Year-End Report Notes Faster Reviews, More Changes at FDA : Device Interaction Alert : Henney Confirmation : PMA "Not Approvable" : Balloon Stent Alert : FDA One-Sidedness Continues : MRA Transition Delayed : CDRH Draft Inspection Handbook

James G. Dickinson

January 1, 1999

10 Min Read
Year-End Report Notes Faster Reviews, More Changes at FDA : Device Interaction Alert : Henney Confirmation : PMA "Not

Medical Device & Diagnostic Industry Magazine
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An MD&DI January 1999 Column

CDRH gives itself high marks for fiscal year 1998 accomplishments.


For fiscal year 1998, FDA's Center for Devices and Radiological Health (CDRH) turned in, in its own words, an "outstanding performance," based on various measures of the time it takes to review premarket approval (PMA) applications and premarket notifications (510(k)s). Glossed over in the Center's report was one traditionally employed performance measure: absolute numbers of approvals. These were marginally down for PMAs and not even mentioned for 510(k)s—about which, more in a moment.

CDRH's report, providing a preliminary glimpse of the soon-to-be-released comprehensive annual report from the Office of Device Evaluation (ODE), focuses more on quality than on quantity, hailing 11 important diagnostic or therapeutic advances among the 46 PMAs. Four of these approvals were humanitarian-device-exemption PMAs for orphan devices intended to meet the needs of fewer than 4000 patients.

The report cites continuing significant reductions in average review times—12.4 months for a PMA compared with 16.6 months in FY 1997 and 25.9 months in FY 1996. "And the median total time to approval in 1998 was just 8.7 months," according to the report. "This year, CDRH had the shortest review time for any substantial number of PMAs in a decade."

One-third of the PMAs passed last year were approved in less than the statutory 180 days allowed, and 63% were approved in less than a year. "Furthermore, 28 of the 46 PMAs were never overdue in any review cycle."

For 510(k) applications, the average review time was 114 days in FY 1998, compared with 130 days in FY 1997 and 145 days in FY 1996. Fifty-nine percent of 510(k)s were reviewed within 90 days, about the same as the previous year (58%) and better than FY 1996 (50%).

The report gives no absolute number for 510(k)s received in FY 1998, but ODE director Susan Alpert told this writer it was 4623. This is 8.4% fewer than in FY 1997 (5049)—a decline Alpert attributes primarily to the Class I devices that were exempted from the premarket notification requirement during the year.

With the absolute number of PMA applications approved remaining virtually static (actually down by two) and 510(k)s down, CDRH is driven to soft measures of its performance, such as maintaining for the second year a zero backlog of 510(k)s, PMAs, and PMA supplements, and recitation of unquantifiable achievements such as continuing improvement in communications with industry and creative management initiatives.

Alpert stated that original IDE submissions increased significantly in FY 1998, with about 70% being approved, and "that's quite good." The new IDE review board, formed to ensure a consistent FDA approach to scientific issues, has been meeting quarterly, Alpert said, and "is working quite well."

Two IDEs have so far been appealed to this board by their sponsors. "We got some very strong recommendations," said Alpert. "In one, the board agreed with the division in terms of what was needed, but made some suggestions about how to communicate that better to the company. In the second case, there were several issues raised by the division that the board felt weren't necessarily showstoppers—and that's the kind of leveling that we want to get from this board."

Alpert declined to give more specifics because the identity of investigational devices is confidential. The IDE review board comprises all of the division directors, representatives of Alpert's office, senior clinical people from the divisions, and a senior manager from one of the other FDA program centers. In addition to any company appeals that may come in, the board routinely examines the IDE letters most recently issued by the office as to their scientific and communications qualities.

Among other achievements that don't show up in hard numbers, Alpert cited the elimination of "a lot of old PMAs. . . . We have worked through them or worked with the companies to understand their fate. We're not carrying a lot of deadwood in the system anymore. And all of the ones we're carrying are active. That means that the staff is working on things that are current and have a goal. This has been a tremendous benefit."

The ODE director also hailed the new real-time review process for supplements, a process in which reviews are conducted live with company participation and final decisions made within days rather than weeks or months. "People don't even think of it as something new anymore—they just automatically do it," Alpert said. "That releases a tremendous amount of resources. It changes the entire interaction, and it gives you a focused time, a focused issue, and it gives you dialogue. We've done more than 70."

