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IoM to Study Effectiveness of FDA's 510(k) Review Process for Medical Devices

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By Turna Ray

After the Government Accountability Office reported earlier this year that the US Food and Drug Administration may be clearing too many high-risk devices through the less stringent 510(k) process, the FDA this week commissioned the Institute of Medicine to examine the strengths and weaknesses of its premarket notification program and issue recommendations for improving the system.

The evaluation comes as regulation for genetic tests is in flux at the FDA's device division. In expressing its intent to regulate a subset of complex laboratory-developed tests, so-called in vitro diagnostic multivariate index assays, the agency has said most IVDMIAs will fall into the Class II or Class III device category, requiring either 510(k) or PMAs [see PGx Reporter 02-14-2007]. IoM's recommendations regarding the FDA's regulatory processes would certainly have implications for this subset of devices.

As part of its review of the FDA's 510(k) regulatory process for medical devices, the IoM will hold two public workshops during the next nine months and form a committee to investigate whether the regulatory process "optimally" protects patients and promotes innovation. If the committee finds the 510(k) process not up to par, then it will issue recommendations for regulatory, legislative, and administrative changes. The group's findings and recommendations will be finalized and published in March 2011.

While the two-year IoM study is ongoing, the FDA's Center for Devices and Radiological Health will convene an internal working group "to evaluate and improve the consistency of the FDA decision making in the 510(k) process," the agency said in a statement last week.

"Good government conducts periodic reviews and evaluations of its programs," Jeffrey Shuren, CDRH's acting director, said in a statement. "Our working group and the IoM's independent evaluation will help us determine how the 510(k) process can be improved to better support the FDA's mission to protect and promote the public health."

The FDA's efforts follow a GAO report released in January, titled "FDA Should Take Steps to Ensure That High-Risk Device Types Are Approved through the Most Stringent Premarket Review Process." In the report, the federal auditing body found that between 2003 and 2007, the FDA reviewed 342 submissions for class III devices through the 510(k) process, clearing 67 percent, or 228 submissions, for marketing.

"Although Congress envisioned that class III devices would be approved through the more stringent [premarket approval] process, and the [Safe Medical Devices Act of 1990] required that the FDA establish a schedule for doing so, this process remains incomplete," the GAO states in its report.

For class III devices cleared by 510(k) notification, the GAO specifically recommends the FDA to either reclassify these into lower risk classes (class I or II), or for device types maintaining their class III status, to require they undergo PMA. According to the GAO, the HHS agreed with the conclusions and recommendations in the report.

Based on the level of risk a particular device poses to the public's health, the FDA classifies medical devices into three categories: class I, II, or III. Class III devices — for example, heart valves, intraocular lenses, and certain algorithm-based multiplex genetic tests such as DxS' KRAS mutation test kit — represent the highest risk devices and therefore generally require PMA.

By comparison, Class I and Class II devices pose lower risks because they are "substantially equivalent" to legally marketed products. Therefore, these products can be marketed following premarket notifications, so called 510(k) applications.

The GAO recommends the FDA "expeditiously take steps to issue regulations for each class III device type currently allowed to enter the market through the 510(k) process."

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One example of this occurred in May 2007, when the FDA issued a "special controls" guidance assigning Class II status to gene-expression tests that provide breast cancer prognosis information, but are not used to make treatment decisions. These tests would require 510(k) clearance, the agency notified device makers in the guidance [see PGx Reporter 05-16-2007].

Heeding the GAO's recommendations, the FDA commissioned the IoM to conduct an independent review of its 510(k) process. According to the agency, given the pace of technological advancement, the time is ripe for an assessment of whether its clearance process effectively ensures public safety.

"During the past three decades, technology and the medical device industry have changed dramatically, making it an appropriate time for CDRH to review the adequacy of the premarket notification program," the FDA said in a statement.

The IoM's review will cost $1.3 million. CDRH's Shuren has identified the IoM's review of the FDA's 510(k) process as one of the center's priorities.

Changing Processes

The 510(k) premarket notification process was established under the Medical Device Amendments of 1976, aiming to advance safe and effective devices to the public, and promote innovation in the medical device industry.

Although most class III devices are approved through PMA, certain types of high-risk devices that are similar in terms of technology and intended use to pre-amendment device types — or class III products on the market before May 28, 1976 — can be cleared through 510(k), until the FDA publishes regulations requiring them to go through PMA or reclassifies them into a lower class.

The Safe Medical Devices Act of 1990 required the FDA re-evaluate the pre-amendment class III device types to consider whether they should be reclassified to class I or II or remain in class III. The SMDA also asked the FDA to develop a schedule for issuing regulations for pre-amendment device types that are maintaining their class III status, requiring FDA approval through PMA.

Ultimately, under the law, all class III devices are eventually to be reviewed through the PMA process," the GAO notes in its report.

In investigating the FDA's regulatory processes, the GAO analyzed data from the agency's 510(k) and PMA databases, and interviewed agency officials.

In the five-year period reviewed by the GAO, the agency cleared for submission 24 class III device types under the 510(k) process. "These submissions were more likely than class I or class II submissions to be implantable or life sustaining, or to pose significant risk to the health, safety, or welfare of a patient," the GAO report states.

As of October 2008, four of the 24 class III device types cleared had been reclassified as class II.

Although between 2005 through 2007, "relatively few" class II and III devices reviewed through the 510(k) process had a new intended use or new technological characteristics," the GAO did identify instances where FDA regulatory action was warranted, requiring either reclassifications or new regulations.

During this three-year period, 5,063 class II or class III 510(k) submissions received either "substantially equivalent" or "not substantially equivalent" determinations from the FDA. Of these, the GAO found that 1 percent had a new intended use and about 15 percent had new technological characteristics.

Of the devices the agency cleared as substantially equivalent to pre-amendment devices, all had the same intended use and 86 percent had the same technological characteristics as a device already on the market. However, 248 devices found not substantially equivalent, the FDA determined that more than 50 percent had a new intended use or new technological characteristics.

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"FDA officials have acknowledged the importance of publishing regulations requiring PMA submissions or reclassifying pre-amendment class III device types," the GAO states in the report. "When asked for their time frame for doing so, however, the officials did not provide one."

According to the FDA, it asked the IoM to look at its 510(k) process to see if the agency's methods are upholding the public's health by introducing safe and effective products and encouraging innovation within the medical device industry.

FDA's dual responsibility came under fire recently when it said most IVDMIAs were more complex laboratory-developed tests, and would require either regulatory clearance under 510(k) or PMA. However, device developers have criticized the agency's plans as being cumbersome and disincentivising innovation [see PGx Reporter 08-01-2007].

However, Alberto Gutierrez, director of the FDA's Office of In Vitro Diagnostic Device Evaluation and Safety, recently said that the agency was restructuring a lot of its regulatory processes under the Obama Administration [see PGx Reporter 08-12-2009].

The IoM's review of FDA's 510(k) process is one of six priority areas CDRH's Shuren recently identified for the center.

Other priorities include creating an internal task force on the use of science in regulatory decision-making; developing an effective compliance strategy; optimally integrating premarket and postmarket information; increasing transparency in the center's decision-making; and establishing clear procedures to resolve differences of opinion.

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