Medical device industry followers cannot escape the clash.  A steady procession of headlines cries out against the regulatory system for failing to protect U.S. patients from unsafe devices.  An equally impassioned series of headlines express fear that the growing regulatory burden is killing the device industry, or at least driving it overseas.  At the center of the controversy is the pre-market notification pathway, commonly referred to by its section name of "510(k)," by which many devices enter the U.S. market. 

The Institute of Medicine (IOM) entered this controversy in July 2011, with a much-anticipated report offering perspective on the process.  The recommendation to end 510(k) altogether surprised many, particularly when the authors conceded there was not evidence to support a real safety concern. 

The IOM report echoed a rising global focus on "essential principles."  Our country's path forward may require the more express integration of current systems with these principles, while also doing more to ensure that the device industry can adapt quickly to advancing technology and get novel devices to market.  The FDA's Center for Devices and Radiologic Health (CDRH) is moving forward, though its methods appear firmly rooted in the existing system.    

The Framework

Moderate risk devices may be cleared through the 510(k) process if it can be demonstrated that they are "substantially equivalent" to one or more "predicate devices."  In broad brush, the concept is to get technological advances and adjustments to patients in a timely manner, without compromising device safety and effectiveness.  As the regulatory history and scientific world become increasingly complex, however, the consistent application of this system to actual devices has proved difficult.  The system is under attack from both sides:  unfairly inhibiting innovation, some say; unable to ensure safety, say others. 

Separately, there is concern about the lack of a straightforward path to market for new types of low or moderate-risk devices that are not substantially equivalent to a predicate device.  These devices may be classified automatically into Class III, requiring a full and detailed premarket review that is not warranted by the degree of product risk.  The road out from this burden can be maddening, as it requires a detour through the 510(k) process – although the substantial equivalence determination is expected to be negative – before the company can seek reclassification through de novo review.

The Questions

The CDRH, with responsibility for medical devices, is trying to address these concerns.  In August 2010, an internal 510(k) Working Group issued its Preliminary Report and Recommendations.  This report identified many potential issues with the process, along with concrete actions that could be taken to address them. 

Meanwhile, to assist in the evaluation, the IOM was commissioned in September 2009 to answer two related questions:  1. Does the current 510(k) clearance process optimally protect patients and promote innovation in support of public health?  2. If not, what legislative, regulatory, or administrative changes are recommended to optimally achieve the goals of the 510(k) clearance process?

The Answers

Nearly two years later, in July 2011, the IOM issued its surprising answers, indicating that the 510(k) process is not designed to evaluate safety and effectiveness and cannot be revised to do this; information is not available to allow a determination of the impact on useful innovation, though the process as implemented may stifle innovation; and the FDA should go back to the drawing board and start over, with a completely new device clearance process.[1] 

Although these answers may have been unexpected, they were not without precedent.  In its own report, the CDRH Working Group observed that people within and outside the agency had questioned whether the 510(k) program should be "fundamentally re-thought," since a determination of substantial equivalence to a predicate device, some say, "is insufficient to provide reasonable assurance" of safety and effectiveness.[2]  The Working Group also cited concern that a lack of transparency and consistency in program administration "may be hindering innovation."   

With all stakeholders complaining, some degree of change clearly is needed.  Following its January 2011 Plan of Action and its February 2011 Innovation Initiative, CDRH began to implement revisions.  Controversy remains, however, for several major changes the Working Group proposed.  CDRH expressly waited to receive the IOM report before deciding how to tackle these issues.  Unfortunately, the IOM report did not offer much by way of practical advice.  Clocking in at over 200 pages, the report primarily offers a detailed accounting of regulatory history and global context.  The report provides very little specific guidance about how to structure a new and improved framework. 

An Integration?

As the IOM report authors correctly observe, the 510(k) pathway is focused by its terms on device comparisons, rather than what could be referred to as "first principles" of safety and effectiveness.  Yet these principles are incorporated by definition into the 510(k) inquiry, and form a foundation for medical device classification under the U.S. system.[3]  A fresh start can be enticing, yet the substantial costs of re-invention may be hard to justify when so many detailed recommendations already have been fashioned based on the existing system.  In fact, CDRH director Dr. Jeffrey Shuren noted that congressional action may be required before the agency could implement the IOM recommendation to replace the 510(k) process with a new regulatory framework.[4]  Such counsel seems wise, given the detailed legislative specifications underlying the current process.[5]

Meanwhile, in the European Union, it has been noted that "new and emerging technologies have challenged the current framework, highlighting gaps or pointing to potential loopholes including the scarcity of expertise needed to independently assess such technologies."[6]  In this 2011 Roadmap and other documents, a desire is expressed for ensuring a "high level of safety" for patients and users. 

The centralized European councils increasingly aspire to follow the "essential principles" model set forth through the Global Harmonization Task Force (GHTF) for medical devices.  The GHTF concept, initiated in 1992 by several countries, including the United States, was intended to design a consistent structure regulating medical devices to foster free commerce throughout global health care markets.  Like the GHTF essential principles, the EU "essential requirements" begin with the premise that medical devices, when used as intended, "will not compromise the clinical condition or the safety" of patients, and that the risks of the devices are "acceptable" in light of their expected benefits and are "compatible with a high level of protection of health and safety."[7] 

The bedrock is a starting inquiry into safety and effectiveness, risk versus benefit. 

Americans are accustomed to these principles, which expressly underlie our drug approval system.  The 510(k) process uses some different language, but safety and effectiveness are touchstones there as well.  In fact, those charged with classifying medical devices into Class I, II, or III are expressly directed to account for device safety and effectiveness and the risk-benefit balance, in an effort to provide "reasonable assurance" that the devices are "safe and effective" for their intended uses."[8] 

A more straightforward focus on these foundational principles actually could benefit industry.  The opportunity to demonstrate safety and effectiveness, without a need for comparison to previous devices, could pave an easier path to market for some devices.  The increasing use of standards against which a device could be designed also may help, particularly if this opens out the possibility for more independent, non-governmental agency experts to conduct reviews – a system that has proven very successful in Europe.   

It also seems important to highlight the term "reasonable," drawn from the U.S. classification goal that there will be reasonable assurances of device safety and effect.  Our bedrock principles also include this:  we are not guaranteed safety in absolute terms.  There is an understanding that drugs and devices have side effects; a knowledge that risks are ever-present.  To the extent that the GHTF language results otherwise, its principles would conflict with ours.

Real challenges remain after the IOM report, which largely avoided the question of what the ideal approval process would look like.  While simplification surely may be enticing, starting a new statutory and regulatory scheme from scratch is not actually so simple. 

CDRH apparently agrees.  On the last day of September, 2011, CDRH took one more step on its own path to fix the current system.  A Draft Guidance Document was released, outlining a more streamlined de novo pathway for novel, low to moderate risk device types.  Now, instead of waiting for the "not substantially equivalent" finding under 510(k) before filing an application for de novo review, a manufacturer may file the applications concurrently.  This may be done when the company first consults with CDRH, early in the process, to align views about the safety and effectiveness data needed to support clearance.[9]  This pathway could be promising, depending on how it is implemented. 

We await further developments, with interest .