leans on manufacturers to try to prevent unapproved use of devices.

“FDA is not allowed to go down that road [of regulating the practice of medicine], but it has been gradually working that angle for a long time,” says Klepinski.

What’s resulted is a situation in which FDA is trying to get around its prohibition on influencing the practice of medicine, and industry is trying to get around its prohibition on off-label promotion.

Klepinski believes that firms resort to off-label promotion because “the premarket approval bar is set so high” and because doing clinical trials for new indications can be prohibitively expensive. Yet, he says, FDA doesn’t allow real-world off-label experience to be considered when deciding whether to approve a new indication. That makes getting a new indication approved burdensome and may tacitly encourage firms to try to flout the promotion rules instead. “So FDA traps itself in a vicious cycle. What we need is a less shortsighted approval process. Sometimes FDA’s pursuit of so-called good science lags behind the real science of treating patients.”

It’s time to bring the issues into the open. Step up surveillance of any safety problems related to off-label use. But acknowledge that it does happen and allow the real-world data to be used more freely. That acknowledgment could create a more streamlined, less burdensome process for new indication applications, and it could cut down on unsafe use of devices. The current system encourages, albeit unintentionally, breaking the rules, at a potential cost to patient safety. It’s time to encourage companies to follow them.

- Erik Swain

CDRH has debuted a Web site that will keep the public informed about the status of studies mandated by the center as a condition of approval for certain medical devices. It will include all post-approval studies ordered by CDRH since Jan. 1, 2005. It is based on information reported by firms, who are required to update the center every six months during the first two years of a study, and every year thereafter. Each listing includes the company’s name, the product’s name, the approval number and date, and describes the study and whether it is meeting its reporting deadlines. Detailed information on clinical data is not included because of privacy and other issues.

The site, which can be viewed here, was first suggested by the Institute of Medicine in 2005, and is long overdue.

– from MD&DI’s blog.

An FDA project that’s examining tubing misconnection problems could push manufacturers to change their product designs. The patient safety initiative involving the Medical Product Safety Network (MedSun) and a team of healthcare experts is looking at how to prevent tubing and catheter errors in pediatric intensive-care units.“Many connectors look very similar,” notes Izabella Gieras, director of technology management at the Beaumont Technology Usability Center (Royal Oak, MI). “And there’s potential for misconnecting something that’s infusing medication with something that’s infusing air or formula. The results could be adverse.”

It’s possible that the program’s findings could mean manufacturers would have to modify the design of certain types of medical devices. “The risk assessment will identify potential misconnection errors. Therefore, the focus on administrative controls such as education and policy changes could lead to physical design changes,” says Gieras. “The design of the devices susceptible to misconnections should incorporate some type of forcing function” that prevents clinicians from connecting devices that should not fit together.

The Beaumont center began working on the MedSun project last November. The center’s team is composed of human factors and clinical engineers and clinical staff. The team developed a risk assessment process to classify and evaluate the connectors and the severity of all possible misconnections in the pediatric ICU.

The project is scheduled to end in April.

– Maria Fontanazza

FDA is exploring how to use information technology to create an integrated electronic postmarket safety network. The proposed Sentinel Network would combine postmarket study efforts of both public and private sectors. The goal is to deliver comprehensive product safety information directly to clinicians.

According to FDA, current postmarket safety actions are hindered by “limitations in the quality, quantity, and timeliness” of available data. The ability to quickly conduct postmarket studies is also limited. The proposed network will use electronic databases and surveillance systems to provide a “seamless, timely flow” of product information while also protecting patient privacy. Data collection, risk identification and analysis, and risk communication would be the main actions of the network.

FDA held a two-day public meeting in March to discuss the network. The goal was to hear examples from industry groups that have access to “electronic, population-based data sets” that could be used for monitoring postmarket safety. The meeting also discussed

• Potential obstacles and incentives for developing the network.
• How postmarket device safety data collection can be effectively incorporated into clinical practice work flow at the point of care.
• How electronic health records can be used as a means for data collection related to device safety in the least burdensome manner for clinicians and patients.
• How the network can guarantee the privacy of patient information.

– Maria Fontanazza

President Bush in January signed an executive order that allows the White House to review guidance documents from federal agencies, including FDA. The order could have a significant effect on industry, as it could serve as a check against overly burdensome guidances.Under the order, agencies must have any guidance that could cost industry $100 million or more reviewed by the Office of Management and Budget. They must also justify such guidances publicly and cite a “specific market failure” that the guidance would correct.

Some media reports portrayed the order as a power grab. These reports indicated that the order would curtail federal agencies’ ability to regulate through guidance and wrest control of the authority to oversee the regulatory process from Congress. But FDA observers in Washington don’t see it that way. They say FDA guidances are already reviewed heavily by the agency and the public. The order merely grafts one more review onto the existing process. The order, in fact, is merely a revision of one signed by President Clinton in 1998 covering procedures for proposed rules, final rules, and notices. It clarifies that Clinton’s order applies to guidances, too.

“It sounds like it’s just another layer of review,” says Jonathan Kahan, a partner at Washington, DC–based law firm Hogan & Hartson. “And knowing what we know about CDRH’s guidance documents, I’m not sure that many of them would meet the $100 million threshold anyway. Anyone saying it’s a case of the White House hamstringing federal agencies is probably crying wolf. But anyone saying it would have no effect probably doesn’t know what they’re talking about, either.”

Larry Pilot, a partner at another DC law firm, McKenna, Long & Aldridge, says the order could prove quite useful if it pushes FDA to think harder about whether a guidance is really necessary. “A good question that needs to be asked more often is this: ‘Is the time that will be invested in preparing this guidance worth the investment?’” he says. “Does it fulfill a need? How is that need established? If there are only three manufacturers of a type of device, why prepare a guidance document? Who benefits?”

– Erik Swain

A Washington Post column ponders whether FDA’s increasing reliance on user fees makes the agency too beholden to industry. It discusses this in the context of the pending reauthorization of the drug user fee act. But you can bet these same issues will come up when it comes time for MDUFMA to be reauthorized.

The reality is, Congress, even when controlled by the Democrats, isn’t willing to fully fund what it takes for FDA to accomplish its mission. Therefore, user fees are inevitable. The ongoing reforms to the agency’s postmarket surveillance system should hopefully take care of many of the safety issues that concern those who are against user fees.

– from MD&DI’s blog.