While technological advances have provided us with an abundance of innovative and useful products, many of these enter the market with limited or no clinical data. Medical devices are becoming increasingly complex, and the means of reviewing them for safety have become severely inadequate. Over the past several years, critics have repeatedly pointed to the urgent need for the FDA to strengthen the approval process for medical devices - particularly the 510(k) process - and to increase and improve safety surveillance requirements. Innovation - crucial to the US maintaining its role atop the medical device world - must share the podium with a focus on protecting the consumer. The FDA must carefully balance both interests, allowing products to move through the process in a predictable manner, while still thoroughly collecting safety data.
So what is the right amount of regulation to create optimal levels of safety and innovation? While there is no definitive answer that covers every product - medical devices must be examined on a per-product basis - the FDA is tasked with ensuring safety and limiting risk, but it also has a duty to help foster - or at least not get in the way of - innovation.
On the one hand, safety is the original mandate behind the FDA. Protecting the public from harmful products should remain an essential priority. But at some point, too much regulation may impede technological advances in medicine, and ironically inhibit the public's access to new devices. The FDA must first and foremost take a consistent, predictable approach so that manufacturers can readily meet their requirements. The process must be logical and easy to follow, and clearly communicated - with constructive information exchanges between manufacturers and the agency. This means that product review processes must be overhauled, as currently, they are riddled with inconsistencies.
Product recalls and adverse events have consistently been in the news for the past decade. The FDA indicates that approximately 2,500 medical devices were recalled for potential safety problems in fiscal 2008, nearly double the number reported in 2007, and a 164 percent increase since 2000. In fact, more than 1,000 recall notices were sent out in the first seven months of 2009, 100 of which were ranked as "Class 1" recalls, which indicate a significant risk of injury or death. Of the devices recalled between 2005 and 2009, 80% were cleared through the 510(k) process or exempt from any approval process.
The DePuy ASR Hip Replacement helps to highlight this issue and the need for better regulatory balance by the FDA. DePuy created two products that utilized a metal-on-metal "cup and ball" implant, but differed in that one required bone resurfacing. The ASR XL Acetabular System - deemed similar enough to a predicate (previous) device that used metal-on-plastic - went through the 510(k) process of review, which requires minimal pre-market studies, and was approved. The ASR Hip Resurfacing System - although it used similar materials - was deemed to be too dissimilar from predicates, given the additional procedure of bone resurfacing - and went through the more stringent Pre-Market Approval process (PMA). Ultimately, the ASR Hip Resurfacing System was not approved for U.S. use due to a lack of clinical data demonstrating safety. DePuy decided not to pursue approval in the U.S. - even though the product was approved for use in Europe and Australia - given their belief that interest was waning in the resurfacing technique.
Both devices were later voluntarily recalled worldwide after DePuy determined (through post-market surveillance) a high rate of premature failure. Though the FDA's tough PMA process restricted one device from getting to the market, they still approved the other through the 510(k) process. Consequently, the FDA succeeded and failed at the same time!
Even though one device required bone-resurfacing, most of the failure issues were linked to problems with the materials they both had in common. Why is it that two devices using the same materials - ultimately recalled for the same reason - went through two different approval processes and met two different fates? While the specifics are beyond the scope of this article, the example points to a large gap in the way the FDA balances safety and innovation.
The process seems flawed in that two very similar - though not identical - devices would receive two different levels of scrutiny. The FDA must reassess the criteria it uses to determine when a product needs a tougher review, and when it can ease safety requirements to increase innovation. In the case of the hip implants, the only clear answer is that the 510(k) process did not do an adequate job of finding that balance.
Our current example shines a light on a much bigger picture than just one product recall, and that is that most devices are ultimately approved via the 510(k) process. Such products are not likely to have had clinical studies performed pre-market, resulting in insufficient data on safety issues prior to launch. Even so, pre-market clinical trials (even large ones) have limited power to identify the potential for post-market adverse events or failures, especially given the relatively short lifecycle of these products. Consequently, this minimizes the likelihood of identifying low-frequency adverse events.
As NAI discusses in Post-Market Safety Surveillance and Medical Devices , this results in a greater burden on a passive post-approval surveillance system, which has not proven effective. Accordingly, ongoing (active) review of patient registries may be increasingly necessary. While the concept of registry reviews makes sense, current U.S. use of registry data may not be adequate. But if the FDA made monitoring and auditing of registries a part of their review processes, this could be a viable option.
But this type of analysis is a two-way street. The FDA must work closer with companies throughout the product lifecycle to identify safety concerns. This will enable the FDA to effectively communicate a consistent message balancing both safety and innovation. Presently, discussions to reauthorize the Medical Device User Fee and Modernization Act (MDUFA) are focused on building a more collaborative process between the agency and manufacturers, which I believe represents a significant move in the right direction.
MDUFA was originally enacted in 2002 to enable the FDA to collect user fees for pre-market reviews of certain medical device submissions, which would in turn allow the FDA to increase resources and reduce the time it takes to approve a product. FDA committed to implementing a more aggressive and interactive review process, and MDUFA was extended in 2007. The current reauthorization aims to further solidify these goals, as well as add some additional efforts to improve the process.
By paying $595 million over the next five years, the medical device industry hopes that MDUFA reauthorization will reduce review time, but also improve the efficiency and consistency of the process. Some of the current issues that are being considered include shorter cycle times for 510(k) submissions, greater predictability and transparency (including an additional "Product Development Fee" to allow for more collaboration before submission), stopping the "review clock" to allow for more questions, and better rationing of resources per review.
MDUFA reauthorization has the potential to benefit the industry and regulators alike. The issues discussed in connection with hip implants are not uncommon across the device spectrum. Encouraging greater collaboration among stakeholders represents an excellent way to achieve better balance between safety and innovation. Manufacturers want reduced cycle times for 510(k) submissions, but this can only be done safely if the FDA sets clear requirements, and both parties communicate frequently throughout the process. The revenue created by MDUFA should provide the means for enhanced review and better analysis, ultimately enabling good products to come to market faster.