Industry Leaders Choose Sides Over IOM’s 510(k) Report

With the release of its 510(k) report, the Institute of Medicine (IOM) and U.S. Food and Drug Administration (FDA) clearly are at odds about revamping the much-criticizedmedical device clearance process. Since the report was released on July 29, both the IOM and the FDA have found allies willing to support their respective positionsregarding the recommendations, with major device firms dismissing the proposal to scrap the 510(k) program and start anew, and medical journals calling for major reform.

Most recently, The New England Journal of Medicine published an editorial supporting the IOM’s report, claiming the 510(k) process has not kept up with the times.

“As devices have evolved and become more complex, our device-approval system has become incapable of assuring safety and effectiveness,” wrote Gregory Curfman, M.D., executive editor of the NEJM and Rita Redburg, M.D., editor of the Archives of Internal Medicine. “The system we use today was created 35 years ago in an era of much simpler and fewer devices, and is now outdated.”

Shortly after the release of the report, titled, “Medical Devices and the Public’s Health: The FDA 510(k) Clearance Process at 35 Years,” device companies spoke out mostly in support of the FDA.
Minneapolis, Minn.-headquartered Medtronic Inc. was among them: “As a company, we are supportive of regulatory changes that will continue to add clarity and consistency to the process and that are in the best interest of patients, including ensuring that innovative therapies can reach the market,” a company statement read.

The NEJM editorial insisted that the 510(k) process as it currently exists offers no advantage to the industry or patients. Until a long-term solution is crafted, the report recommends the FDA exclude all Class III devices from the 510(k) process, stop clearing products based on predicate devices, and implement a formal post-market surveillance program.

“We believe that the IOM report is insightful, judicious, sensible and long overdue,” the NEJM editorial read. “We support the IOM committee’s recommendation that the 510(k) process be replaced with an evaluation of safety and effectiveness. It is important to maintain and encourageinnovation in medical devices. But trueinnovation requires that safety and effectiveness be proven by scientific study in clinical trials.”

Though industry analysts believe the FDA will not scrap the 510(k) program, they are confident the agency will nonetheless attempt to improve the device approval process and address companies’ concerns.

“I don’t think we should eliminate [the 510(k)] process in its entirety,” said Jeffrey Shuren, M.D., director of the FDA’s Center for Devices and Radiological Health, at an Aug. 2 town hall meeting in St. Paul, Minn. “It does need some fine-tuning.” He then acknowledged that those tune-ups should come in the form of better predictability, transparency and timeliness.

Shortly before the NEJM published its editorial, the FDA issued a draft guidance that clarifies when changes or modifications to a previously cleared 510(k) device require a new premarket submission.

In keeping with tradition, changes thatsignificantly could affect a product’s safety, effectiveness or intended use require an additional 510(k) submission. But the draft guidance names the specifics manufacturers have been asking for. According to the draft, changes that require action include specific types of labeling revisions, changes to technology, changes in performance specifications, manufacturing alterations, and changes in the materials used to make the device.

“We are making the regulatory process for medical devices less challenging by better describing our expectations,” Shuren said. “In particular, manufacturers can continue to make innovative improvements to their devices and better plan for any updated submissions. This saves time and money.”

The draft guidance is one of 25 action items listed in the FDA’s Plan of Action for Implementation of 510(k) and Science Recommendations launched earlier this year to enhance predictability, consistency and transparency of the agency’s premarket review programs. When it is final, it will supersede the “Deciding When to Submit a 510(k) for a Change to an Existing Device” guidance document from 1997.

The FDA is gathering public comment about the 510(k) process and the IOM’s suggested changes. A public meeting is scheduled for Sept. 16 in Silver Spring, Md. The deadline for public comments on the IOM’s recommendations is Sept. 30.

FDA Gives $9.5 Million Back to Industry in User Fee Relief

Medical device firms are going to have a little more money in their coffers next year, courtesy of the U.S. Food and Drug Administration (FDA). The agency recently informed companies that it is cutting user fees by about 7 percent in 2012, when the current medical device user fee act is up for renewal. Considering the tension andrestless (yet slow-moving) negotiatingbetween the device industry and the FDA, a reduction in user fees might be viewed a small victory for those on the device side.

According to documents released by the agency, the annual user fee for medical device companies will be $2,029 in 2012, compared with $2,179 in 2011. Any company wishing to market a medical device in the United States must pay the fee,regardless of size.

