In 2012, the FDA will seek congressional reauthorization of two acts related to drugs and medical devices. The battle lines have been drawn as industry has slammed the burdensome FDA approval process and its consequent defection of innovation from the U.S. to Europe, while the FDA testified before Congress about its robust approval process and innovative plans to make it even better.

In February, the California Healthcare Institute (CHI) issued a report, "Competitiveness and Regulation: The FDA and the Future of America's Biomedical Industry," to coincide with the U.S. House Energy and Commerce Committee Health Subcommittee's hearing on the impact of medical device regulation.

"The data clearly indicate that today's FDA is not keeping pace with U.S. biomedical innovation," wrote David Gollaher, PhD, president and CEO of CHI, in the report. "The agency-industry partnership is strained by unexplained regulatory delays, by a lack of clear standards for what clinical data are necessary for product approval and by a bureaucracy whose communications are neither consistent nor predictable."

Testifying before Congress on Feb. 17, Jeffrey Shuren, MD, director of the FDA's Center for Devices and Radiological Health (CDRH), acknowledged that "in many areas, insufficient clarity, consistency and predictability on our part contributes" to the expense of medical device development. Yet, Shuren had many positive things to say about the agency's performance over the last decade.

The CHI report mentioned some points of discontent, including:

• Comparing the most recent year for which a representative set of submission data is available (2008) with the average for 2003 to 2007, review times for drugs and biologics have increased by 28 percent.
• For medical devices, comparing 2010 with the period 2003 to 2007, 510(k) clearances have slowed by 43 percent and premarket approval (PMA) times have lengthened by 75 percent.
• Where new medicines were approved first in the U.S. by an average of nearly seven months between 2004 and 2006, recent data show products approved on average two-and-a-half months earlier in the European Union (EU), a shift of nine months.
• Complex medical devices approved via the PMA process in the U.S. are approved in Europe on average nearly four years ahead of the U.S., up from just over a year earlier this decade.

Class III devices, which are the highest risk category of devices, are subject to PMA application containing scientific evidence of the devices' safety and effectiveness.

Shuren took notable exception to the comparison with the EU model of approval. First, the CE mark conferred on products in the EU does not prove the device's effectiveness, only its safety and performance, meaning the device must perform as indicated in the device description and is not required to show benefit to the patient.

"For example," Shuren testified, "if a manufacturer wishes to market a laser to incise heart tissue to treat arrhythmia in the EU, the manufacturer must only show that the laser incises heart tissue. In the U.S., however, the manufacturer must show that the laser incises heart tissue and also treats the arrhythmia."

He also pointed out that, unlike the U.S. medical device regulatory system, the European system:

• Does not require government review before a company may market a device;
• Allows manufacturers to "forum-shop" their applications among third-party reviewers who are subject to minimal oversight;
• Provides minimal information to the public about the evidence supporting company claims;
• Has no centralized authority for tracking safety information related to medical devices and no EU-wide post-market surveillance system; and
• Has no centralized database of information about the performance of the various regulatory systems, making it difficult to compare the performance of the EU and U.S. systems.

The CHI report touted the EU approval process as one that is transparent and fosters innovation, "a consistent path that enables the EU's regulatory agencies to deliver on their 210-day time limit for new drug application reviews and the 90-day limit for Class III medical devices."

The report also noted a correlation between a device's complexity and its longer lag-time to approval in the U.S. In fact, "the more complex, and often cutting edge, a product is, the more likely it is to be approved first in Europe versus the U.S."

Shuren, however, testified that the European Commission acknowledged limitations in its regulatory framework for medical devices and sought public comment on ways to strengthen its system. In fact, regulators and physicians from the U.S. and the EU met in January in France to discuss ways to improve the EU medical device approval process.

Shuren's testimony and CHI's report seemed to be a classic example of he said-she said, each side using statistics to plead its case.

Shuren said that comparisons of safety data are problematic. "Since the number of approval submissions or 'on-market' devices in the EU cannot be determined from publicly available information—nor can the number of recalls or adverse event reports—calculation of accurate rates of safety problems is not possible."

In addition, he noted that according to a Boston Consulting Group study, 85 percent of medical device safety reports in the EU come from only five member states of the 24 countries reviewed, "underscoring the potential for underreporting of safety events in the EU."

The bottom line is that the FDA is seeking reauthorization of the Prescription Drug User Fee Act (PDUFA) and subsequent Medical Device User Fee and Modernization Act (MDUFMA), originally enacted in 1992 and 2003, respectively. The idea was to provide additional resources to make FDA reviews more timely, predictable and transparent. User fees would help the FDA expand available expertise, modernize its information management systems, offer new review options and provide more guidance to prospective applicants.

The CHI report noted that the success of the PDUFA spawned a likeminded act for devices and that the MDUFMA was initially successful. However, each time Congress reauthorized the MDUFMA (every five years), it added new and expanded demands on the FDA without concomitant funding. Consequently, the FDA relied heavily on user fees to complete more—and often more extensive—device reviews.

"With PDUFA and MDUFMA due for renewal in 2012, Congress must focus on the FDA's mission, on the optimum balance between benefits and risks, and on the direct and indirect costs regulation imposes on public health, biomedical innovation, the economy, job creation and American competitiveness," the report concluded.

For his part, Shuren cited statistics showing the growth of the U.S. medical device industry. "In 2000, [it] ranked thirteenth in venture capital investment. Now, 10 years later, it's our country's fourth largest sector for venture capital investment."

He quoted a January report on medical technology innovation by PricewaterhouseCoopers that stated, "U.S. success in medical technology during recent decades stems partially from global leadership of the FDA. The FDA's standards and guidelines to ensure safety and efficacy have instilled confidence in the industry's products worldwide."

He said the FY2010 MDUFMA Performance Report to Congress indicates "FDA's device review performance has been consistently strong," including:

• 95 percent of the more than 4,000 medical device applications subject to user fees that FDA reviews every year (FDA reviews over 9,000 submissions annually in total) are reviewed within the goals that were agreed to by the medical device industry.
• Under the 510(k) program—the pathway used by 90 percent of the devices the FDA examines each year—90 percent of the reviews were completed in 90 days or less, and 98 percent of reviews were completed in 150 days or less, "as we committed to do under MDUFMA."

Shuren detailed recommendations to better the 510(k) process, as well as suggestions to speed approval of breakthrough medical devices.

Nonetheless, industry wants to see some changes that will help the U.S. keep its competitive edge in the biomedical industry, including addressing the "serious inefficiencies within the FDA and performance breakdowns of recent years, and finding a more appropriate balance between benefit and risk.

"Today, the FDA, the press, Congress, consumer groups and others overwhelmingly focus on 'direct' risks: side effects, adverse events and technical product failures. Just as important to consider are 'indirect' risks—distortions in the regulatory process, for example. How do we calculate and consider the public health loss to patients if investors and companies avoid entire diseases and conditions because the FDA's demands for clinical data are so extensive and its standards for approval of new products so uncertain?" the report concluded.