Alpert acknowledged that the process "wouldn't be possible without industry's willingness to change the way it works with FDA. They have to send in clean and complete submissions, and they have to do a different kind of work to do a real-time review. And they've done it."In October, CDRH director Bruce Burlington issued a "dear colleague" alert advising that minute ventilation rate-adaptive implantable pacemakers may occasionally interact with certain cardiac monitoring and diagnostic equipment, causing the pacemakers to pace at their maximum programmed rate.The CDRH letter cited Telectronics' (St. Jude Medical) META and Tempo series, Medtronic's Legend Plus and Kappa 400 series, and ELA Medical's Chorus RM and Opus RM series as examples. It referenced several reported incidents in the preceding year in which minute ventilation rate-adaptive pacemakers paced at their maximum rate when patients were connected to cardiac monitoring and diagnostic equipment. While none of the incidents resulted in patient death or injury, CDRH said it was "concerned that this unexpected rise in the pacing rate could be misdiagnosed as clinically significant tachycardia, resulting in unnecessary therapy, or that patients with compromised cardiac reserve (e.g., with unstable angina or myocardial infarction) may poorly tolerate the higher pacing rates."The cause of the problem, according to the letter, was a mixing of bioelectric impedance—measurement equipment signals from other devices in the vicinity of the pacemakers—for example, cardiac monitors, echocardiograph equipment, apnea monitors, respiration monitors, or external defibrillators.CDRH urged deactivation of the minute ventilation sensor during treatment with such other devices, selection of the appropriate maximum pacing rate to minimize risk, and cautioning of pacemaker patients.As its last act of official business before adjournment, the U.S. Senate confirmed the Clinton administration's nomination of Jane E. Henney as FDA's new commissioner. In the partisan wrangling over the 1999 federal budget, abortion, tobacco, and other issues, there had been doubt that her nomination would reach the floor at all.In the end, only Senate majority whip Don Nickles (R–OK) stood in the way of Henney's confirmation. The nominee flew to Washington to assure him, with reinforcement from HHS secretary Donna Shalala, that she would not be, as he feared, "a tool of the administration to push its liberal political agenda"—especially on using FDA to find a commercial sponsor for the abortion drug RU-486. Nickles relented, issuing a statement that he believed Henney "won't try to implement legislation through regulation."Several major Washington industry associations issued statements immediately after the Senate vote applauding her success. The Health Industry Manufacturers Association (HIMA) was not among them. Its only comment on Henney thus far was made last June, when news of her nomination was officially announced. Then, HIMA said it "expressed hope that the president's nominee for FDA commissioner, Dr. Jane Henney, will make a priority of new initiatives intended to speed up delivery of medical technology to patients."The younger, smaller, and more aggressive Medical Device Manufacturers Association (MDMA), however, quickly issued a statement welcoming Henney as the new commissioner. In a public letter to her, chairman Wayne Barlow and executive director Stephen Northrup told Henney she now had "the opportunity to make a tremendous difference in the lives of our nation's citizens, the vast majority of whom at one point in their lives will rely upon the life-enhancing and lifesaving products developed by the medical device industry. As you prepare the FDA to meet the promise and the challenges of the next century, MDMA and its members stand ready to work with you as we together seek to bring safe, effective, and innovative medical technologies to patients with all deliberate speed."Anika Therapeutics (Woburn, MA) has received word from CDRH that its PMA for Orthovisc sodium hyaluronate, a device for treating osteoarthritis of the knee, is not approvable, and that additional clinical data are needed to show effectiveness. In its letter to the firm, CDRH suggested an agency consultation in the design of a new study.With a nationwide total product recall under way by Boston Scientific/Scimed (Natick, MA) less than two months after approval, CDRH director of surveillance and biometrics Larry G. Kessler issued a "dear colleague" letter on October 8 about the firm's NIR ON Ranger w/SOX Premounted Stent System.Kessler said his office had received "reports of device failures, including balloon ruptures leading to vessel dissection, balloon leaks resulting in incomplete stent deployment and/or stent migration, and difficulty deflating and removing the stent delivery system." As of October 8, Boston Scientific/Scimed had knowledge of one patient death and 26 patient injuries associated with these failures, Kessler said."We have recently learned that the balloon portion of the delivery catheter develops pinhole leaks and ruptures at inflation pressures as low as 3 atm," Kessler wrote. "This problem manifests during the stent deployment procedure. Preliminary failure investigation conducted by the manufacturer indicates that the cause of the balloon problem appears to be related to the SOX manufacturing process."He urged immediate discontinuation of any use of the product and return of unused catheters to the manufacturer for a no-cost exchange with the company's NIR ON Ranger without SOX. Through its so-called grassroots regulatory partnership movement, CDRH reengineering, reinvention of government, and the FDA Modernization Act, FDA has come a considerable distance toward meeting industry halfway on many issues.On one overture from industry, however, the agency will not be budging: FDA will not present the affected company's side of the case when it posts warning letters on its Internet home page.The suggestion came from a Glaxo Wellcome attorney at a FDLI seminar in September. He argued that simple fairness demanded that firms at least be given the option of including their responses to such agency letters, either by simultaneous attachment to the warning letter itself on FDA's site or by a link to the company's own home page.This, he felt, would mitigate some of the marketplace damage that occurs when trade competitors use FDA letters to disadvantage rivals in the purchasing community. His comment did not address the fact that most companies in the past have seemed reluctant to add weight to those unfortunate letters by offering any public comment on them whatsoever—but perhaps the new communications opportunities provided by the World Wide Web will change that traditional hesitancy.An internal FDA working group took up the idea in October but ruled against it. FDA communications staff director William Rados said the working group felt there were too many legal and logistical concerns. FDA would have to delay the posting of its letters if it were to include the company responses, and there were confidential commercial data issues as well as potential copyright issues to be negotiated in specific cases.Already the subject of congressional skepticism because of its ambitious scope, the U.S.-EU mutual recognition agreement transition period for medical device and drug inspections that had been scheduled to begin on November 1 was delayed for at least a month. The cited reason: "minor technical issues" that had delayed a triggering exchange of letters between FDA and EU that should have taken place before October 1.CDRH has released its draft handbook for performing inspections under the center's Quality Systems Inspections Technique (QSIT). An 18-month pilot program implementing the technique in three FDA districts started in October. The 85-page handbook is available on-line at ©1999 Medical Device & Diagnostic Industry

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