A new rule published in the June 6 issue of the Federal Register expands on the postmarket surveillance powers of the FDA, an expansion that some critics says could cause problems for smaller medical manufacturers. Covering section 519 of the Federal Food, Drug and Cosmetic Act, the regulation is focused on earlier evaluation of technologies that could endanger public health. It enables the agency to require product monitoring for as much as three years but, what is more likely, a time period agreed to by the manufacturing and the agency.

The discretion that the guidance gives the agency enables it "to focus on devices thought to be more of a risk, such as newer ones whose side effects aren't fully known yet," said David Daly, director of the issues management staff in the Office of Surveillance and Biometrics at the FDA's Center for Devices and Radiological Health. "The vision behind the rule is that we identify a problem and then go to the manufacturer and say 'This is the question we have,' and the manufacturer is then required to answer the question," Daly told The BBI Newsletter's sister publication Medical Device Daily. "The manufacturers can be really creative in how they answer the question. It could be as simple as looking at their own complaints from physicians and patients to using existing data collection to identify a solution," he said.

The agency will notify manufacturers in advance that it will require a product to be monitored for up to three years or a mutually agreed-upon monitoring term. The goal is to evaluate as early as possible rare but potentially dangerous events that could endanger public health, according to the published rule. A surveillance notification can come from FDA officials during review of a product's marketing application, as the device goes to market, or after the device has been marketed for a period of time, according to the rule. Companies will be required to then submit a surveillance plan within 30 days of receiving the oder. The FDA then has 60 days to approve or disapprove the plan with the manufacturer.

"Many problems or risks associated with a medical device cannot be predicted before the device enters commerce, even with clinical studies," said Deputy Commissioner Lester Crawford in announcing the new rule, which takes effect July 8. Devices included in the surveillance are those "reasonably likely to have severe adverse health consequences, devices implanted into the body for more than one year, and devices that sustain or support life and are used outside a medical facility," according to the rule's language. "Postmarket surveillance will allow FDA and manufacturers to identify less common, but potentially serious, problems that were not evident during product development or to address problems that were not seen as serious enough to warrant keeping the product from reaching the market," Crawford said.

The FDA estimates that issuing 30 postmarket surveillance orders annually will cost nearly $1 million to the agency, for five additional employees. Estimated cost to manufacturers will be $4.3 million. "The figure in the rule [30] was just an estimate," Daly said. "It could be that we identify one device with a potential risk and there are only two vendors, or we could identify two devices with 15 vendors each. We didn't have our crystal ball out, so we used an average instead."

Failure to produce a surveillance plan or failure to conduct postmarket surveillance will result in the device being misbranded, according to the rule. The FDA would then "initiate actions against products that are adulterated or misbranded and against persons who commit prohibited acts. Adulterated or misbranded devices can be seized. Persons who commit prohibited acts can be required to pay civil money penalties or be prosecuted," the rule states. "That's the standard procedure for how the agency would handle a misbranded device. There's nothing new in this rule in regard to penalties," Daly said.

The Advanced Medical Technology Association (AdvaMed; Washington), an early critic of the rule, said it would impose substantial and unnecessary burdens on device manufacturers and has the potential to drive some small manufacturers out of business and create entry barriers for others.

While the FDA acknowledged that the costs create a burden for smaller companies, it also noted that it had provided opportunity for small companies to give their input. "Here again, the rule allows for some flexibility in how a company provides the surveillance, and it allows for some exemptions and variances, so I don't foresee it as a huge problem," Daly said.

Suggestions AdvaMed recommended that were included in the rule include holding meetings with manufacturers prior to issuing a postmarket order, publicly listing devices subject to postmarket surveillance and providing a justification for requiring postmarket surveillance over other alternatives.

MDMA seeks small firm user fee protection

Executives of the Medical Device Manufacturers Association (MDMA; Washington) modified their stand on the FDA user fee issue last month, giving reluctant support to such fees if the interests of startup firms and small manufacturers in the industry are protected. The proposal for fees to be paid to the FDA by medical device firms to support the regulatory clearance process was negotiated by the Advanced Medical Technology Association (AdvaMed: Washington) as a late add-on to a comprehensive bioterrorism bill. But the lack of early thorough planning appeared to work against the proposal, and it was dropped from the final legislation. Afterwards, the MDMA delivered some sharp criticism concerning how the proposal was put together, saying that it and other sectors of the industry had not been included in developing the proposal. But perhaps sensing changing winds on this issue, the organization then modified its stance a bit, saying that user fees might be possible if the interests of small and emerging firms are not damaged by them.

Paul Touhey, senior vice president of Fujirebio Diagnostics (Malvern, Pennsylvania) and chairman of the MDMA board, said the basic philosophy of the organization concerning user fees hasn't changed: "We are still adamantly opposed to them, but the FDA has asked us to work with them and consider fees as an option. If that's the only option, then we are willing to help as long as the small companies are heard," Touhey told BBI. He said that the group would meet with the acting FDA commissioner and David Feigal, head of the Center for Devices and Radiological Health (CDRH), and he promised cooperation with the agency on the issue "as long as the small company was represented and that any solution wouldn't affect the way we do business."

Touhey listed a variety of problems which the agency itself has pointed to as the basis for additional funds to aid in the process of reviewing and clearing new products to market. These include the large percentage of long-time staff members facing retirement — and the resultant loss of their expertise — and the growing number of complex technologies requiring more sophisticated science in the review process. "We hoped [the FDA] would get the resources through [public] funding," said Touhey. "But with the state of defense [against terrorism] in our country needing additional funds, I think that's unlikely."

Touhey continued to maintain that the user fee proposal developed by AdvaMed was geared toward large companies "and some of their small-company members have felt left out of the process, I'm told." Among the larger firms which he identified as having a major hand in developing the plan was Medtronic (Minneapolis, Minnesota).

Mark Leahey, director of federal affairs at MDMA, echoed Touhey's openness to developing a user fee plan. "We will look at all the possibilities," he said, noting that a key item to be hammered out in any negotiations will be the development of fee exemptions and who might get them. "The AdvaMed proposal has some first-time exemptions as a deferral in the first year of business, but some of the smaller companies may not see a profit until year four or five, and that exemption just doesn't help them enough," Leahey said. He added: "We're going to see what the FDA says is their magic number that they need, and we'll go from there."

Britain to merge drugs, device agencies

Britain's health ministry reported in mid-June that it plans to combine the country's Medical Devices Agency and Medicines Control Agency into a single entity, with the merger to take place by April of next year. The move is intended to reflect the growing integration and combination of devices and pharmaceuticals, according to Health Minister Lord Philip Hunt, with integration of some functions but little change in the particular regulatory processes. He said that companies will continue to deal with the agency "dedicated to the specific needs of their sector."

"As technology develops, there are likely to be growing numbers of products that cross the borderline between medicines and devices," he said in a statement. "For instance, some products are already a combination of drugs and devices. The boundaries will become even more blurred in the future. Through this change, the agency will be well placed to respond to the changing world of medicines and medical devices control."

The Medical Devices Agency investigates adverse incidents associated with devices and ensures that devices comply with European regulations. The Medicines Control Agency licenses drugs, conducts post-marketing surveillance of pharmaceuticals and regulates drug promotion. One person as chairman will head the merged body — which has not received a name as yet — and issue the agency's public decisions.

The health ministry said that it will issue more details concerning the merger and its budget over the next few months.

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