MX: Marketing A Fresh Process

Over the past several years, the medical device industry has been rocked by product recalls, U.S. Department of Justice investigations into improper marketing practices, and increased focus on potential conflicts of interest by physicians. Product safety concerns predominate, given FDA reports that from 2005 through 2009 over 3500 medical devices were recalled for potential safety problems. In the first seven months of 2009 more than 1000 recall notices were sent out, of which over 100 were ranked as Class I—that is, involving a defect serious enough to create a "reasonable probability of adverse health consequences or death." To address concerns about device safety and the medical device approval process, the Center for Devices and Radiological Health (CDRH) conducted an internal review and commissioned the Institute of Medicine (IOM) to review the 510(k) process in 2011.

Perhaps in anticipation of the IOM’s report, FDA has already taken a number of steps to address concerns related to the 510(k) process. Released in August 2010, CDRH’s plan specified 25 actions to be taken in order to overhaul the process, including issuing draft guidance and proposed regulations.1 FDA’s plan leaves the current regulatory framework intact, with substantial revisions and an increased emphasis on the scientific evaluation of medical devices in the hope of avoiding future recalls by approving only innovative, safe products.

The IOM released its independent review in July 2011. The taskforce concluded that the 510(k) process is not a reliable premarket screen of safety and effectiveness, and it recommended that FDA would be better served by eliminating the process altogether rather than expending any additional resources attempting to improve it. It recommended replacing the current system with an integrated premarket and postmarket regulatory framework to ensure the safety and effectiveness of future devices.

As FDA’s actions demonstrate, even without the IOM’s critical findings and recommendations, device companies must expect additional, significant changes to the 510(k) process and postmarket safety requirements. When viewed in the broader context of healthcare reform, comparative effectiveness research, and other current challenges, changes to the 510(k) process have serious implications for device companies.

510(k) Shortcomings

Some of the shortcomings of the 510(k) process detailed by the CDRH and the IOM are the result of its history. That history will be familiar to most readers. Before 1976, medical devices were largely unregulated. A number of high-profile device failures in the 1970s, such as the Dalkon Shield, led to regulatory changes, beginning with the Medical Device Amendments of 1976, including section 510(k), which amended the Federal Food, Drug, and Cosmetic Act. Section 510(k) requires device manufacturers to notify FDA at least 90 days in advance of their intent to market a medical device. This section allows FDA to determine whether the device is equivalent to a device already placed into one of the three classes. Any Class I or Class II device that reaches market through a 510(k) notification must be "substantially equivalent" or have the same intended use as a device legally marketed before May 28, 1976 (a "predicate device"). It also must have the same technological characteristics as that predicate device. Class III devices are considered high risk and subject to the stricter premarket approval (PMA) process.

Much of the recent scrutiny of the 510(k) process has focused on concerns about the safety of Class III devices that have been cleared through the process. The Safe Medical Devices Act of 1990 required FDA to reclassify or establish a schedule for requiring PMAs for Class III device types. However, the Government Accountability Office (GAO)has found that this process remains incomplete and that more than 200 Class III devices were cleared through 510(k) between 2003 and 2007. In fact, even as medical devices increase in complexity, more than 90% of the devices introduced from 2003 to 2007 came through the 510(k) process, meaning they had to prove only that they were “substantially equivalent” to an existing product, according to GAO findings.

Critics of the 510(k) process, including the IOM, point out that FDA does not currently require proof of the safety and effectiveness of predicate devices, which can result in safety issues and device recalls. As a result of the overuse of the 510(k) process, 78% of the medical devices recalled by FDA due to serious risks over the past five years were approved through the 510(k) regulatory process or were completely exempt from regulatory review, according to a recent study.2

In part because of these issues, the IOM made its recommendation that FDA would be better served by eliminating the 510(k) process than by attempting to improve it. The IOM instead recommended the development of a new, integrated premarket and postmarket regulatory framework to ensure the safety and effectiveness of future devices throughout the product lifecycle.

While FDA has rejected the IOM’s recommendation to replace the 510(k) process, it apparently anticipated this criticism. Within a month of the release of the IOM’s report, FDA issued a number of guidance documents concerning 510(k) modifications, design of medical device clinical studies, postmarket surveillance studies, postmarket requirements, and new methods of monitoring clinical trials.3

Implications For Device Industry

While it’s impossible to eliminate risks associated with medical devices, it is clear that FDA will require more effort—both premarket and postmarket—from device makers to improve safety. There’s clearly tension between getting a safe product to the market quickly versus obtaining additional data to ensure safety.