Companies will be required to pay $4,049 per 510(k) premarket submission, compared with the $4,348 they paid this year. For premarket applications, companies will have to pay $220,050 per submission, compared with $236,298 last year.

A small business discount will be applied for companies with less than $100 million in annual sales, making their new total for 510(k) premarket submissions $2,024 in 2012, compared with $2,174. For premarket applications, small businesses will pay $55,013 in 2012, compared with the $59,075 they paid in 2011.

Finally, companies with less than $30 million in sales qualify for a waiver of the first PMA (premarket approval) fee.

The total amount of money collected by the FDA in user fees in 2011 is expected to be more than $18 million higher than the $61.8 million appropriated to the agency by the Medical Device User Fee and Modernization Act II—about $8.5 million of that total is classified as unearned revenue, leaving $9.5 million to go back to the industry in the form of user fees.

FDA Analyzes Premarket Review Times Under 510(k)

In an analysis of premarket review procedures, the U.S. Food and Drug Administration (FDA) concluded that the overall review time for 510(k) submissions isincreasing primarily because of an increase in the number of review cycles and the amount of time it takes device manufacturers to respond to the FDA’s requests for additional information.

In response to recent studies sponsored by the medical device industry thatreported delays in the FDA’s review of premarket applications submitted under the 510(k) pathway, the FDA conducted its own analysis using Additional Information (AI) letters, which are sent when moreinformation is needed—each AI letter sent stops the clock on the review time andcreates a new cycle in the review process.

Two analyses were conducted by staff familiar with but not involved in the sampled submissions. In Cohort 1, 100 submissions were assessed for incoming submission quality. In Cohort 2, 134 submissions were assessed for the drivers of the increasing numbers of review cycles. A list of deficiencies and a sub-list of those related to poor quality were created. Deficiencies indicating poor quality were identified as: inadequate device description; discrepancies throughout submission; problems with indications for use; failure to follow or otherwise address current guidance documents or recognized standards; performance data not provided; and clinical data not provided. Letters also were examined to determine how often inappropriate information was requested by the FDA, such as data not permissible as a matter of federal law or FDA policy, orunnecessary data.

Results showed that 83 percent of the submissions in Cohort 1 and 82 percent of the submissions in Cohort 2 contained at least one quality deficiency. In Cohort 1, 52 percent of quality issues were related to device description; 24 percent failed to show a current guidance document; and 22 percent showed discrepancies throughout the submission related to indications for use or device description.
In Cohort 2, 50 percent of quality issues were related to device description. Almost 60 percent of submissions failed to address current guidance documents. Cohort 2 included only submissions that contained at least two AI letters, which indicated a more problematic situation.

“Although these cohorts are unrelated, the distribution of deficiencies among them is strikingly similar,” the FDA report stated. “Problems with submissions quality are contributing to an overall increase in review times.”

Less than 20 percent of submissions in each cohort contained deficiencies that were not related to quality, but still would be addressed with an AI letter, and therefore, also would stop the review clock.
The Cohort 2 analysis showed that second round AI letters were sent because the sponsor did not address requests made in the first round AI letter (66 percent); the sponsor’s response to the first round AI letter raised issues for the FDA (63 percent); or the FDA reviewer raised new questions that should have been raised in the first round (4 percent).

“In 93 percent of the submissions analyzed, the sponsor had either failed to address questions raised in the initial AI letter and/or provided information in response to the deficiencies that did not support a determination that the device was substantially equivalent and, therefore, FDA sent a second AI letter to give the sponsor a second opportunity to address these problems rather than determine that the device is not substantially equivalent,” the FDA report stated.

Inappropriate requests for information were made in 12 percent of the cases in Cohort 1 and 4 percent of the cases inCohort 2. These requests included data beyond that which had been asked for in the past and were not scientifically justifiable; data not consistently required; information inconsistent with current guidance; unnecessary additional testing; and information to support a standard government form specifically created to avoid the submission of the related underlying data as part of 510(k).

The FDA has drafted Standard Operating Procedures for Notice to Industryletters to help facilitate that goal. The FDA also is enhancing training for staff and the device industry to reduce inappropriate requests and help sponsors understand when they must submit data.

“It is our hope that taking actions toincrease submission quality and avoidinappropriate requests for additional information will prevent avoidable delays and reduce review times, which will, in turn, get safe and effective devices to market faster,”the report concluded.