In the current environment, companies should be aware that FDA is sensitive to criticism that the 510(k) review process is becoming slower and impeding innovation. In response to these concerns, FDA conducted its own study. The government agency claims that the time required to review an application has increased due to the poor quality of submissions and that sponsors’ failure to address deficiencies and requests for information has caused review time to increase.4

Given FDA’s ongoing plans to address the 510(k) process, device companies should expect the government body to be more demanding in reviewing submissions. In addition, companies will need to expand their views of device development and approval to include planning for postmarket safety requirements. While FDA rejects the IOM’s proposed elimination of the 510(k) process, as a practical matter there is much less disagreement with the IOM’s recommendations to improve postmarket surveillance capabilities. As companies respond to demands for clinical evidence to obtain clearance, they need to plan for increased postmarket safety requirements as well. For purposes of postmarket safety surveillance, companies need to examine whether pre-clinical, clinical, and product development insights about devices are used sufficiently in developing robust postmarket surveillance strategies.

There are a number of implications beyond postmarket requirements for the industry as well. In the short-term, companies should continue to expect longer 510(k) reviews, as FDA focuses on its internal processes, safety, and possibly additional oversight. To a certain extent, however, companies should be able to anticipate issues. If a device is invasive or is based on new technology, heightened scrutiny or demands for clinical data—or both—should be expected. In light of the CDRH and IOM reviews, companies should recognize that if there is something new in a device it will be more difficult to compare it to a predicate and therefore more likely FDA will require clinical data. As a result, companies probably should expect higher research and development costs and longer product development cycles.

A More Demanding Future

For companies that have relied on fast approval cycles and limited or no clinical data, the future will likely be far more demanding. They will be confronted with greater clinical data requirements—and their associated expenses—and will need to develop an improved understanding of the clinical value of their products. As FDA addresses its internal process issues, however, companies may benefit from the development of clearer standards that enable them to gain a better understanding of FDA expectations and requirements. By extension, they will be able to anticipate any hurdles to regulatory approval and plan appropriately.

In the long term, device companies also should expect greater importance to be placed on health economics data. This will present a number of challenges for device companies in a few years. Meanwhile, as FDA deals with internal disputes about process, companies must be clear about the path they want to take, work with reviewers to make their case for comparison to a predicate very clear, and know the rules and regulations better than reviewers.

References
1. CDRH Plan of Action for 510(k) and Science—Implementation of Recommendations from the 510(k) and Science Reports. Accessed at: http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHReports/ucm239448.htm
2.“Medical Device Recalls and the FDA Approval Process,” Diana M. Zuckerman, PhD; Paul Brown, BS; Steven E. Nissen, MD; Arch Intern Med.(Published online February 14, 2011).
doi:10.1001/archinternmed.2011.30.
3. Draft Guidance for Industry and FDA Staff—510(k) Device Modifications: Deciding When to Submit a 510(k) for a Change to an Existing Device (July 27, 2011); Draft Guidance for Industry, Clinical Investigators, and Food and Drug Administration Staff—Design Considerations for Pivotal Clinical Investigations for Medical Devices (August 15, 2011); Draft Guidance for Industry and Food and Drug Administration Staff—Factors to Consider when Making Benefit-Risk Determinations in Medical Device Premarket Review (August 15, 2011); Draft Guidance for Industry and Food and Drug Administration Staff—Procedures for Handling Section 522 Postmarket Surveillance Studies (August 16, 2011); Guidance for Industry—Oversight of Clinical Investigations—A Risk-Based Approach (August 2011).
4.Analysis of Premarket Review Times Under the 510(k) Program, Center for Devices and Radiological Health, Food and Drug Administration (July 2011). Accessed at: http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHReports/ucm263385.htm

Stephen R. Rothenberg is a consultant at Numerof &Associates Inc.(NAI; St. Louis), a strategic management consulting firm. He may be contacted at [email protected].
 

Jill E. Sackman is a senior consultant at Numerof &Associates Inc.(NAI; St. Louis), a strategic management consulting firm. She may be contacted at [email protected].